{"text": "There is a single methionine codon-initiated open reading frame of 1,458 nt in frame with a homeobox and a CAX repeat , and the open reading frame is predicted to encode a protein of 51,659 daltons.", "entity": [{"entity": "homeobox", "entity_type": "DNA", "pos": [92, 100]}, {"entity": "methionine codon-initiated open reading frame", "entity_type": "DNA", "pos": [18, 63]}, {"entity": "open reading frame", "entity_type": "DNA", "pos": [45, 63]}, {"entity": "CAX repeat", "entity_type": "DNA", "pos": [107, 117]}], "task": "NER"}
{"text": "When the homeodomain from HB24 was compared to known mammalian and Drosophila homeodomains it was found to be only moderately conserved, but when it was compared to a highly diverged Drosophila homeodomain , H2.0, it was found to be 80% identical.", "entity": [{"entity": "homeodomain", "entity_type": "DNA", "pos": [9, 20]}, {"entity": "homeodomain", "entity_type": "DNA", "pos": [78, 89]}, {"entity": "HB24", "entity_type": "DNA", "pos": [26, 30]}, {"entity": "Drosophila homeodomain", "entity_type": "DNA", "pos": [67, 89]}], "task": "NER"}
{"text": "The HB24 mRNA was absent or present at low levels in normal B and T lymphocytes ; however, with the appropriate activation signal HB24 mRNA was induced within several hours even in the presence of cycloheximide .", "entity": [{"entity": "HB24 mRNA", "entity_type": "RNA", "pos": [4, 13]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [66, 79]}, {"entity": "HB24 mRNA", "entity_type": "RNA", "pos": [130, 139]}], "task": "NER"}
{"text": "Characterization of HB24 expression in lymphoid and select developing tissues was performed by in situ hybridization .", "entity": [{"entity": "HB24", "entity_type": "DNA", "pos": [20, 24]}], "task": "NER"}
{"text": "Positive hybridization was found in thymus , tonsil , bone marrow , developing vessels , and in fetal brain .", "entity": [], "task": "NER"}
{"text": "HB24 is likely to have an important role in lymphocytes as well as in certain developing tissues .", "entity": [{"entity": "HB24", "entity_type": "DNA", "pos": [0, 4]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [44, 55]}], "task": "NER"}
{"text": "Platelet-activating factor induces phospholipid turnover , calcium flux , arachidonic acid liberation , eicosanoid generation , and oncogene expression in a human B cell line .", "entity": [{"entity": "Platelet-activating factor", "entity_type": "protein", "pos": [0, 26]}, {"entity": "oncogene", "entity_type": "DNA", "pos": [132, 140]}, {"entity": "human B cell line", "entity_type": "cell line", "pos": [157, 174]}], "task": "NER"}
{"text": "Platelet-activating factor is a potent mediator of the inflammatory response .", "entity": [{"entity": "Platelet-activating factor", "entity_type": "protein", "pos": [0, 26]}], "task": "NER"}
{"text": "Studies of the actions of platelet-activating factor have centered mainly around neutrophils , monocytes , and platelets .", "entity": [{"entity": "platelet-activating factor", "entity_type": "protein", "pos": [26, 52]}, {"entity": "platelets", "entity_type": "cell type", "pos": [111, 120]}, {"entity": "neutrophils", "entity_type": "cell type", "pos": [81, 92]}, {"entity": "monocytes", "entity_type": "cell type", "pos": [95, 104]}], "task": "NER"}
{"text": "In this report we begin to uncover the influence of platelet-activating factor on B lymphocytes .", "entity": [{"entity": "platelet-activating factor", "entity_type": "protein", "pos": [52, 78]}, {"entity": "B lymphocytes", "entity_type": "cell type", "pos": [82, 95]}], "task": "NER"}
{"text": "Employing the EBV-transformed human B cell line SKW6.4 , we demonstrate that platelet-activating factor significantly alters membrane phospholipid metabolism indicated by the incorporation of 32P into phosphatidylcholine , phosphatidylinositol , and phosphatidic acid but not significantly into phosphatidylethanolamine at concentrations ranging from 10(-9) to 10(-6) M.", "entity": [{"entity": "SKW6.4", "entity_type": "cell line", "pos": [48, 54]}, {"entity": "human B cell line", "entity_type": "cell line", "pos": [30, 47]}, {"entity": "EBV-transformed human B cell line", "entity_type": "cell line", "pos": [14, 47]}, {"entity": "platelet-activating factor", "entity_type": "protein", "pos": [77, 103]}], "task": "NER"}
{"text": "The inactive precursor, lyso-platelet-activating factor , at a concentration as high as 10(-7) M had no effect on any of the membrane phospholipids .", "entity": [{"entity": "lyso-platelet-activating factor", "entity_type": "protein", "pos": [24, 55]}], "task": "NER"}
{"text": "We also show that platelet-activating factor from 10(-12) to 10(-6) M induced rapid and significant elevation in intracellular calcium levels , whereas lyso- platelet-activating factor was again ineffective.", "entity": [{"entity": "platelet-activating factor", "entity_type": "protein", "pos": [18, 44]}, {"entity": "platelet-activating factor", "entity_type": "protein", "pos": [158, 184]}], "task": "NER"}
{"text": "We further demonstrate the impact of platelet-activating factor binding to B cells by measuring platelet-activating factor induced arachidonic acid release and 5-hydroxyeicosatetraenoic acid production.", "entity": [{"entity": "platelet-activating factor", "entity_type": "protein", "pos": [37, 63]}, {"entity": "platelet-activating factor", "entity_type": "protein", "pos": [96, 122]}, {"entity": "B cells", "entity_type": "cell type", "pos": [75, 82]}], "task": "NER"}
{"text": "Moreover, platelet-activating factor was capable of inducing transcription of the nuclear proto-oncogenes c-fos and c-jun .", "entity": [{"entity": "c-fos", "entity_type": "DNA", "pos": [106, 111]}, {"entity": "nuclear proto-oncogenes", "entity_type": "DNA", "pos": [82, 105]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [116, 121]}, {"entity": "platelet-activating factor", "entity_type": "protein", "pos": [10, 36]}], "task": "NER"}
{"text": "Finally we explored the possible role of 5-hydroxyeicosatetraenoic acid as a regulator of arachidonic acid liberation demonstrating that endogenous 5-lipoxygenase activity modulates platelet-activating factor induced arachidonic acid release perhaps acting at the level of phospholipase A2 .", "entity": [{"entity": "phospholipase A2", "entity_type": "protein", "pos": [273, 289]}, {"entity": "platelet-activating factor", "entity_type": "protein", "pos": [182, 208]}, {"entity": "5-lipoxygenase", "entity_type": "protein", "pos": [148, 162]}], "task": "NER"}
{"text": "In summary, platelet-activating factor is shown here to have a direct and profound effect on a pure B cell line .", "entity": [{"entity": "pure B cell line", "entity_type": "cell line", "pos": [95, 111]}, {"entity": "platelet-activating factor", "entity_type": "protein", "pos": [12, 38]}], "task": "NER"}
{"text": "Positive and negative regulation of immunoglobulin gene expression by a novel B-cell-specific enhancer element .", "entity": [{"entity": "immunoglobulin gene", "entity_type": "DNA", "pos": [36, 55]}, {"entity": "B-cell-specific enhancer element", "entity_type": "DNA", "pos": [78, 110]}], "task": "NER"}
{"text": "A new B-cell-specific enhancer element has been identified 3' of E4 and the octamerlike motifs in the human immunoglobulin heavy-chain gene enhancer .", "entity": [{"entity": "human immunoglobulin heavy-chain", "entity_type": "protein", "pos": [102, 134]}, {"entity": "B-cell-specific enhancer element", "entity_type": "DNA", "pos": [6, 38]}, {"entity": "human immunoglobulin heavy-chain gene enhancer", "entity_type": "DNA", "pos": [102, 148]}], "task": "NER"}
{"text": "Tandem copies of this 67-bp MnlI-AluI fragment , when fused to the chloramphenicol acetyltransferase gene driven by the conalbumin promoter , stimulated transcription in B cells but not in Jurkat T cells or HeLa cells .", "entity": [{"entity": "HeLa cells", "entity_type": "cell line", "pos": [207, 217]}, {"entity": "67-bp MnlI-AluI fragment", "entity_type": "DNA", "pos": [22, 46]}, {"entity": "conalbumin promoter", "entity_type": "DNA", "pos": [120, 139]}, {"entity": "B cells", "entity_type": "cell type", "pos": [170, 177]}, {"entity": "Jurkat T cells", "entity_type": "cell line", "pos": [189, 203]}, {"entity": "chloramphenicol acetyltransferase gene", "entity_type": "DNA", "pos": [67, 105]}], "task": "NER"}
{"text": "Footprinting analysis revealed that the identical sequence CCGAAACTGAAAAGG , designated E6 , was protected by nuclear extracts from B cells , T cells , or HeLa cells.", "entity": [{"entity": "E6", "entity_type": "DNA", "pos": [88, 90]}, {"entity": "T cells", "entity_type": "cell type", "pos": [142, 149]}, {"entity": "B cells", "entity_type": "cell type", "pos": [132, 139]}], "task": "NER"}
{"text": "Gel mobility shift assays using a synthetic E6 motif detected a B-cell-specific complex in addition to a ubiquitous band found also in T cells and HeLa cells .", "entity": [{"entity": "synthetic E6 motif", "entity_type": "DNA", "pos": [34, 52]}, {"entity": "B-cell-specific complex", "entity_type": "protein", "pos": [64, 87]}, {"entity": "T cells", "entity_type": "cell type", "pos": [135, 142]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [147, 157]}], "task": "NER"}
{"text": "In agreement with the results of gel retardation assays , tandem copies of the E6 motif stimulated transcription in ARH77 and Raji cells but not in Jurkat or HeLa cells .", "entity": [{"entity": "Raji cells", "entity_type": "cell line", "pos": [126, 136]}, {"entity": "ARH77", "entity_type": "cell line", "pos": [116, 121]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [158, 168]}, {"entity": "Jurkat", "entity_type": "cell line", "pos": [148, 154]}, {"entity": "E6 motif", "entity_type": "DNA", "pos": [79, 87]}], "task": "NER"}
{"text": "Furthermore, a mutant E6 motif lost both in vitro binding activity and in vivo enhancer activity .", "entity": [{"entity": "mutant E6 motif", "entity_type": "DNA", "pos": [15, 30]}], "task": "NER"}
{"text": "In striking contrast to the mouse Ig heavy-chain enhancer , in which the octamer motif acts as a B-cell-specific enhancer element , the human enhancer contains an octamerlike sequence with one base substitution which bound octamer-binding proteins with only very low affinity and showed no enhancer activity of its own.", "entity": [{"entity": "human enhancer", "entity_type": "DNA", "pos": [136, 150]}, {"entity": "octamerlike sequence", "entity_type": "DNA", "pos": [163, 183]}, {"entity": "B-cell-specific enhancer element", "entity_type": "DNA", "pos": [97, 129]}, {"entity": "mouse Ig heavy-chain enhancer", "entity_type": "DNA", "pos": [28, 57]}, {"entity": "octamer motif", "entity_type": "DNA", "pos": [73, 86]}, {"entity": "octamer-binding proteins", "entity_type": "protein", "pos": [223, 247]}], "task": "NER"}
{"text": "Interestingly, the MnlI-AluI fragment could suppress the basal-level activity of the conalbumin promoter in both Jurkat and HeLa cells .", "entity": [{"entity": "conalbumin promoter", "entity_type": "DNA", "pos": [85, 104]}, {"entity": "MnlI-AluI fragment", "entity_type": "DNA", "pos": [19, 37]}, {"entity": "Jurkat", "entity_type": "cell line", "pos": [113, 119]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [124, 134]}], "task": "NER"}
{"text": "Moreover, simian virus 40 enhancer activity was blocked by the MnlI-AluI fragment in HeLa cells but not in B cells .", "entity": [{"entity": "MnlI-AluI fragment", "entity_type": "DNA", "pos": [63, 81]}, {"entity": "B cells", "entity_type": "cell type", "pos": [107, 114]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [85, 95]}], "task": "NER"}
{"text": "Thus, the novel enhancer element identified in this study is probably a target site for both positive and negative factors .", "entity": [{"entity": "positive and negative factors", "entity_type": "protein", "pos": [93, 122]}, {"entity": "negative factors", "entity_type": "protein", "pos": [106, 122]}, {"entity": "positive", "entity_type": "protein", "pos": [93, 101]}], "task": "NER"}
{"text": "Charybdotoxin-sensitive, Ca(2+) -dependent membrane potential changes are not involved in human T or B cell activation and proliferation .", "entity": [], "task": "NER"}
{"text": "The involvement of ion channels in B and T lymphocyte activation is supported by many reports of changes in ion fluxes and membrane potential after mitogen binding .", "entity": [{"entity": "ion channels", "entity_type": "protein", "pos": [19, 31]}, {"entity": "mitogen", "entity_type": "protein", "pos": [148, 155]}], "task": "NER"}
{"text": "Human T and B lymphocytes demonstrate an early and transient hyperpolarization after ligand binding .", "entity": [], "task": "NER"}
{"text": "Inasmuch as the change in membrane potential is dependent on elevation of free cytosolic calcium , the hyperpolarization is presumably through opening of Ca(2+)-stimulated K+ channels.", "entity": [], "task": "NER"}
{"text": "We have used charybdotoxin , a known inhibitor of Ca(2+)-dependent K+ channels , to study the role of these channels in lymphocyte activation and mitogenesis .", "entity": [{"entity": "Ca(2+)-dependent K+ channels", "entity_type": "protein", "pos": [50, 78]}], "task": "NER"}
{"text": "We demonstrate that charybdotoxin inhibits the ligand-induced transient membrane hyperpolarization in B and T cells in a dose-dependent fashion, without affecting changes in cytosolic Ca2+ .", "entity": [], "task": "NER"}
{"text": "However, blockade of the Ca(2+)-activated K+ channel is not associated with changes in cell-cycle gene activation , IL-2 production , IL-2R expression or B and T cell mitogenesis .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [116, 120]}, {"entity": "IL-2R", "entity_type": "protein", "pos": [134, 139]}, {"entity": "Ca(2+)-activated K+ channel", "entity_type": "protein", "pos": [25, 52]}], "task": "NER"}
{"text": "These results imply that membrane potential changes secondary to the ligand-dependent opening of Ca(2+)-activated K+ channels are not involved in B and T lymphocyte activation and mitogenesis .", "entity": [{"entity": "Ca(2+)-activated K+ channels", "entity_type": "protein", "pos": [97, 125]}], "task": "NER"}
{"text": "Activity of the kappa B enhancer of the interleukin-2 receptor alpha chain in somatic cell hybrids is accompanied by the nuclear localization of NF-kappa B .", "entity": [{"entity": "kappa B enhancer", "entity_type": "DNA", "pos": [16, 32]}, {"entity": "interleukin-2 receptor alpha chain", "entity_type": "protein", "pos": [40, 74]}, {"entity": "somatic cell hybrids", "entity_type": "cell line", "pos": [78, 98]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [145, 155]}], "task": "NER"}
{"text": "The two nuclear proteins NF-kappa B (consisting of subunits p50 an dp65 ) and the DNA-binding subunit of NF-kappa B ( p50 ) by itself, also called KBF1 , are constitutively expressed and localized in the nucleus of the human T-cell line IARC 301.5 .", "entity": [{"entity": "human T-cell line", "entity_type": "cell line", "pos": [219, 236]}, {"entity": "KBF1", "entity_type": "protein", "pos": [147, 151]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [25, 35]}, {"entity": "two nuclear proteins", "entity_type": "protein", "pos": [4, 24]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [105, 115]}, {"entity": "IARC 301.5", "entity_type": "cell line", "pos": [237, 247]}, {"entity": "dp65", "entity_type": "protein", "pos": [67, 71]}, {"entity": "DNA-binding subunit", "entity_type": "protein", "pos": [82, 101]}, {"entity": "p50", "entity_type": "protein", "pos": [60, 63]}, {"entity": "p50", "entity_type": "protein", "pos": [118, 121]}], "task": "NER"}
{"text": "In order to define the roles of these two factors , which bind to the same kappa B enhancers , in transcription activation we have prepared somatic cell hybrids between IARC 301.5 and a murine myeloma .", "entity": [{"entity": "factors", "entity_type": "protein", "pos": [42, 49]}, {"entity": "kappa B enhancers", "entity_type": "DNA", "pos": [75, 92]}, {"entity": "IARC 301.5", "entity_type": "cell line", "pos": [169, 179]}, {"entity": "murine myeloma", "entity_type": "cell line", "pos": [186, 200]}], "task": "NER"}
{"text": "Most hybrids express both KBF1 and NF-kappa B in their nuclei , but one hybrid expresses only KBF1 .", "entity": [{"entity": "KBF1", "entity_type": "protein", "pos": [26, 30]}, {"entity": "KBF1", "entity_type": "protein", "pos": [94, 98]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [35, 45]}], "task": "NER"}
{"text": "The kappa B enhancer of the gene encoding the interleukin-2 ( IL-2 ) receptor alpha chain ( IL-2R alpha ) is functional only in the hybrids expressing nuclear NF-kappa B .", "entity": [{"entity": "nuclear NF-kappa B", "entity_type": "protein", "pos": [151, 169]}, {"entity": "IL-2R alpha", "entity_type": "protein", "pos": [92, 103]}, {"entity": "interleukin-2 ( IL-2 ) receptor alpha chain", "entity_type": "protein", "pos": [46, 89]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [159, 169]}, {"entity": "hybrids", "entity_type": "cell line", "pos": [132, 139]}, {"entity": "IL-2", "entity_type": "protein", "pos": [62, 66]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [46, 59]}, {"entity": "kappa B enhancer", "entity_type": "DNA", "pos": [4, 20]}], "task": "NER"}
{"text": "These findings show that nuclear NF-kappa B is necessary to activate the kappa B enhancer , while KBF1 by itself is not sufficient.", "entity": [{"entity": "KBF1", "entity_type": "protein", "pos": [98, 102]}, {"entity": "kappa B enhancer", "entity_type": "DNA", "pos": [73, 89]}, {"entity": "nuclear NF-kappa B", "entity_type": "protein", "pos": [25, 43]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [33, 43]}], "task": "NER"}
{"text": "We propose that KBF1 is a competitive inhibitor of NF-kappa B and discuss how these factors may be involved in the transient expression of IL-2 and IL-2 alpha genes during the immune response .", "entity": [{"entity": "KBF1", "entity_type": "protein", "pos": [16, 20]}, {"entity": "IL-2", "entity_type": "protein", "pos": [139, 143]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [51, 61]}, {"entity": "IL-2 alpha", "entity_type": "protein", "pos": [148, 158]}], "task": "NER"}
{"text": "T-helper-cell determinants in protein antigens are preferentially located in cysteine-rich antigen segments resistant to proteolytic cleavage by cathepsin B , L , and D .", "entity": [{"entity": "cysteine-rich antigen segments", "entity_type": "protein", "pos": [77, 107]}, {"entity": "T-helper-cell determinants", "entity_type": "protein", "pos": [0, 26]}, {"entity": "protein antigens", "entity_type": "protein", "pos": [30, 46]}], "task": "NER"}
{"text": "We report on a computer algorithm capable of predicting the location of T-helper-cell epitopes in protein antigen ( Ag ) by analysing the Ag amino acid sequence .", "entity": [{"entity": "amino acid sequence", "entity_type": "protein", "pos": [141, 160]}, {"entity": "Ag", "entity_type": "protein", "pos": [116, 118]}, {"entity": "protein antigen", "entity_type": "protein", "pos": [98, 113]}, {"entity": "Ag", "entity_type": "protein", "pos": [138, 140]}, {"entity": "T-helper-cell epitopes", "entity_type": "protein", "pos": [72, 94]}], "task": "NER"}
{"text": "The algorithm was constructed with the aim of identifying segments in Ag which are resistant to proteolytic degradation by the enzymes cathepsin B , L , and D .", "entity": [{"entity": "Ag", "entity_type": "protein", "pos": [70, 72]}], "task": "NER"}
{"text": "These are prominent enzymes in the endocytic pathway through which soluble protein Ag enter APC , and resistant segments in Ag may, therefore, be expected to contain more T-cell determinants than susceptible segments .", "entity": [{"entity": "APC", "entity_type": "protein", "pos": [92, 95]}, {"entity": "T-cell determinants", "entity_type": "protein", "pos": [171, 190]}, {"entity": "enzymes", "entity_type": "protein", "pos": [20, 27]}, {"entity": "susceptible segments", "entity_type": "protein", "pos": [196, 216]}, {"entity": "soluble protein Ag", "entity_type": "protein", "pos": [67, 85]}, {"entity": "resistant segments", "entity_type": "protein", "pos": [102, 120]}, {"entity": "Ag", "entity_type": "protein", "pos": [83, 85]}, {"entity": "Ag", "entity_type": "protein", "pos": [124, 126]}], "task": "NER"}
{"text": "From information available in the literature on the substrate specificity of the three enzymes , it is clear that a cysteine is not accepted in any of the S2 , S1 , S1' , and S2' subsites of cathepsin B and L , and not in the S1 and S1' subsites of cathepsin D .", "entity": [{"entity": "enzymes", "entity_type": "protein", "pos": [87, 94]}, {"entity": "S1'", "entity_type": "protein", "pos": [165, 168]}, {"entity": "cathepsin D", "entity_type": "protein", "pos": [249, 260]}, {"entity": "S1", "entity_type": "protein", "pos": [160, 162]}], "task": "NER"}
{"text": "Moreover, we have noticed that cysteine -containing T-cell determinants in a number of protein Ag are particularly rich in the amino acids alanine , glycine , lysine , leucine , serine , threonine , and valine .", "entity": [{"entity": "Ag", "entity_type": "protein", "pos": [95, 97]}, {"entity": "cysteine -containing T-cell determinants", "entity_type": "protein", "pos": [31, 71]}, {"entity": "protein Ag", "entity_type": "protein", "pos": [87, 97]}], "task": "NER"}
{"text": "By searching protein Ag for clusters of amino acids containing cysteine and two of the other amino acids we were able to predict 17 out of 23 empirically known T-cell determinants in the Ag with a relatively low number of false (positive) predictions.", "entity": [{"entity": "Ag", "entity_type": "protein", "pos": [21, 23]}, {"entity": "T-cell determinants", "entity_type": "protein", "pos": [160, 179]}, {"entity": "Ag", "entity_type": "protein", "pos": [187, 189]}], "task": "NER"}
{"text": "Furthermore, we present a new principle for searching Ag for potential amphipatic alpha-helical protein segments .", "entity": [{"entity": "amphipatic alpha-helical protein segments", "entity_type": "protein", "pos": [71, 112]}, {"entity": "Ag", "entity_type": "protein", "pos": [54, 56]}], "task": "NER"}
{"text": "Such segments accord well with empirically known T-cell determinants and our algorithm produces a lower number of false positive predictions than the principle based on discrete Fourier transformations previously described.", "entity": [{"entity": "T-cell determinants", "entity_type": "protein", "pos": [49, 68]}], "task": "NER"}
{"text": "Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1 : distinct patterns of viral growth are determined by T-cell types .", "entity": [{"entity": "T-cell types", "entity_type": "cell type", "pos": [171, 183]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [16, 26]}, {"entity": "Sp1 binding motifs", "entity_type": "DNA", "pos": [31, 49]}], "task": "NER"}
{"text": "Starting with a replication-incompetent molecular clone of human immunodeficiency virus type 1 , lacking all the NF-kappa B and Sp1 binding sites present in the native long terminal repeat ( LTR ), proviruses containing reconstructed LTRs with individual or combinations of NF-kappa B and Sp1 elements were generated and evaluated for their capacity to produce virus progeny following transfection-cocultivation .", "entity": [{"entity": "native long terminal repeat", "entity_type": "DNA", "pos": [161, 188]}, {"entity": "LTR", "entity_type": "DNA", "pos": [191, 194]}, {"entity": "reconstructed LTRs", "entity_type": "DNA", "pos": [220, 238]}], "task": "NER"}
{"text": "Virus stocks obtained from these experiments exhibited a continuum of replicative capacities in different human T-cell types depending on which element (s) was present in the LTR .", "entity": [{"entity": "LTR", "entity_type": "DNA", "pos": [175, 178]}, {"entity": "human T-cell types", "entity_type": "cell type", "pos": [106, 124]}, {"entity": "T-cell types", "entity_type": "cell type", "pos": [112, 124]}, {"entity": "element", "entity_type": "DNA", "pos": [144, 151]}], "task": "NER"}
{"text": "For example, in experiments involving proviral clones with LTRs containing one or two NF-kappa B elements (and no Sp1 binding sites ), a hierarchy of cellular permissivity to virus replication ( peripheral blood lymphocytes = MT4 greater than H9 greater than CEM greater than Jurkat ) was observed.", "entity": [{"entity": "H9", "entity_type": "cell line", "pos": [243, 245]}, {"entity": "Sp1 binding sites", "entity_type": "DNA", "pos": [114, 131]}, {"entity": "LTRs", "entity_type": "DNA", "pos": [59, 63]}, {"entity": "peripheral blood lymphocytes", "entity_type": "cell type", "pos": [195, 223]}, {"entity": "MT4", "entity_type": "cell line", "pos": [226, 229]}, {"entity": "NF-kappa B elements", "entity_type": "DNA", "pos": [86, 105]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [212, 223]}, {"entity": "Jurkat", "entity_type": "cell line", "pos": [276, 282]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [86, 96]}, {"entity": "CEM", "entity_type": "cell line", "pos": [259, 262]}], "task": "NER"}
{"text": "Of note was the associated emergence of second-site LTR revertants which involved an alteration of the TATA box .", "entity": [{"entity": "TATA box", "entity_type": "DNA", "pos": [103, 111]}, {"entity": "second-site LTR", "entity_type": "DNA", "pos": [40, 55]}], "task": "NER"}
{"text": "These results suggest that the human immunodeficiency virus type 1 LTR possesses functional redundancy which ensures virus replication in different T-cell types and is capable of changing depending on the particular combination of transcriptional factors present.", "entity": [{"entity": "T-cell types", "entity_type": "cell type", "pos": [148, 160]}, {"entity": "transcriptional factors", "entity_type": "protein", "pos": [231, 254]}, {"entity": "human immunodeficiency virus type 1 LTR", "entity_type": "DNA", "pos": [31, 70]}], "task": "NER"}
{"text": "Stimulation of interferon beta gene transcription in vitro by purified NF-kappa B and a novel TH protein .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [71, 81]}, {"entity": "TH protein", "entity_type": "protein", "pos": [94, 104]}, {"entity": "interferon beta gene", "entity_type": "DNA", "pos": [15, 35]}], "task": "NER"}
{"text": "The human interferon beta ( IFN-beta ) regulatory element consists of multiple enhanson domains which are targets for transcription factors involved in inducible expression of the promoter .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [118, 139]}, {"entity": "human interferon beta ( IFN-beta ) regulatory element", "entity_type": "DNA", "pos": [4, 57]}, {"entity": "promoter", "entity_type": "DNA", "pos": [180, 188]}, {"entity": "enhanson domains", "entity_type": "DNA", "pos": [79, 95]}, {"entity": "human interferon beta", "entity_type": "protein", "pos": [4, 25]}, {"entity": "IFN-beta", "entity_type": "protein", "pos": [28, 36]}], "task": "NER"}
{"text": "To further characterize the protein-DNA interactions mediating IFN-beta induction , positive regulatory domain (PRD) II binding proteins were purified from phorbol ester induced Jurkat T-cells and from IFN primed, cycloheximide/polyinosinic-polycytidylic acid treated HeLa S3 cells .", "entity": [{"entity": "IFN-beta", "entity_type": "protein", "pos": [63, 71]}, {"entity": "positive regulatory domain (PRD) II", "entity_type": "DNA", "pos": [84, 119]}, {"entity": "IFN", "entity_type": "protein", "pos": [63, 66]}, {"entity": "Jurkat T-cells", "entity_type": "cell line", "pos": [178, 192]}, {"entity": "positive regulatory domain (PRD) II binding proteins", "entity_type": "protein", "pos": [84, 136]}, {"entity": "IFN primed, cycloheximide/polyinosinic-polycytidylic acid treated HeLa S3 cells", "entity_type": "cell line", "pos": [202, 281]}], "task": "NER"}
{"text": "From HeLa cells , two major proteins of 52 and 45 kilodaltons (kD) copurified with DNA binding activity , whereas from T-cells , four proteins--a major protein of 52 kD and three minor proteins of 82 , 67 , and 43-47 kD --were purified.", "entity": [{"entity": "82", "entity_type": "protein", "pos": [197, 199]}, {"entity": "43-47 kD", "entity_type": "protein", "pos": [211, 219]}, {"entity": "major protein", "entity_type": "protein", "pos": [22, 35]}, {"entity": "T-cells", "entity_type": "cell type", "pos": [119, 126]}, {"entity": "minor proteins", "entity_type": "protein", "pos": [179, 193]}, {"entity": "67", "entity_type": "protein", "pos": [202, 204]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [5, 15]}, {"entity": "52 kD", "entity_type": "protein", "pos": [163, 168]}], "task": "NER"}
{"text": "Also, an induction specific DNA binding protein was purified from HeLa cells that interacted with the ( AAGTGA )4 tetrahexamer sequence and the PRDI domain .", "entity": [{"entity": "HeLa cells", "entity_type": "cell line", "pos": [66, 76]}, {"entity": "specific DNA binding protein", "entity_type": "protein", "pos": [19, 47]}, {"entity": "tetrahexamer sequence", "entity_type": "DNA", "pos": [114, 135]}, {"entity": "PRDI domain", "entity_type": "DNA", "pos": [144, 155]}], "task": "NER"}
{"text": "This protein is immunologically distinct from IRF-1/ISGF2 .", "entity": [{"entity": "IRF-1/ISGF2", "entity_type": "protein", "pos": [46, 57]}], "task": "NER"}
{"text": "Uninduced or Sendai virus induced HeLa extracts were used to examine transcription in vitro using a series of IFN beta promoter deletions .", "entity": [{"entity": "IFN beta promoter deletions", "entity_type": "DNA", "pos": [110, 137]}], "task": "NER"}
{"text": "Deletions upstream of the PRDII element increased transcription in the uninduced extract, indicating predominantly negative regulation of the promoter .", "entity": [{"entity": "promoter", "entity_type": "DNA", "pos": [142, 150]}, {"entity": "PRDII element", "entity_type": "DNA", "pos": [26, 39]}], "task": "NER"}
{"text": "A 2-4-fold increase in IFN-beta promoter transcription was observed in Sendai virus induced extracts , and deletion of PRDI and PRDII elements decreased this induced level of transcription .", "entity": [{"entity": "PRDII elements", "entity_type": "DNA", "pos": [128, 142]}, {"entity": "IFN-beta promoter", "entity_type": "DNA", "pos": [23, 40]}, {"entity": "PRDI", "entity_type": "DNA", "pos": [119, 123]}, {"entity": "PRDII", "entity_type": "DNA", "pos": [128, 133]}], "task": "NER"}
{"text": "When purified PRDII and tetrahexamer binding proteins were added to the induced extract, a 4-fold increase in transcription was observed.", "entity": [], "task": "NER"}
{"text": "These experiments demonstrate that it is possible to modulate IFN-beta transcription in vitro but indicate that additional proteins may be required to fully activate IFN-beta transcription .", "entity": [{"entity": "IFN-beta", "entity_type": "protein", "pos": [62, 70]}], "task": "NER"}
{"text": "The rhombotin family of cysteine -rich LIM-domain oncogenes : distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13 .", "entity": [{"entity": "cysteine -rich LIM-domain oncogenes", "entity_type": "DNA", "pos": [24, 59]}, {"entity": "rhombotin family", "entity_type": "DNA", "pos": [4, 20]}, {"entity": "T-cell translocations", "entity_type": "DNA", "pos": [95, 116]}], "task": "NER"}
{"text": "A chromosomal translocation in a T-cell leukemia involving the short arm of human chromosome 11 at band 11p15 disrupts the rhombotin gene .", "entity": [{"entity": "human chromosome 11", "entity_type": "DNA", "pos": [76, 95]}, {"entity": "band 11p15", "entity_type": "DNA", "pos": [99, 109]}, {"entity": "short arm", "entity_type": "DNA", "pos": [63, 72]}, {"entity": "rhombotin gene", "entity_type": "DNA", "pos": [123, 137]}], "task": "NER"}
{"text": "This gene encodes a protein with duplicated cysteine -rich regions called LIM domains , which show homology to zinc-binding proteins and to iron-sulfur centers of ferredoxins .", "entity": [{"entity": "ferredoxins", "entity_type": "protein", "pos": [163, 174]}, {"entity": "iron-sulfur centers", "entity_type": "protein", "pos": [140, 159]}, {"entity": "cysteine -rich regions", "entity_type": "protein", "pos": [44, 66]}, {"entity": "zinc-binding proteins", "entity_type": "protein", "pos": [111, 132]}, {"entity": "LIM domains", "entity_type": "protein", "pos": [74, 85]}], "task": "NER"}
{"text": "Two homologues of the rhombotin gene have now been isolated.", "entity": [{"entity": "rhombotin gene", "entity_type": "DNA", "pos": [22, 36]}], "task": "NER"}
{"text": "One of these, designated Rhom-2 , is located on human chromosome 11 at band 11p13 , where a cluster of T-cell leukemia-specific translocations occur; all translocation breakpoints at 11p13 are upstream of the Rhom-2 gene .", "entity": [{"entity": "Rhom-2", "entity_type": "DNA", "pos": [25, 31]}, {"entity": "T-cell leukemia-specific translocations", "entity_type": "DNA", "pos": [103, 142]}, {"entity": "human chromosome 11", "entity_type": "DNA", "pos": [48, 67]}, {"entity": "Rhom-2 gene", "entity_type": "DNA", "pos": [209, 220]}, {"entity": "band 11p13", "entity_type": "DNA", "pos": [71, 81]}, {"entity": "Rhom-2", "entity_type": "DNA", "pos": [209, 215]}, {"entity": "11p13", "entity_type": "DNA", "pos": [76, 81]}], "task": "NER"}
{"text": "Human and mouse Rhom-2 are highly conserved and, like rhombotin , encode two tandem cysteine -rich LIM domains .", "entity": [{"entity": "tandem cysteine -rich LIM domains", "entity_type": "DNA", "pos": [77, 110]}, {"entity": "rhombotin", "entity_type": "DNA", "pos": [54, 63]}, {"entity": "LIM domains", "entity_type": "protein", "pos": [99, 110]}], "task": "NER"}
{"text": "Rhom-2 mRNA is expressed in early mouse development in central nervous system , lung , kidney , liver , and spleen but only very low levels occur in thymus .", "entity": [{"entity": "Rhom-2 mRNA", "entity_type": "RNA", "pos": [0, 11]}, {"entity": "Rhom-2", "entity_type": "DNA", "pos": [0, 6]}], "task": "NER"}
{"text": "The other gene, designated Rhom-3 , is not on chromosome 11 but also retains homology to the LIM domain of rhombotin .", "entity": [{"entity": "Rhom-3", "entity_type": "DNA", "pos": [27, 33]}, {"entity": "LIM domain", "entity_type": "DNA", "pos": [93, 103]}, {"entity": "rhombotin", "entity_type": "DNA", "pos": [107, 116]}], "task": "NER"}
{"text": "Since the Rhom-2 gene is such a common site of chromosomal damage in T-cell tumors , the consistency of translocations near the rhombotin gene was further examined.", "entity": [{"entity": "rhombotin", "entity_type": "DNA", "pos": [128, 137]}, {"entity": "Rhom-2", "entity_type": "DNA", "pos": [10, 16]}, {"entity": "Rhom-2 gene", "entity_type": "DNA", "pos": [10, 21]}, {"entity": "T-cell tumors", "entity_type": "cell type", "pos": [69, 82]}, {"entity": "rhombotin gene", "entity_type": "DNA", "pos": [128, 142]}], "task": "NER"}
{"text": "A second translocation adjacent to rhombotin was found and at the same position as in the previous example.", "entity": [{"entity": "rhombotin", "entity_type": "DNA", "pos": [35, 44]}], "task": "NER"}
{"text": "Therefore, chromosome bands 11p15 ( rhombotin ) and 11p13 ( Rhom-2 ) are consistent sites of chromosome translocation in T-cell leukemia , with the 11p15 target more rarely involved.", "entity": [{"entity": "11p13", "entity_type": "DNA", "pos": [52, 57]}, {"entity": "chromosome bands 11p15", "entity_type": "DNA", "pos": [11, 33]}, {"entity": "rhombotin", "entity_type": "DNA", "pos": [36, 45]}, {"entity": "11p15 target", "entity_type": "DNA", "pos": [148, 160]}, {"entity": "Rhom-2", "entity_type": "DNA", "pos": [60, 66]}], "task": "NER"}
{"text": "The results define the rhombotin gene family as a class of T-cell oncogenes with duplicated cysteine -rich LIM domains .", "entity": [{"entity": "cysteine -rich LIM domains", "entity_type": "DNA", "pos": [92, 118]}, {"entity": "T-cell oncogenes", "entity_type": "DNA", "pos": [59, 75]}, {"entity": "LIM domains", "entity_type": "protein", "pos": [107, 118]}, {"entity": "rhombotin", "entity_type": "DNA", "pos": [23, 32]}], "task": "NER"}
{"text": "NF-kappa B activation by tumor necrosis factor alpha in the Jurkat T cell line is independent of protein kinase A , protein kinase C , and Ca(2+) -regulated kinases .", "entity": [{"entity": "tumor necrosis factor alpha", "entity_type": "protein", "pos": [25, 52]}, {"entity": "Ca(2+) -regulated kinases", "entity_type": "protein", "pos": [139, 164]}, {"entity": "Jurkat T cell line", "entity_type": "cell line", "pos": [60, 78]}, {"entity": "protein kinase A", "entity_type": "protein", "pos": [97, 113]}, {"entity": "protein kinase C", "entity_type": "protein", "pos": [116, 132]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [0, 10]}], "task": "NER"}
{"text": "NF-kappa B is a DNA-binding regulatory factor able to control transcription of a number of genes, including human immunodeficiency virus ( HIV ) genes .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [0, 10]}, {"entity": "human immunodeficiency virus ( HIV ) genes", "entity_type": "DNA", "pos": [108, 150]}, {"entity": "DNA-binding regulatory factor", "entity_type": "protein", "pos": [16, 45]}], "task": "NER"}
{"text": "In T cells , NF-kappa B is activated upon cellular treatment by phorbol esters and the cytokine tumor necrosis factor alpha ( TNF alpha ).", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [3, 10]}, {"entity": "tumor necrosis factor alpha", "entity_type": "protein", "pos": [96, 123]}, {"entity": "TNF alpha", "entity_type": "protein", "pos": [126, 135]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [13, 23]}], "task": "NER"}
{"text": "In the present work, we investigated the molecular events leading to NF-kappa B activation by TNF alpha in a human T cell line ( Jurkat ) and its subclone JCT6 , which presents a deficiency in the PKA transduction pathway .", "entity": [{"entity": "JCT6", "entity_type": "cell line", "pos": [155, 159]}, {"entity": "TNF alpha", "entity_type": "protein", "pos": [94, 103]}, {"entity": "PKA", "entity_type": "protein", "pos": [197, 200]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [69, 79]}, {"entity": "Jurkat", "entity_type": "cell line", "pos": [129, 135]}, {"entity": "human T cell line", "entity_type": "cell line", "pos": [109, 126]}], "task": "NER"}
{"text": "We found that in both cell lines, both phorbol ester and TNF alpha were able to activate NF-kappa B .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [89, 99]}, {"entity": "TNF alpha", "entity_type": "protein", "pos": [57, 66]}], "task": "NER"}
{"text": "Phorbol activation was positively modulated by Ca2+ influx while TNF alpha activation was not.", "entity": [{"entity": "TNF alpha", "entity_type": "protein", "pos": [65, 74]}], "task": "NER"}
{"text": "Furthermore, while PMA activation was inhibited by the PKC inhibitor staurosporin , the TNF alpha effect was unchanged.", "entity": [{"entity": "TNF alpha", "entity_type": "protein", "pos": [88, 97]}, {"entity": "PKC", "entity_type": "protein", "pos": [55, 58]}], "task": "NER"}
{"text": "TNF alpha did not activate cAMP production and its signal was not modulated by cAMP activators .", "entity": [{"entity": "TNF alpha", "entity_type": "protein", "pos": [0, 9]}], "task": "NER"}
{"text": "Moreover, cAMP activators did not activate NF-kappa B in Jurkat cells .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [43, 53]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [57, 69]}], "task": "NER"}
{"text": "Thus, TNF alpha -induced NF-kappa B activation was found to be mediated by none of the major signal-mediating kinases such as protein kinase C ( PKC ), protein kinase A , or Ca(2+)-regulated kinases .", "entity": [{"entity": "protein kinase A", "entity_type": "protein", "pos": [152, 168]}, {"entity": "Ca(2+)-regulated kinases", "entity_type": "protein", "pos": [174, 198]}, {"entity": "signal-mediating kinases", "entity_type": "protein", "pos": [93, 117]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [25, 35]}, {"entity": "TNF alpha", "entity_type": "protein", "pos": [6, 15]}, {"entity": "PKC", "entity_type": "protein", "pos": [145, 148]}, {"entity": "protein kinase C", "entity_type": "protein", "pos": [126, 142]}], "task": "NER"}
{"text": "Furthermore, we found that cytoplasmic acidification facilitated NF-kappa B activation by both TNF alpha and PKC , by a mechanism that increases NF-kappa B /I kappa B dissociation without affecting the NF-kappa B translocation step .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [65, 75]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [145, 155]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [202, 212]}, {"entity": "/I kappa B", "entity_type": "protein", "pos": [156, 166]}, {"entity": "TNF alpha", "entity_type": "protein", "pos": [95, 104]}, {"entity": "PKC", "entity_type": "protein", "pos": [109, 112]}], "task": "NER"}
{"text": "The functional domains of the murine Thy-1 gene promoter .", "entity": [{"entity": "murine Thy-1 gene promoter", "entity_type": "DNA", "pos": [30, 56]}], "task": "NER"}
{"text": "The Thy-1 gene promoter resembles a \"housekeeping\" promoter in that it is located within a methylation-free island , lacks a canonical TATA box , and displays heterogeneity in the 5'-end termini of the mRNA .", "entity": [{"entity": "canonical TATA box", "entity_type": "DNA", "pos": [125, 143]}, {"entity": "\"housekeeping\" promoter", "entity_type": "DNA", "pos": [36, 59]}, {"entity": "methylation-free island", "entity_type": "DNA", "pos": [91, 114]}, {"entity": "5'-end termini", "entity_type": "RNA", "pos": [180, 194]}, {"entity": "Thy-1 gene promoter", "entity_type": "DNA", "pos": [4, 23]}, {"entity": "mRNA", "entity_type": "RNA", "pos": [202, 206]}], "task": "NER"}
{"text": "Using transgenic mice , we show that this promoter does not confer any tissue specificity and is active only in a position-dependent manner .", "entity": [{"entity": "promoter", "entity_type": "DNA", "pos": [42, 50]}], "task": "NER"}
{"text": "It can only be activated in a tissue-specific manner by elements that lie downstream of the initiation site .", "entity": [{"entity": "initiation site", "entity_type": "DNA", "pos": [92, 107]}], "task": "NER"}
{"text": "We have analyzed the functional domains of the minimal Thy-1 promoter and show that the dominant promoter elements consist of multiple binding sites for the transcription factor Sp1 , an inverted CCAAT box , and sequences proximal to the transcription start site .", "entity": [{"entity": "Sp1", "entity_type": "protein", "pos": [178, 181]}, {"entity": "dominant promoter elements", "entity_type": "DNA", "pos": [88, 114]}, {"entity": "minimal Thy-1 promoter", "entity_type": "DNA", "pos": [47, 69]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [157, 177]}, {"entity": "multiple binding sites", "entity_type": "DNA", "pos": [126, 148]}, {"entity": "CCAAT box", "entity_type": "DNA", "pos": [196, 205]}, {"entity": "transcription start site", "entity_type": "DNA", "pos": [238, 262]}], "task": "NER"}
{"text": "DNase I and gel mobility shift assays show the binding of a number of nuclear factors to these elements , including Sp1 and CP1 .", "entity": [{"entity": "elements", "entity_type": "DNA", "pos": [95, 103]}, {"entity": "CP1", "entity_type": "protein", "pos": [124, 127]}, {"entity": "Sp1", "entity_type": "protein", "pos": [116, 119]}, {"entity": "nuclear factors", "entity_type": "protein", "pos": [70, 85]}], "task": "NER"}
{"text": "Our results show that the structure of this promoter only permits productive interactions of the two transcription factors Sp1 and CP1 with the basal transcription machinery in the presence of enhancer sequences .", "entity": [{"entity": "enhancer sequences", "entity_type": "DNA", "pos": [193, 211]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [101, 122]}, {"entity": "CP1", "entity_type": "protein", "pos": [131, 134]}, {"entity": "promoter", "entity_type": "DNA", "pos": [44, 52]}, {"entity": "Sp1", "entity_type": "protein", "pos": [123, 126]}], "task": "NER"}
{"text": "Nuclear factor kappa B activates proenkephalin transcription in T lymphocytes .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [64, 77]}, {"entity": "Nuclear factor kappa B", "entity_type": "protein", "pos": [0, 22]}], "task": "NER"}
{"text": "Upon activation, T lymphocytes accumulate high levels of the neuropeptide enkephalin which correlate with high levels of proenkephalin mRNA in the cells.", "entity": [{"entity": "proenkephalin mRNA", "entity_type": "RNA", "pos": [121, 139]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [17, 30]}], "task": "NER"}
{"text": "Here we investigated the transcriptional basis for these changes.", "entity": [], "task": "NER"}
{"text": "The proenkephalin promoter contains a sequence GGGGACGTCCCC , named B2 , which is similar to the kappa B sequence GGGGACTTTCC , the binding site of the transcription factor nuclear factor (NF)-kappa B .", "entity": [{"entity": "nuclear factor (NF)-kappa B", "entity_type": "protein", "pos": [173, 200]}, {"entity": "B2", "entity_type": "DNA", "pos": [68, 70]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [152, 172]}, {"entity": "kappa B sequence", "entity_type": "DNA", "pos": [97, 113]}], "task": "NER"}
{"text": "Activation of T lymphocytes induces an NF-kappa B -like binding activity to the B2 site, concomitant with activation of the proenkephalin promoter .", "entity": [{"entity": "proenkephalin promoter", "entity_type": "DNA", "pos": [124, 146]}, {"entity": "B2", "entity_type": "DNA", "pos": [80, 82]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [39, 49]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [14, 27]}], "task": "NER"}
{"text": "Mutations at the B2 site abolish this transcriptional activation .", "entity": [{"entity": "B2", "entity_type": "DNA", "pos": [17, 19]}], "task": "NER"}
{"text": "The purified homodimer (two p50s ) of the DNA-binding subunit of NF-kappa B binds the B2 site of proenkephalin relatively better than does the heterotetramer (two p65s plus two p50s ) form of the factor.", "entity": [{"entity": "p65s", "entity_type": "protein", "pos": [163, 167]}, {"entity": "B2", "entity_type": "DNA", "pos": [86, 88]}, {"entity": "DNA-binding subunit", "entity_type": "protein", "pos": [42, 61]}, {"entity": "heterotetramer", "entity_type": "protein", "pos": [143, 157]}, {"entity": "p50s", "entity_type": "protein", "pos": [28, 32]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [65, 75]}, {"entity": "p50s", "entity_type": "protein", "pos": [177, 181]}, {"entity": "homodimer", "entity_type": "protein", "pos": [13, 22]}], "task": "NER"}
{"text": "Thus, it appears that the T-cell-specific activation of the proenkephalin promoter is mediated by NF-kappa B .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [98, 108]}, {"entity": "proenkephalin promoter", "entity_type": "DNA", "pos": [60, 82]}], "task": "NER"}
{"text": "However, as NF-kappa B is ubiquitous and the transcriptional activation through the B2 site is T cell specific , yet another T-cell-specific factor which synergizes with NF-kappa B should be considered.", "entity": [{"entity": "B2", "entity_type": "DNA", "pos": [84, 86]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [12, 22]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [170, 180]}, {"entity": "T-cell-specific factor", "entity_type": "protein", "pos": [125, 147]}], "task": "NER"}
{"text": "Induction of NF-KB during monocyte differentiation by HIV type 1 infection .", "entity": [{"entity": "monocyte", "entity_type": "cell type", "pos": [26, 34]}, {"entity": "NF-KB", "entity_type": "protein", "pos": [13, 18]}], "task": "NER"}
{"text": "The production of human immunodeficiency virus type 1 ( HIV-1 ) progeny was followed in the U937 promonocytic cell line after stimulation either with retinoic acid or PMA , and in purified human monocytes and macrophages .", "entity": [{"entity": "U937 promonocytic cell line", "entity_type": "cell line", "pos": [92, 119]}], "task": "NER"}
{"text": "Electrophoretic mobility shift assays and Southwestern blotting experiments were used to detect the binding of cellular transactivation factor NF-KB to the double repeat-KB enhancer sequence located in the long terminal repeat .", "entity": [{"entity": "long terminal repeat", "entity_type": "DNA", "pos": [206, 226]}, {"entity": "NF-KB", "entity_type": "protein", "pos": [143, 148]}, {"entity": "double repeat-KB enhancer sequence", "entity_type": "DNA", "pos": [156, 190]}, {"entity": "cellular transactivation factor", "entity_type": "protein", "pos": [111, 142]}], "task": "NER"}
{"text": "PMA treatment , and not retinoic acid treatment of the U937 cells acts in inducing NF-KB expression in the nuclei .", "entity": [{"entity": "NF-KB", "entity_type": "protein", "pos": [83, 88]}, {"entity": "U937 cells", "entity_type": "cell line", "pos": [55, 65]}], "task": "NER"}
{"text": "In nuclear extracts from monocytes or macrophages , induction of NF-KB occurred only if the cells were previously infected with HIV-1 .", "entity": [{"entity": "NF-KB", "entity_type": "protein", "pos": [65, 70]}, {"entity": "monocytes", "entity_type": "cell type", "pos": [25, 34]}, {"entity": "macrophages", "entity_type": "cell type", "pos": [38, 49]}], "task": "NER"}
{"text": "When U937 cells were infected with HIV-1 , no induction of NF-KB factor was detected, whereas high level of progeny virions was produced, suggesting that this factor was not required for viral replication .", "entity": [{"entity": "U937 cells", "entity_type": "cell line", "pos": [5, 15]}, {"entity": "NF-KB factor", "entity_type": "protein", "pos": [59, 71]}, {"entity": "NF-KB", "entity_type": "protein", "pos": [59, 64]}], "task": "NER"}
{"text": "These results indicate that in monocytic cell lineage , HIV-1 could mimic some differentiation/activation stimuli allowing nuclear NF-KB expression .", "entity": [{"entity": "NF-KB", "entity_type": "protein", "pos": [131, 136]}, {"entity": "monocytic cell lineage", "entity_type": "cell line", "pos": [31, 53]}], "task": "NER"}
{"text": "Disruption of the human SCL locus by \" illegitimate\" V-(D)-J recombinase activity .", "entity": [{"entity": "human SCL locus", "entity_type": "DNA", "pos": [18, 33]}], "task": "NER"}
{"text": "A fusion complementary DNA in the T cell line HSB-2 elucidates a provocative mechanism for the disruption of the putative hematopoietic transcription factor SCL .", "entity": [{"entity": "T cell line HSB-2", "entity_type": "cell line", "pos": [34, 51]}, {"entity": "hematopoietic transcription factor", "entity_type": "protein", "pos": [122, 156]}, {"entity": "fusion complementary DNA", "entity_type": "DNA", "pos": [2, 26]}, {"entity": "SCL", "entity_type": "protein", "pos": [157, 160]}], "task": "NER"}
{"text": "The fusion cDNA results from an interstitial deletion between a previously unknown locus , SIL ( SCL interrupting locus ), and the 5' untranslated region of SCL .", "entity": [{"entity": "SIL", "entity_type": "DNA", "pos": [91, 94]}, {"entity": "SCL", "entity_type": "protein", "pos": [97, 100]}, {"entity": "unknown locus", "entity_type": "DNA", "pos": [75, 88]}, {"entity": "fusion cDNA", "entity_type": "DNA", "pos": [4, 15]}, {"entity": "SCL interrupting locus", "entity_type": "DNA", "pos": [97, 119]}, {"entity": "5' untranslated region", "entity_type": "DNA", "pos": [131, 153]}, {"entity": "SCL", "entity_type": "protein", "pos": [157, 160]}], "task": "NER"}
{"text": "Similar to 1;14 translocations , this deletion disrupts the SCL 5' regulatory region .", "entity": [{"entity": "SCL", "entity_type": "protein", "pos": [60, 63]}, {"entity": "SCL 5' regulatory region", "entity_type": "DNA", "pos": [60, 84]}], "task": "NER"}
{"text": "This event is probably mediated by V-(D)-J recombinase activity , although neither locus is an immunoglobulin or a T cell receptor .", "entity": [{"entity": "T cell receptor", "entity_type": "protein", "pos": [115, 130]}, {"entity": "immunoglobulin", "entity_type": "protein", "pos": [95, 109]}], "task": "NER"}
{"text": "Two other T cell lines , CEM and RPMI 8402 , have essentially identical deletions.", "entity": [{"entity": "RPMI 8402", "entity_type": "cell line", "pos": [33, 42]}, {"entity": "T cell lines", "entity_type": "cell line", "pos": [10, 22]}, {"entity": "CEM", "entity_type": "cell line", "pos": [25, 28]}], "task": "NER"}
{"text": "Thus, in lymphocytes , growth-affecting genes other than immune receptors risk rearrangements .", "entity": [{"entity": "immune receptors", "entity_type": "protein", "pos": [57, 73]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [9, 20]}, {"entity": "growth-affecting genes", "entity_type": "DNA", "pos": [23, 45]}], "task": "NER"}
{"text": "Thyroid hormone receptors form distinct nuclear protein- dependent and independent complexes with a thyroid hormone response element .", "entity": [{"entity": "thyroid hormone response element", "entity_type": "DNA", "pos": [100, 132]}, {"entity": "Thyroid hormone receptors", "entity_type": "protein", "pos": [0, 25]}], "task": "NER"}
{"text": "We have examined the binding of nuclear proteins and recombinant thyroid hormone receptors ( TRs ) to the palindromic thyroid hormone responsive element AGGTCATGACCT ( TREp ) using a gel electrophoretic mobility shift assay .", "entity": [{"entity": "TRs", "entity_type": "protein", "pos": [93, 96]}, {"entity": "TREp", "entity_type": "DNA", "pos": [168, 172]}, {"entity": "recombinant thyroid hormone receptors", "entity_type": "protein", "pos": [53, 90]}, {"entity": "palindromic thyroid hormone responsive element", "entity_type": "DNA", "pos": [106, 152]}, {"entity": "nuclear proteins", "entity_type": "protein", "pos": [32, 48]}], "task": "NER"}
{"text": "Four specific protein-DNA complexes were detected after incubation of nuclear extracts ( NE ) from T3-responsive pituitary (GH3) cells with a TREp -containing DNA fragment .", "entity": [{"entity": "T3-responsive pituitary (GH3) cells", "entity_type": "cell line", "pos": [99, 134]}, {"entity": "TREp -containing DNA fragment", "entity_type": "DNA", "pos": [142, 171]}, {"entity": "protein-DNA complexes", "entity_type": "protein", "pos": [14, 35]}, {"entity": "TREp", "entity_type": "DNA", "pos": [142, 146]}], "task": "NER"}
{"text": "This was compared with the TREp binding of reticulocyte lysate-synthesized TRs .", "entity": [{"entity": "TREp", "entity_type": "DNA", "pos": [27, 31]}, {"entity": "reticulocyte lysate-synthesized TRs", "entity_type": "protein", "pos": [43, 78]}, {"entity": "TRs", "entity_type": "protein", "pos": [75, 78]}], "task": "NER"}
{"text": "TR alpha 1 and TR beta 2 each formed a single major TR : TREp complex which comigrated with the least retarded complex formed by GH3 NE , while TR beta 1 formed multiple complexes suggesting that it can bind to TREp as an oligomer .", "entity": [{"entity": "oligomer", "entity_type": "protein", "pos": [222, 230]}, {"entity": "TR alpha 1", "entity_type": "protein", "pos": [0, 10]}, {"entity": "TREp", "entity_type": "DNA", "pos": [57, 61]}, {"entity": "TR", "entity_type": "protein", "pos": [0, 2]}, {"entity": "TR beta 1", "entity_type": "protein", "pos": [144, 153]}, {"entity": "TREp", "entity_type": "DNA", "pos": [211, 215]}, {"entity": "TR : TREp complex", "entity_type": "protein", "pos": [52, 69]}, {"entity": "TR beta 2", "entity_type": "protein", "pos": [15, 24]}], "task": "NER"}
{"text": "Interestingly, coincubation of 35S- TR alpha 1 , GH3 NE , and unlabeled TREp resulted in not only the 35S-TR: TREp complex , but in two additional more greatly retarded complexes containing 35S- TR alpha 1 and comigrating with those formed by GH3 extract alone.", "entity": [{"entity": "35S-TR: TREp complex", "entity_type": "protein", "pos": [102, 122]}, {"entity": "TR alpha 1", "entity_type": "protein", "pos": [36, 46]}, {"entity": "TR alpha 1", "entity_type": "protein", "pos": [195, 205]}, {"entity": "35S- TR alpha 1", "entity_type": "protein", "pos": [31, 46]}, {"entity": "TREp", "entity_type": "DNA", "pos": [72, 76]}, {"entity": "TREp", "entity_type": "DNA", "pos": [110, 114]}, {"entity": "35S- TR alpha 1", "entity_type": "protein", "pos": [190, 205]}], "task": "NER"}
{"text": "Incubation of each of the TRs with NE from COS-7 cells , which do not possess sufficient endogenous TRs to mediate T3-responses , resulted in formation of a new, more greatly shifted complex .", "entity": [{"entity": "COS-7 cells", "entity_type": "cell line", "pos": [43, 54]}, {"entity": "greatly shifted complex", "entity_type": "protein", "pos": [167, 190]}, {"entity": "TRs", "entity_type": "protein", "pos": [26, 29]}, {"entity": "TRs", "entity_type": "protein", "pos": [100, 103]}], "task": "NER"}
{"text": "A similar, heat labile activity which altered mobility of the TR:TRE complex was also present in NE from T3-unresponsive JEG-3 cells .", "entity": [{"entity": "T3-unresponsive JEG-3 cells", "entity_type": "cell line", "pos": [105, 132]}, {"entity": "TR:TRE complex", "entity_type": "protein", "pos": [62, 76]}], "task": "NER"}
{"text": "At high concentration of NE , all of the TR bound to TREp was more greatly retarded than in the absence of NE .", "entity": [{"entity": "TREp", "entity_type": "DNA", "pos": [53, 57]}, {"entity": "TR", "entity_type": "protein", "pos": [41, 43]}], "task": "NER"}
{"text": "Truncation of TR alpha 1 at amino acid 210 prevented additional complex formation in the presence of NE without affecting DNA binding , suggesting that the carboxyl-terminus of the TRs is essential for interaction with nuclear proteins .", "entity": [{"entity": "TRs", "entity_type": "protein", "pos": [181, 184]}, {"entity": "carboxyl-terminus", "entity_type": "protein", "pos": [156, 173]}, {"entity": "TR alpha 1", "entity_type": "protein", "pos": [14, 24]}, {"entity": "nuclear proteins", "entity_type": "protein", "pos": [219, 235]}, {"entity": "amino acid 210", "entity_type": "protein", "pos": [28, 42]}], "task": "NER"}
{"text": "(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": [], "task": "NER"}
{"text": "Cell-specific differences in activation of NF-kappa B regulatory elements of human immunodeficiency virus and beta interferon promoters by tumor necrosis factor .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [43, 53]}, {"entity": "NF-kappa B regulatory elements", "entity_type": "DNA", "pos": [43, 73]}, {"entity": "tumor necrosis factor", "entity_type": "protein", "pos": [139, 160]}], "task": "NER"}
{"text": "Three aspects of the involvement of tumor necrosis factor in human immunodeficiency virus ( HIV ) pathogenesis were examined.", "entity": [{"entity": "tumor necrosis factor", "entity_type": "protein", "pos": [36, 57]}], "task": "NER"}
{"text": "Tumor necrosis factor alpha ( TNF-alpha ) mRNA production was analyzed by polymerase chain reaction amplification in monocytic U937 cells and in a chronically HIV infected U937 cell line ( U9-IIIB ).", "entity": [{"entity": "U9-IIIB", "entity_type": "cell line", "pos": [189, 196]}, {"entity": "monocytic U937 cells", "entity_type": "cell line", "pos": [117, 137]}, {"entity": "Tumor necrosis factor alpha ( TNF-alpha ) mRNA", "entity_type": "RNA", "pos": [0, 46]}, {"entity": "chronically HIV infected U937 cell line", "entity_type": "cell line", "pos": [147, 186]}, {"entity": "Tumor necrosis factor alpha", "entity_type": "protein", "pos": [0, 27]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [30, 39]}], "task": "NER"}
{"text": "TNF-alpha RNA was undetectable in U937 cells , whereas a low constitutive level was detected in U9-IIIB cells .", "entity": [{"entity": "U9-IIIB cells", "entity_type": "cell line", "pos": [96, 109]}, {"entity": "TNF-alpha RNA", "entity_type": "RNA", "pos": [0, 13]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [0, 9]}, {"entity": "U937 cells", "entity_type": "cell line", "pos": [34, 44]}], "task": "NER"}
{"text": "Paramyxovirus infection induced a 5- to 10-fold increase in the steady-state level of TNF-alpha RNA in U9-IIIB cells compared with U937 cells , suggesting that HIV-infected monocytic cells produced higher levels of TNF-alpha than did normal cells after a secondary virus infection .", "entity": [{"entity": "TNF-alpha", "entity_type": "protein", "pos": [86, 95]}, {"entity": "U9-IIIB cells", "entity_type": "cell line", "pos": [103, 116]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [215, 224]}, {"entity": "HIV-infected monocytic cells", "entity_type": "cell line", "pos": [160, 188]}, {"entity": "TNF-alpha RNA", "entity_type": "RNA", "pos": [86, 99]}, {"entity": "U937 cells", "entity_type": "cell line", "pos": [131, 141]}], "task": "NER"}
{"text": "The effects of TNF-alpha on gene expression were examined by transient expression assays using reporter chloramphenicol acetyltransferase plasmids linked to regulatory elements from the HIV long terminal repeat ( LTR ) and the beta interferon promoter .", "entity": [{"entity": "beta interferon promoter", "entity_type": "DNA", "pos": [227, 251]}, {"entity": "regulatory elements", "entity_type": "DNA", "pos": [157, 176]}, {"entity": "HIV long terminal repeat", "entity_type": "DNA", "pos": [186, 210]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [15, 24]}, {"entity": "LTR", "entity_type": "DNA", "pos": [213, 216]}, {"entity": "reporter chloramphenicol acetyltransferase plasmids", "entity_type": "DNA", "pos": [95, 146]}], "task": "NER"}
{"text": "In U937 and Jurkat T lymphoid cells , the inducibility of the different hybrid promoters by TNF-alpha or phorbol ester varied in a cell type- and promoter context-specific manner; the levels of gene activity of NF-kappa B -containing plasmids correlated directly with induction of NF-kappa B DNA-binding activity .", "entity": [{"entity": "TNF-alpha", "entity_type": "protein", "pos": [92, 101]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [211, 221]}, {"entity": "NF-kappa B -containing plasmids", "entity_type": "DNA", "pos": [211, 242]}, {"entity": "hybrid promoters", "entity_type": "DNA", "pos": [72, 88]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [281, 291]}], "task": "NER"}
{"text": "Although the intact beta interferon promoter was only weakly stimulated by phorbol ester or TNF-alpha , multimers of the PRDII NF-kappa B -binding domain were inducible by both agents.", "entity": [{"entity": "TNF-alpha", "entity_type": "protein", "pos": [92, 101]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [127, 137]}, {"entity": "PRDII NF-kappa B -binding domain", "entity_type": "DNA", "pos": [121, 153]}, {"entity": "beta interferon promoter", "entity_type": "DNA", "pos": [20, 44]}], "task": "NER"}
{"text": "TNF-alpha was able to increase expression of the HIV LTR in T cells , but in monocytic cells , TNF-alpha did not induce the HIV LTR above a constitutive level of activity .", "entity": [{"entity": "monocytic cells", "entity_type": "cell type", "pos": [77, 92]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [0, 9]}, {"entity": "HIV LTR", "entity_type": "DNA", "pos": [49, 56]}, {"entity": "HIV LTR", "entity_type": "DNA", "pos": [124, 131]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [95, 104]}, {"entity": "T cells", "entity_type": "cell type", "pos": [60, 67]}], "task": "NER"}
{"text": "This level of NF-kappa B -independent activity appears to be sufficient for virus multiplication , since TNF-alpha treatment had no effect on the kinetics of de novo HIV type 1 ( HIV-1 ) infection and viral RNA production in U937 cells .", "entity": [{"entity": "U937 cells", "entity_type": "cell line", "pos": [225, 235]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [14, 24]}, {"entity": "viral RNA", "entity_type": "RNA", "pos": [201, 210]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [105, 114]}], "task": "NER"}
{"text": "However, in Jurkat cells , TNF-alpha dramatically enhanced the spread of HIV-1 through the cell population and increased viral RNA synthesis , indicating that in T cells HIV-1 multiplication was stimulated by TNF-alpha treatment .", "entity": [{"entity": "TNF-alpha", "entity_type": "protein", "pos": [27, 36]}, {"entity": "T cells", "entity_type": "cell type", "pos": [162, 169]}, {"entity": "viral RNA", "entity_type": "RNA", "pos": [121, 130]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [209, 218]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [12, 24]}], "task": "NER"}
{"text": "Functional analysis of cis-linked regulatory sequences in the HLA DRA promoter by transcription in vitro.", "entity": [{"entity": "HLA DRA promoter", "entity_type": "DNA", "pos": [62, 78]}, {"entity": "cis-linked regulatory sequences", "entity_type": "DNA", "pos": [23, 54]}], "task": "NER"}
{"text": "Two consensus sequences, called X and Y boxes , capable of binding nuclear proteins and regulating expression in B cells have been defined within the immediate upstream region of major histocompatibility complex (MHC) class II promoters .", "entity": [{"entity": "nuclear proteins", "entity_type": "protein", "pos": [67, 83]}, {"entity": "major histocompatibility complex (MHC) class II promoters", "entity_type": "DNA", "pos": [179, 236]}, {"entity": "B cells", "entity_type": "cell type", "pos": [113, 120]}], "task": "NER"}
{"text": "Unlike other class II promoters , the HLA-DR alpha (DRA) promoter also contains one element identical to the \"octamer\" motif of immunoglobulin variable region promoters that is responsible for B cell-specific transcription .", "entity": [{"entity": "\"octamer\" motif", "entity_type": "DNA", "pos": [109, 124]}, {"entity": "HLA-DR alpha (DRA) promoter", "entity_type": "DNA", "pos": [38, 65]}, {"entity": "class II promoters", "entity_type": "DNA", "pos": [13, 31]}, {"entity": "immunoglobulin variable region promoters", "entity_type": "DNA", "pos": [128, 168]}], "task": "NER"}
{"text": "This \" octamer \" in the context of DRA appears capable of binding both the ubiquitous ( OTF-1 ) and lymphoid-specific ( OTF-2 ) \"octamer\" binding proteins , but at least one other distinct \"octamer\" complex was found.", "entity": [{"entity": "OTF-2", "entity_type": "protein", "pos": [120, 125]}, {"entity": "lymphoid-specific ( OTF-2 ) \"octamer\" binding proteins", "entity_type": "protein", "pos": [100, 154]}, {"entity": "OTF-1", "entity_type": "protein", "pos": [88, 93]}, {"entity": "\"octamer\" complex", "entity_type": "protein", "pos": [189, 206]}, {"entity": "DRA", "entity_type": "protein", "pos": [35, 38]}, {"entity": "ubiquitous", "entity_type": "protein", "pos": [75, 85]}, {"entity": "octamer", "entity_type": "DNA", "pos": [7, 14]}], "task": "NER"}
{"text": "In order to characterize the function of cis-acting elements , we have developed an in vitro system in which a DRA promoter construct is transcribed more efficiently in extracts from B cells than in extracts from class II-negative HeLa cells .", "entity": [{"entity": "B cells", "entity_type": "cell type", "pos": [183, 190]}, {"entity": "cis-acting elements", "entity_type": "DNA", "pos": [41, 60]}, {"entity": "class II-negative HeLa cells", "entity_type": "cell line", "pos": [213, 241]}, {"entity": "DRA promoter construct", "entity_type": "DNA", "pos": [111, 133]}], "task": "NER"}
{"text": "5' deletion constructs which lacked the Y box , but retained the \"octamer\" motif and TATA box were completely inactive, and internal deletion of the Y box reduced transcription by 95%.", "entity": [{"entity": "Y box", "entity_type": "DNA", "pos": [40, 45]}, {"entity": "Y box", "entity_type": "DNA", "pos": [149, 154]}, {"entity": "TATA box", "entity_type": "DNA", "pos": [85, 93]}, {"entity": "\"octamer\" motif", "entity_type": "DNA", "pos": [65, 80]}], "task": "NER"}
{"text": "Using supercoiled, but not linear templates, we observed differences in transcription efficiencies from templates lacking or disrupting the X consensus element that reflect effects of random replacement of X box sequences in transient expression assays .", "entity": [{"entity": "X consensus element", "entity_type": "DNA", "pos": [140, 159]}, {"entity": "X box sequences", "entity_type": "DNA", "pos": [206, 221]}], "task": "NER"}
{"text": "Demonstration of the complete dependence on the Y box in this system suggests that, despite its demonstrated importance in the DRA promoter , the DRA \"octamer\" does not utilize OTF-2 in a manner analogous to immunoglobulin promoters in B cells .", "entity": [{"entity": "Y box", "entity_type": "DNA", "pos": [48, 53]}, {"entity": "immunoglobulin promoters", "entity_type": "DNA", "pos": [208, 232]}, {"entity": "DRA \"octamer\"", "entity_type": "DNA", "pos": [146, 159]}, {"entity": "OTF-2", "entity_type": "protein", "pos": [177, 182]}, {"entity": "B cells", "entity_type": "cell type", "pos": [236, 243]}, {"entity": "DRA promoter", "entity_type": "DNA", "pos": [127, 139]}], "task": "NER"}
{"text": "Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression .", "entity": [], "task": "NER"}
{"text": "Lipopolysaccharide ( LPS ) potently stimulates human immunodeficiency virus type 1-long terminal repeat ( HIV-1-LTR ) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line .", "entity": [{"entity": "human immunodeficiency virus type 1-long terminal repeat", "entity_type": "DNA", "pos": [47, 103]}, {"entity": "human immunodeficiency virus type 1-long terminal repeat ( HIV-1-LTR ) CAT constructs", "entity_type": "DNA", "pos": [47, 132]}, {"entity": "HIV-1-LTR", "entity_type": "DNA", "pos": [106, 115]}, {"entity": "T cell line", "entity_type": "cell line", "pos": [196, 207]}, {"entity": "monocyte/macrophage-like cell lines", "entity_type": "cell line", "pos": [150, 185]}], "task": "NER"}
{"text": "This effect appears to be mediated through the induction of nuclear factor kappa B ( NF-kappa B ).", "entity": [{"entity": "nuclear factor kappa B", "entity_type": "protein", "pos": [60, 82]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [85, 95]}], "task": "NER"}
{"text": "Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells .", "entity": [{"entity": "THP-1 cells", "entity_type": "cell line", "pos": [136, 147]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [113, 123]}, {"entity": "U937", "entity_type": "cell line", "pos": [127, 131]}], "task": "NER"}
{"text": "LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line , U1 , which produces very low levels of HIV-1 at baseline.", "entity": [{"entity": "U1", "entity_type": "cell line", "pos": [132, 134]}, {"entity": "chronically infected monocyte/macrophage-like cloned cell line", "entity_type": "cell line", "pos": [67, 129]}], "task": "NER"}
{"text": "The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor ( GM-CSF ) before treatment with LPS .", "entity": [{"entity": "GM-CSF", "entity_type": "protein", "pos": [151, 157]}, {"entity": "granulocyte/macrophage colony-stimulating factor", "entity_type": "protein", "pos": [100, 148]}], "task": "NER"}
{"text": "This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF-kappa B .", "entity": [{"entity": "HIV-1 RNA", "entity_type": "RNA", "pos": [84, 93]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [116, 126]}], "task": "NER"}
{"text": "LPS is not able to induce HIV-1 production in a cloned T cell line .", "entity": [{"entity": "T cell line", "entity_type": "cell line", "pos": [55, 66]}], "task": "NER"}
{"text": "The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection .", "entity": [], "task": "NER"}
{"text": "Steroid dose sparing : pharmacodynamic responses to single versus divided doses of methylprednisolone in man.", "entity": [], "task": "NER"}
{"text": "Inhibitory drug interactions affecting the metabolism of methylprednisolone ( MP ) may produce either steroid sparing or adverse effects partly by increasing the exposure time to the steroid .", "entity": [], "task": "NER"}
{"text": "This phenomenon can be mimicked by administering MP in divided doses.", "entity": [], "task": "NER"}
{"text": "Two types of responses were compared after a single MP dose (40 mg bolus) and a divided regimen (20 mg bolus and a 5 mg bolus 8 hours later) in six healthy male volunteers .", "entity": [], "task": "NER"}
{"text": "The suppression of basophils measured as whole blood histamine and plasma cortisol concentrations was assessed during 32 hours.", "entity": [{"entity": "basophils", "entity_type": "cell type", "pos": [19, 28]}], "task": "NER"}
{"text": "The 37.5% reduction in dose produced a 23% overall decreased blood histamine response .", "entity": [], "task": "NER"}
{"text": "A pharmacodynamic model for basophil cell distribution to and from an extravascular compartment describes the effects of MP after both regimens.", "entity": [], "task": "NER"}
{"text": "A slower initial decline in blood histamine after the divided regimen may be related to incomplete suppression of basophil cell return to blood .", "entity": [{"entity": "basophil cell", "entity_type": "cell type", "pos": [114, 127]}], "task": "NER"}
{"text": "The 50% inhibitory concentrations of MP of about 5 ng/ml were similar for both regimens.", "entity": [], "task": "NER"}
{"text": "The decline and return of cortisol concentrations were similar between MP treatments with suppression continuing for 24 hours.", "entity": [], "task": "NER"}
{"text": "The 50% inhibitory concentrations of MP values for adrenal suppression were about 1 ng/ml.", "entity": [], "task": "NER"}
{"text": "Pharmacodynamic modeling is useful in quantitating corticosteroid responses and generally predicted the \"dose-sparing\" effects that were achieved by prolonging MP plasma concentrations .", "entity": [], "task": "NER"}
{"text": "This study supports previous clinical observations that patients may require morning through evening exposure to MP to optimize efficacy while adrenal suppression is being minimized.", "entity": [], "task": "NER"}
{"text": "1,25(OH)2D2 production by T lymphocytes and alveolar macrophages recovered by lavage from normocalcemic patients with tuberculosis.", "entity": [{"entity": "alveolar macrophages", "entity_type": "cell type", "pos": [44, 64]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [26, 39]}], "task": "NER"}
{"text": "To compare extra-renal 1,25(OH)2D3 production in different types of granulomatous disease , and to identify the cell types responsible, we have evaluated the conversion of 25(OH)D3 in 1,25(OH)2D3 by uncultured cells recovered by bronchoalveolar lavage and blood mononuclear cells from normocalcemic patients with sarcoidosis and tuberculosis.", "entity": [{"entity": "blood mononuclear cells", "entity_type": "cell type", "pos": [256, 279]}, {"entity": "uncultured cells", "entity_type": "cell type", "pos": [199, 215]}], "task": "NER"}
{"text": "1,25(OH)2D3 was produced both by lavage cells (12/12 tuberculosis patients , 2/6 sarcoidosis patients ) and blood mononuclear cells (3/5 tuberculosis patients , 0/3 sarcoidosis patients ) from patients but not controls, but significantly greater amounts were produced by lavage cells from tuberculosis patients than those of sarcoidosis patients (P less than 0.001).", "entity": [{"entity": "lavage cells", "entity_type": "cell type", "pos": [33, 45]}, {"entity": "blood mononuclear cells", "entity_type": "cell type", "pos": [108, 131]}], "task": "NER"}
{"text": "1,25(OH)2D3 production by lavage cells from tuberculosis patients correlated with the number of CD8+ T lymphocytes present but not other cell types.", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [101, 114]}, {"entity": "lavage cells", "entity_type": "cell type", "pos": [26, 38]}], "task": "NER"}
{"text": "T lymphocytes appeared to be an important source of 1,25(OH)2D3 production , since purified T lymphocytes from all patients with tuberculosis produced 1,25(OH)2D3 , and 1,25(OH)2D3 production by these cells correlated closely with that produced by unseparated lavage cells .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [0, 13]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [92, 105]}, {"entity": "lavage cells", "entity_type": "cell type", "pos": [260, 272]}], "task": "NER"}
{"text": "Because 1,25(OH)2D3 can improve the capacity of macrophages to kill mycobacteria , our results support the conclusion that macrophage-lymphocyte interactions , mediated at least in part by 1,25(OH)2D3 , may be an important component of a successful antituberculous immune response .", "entity": [{"entity": "macrophages", "entity_type": "cell type", "pos": [48, 59]}], "task": "NER"}
{"text": "Megakaryocytic and erythrocytic lineages share specific transcription factors .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [56, 77]}], "task": "NER"}
{"text": "Erythroid-specific genes contain binding sites for NF-E1 (also called GF-1 and Eryf-1 ; refs 1-3 respectively), the principal DNA-binding protein of the erythrocytic lineage .", "entity": [{"entity": "Eryf-1", "entity_type": "protein", "pos": [79, 85]}, {"entity": "erythrocytic lineage", "entity_type": "cell type", "pos": [153, 173]}, {"entity": "DNA-binding protein", "entity_type": "protein", "pos": [126, 145]}, {"entity": "GF-1", "entity_type": "protein", "pos": [70, 74]}, {"entity": "Erythroid-specific genes", "entity_type": "DNA", "pos": [0, 24]}, {"entity": "NF-E1", "entity_type": "protein", "pos": [51, 56]}], "task": "NER"}
{"text": "NF-E1 expression seems to be restricted to the erythrocytic lineage .", "entity": [{"entity": "erythrocytic lineage", "entity_type": "cell type", "pos": [47, 67]}, {"entity": "NF-E1", "entity_type": "protein", "pos": [0, 5]}], "task": "NER"}
{"text": "A closely related (if not identical) protein is found in both a human megakaryocytic cell line and purified human megakaryocytes ; it binds to promoter regions of two megakaryocytic-specific genes .", "entity": [{"entity": "purified human megakaryocytes", "entity_type": "cell line", "pos": [99, 128]}, {"entity": "promoter regions", "entity_type": "DNA", "pos": [143, 159]}, {"entity": "human megakaryocytic cell line", "entity_type": "cell line", "pos": [64, 94]}, {"entity": "megakaryocytic-specific genes", "entity_type": "DNA", "pos": [167, 196]}], "task": "NER"}
{"text": "The binding sites and partial proteolysis profile of this protein are indistinguishable from those of the erythroid protein ; also, NF-E1 messenger RNA is the same size in both the megakaryocytic and erythroid cell lines .", "entity": [{"entity": "NF-E1", "entity_type": "protein", "pos": [132, 137]}, {"entity": "erythroid protein", "entity_type": "protein", "pos": [106, 123]}, {"entity": "NF-E1 messenger RNA", "entity_type": "RNA", "pos": [132, 151]}], "task": "NER"}
{"text": "Furthermore, point mutations that abolish binding of NF-E1 result in a 70% decrease in the transcriptional activity of a megakaryocytic-specific promoter .", "entity": [{"entity": "NF-E1", "entity_type": "protein", "pos": [53, 58]}, {"entity": "megakaryocytic-specific promoter", "entity_type": "DNA", "pos": [121, 153]}], "task": "NER"}
{"text": "We also find that NF-E2 , another trans-acting factor of the erythrocytic lineage , is present in megakaryocytes .", "entity": [{"entity": "erythrocytic lineage", "entity_type": "cell type", "pos": [61, 81]}, {"entity": "NF-E2", "entity_type": "protein", "pos": [18, 23]}, {"entity": "trans-acting factor", "entity_type": "protein", "pos": [34, 53]}, {"entity": "megakaryocytes", "entity_type": "cell line", "pos": [98, 112]}], "task": "NER"}
{"text": "Transcriptional effects in both lineages might then be mediated in part by the same specific trans-acting factors .", "entity": [{"entity": "trans-acting factors", "entity_type": "protein", "pos": [93, 113]}], "task": "NER"}
{"text": "Our data strengthen the idea of a close association between the erythrocytic and the megakaryocytic lineages and could also explain the expression of markers specific to the erythrocytic and megakaryocytic lineages in most erythroblastic and megakaryoblastic permanent cell lines .", "entity": [], "task": "NER"}
{"text": "Transcriptional down-regulation of c-myc expression by protein synthesis -dependent and -independent pathways in a human T lymphoblastic tumor cell line .", "entity": [{"entity": "human T lymphoblastic tumor cell line", "entity_type": "cell line", "pos": [115, 152]}, {"entity": "c-myc", "entity_type": "DNA", "pos": [35, 40]}], "task": "NER"}
{"text": "We show that in the human T lymphoblastic tumor cell line Molt4 c-myc mRNA and protein expression is down-regulated after exposure to dimethyl sulfoxide , to phorbol myristate acetate , or to the calcium ionophore A23187 , which raises the intracellular calcium concentration .", "entity": [{"entity": "c-myc", "entity_type": "DNA", "pos": [64, 69]}, {"entity": "human T lymphoblastic tumor cell line", "entity_type": "cell line", "pos": [20, 57]}, {"entity": "Molt4 c-myc mRNA", "entity_type": "RNA", "pos": [58, 74]}], "task": "NER"}
{"text": "A block to RNA elongation is largely responsible for decreased c-myc transcription .", "entity": [{"entity": "c-myc", "entity_type": "DNA", "pos": [63, 68]}], "task": "NER"}
{"text": "Although negative regulation by dimethyl sulfoxide takes place even when protein synthesis is inhibited by cycloheximide , the phorbol myristate acetate effect is blocked to some extent only by cycloheximide .", "entity": [], "task": "NER"}
{"text": "The calcium ionophore-induced c-myc suppression , however, strictly requires de novo protein synthesis .", "entity": [{"entity": "c-myc", "entity_type": "DNA", "pos": [30, 35]}], "task": "NER"}
{"text": "Therefore, two different negative regulatory pathways are involved in c-myc regulation : one which is independent and one which depends on de novo protein synthesis .", "entity": [{"entity": "c-myc", "entity_type": "DNA", "pos": [70, 75]}], "task": "NER"}
{"text": "The latter one appears to be mediated by a rapidly calcium -dependent induced gene product .", "entity": [{"entity": "calcium -dependent induced gene product", "entity_type": "protein", "pos": [51, 90]}], "task": "NER"}
{"text": "Oestrogen receptor ( ER ) analysis in B-cell chronic lymphocytic leukemia : correlation of biochemical and immunocytochemical methods .", "entity": [{"entity": "Oestrogen receptor", "entity_type": "protein", "pos": [0, 18]}, {"entity": "ER", "entity_type": "protein", "pos": [21, 23]}], "task": "NER"}
{"text": "Oestrogen receptors ( ER ) are present in neoplastic lymphoid cells and have been considered a physiological marker of growth rate or differentiation.", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [22, 24]}, {"entity": "Oestrogen receptors", "entity_type": "protein", "pos": [0, 19]}, {"entity": "neoplastic lymphoid cells", "entity_type": "cell type", "pos": [42, 67]}], "task": "NER"}
{"text": "Tamoxifen , an oestrogen antagonist , has been given in some patients with CLL and Hodgkin's disease , with dramatic response in single cases.", "entity": [], "task": "NER"}
{"text": "Until now, ER status has been assessed using a steroid binding assay ( SBA ) which has many inherent problems.", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [11, 13]}], "task": "NER"}
{"text": "Recently, the development of monoclonal antibodies directed against ER has been applied to the study of breast carcinomas and results obtained show good correlation with the quantitative SBA .", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [68, 70]}], "task": "NER"}
{"text": "We studied 49 cases of B-cell chronic lymphocytic leukemia ( CLL ) using immunostaining of cytospin preparations .", "entity": [], "task": "NER"}
{"text": "In 30 of these cases ER enzyme immunoassay ( ER -EIA ) was also performed.", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [21, 23]}, {"entity": "ER", "entity_type": "protein", "pos": [45, 47]}], "task": "NER"}
{"text": "Cultured MCF-7 cells , derived from a pleural effusion of a breast cancer patient , known to contain high levels of ER were used as a positive control (40-48% ER positive cells by immunocytochemistry; 200 fmol/mg protein by EIA).", "entity": [{"entity": "ER positive cells", "entity_type": "cell type", "pos": [159, 176]}, {"entity": "ER", "entity_type": "protein", "pos": [116, 118]}, {"entity": "Cultured MCF-7 cells", "entity_type": "cell line", "pos": [0, 20]}, {"entity": "ER", "entity_type": "protein", "pos": [159, 161]}], "task": "NER"}
{"text": "All of the CLL cases except two (96%) were negative for ER (less than 1% staining; less than 4 fmol/mg protein).", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [56, 58]}], "task": "NER"}
{"text": "The two positive cases expressed granular ER staining over the nucleus (9.2 and 12.1% positive cells) and were positive by EIA and SBA .", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [42, 44]}], "task": "NER"}
{"text": "It is concluded that (i) patients with CLL rarely express ER and (ii) immunocytochemical staining of cytospin preparations is a valid technique for the measurement of ER .", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [58, 60]}, {"entity": "ER", "entity_type": "protein", "pos": [167, 169]}], "task": "NER"}
{"text": "It is of interest that one of the positive cases was diagnosed as CLL with Richter's transformation confirming earlier findings.", "entity": [], "task": "NER"}
{"text": "Type-II estrogen binding sites in a lymphoblastoid cell line and growth-inhibitory effect of estrogen , anti-estrogen and bioflavonoids .", "entity": [{"entity": "lymphoblastoid cell line", "entity_type": "cell line", "pos": [36, 60]}, {"entity": "Type-II estrogen binding sites", "entity_type": "protein", "pos": [0, 30]}], "task": "NER"}
{"text": "Type-II estrogen -binding sites ( type-II EBS ) have been demonstrated in the human lymphoblastoid cell line IM-9 using a whole-cell assay with (6,7-3H) estradiol ( 3H-E2 ) as tracer.", "entity": [{"entity": "lymphoblastoid cell line", "entity_type": "cell line", "pos": [84, 108]}, {"entity": "IM-9", "entity_type": "cell line", "pos": [109, 113]}, {"entity": "type-II EBS", "entity_type": "protein", "pos": [34, 45]}, {"entity": "Type-II estrogen -binding sites", "entity_type": "protein", "pos": [0, 31]}, {"entity": "human lymphoblastoid cell line", "entity_type": "cell line", "pos": [78, 108]}], "task": "NER"}
{"text": "Competition analysis showed that the anti-estrogen tamoxifen and the flavonoids quercetin and rutin competed for (3H)-E2 binding to type-II EBS .", "entity": [{"entity": "type-II EBS", "entity_type": "protein", "pos": [132, 143]}], "task": "NER"}
{"text": "Growth experiments demonstrated that diethylstilbestrol ( DES ) tamoxifen ( TAM ), quercetin and rutin exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM.", "entity": [], "task": "NER"}
{"text": "The relative binding affinity of quercetin , rutin , DES and TAM for type-II EBS correlated well with their potency as cell growth inhibitors .", "entity": [{"entity": "type-II EBS", "entity_type": "protein", "pos": [69, 80]}], "task": "NER"}
{"text": "Moreover, hesperidin, a flavonoid which does not bind to type-II EBS , was ineffective in inhibiting cell growth .", "entity": [{"entity": "type-II EBS", "entity_type": "protein", "pos": [57, 68]}], "task": "NER"}
{"text": "Cell-cycle analysis showed that the growth-inhibitory effect of DES , TAM or quercetin was due to a blocking effect in the G0-G1 phases.", "entity": [], "task": "NER"}
{"text": "Our results suggest that high estrogen and anti-estrogen concentrations and flavonoids may regulate IM-9 cell growth through a common mechanism involving a binding interaction with type-II EBS .", "entity": [{"entity": "type-II EBS", "entity_type": "protein", "pos": [181, 192]}, {"entity": "IM-9", "entity_type": "cell line", "pos": [100, 104]}], "task": "NER"}
{"text": "[ Glucocorticoid receptors in peripheral blood lymphocytes of patients with bronchial asthma ]", "entity": [{"entity": "Glucocorticoid receptors", "entity_type": "protein", "pos": [2, 26]}, {"entity": "peripheral blood lymphocytes", "entity_type": "cell type", "pos": [30, 58]}], "task": "NER"}
{"text": "Quantitation of glucocorticoid receptors ( GCR ) and the study of their affinity for glucocorticosteroids ( GCS ) were made in peripheral blood lymphocytes of bronchial asthma ( BA ) patients in consideration of GCR treatment and serum levels of endogenous cortisol .", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [43, 46]}, {"entity": "GCR", "entity_type": "protein", "pos": [212, 215]}, {"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [16, 40]}, {"entity": "peripheral blood lymphocytes", "entity_type": "cell type", "pos": [127, 155]}], "task": "NER"}
{"text": "It is stated that GCR of healthy controls and GCS -untreated patients outnumbered those of cortisol-dependent BA patients on hormone therapy .", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [18, 21]}], "task": "NER"}
{"text": "Following discontinuation of glucocorticoid drugs GCR count in cortisol -dependent BA tends to rise.", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [50, 53]}], "task": "NER"}
{"text": "Endogenous cortisol has no effect on GCR level estimated by 3H-triamcinolone acetonide .", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [37, 40]}], "task": "NER"}
{"text": "Two glucocorticoid binding sites on the human glucocorticoid receptor .", "entity": [{"entity": "glucocorticoid binding sites", "entity_type": "protein", "pos": [4, 32]}, {"entity": "human glucocorticoid receptor", "entity_type": "protein", "pos": [40, 69]}], "task": "NER"}
{"text": "Glucocorticoids are known to have a lytic effect in leukemic cells via interactions with the glucocorticoid receptor ( GR ).", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [119, 121]}, {"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [93, 116]}, {"entity": "leukemic cells", "entity_type": "cell type", "pos": [52, 66]}], "task": "NER"}
{"text": "Cortisol and various synthetic glucocorticoids bind to the GR with one-site kinetics .", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [59, 61]}], "task": "NER"}
{"text": "Cortivazol ( CVZ ) is a unique, high potency synthetic glucocorticoid , which has a phenylpyrazol fused to the A-ring of the steroid nucleus and displays binding consistent with two or more sites in the cytosol from CEM C7 cells (a human acute lymphoblastic T-cell line ).", "entity": [{"entity": "CEM C7 cells", "entity_type": "cell line", "pos": [216, 228]}, {"entity": "human acute lymphoblastic T-cell line", "entity_type": "cell line", "pos": [232, 269]}], "task": "NER"}
{"text": "It has previously been shown that the lower affinity class of sites are similar in affinity and site molarity to those recognized by dexamethasone .", "entity": [], "task": "NER"}
{"text": "The higher affinity sites bind CVZ with 20- to 50-fold greater affinity , consistent with CVZ 's enhanced biological effects .", "entity": [], "task": "NER"}
{"text": "In mutant leukemic cells resistant to the lytic effects of dexamethasone , CVZ both lyses the cells and recognizes a single class of sites similar to the high affinity site in CEM C7 cells .", "entity": [{"entity": "leukemic cells", "entity_type": "cell type", "pos": [10, 24]}, {"entity": "CEM C7 cells", "entity_type": "cell line", "pos": [176, 188]}], "task": "NER"}
{"text": "We have carried out experiments to define the nature of the higher affinity CVZ binding site .", "entity": [{"entity": "higher affinity CVZ binding site", "entity_type": "protein", "pos": [60, 92]}], "task": "NER"}
{"text": "We now show that: 1) CVZ has more than one binding site in a second, independent, B-cell line , IM-9 ; 2) the antiglucocorticoid RU 38486 is able to block both CVZ 's higher and lower affinity sites; 3) all of CVZ 's binding sites are on a protein immunologically indistinguishable from the human GR ; and 4) freshly isolated clones of CVZ -resistant cells have lost all binding sites for CVZ .", "entity": [{"entity": "B-cell line", "entity_type": "cell line", "pos": [82, 93]}, {"entity": "IM-9", "entity_type": "cell line", "pos": [96, 100]}, {"entity": "GR", "entity_type": "protein", "pos": [297, 299]}, {"entity": "CVZ 's binding sites", "entity_type": "protein", "pos": [210, 230]}], "task": "NER"}
{"text": "These data indicate that CVZ is recognizing two glucocorticoid binding sites on the human GR or a protein very similar to it.", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [90, 92]}, {"entity": "glucocorticoid binding sites", "entity_type": "protein", "pos": [48, 76]}], "task": "NER"}
{"text": "Retroviral mediated transfer and expression of exogenous genes in primary lymphoid cells : assaying for a viral transactivator activity in normal and malignant cells .", "entity": [{"entity": "exogenous genes", "entity_type": "DNA", "pos": [47, 62]}, {"entity": "primary lymphoid cells", "entity_type": "cell type", "pos": [66, 88]}, {"entity": "transactivator", "entity_type": "protein", "pos": [112, 126]}], "task": "NER"}
{"text": "In this report we describe the use of recombinant retroviruses to characterize the activity of an exogenous promoter in primary cells obtained from patients with lymphoproliferative disorders .", "entity": [{"entity": "exogenous promoter", "entity_type": "DNA", "pos": [98, 116]}], "task": "NER"}
{"text": "The infection of a variety of cultured and primary lymphoid cells with a recombinant retrovirus containing a histone promoter-driven beta-galactosidase gene is shown to result in the expression of beta-galactosidase in 50% to 100% of the cells.", "entity": [{"entity": "histone promoter-driven beta-galactosidase gene", "entity_type": "DNA", "pos": [109, 156]}, {"entity": "histone promoter-driven beta-galactosidase", "entity_type": "protein", "pos": [109, 151]}, {"entity": "primary lymphoid cells", "entity_type": "cell type", "pos": [43, 65]}, {"entity": "beta-galactosidase", "entity_type": "protein", "pos": [133, 151]}], "task": "NER"}
{"text": "A similar infection with a recombinant retrovirus containing the beta-galactosidase gene with an adenovirus E2 promoter , results in beta-galactosidase activity in a limited number of cultured and primary cells .", "entity": [{"entity": "cultured", "entity_type": "cell line", "pos": [184, 192]}, {"entity": "primary cells", "entity_type": "cell type", "pos": [197, 210]}, {"entity": "adenovirus E2 promoter", "entity_type": "DNA", "pos": [97, 119]}, {"entity": "beta-galactosidase gene", "entity_type": "DNA", "pos": [65, 88]}, {"entity": "beta-galactosidase", "entity_type": "protein", "pos": [65, 83]}, {"entity": "beta-galactosidase", "entity_type": "protein", "pos": [133, 151]}], "task": "NER"}
{"text": "Since the adenovirus E2 promoter has been well characterized and is known to be regulated by transactivators encoded by many viruses , the activity of this promoter in specific cell types is discussed in reference to both the biology of the cell and the possible presence of as yet undetected viral gene products .", "entity": [{"entity": "viral gene products", "entity_type": "protein", "pos": [293, 312]}, {"entity": "transactivators", "entity_type": "protein", "pos": [93, 108]}, {"entity": "adenovirus E2 promoter", "entity_type": "DNA", "pos": [10, 32]}], "task": "NER"}
{"text": "[The effect of 24,25-dihydroxyvitamin D3 ( dioxyvit ) on Ca metabolism and immune status during chronic kidney failure ]", "entity": [], "task": "NER"}
{"text": "Active metabolite of vitamin D3 , 24R,25 (OH)2D3 ( dioxyvit ) was used at a daily dose of 100 micrograms in treatment of children affected with tubulointerstitial disease of kidney and with chronic glomerulonephritis under conditions of kidney insufficiency .", "entity": [], "task": "NER"}
{"text": "The drug exhibited distinct normalizing effect on patterns of calcium metabolism : increase of total and ionized Ca2+ and of 25-OHD , decrease in concentration of parath hormone and osteocalcine in blood serum as well as on immunological parameters : restoration of decreased content of T- and 0- lymphocytes .", "entity": [], "task": "NER"}
{"text": "Concentration of receptors of hormonal form of 1,25(OH)2D3 was found to be minimal in lymphocytes under conditions of chronic kidney insufficiency , while their expression, after the dioxyvit action, was detected only in patients with glomerulonephritis .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [86, 97]}], "task": "NER"}
{"text": "Specific calcitropic effect of dioxyvit with simultaneous correction of vitamin D deficiency were apparently responsible for high efficacy of the drug in treatment of calcium metabolism and immunity impairments in children with renal deteriorations at the step of chronic kidney insufficiency .", "entity": [], "task": "NER"}
{"text": "[The role of glucocorticoid receptors and HLA antigens in the pathogenesis of Cushing's syndrome ]", "entity": [{"entity": "HLA antigens", "entity_type": "protein", "pos": [42, 54]}, {"entity": "Cushing's syndrome", "entity_type": "protein", "pos": [78, 96]}, {"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [13, 37]}], "task": "NER"}
{"text": "Lymphocytic levels of glucocorticoid receptors were evaluated in 114 patients suffering from Icenko- Cushing's syndrome .", "entity": [{"entity": "Cushing's syndrome", "entity_type": "protein", "pos": [101, 119]}, {"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [22, 46]}], "task": "NER"}
{"text": "Incidence of HLA antigens was determined in 94 of them.", "entity": [{"entity": "HLA antigens", "entity_type": "protein", "pos": [13, 25]}], "task": "NER"}
{"text": "A significant rise of A10 and B27 antigen incidence compared to that in normal subjects allows these antigens to be considered genetic markers of Icenko- Cushing's syndrome .", "entity": [{"entity": "A10", "entity_type": "protein", "pos": [22, 25]}, {"entity": "B27 antigen", "entity_type": "protein", "pos": [30, 41]}, {"entity": "Cushing's syndrome", "entity_type": "protein", "pos": [154, 172]}], "task": "NER"}
{"text": "The levels of glucocorticoid receptors in lymphocytes of the patients are lower than in normal subjects both in the active stage of the disease and following bilateral total adrenalectomy .", "entity": [{"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [14, 38]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [42, 53]}], "task": "NER"}
{"text": "The patients carrying B27 antigen had lymphocytic receptor concentrations under the levels of such in patients free of the antigen carriage.", "entity": [{"entity": "B27 antigen", "entity_type": "protein", "pos": [22, 33]}], "task": "NER"}
{"text": "Antigen B27 seems to be a cause of lower levels of glucocorticoid receptors in blood lymphocytes .", "entity": [{"entity": "Antigen B27", "entity_type": "protein", "pos": [0, 11]}, {"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [51, 75]}, {"entity": "blood lymphocytes", "entity_type": "cell type", "pos": [79, 96]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [85, 96]}], "task": "NER"}
{"text": "Effects of 1 alpha, 25-dihydroxyvitamin D3 on the human chronic myelogenous leukemia cell line RWLeu-4 .", "entity": [{"entity": "human chronic myelogenous leukemia cell line", "entity_type": "cell line", "pos": [50, 94]}, {"entity": "RWLeu-4", "entity_type": "cell line", "pos": [95, 102]}], "task": "NER"}
{"text": "The effects of 1 alpha, 25-dihydroxyvitamin D3 ( VD3 ) on proliferation , differentiation , and macromolecular synthesis in the new Philadelphia chromosome-positive chronic myelogenous leukemia cell line , RWLeu-4 , were investigated.", "entity": [{"entity": "RWLeu-4", "entity_type": "cell line", "pos": [206, 213]}, {"entity": "Philadelphia chromosome-positive chronic myelogenous leukemia cell line", "entity_type": "cell line", "pos": [132, 203]}], "task": "NER"}
{"text": "Binding of [3H]VD3 was saturable, with approximately 2000-3000 sites/cell, and half-maximal binding occurring at 0.21-0.33 nM.", "entity": [], "task": "NER"}
{"text": "Treatment of RWLeu-4 cells with VD3 induced 24R-hydroxylase activity , a marker of vitamin D3 responsiveness in many tissues.", "entity": [{"entity": "24R-hydroxylase", "entity_type": "protein", "pos": [44, 59]}, {"entity": "RWLeu-4 cells", "entity_type": "cell line", "pos": [13, 26]}], "task": "NER"}
{"text": "Exposure of RWLeu-4 cells to VD3 also inhibited proliferation and DNA synthesis with a 50% effective dose of 3.5-10 nM within 72 h; in addition, protein and RNA synthesis were inhibited by VD3 treatment .", "entity": [{"entity": "RWLeu-4 cells", "entity_type": "cell line", "pos": [12, 25]}], "task": "NER"}
{"text": "Exposure of RWLeu-4 cells to 5 nM VD3 for 72 h caused 50% of the cells to differentiate into macrophage/monocyte type cells as judged by nitroblue tetrazolium staining and adherence to plastic.", "entity": [{"entity": "macrophage/monocyte type cells", "entity_type": "cell type", "pos": [93, 123]}, {"entity": "RWLeu-4 cells", "entity_type": "cell line", "pos": [12, 25]}], "task": "NER"}
{"text": "Progressive expression of cell surface maturation-specific antigens of the monocyte/macrophage lineage was induced by treatment of RWLeu-4 cells with VD3 for 24 to 72 h at doses that inhibited cellular proliferation .", "entity": [{"entity": "monocyte/macrophage lineage", "entity_type": "cell type", "pos": [75, 102]}, {"entity": "RWLeu-4 cells", "entity_type": "cell line", "pos": [131, 144]}, {"entity": "cell surface maturation-specific antigens", "entity_type": "protein", "pos": [26, 67]}], "task": "NER"}
{"text": "c-myc RNA , which is constitutively expressed in RWLeu-4 cells , increased after 0.5 h of treatment with 50 nM VD3 and then rapidly decreased to barely detectable levels after 4 h of treatment.", "entity": [{"entity": "c-myc RNA", "entity_type": "RNA", "pos": [0, 9]}, {"entity": "RWLeu-4 cells", "entity_type": "cell line", "pos": [49, 62]}], "task": "NER"}
{"text": "Finally, the in vitro tyrosine kinase activity associated with the p210bcr-abl oncogene product was decreased approximately 50% by VD3 treatment .", "entity": [{"entity": "p210bcr-abl oncogene", "entity_type": "DNA", "pos": [67, 87]}, {"entity": "p210bcr-abl oncogene product", "entity_type": "protein", "pos": [67, 95]}], "task": "NER"}
{"text": "Because of the presence of a functional receptor-effector system for VD3 and multiple biological responses to the hormone, these cells provide a unique model system with which to probe the specific effects of VD3 on cell growth and differentiation in chronic myelogenous leukemia .", "entity": [], "task": "NER"}
{"text": "A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter .", "entity": [{"entity": "HLA DR alpha promoter", "entity_type": "DNA", "pos": [71, 92]}, {"entity": "leucine zipper class", "entity_type": "protein", "pos": [20, 40]}, {"entity": "leucine zipper", "entity_type": "protein", "pos": [20, 34]}], "task": "NER"}
{"text": "Several mutants derived from transformed human B cell lines are defective in expressing major histocompatibility complex (MHC) class II genes .", "entity": [{"entity": "transformed human B cell lines", "entity_type": "cell line", "pos": [29, 59]}, {"entity": "major histocompatibility complex (MHC) class II genes", "entity_type": "DNA", "pos": [88, 141]}], "task": "NER"}
{"text": "The failure to express a class II gene in at least one such mutant line has been mapped to the MHC class II X box , a conserved transcriptional element in the promoter region .", "entity": [{"entity": "promoter region", "entity_type": "DNA", "pos": [159, 174]}, {"entity": "class II gene", "entity_type": "DNA", "pos": [25, 38]}, {"entity": "MHC class II X box", "entity_type": "DNA", "pos": [95, 113]}, {"entity": "conserved transcriptional element", "entity_type": "DNA", "pos": [118, 151]}, {"entity": "mutant line", "entity_type": "cell line", "pos": [60, 71]}], "task": "NER"}
{"text": "A complementary DNA encoding a DNA-binding protein ( human X box binding protein , hXBP-1 ) whose target is the human DR alpha X box and the 3' flanking region has now been cloned.", "entity": [{"entity": "DNA-binding protein", "entity_type": "protein", "pos": [31, 50]}, {"entity": "3' flanking region", "entity_type": "DNA", "pos": [141, 159]}, {"entity": "complementary DNA", "entity_type": "DNA", "pos": [2, 19]}, {"entity": "human DR alpha X box", "entity_type": "DNA", "pos": [112, 132]}, {"entity": "hXBP-1", "entity_type": "protein", "pos": [83, 89]}, {"entity": "human X box binding protein", "entity_type": "protein", "pos": [53, 80]}], "task": "NER"}
{"text": "This complementary DNA encoded a protein with structural similarities to the c-jun proto-oncogene product , and its target sequence was closely related to the palindromic target sequence of c-jun .", "entity": [{"entity": "complementary DNA", "entity_type": "DNA", "pos": [5, 22]}, {"entity": "c-jun proto-oncogene product", "entity_type": "protein", "pos": [77, 105]}, {"entity": "palindromic target sequence", "entity_type": "DNA", "pos": [159, 186]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [77, 82]}], "task": "NER"}
{"text": "Mutation of the hXBP-1 DNA target sequence decreased DR alpha promoter activity in vivo.", "entity": [{"entity": "hXBP-1 DNA target sequence", "entity_type": "DNA", "pos": [16, 42]}, {"entity": "hXBP-1", "entity_type": "protein", "pos": [16, 22]}, {"entity": "DR alpha promoter", "entity_type": "DNA", "pos": [53, 70]}], "task": "NER"}
{"text": "These studies suggest that the hXBP-1 protein acts as a transcription factor in B cells .", "entity": [{"entity": "transcription factor", "entity_type": "protein", "pos": [56, 76]}, {"entity": "hXBP-1 protein", "entity_type": "protein", "pos": [31, 45]}, {"entity": "B cells", "entity_type": "cell type", "pos": [80, 87]}, {"entity": "hXBP-1", "entity_type": "protein", "pos": [31, 37]}], "task": "NER"}
{"text": "Pseudohypoaldosteronism in eight families: different forms of inheritance are evidence for various genetic defects .", "entity": [], "task": "NER"}
{"text": "Pseudohypoaldosteronism is a rare hereditary disorder presenting in early infancy with renal salt loss leading to hyponatremia and hyperkalemia despite high levels of plasma aldosterone .", "entity": [], "task": "NER"}
{"text": "The patients are insensitive to mineralocorticoids ; however, sodium supplementation is able to correct electrolyte abnormalities .", "entity": [], "task": "NER"}
{"text": "Absent or greatly diminished type I aldosterone receptors in peripheral mononuclear leucocytes have been recently demonstrated and explain the lack of response to mineralocorticoids .", "entity": [{"entity": "peripheral mononuclear leucocytes", "entity_type": "cell type", "pos": [61, 94]}, {"entity": "I aldosterone receptors", "entity_type": "protein", "pos": [34, 57]}], "task": "NER"}
{"text": "We have studied the mode of inheritance in eight families with a total of nine patients .", "entity": [], "task": "NER"}
{"text": "There was evidence for an autosomal recessive form of inheritance in four families, while the other four families appeared to have an autosomal dominant mode of transmission .", "entity": [], "task": "NER"}
{"text": "In three families the autosomal recessive form was characterized by normal receptor as well as hormone data in both parents, while in one family receptor levels in both parents were greatly reduced, but hormone levels were normal.", "entity": [{"entity": "normal receptor", "entity_type": "protein", "pos": [68, 83]}], "task": "NER"}
{"text": "In the four families with an autosomal dominant mode of transmission there was always one parent with reduced receptor binding in peripheral mononuclear leucocytes and elevated serum hormone levels .", "entity": [{"entity": "peripheral mononuclear leucocytes", "entity_type": "cell type", "pos": [130, 163]}], "task": "NER"}
{"text": "These parents were entirely asymptomatic .", "entity": [], "task": "NER"}
{"text": "In an extended family we were able to study an aunt and her newborn daughter, who were both also biochemically affected but clinically asymptomatic .", "entity": [], "task": "NER"}
{"text": "It, therefore, appears that this dual pattern of genetic transmission may indicate differing genetic defects which cause the same clinical picture of pseudohypoaldosteronism .", "entity": [], "task": "NER"}
{"text": "Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients .", "entity": [{"entity": "estrogen/progesterone receptor", "entity_type": "protein", "pos": [35, 65]}, {"entity": "natural killer cell activity", "entity_type": "protein", "pos": [90, 118]}, {"entity": "natural killer cell", "entity_type": "cell type", "pos": [90, 109]}], "task": "NER"}
{"text": "This report is concerned with the prediction of natural killer (NK) cell activity in 61 Stage I and II breast cancer patients , between the ages of 25 and 70, who were accrued to this project.", "entity": [{"entity": "killer (NK) cell", "entity_type": "cell type", "pos": [56, 72]}], "task": "NER"}
{"text": "All baseline interview and testing data were obtained either just before patients were discharged from the hospital, or at their first outpatient visit, within two weeks of discharge.", "entity": [], "task": "NER"}
{"text": "A major interest of this project is the predictive value of perceived social support, as a potential \"stress\" buffer, related to NK activity .", "entity": [], "task": "NER"}
{"text": "In the main model reported here, we found that a significant amount of NK activity variance could be explained by five variables.", "entity": [], "task": "NER"}
{"text": "Higher NK activity could be predicted by the perception of high quality emotional support from a spouse or intimate other , perceived social support from the patient's physician , estrogen receptor -negative tumor status , having an excisional biopsy as surgical treatment , and actively seeking social support as a major coping strategy (R2 = 0.33, F(5,55) = 5.5, p less than 0.0004).", "entity": [{"entity": "social support", "entity_type": "protein", "pos": [134, 148]}, {"entity": "surgical treatment", "entity_type": "protein", "pos": [254, 272]}, {"entity": "estrogen receptor", "entity_type": "protein", "pos": [180, 197]}, {"entity": "excisional biopsy", "entity_type": "protein", "pos": [233, 250]}], "task": "NER"}
{"text": "Findings are discussed in terms of host interaction with tumor endocrine status , and the role that social support might play in modulating such activity.", "entity": [{"entity": "tumor endocrine status", "entity_type": "protein", "pos": [57, 79]}, {"entity": "social support", "entity_type": "protein", "pos": [100, 114]}], "task": "NER"}
{"text": "[ Estrogen receptor content of peripheral blood lymphocytes in patients with systemic lupus erythematosus ]", "entity": [{"entity": "Estrogen receptor", "entity_type": "protein", "pos": [2, 19]}, {"entity": "peripheral blood lymphocytes", "entity_type": "cell type", "pos": [31, 59]}], "task": "NER"}
{"text": "ER content in lymphocytes of peripheral blood from 27 SLE patients and 20 healthy controls were determined by dextran-coated charcoal assay .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [14, 25]}], "task": "NER"}
{"text": "ER content in lymphocytes of each sample was expressed by both fmol/mg of lymphocyte cytosolic protein and fmol/micrograms of lymphocyte DNA .", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [0, 2]}, {"entity": "lymphocyte DNA", "entity_type": "DNA", "pos": [126, 140]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [14, 25]}, {"entity": "lymphocyte cytosolic protein", "entity_type": "protein", "pos": [74, 102]}], "task": "NER"}
{"text": "The results showed that there was no significant difference between the ER content of lymphocytes from the controls and that from patients with SLE .", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [72, 74]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [86, 97]}], "task": "NER"}
{"text": "But the logarithmic mean of ER content in lymphocytes , expressed by fmol/mg of cytosolic protein , in 14 patients with active SLE (0.9356 +/- 0.31) was significantly higher than that in 13 patients with inactive SLE (0.2979 +/- 0.23, P less than 0.001) and in the controls (0.6204 +/- 0.52, P less than 0.001).", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [42, 53]}, {"entity": "ER", "entity_type": "protein", "pos": [28, 30]}, {"entity": "cytosolic protein", "entity_type": "protein", "pos": [80, 97]}], "task": "NER"}
{"text": "The normal upper limit of ER content in lymphocytes , expressed by fmol/micrograms of DNA, was 0.136.", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [26, 28]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [40, 51]}], "task": "NER"}
{"text": "The elevated rate of ER content in lymphocytes in 14 active SLE (92.9%) was also higher than that in quieiescent patients (23.1%, P less than 0.001) and in the controls (10%, P less than 0.001).", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [21, 23]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [35, 46]}], "task": "NER"}
{"text": "Moreover, the elevated level of ER content was found to be related to the positive antidsDNA antibody and hypocomplementemia .", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [32, 34]}, {"entity": "antidsDNA antibody", "entity_type": "protein", "pos": [83, 101]}], "task": "NER"}
{"text": "An in vitro globin gene switching model based on differentiated embryonic stem cells .", "entity": [{"entity": "globin gene", "entity_type": "DNA", "pos": [12, 23]}, {"entity": "differentiated embryonic stem cells", "entity_type": "cell type", "pos": [49, 84]}], "task": "NER"}
{"text": "We used mouse embryonic stem (ES) cells to study globin gene expression and switching in vitro.", "entity": [{"entity": "globin gene", "entity_type": "DNA", "pos": [49, 60]}, {"entity": "mouse embryonic stem (ES) cells", "entity_type": "cell type", "pos": [8, 39]}], "task": "NER"}
{"text": "We show that ES-derived embryoid bodies express the full complement of mouse embryonic globin genes in the correct temporal order and that on further differentiation , a switch occurs to the fetal/adult genes .", "entity": [{"entity": "fetal/adult genes", "entity_type": "DNA", "pos": [191, 208]}, {"entity": "ES-derived embryoid bodies", "entity_type": "cell type", "pos": [13, 39]}, {"entity": "mouse embryonic globin genes", "entity_type": "DNA", "pos": [71, 99]}], "task": "NER"}
{"text": "In addition, the erythroid-specific transcription factor NF-E1 was shown to be expressed coordinately with that of globin in embryoid bodies .", "entity": [{"entity": "NF-E1", "entity_type": "protein", "pos": [57, 62]}, {"entity": "globin", "entity_type": "protein", "pos": [115, 121]}, {"entity": "embryoid bodies", "entity_type": "cell type", "pos": [125, 140]}, {"entity": "erythroid-specific transcription factor", "entity_type": "protein", "pos": [17, 56]}], "task": "NER"}
{"text": "We conclude from these experiments that the ES cell system provides a good model to study hematopoietic development .", "entity": [], "task": "NER"}
{"text": "When the human epsilon- or beta- globin genes driven by the dominant control region ( DCR ) are introduced into this system, the human epsilon- globin gene , in contrast to the beta- globin gene , is not deregulated by the presence of the DCR and is expressed strictly as an embryonic gene .", "entity": [{"entity": "DCR", "entity_type": "DNA", "pos": [86, 89]}, {"entity": "globin gene", "entity_type": "DNA", "pos": [33, 44]}, {"entity": "beta- globin gene", "entity_type": "DNA", "pos": [27, 44]}, {"entity": "embryonic gene", "entity_type": "DNA", "pos": [275, 289]}, {"entity": "dominant control region", "entity_type": "DNA", "pos": [60, 83]}, {"entity": "globin gene", "entity_type": "DNA", "pos": [144, 155]}, {"entity": "human epsilon- globin gene", "entity_type": "DNA", "pos": [129, 155]}, {"entity": "DCR", "entity_type": "DNA", "pos": [239, 242]}], "task": "NER"}
{"text": "We conclude from this that the epsilon- globin gene is not regulated by competition with other genes in the human beta-globin locus .", "entity": [{"entity": "human beta-globin locus", "entity_type": "DNA", "pos": [108, 131]}, {"entity": "epsilon- globin gene", "entity_type": "DNA", "pos": [31, 51]}, {"entity": "globin gene", "entity_type": "DNA", "pos": [40, 51]}], "task": "NER"}
{"text": "Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs .", "entity": [{"entity": "mitogen-inducible gene", "entity_type": "DNA", "pos": [13, 35]}, {"entity": "kappa B DNA-binding protein", "entity_type": "protein", "pos": [47, 74]}, {"entity": "rel oncogene", "entity_type": "DNA", "pos": [96, 108]}, {"entity": "cell-cycle motifs", "entity_type": "DNA", "pos": [116, 133]}], "task": "NER"}
{"text": "We have cloned and characterized a mitogen-inducible gene isolated from human T cells that predicts a protein of 968 amino acids .", "entity": [{"entity": "mitogen-inducible gene", "entity_type": "DNA", "pos": [35, 57]}, {"entity": "968 amino acids", "entity_type": "protein", "pos": [113, 128]}, {"entity": "human T cells", "entity_type": "cell type", "pos": [72, 85]}], "task": "NER"}
{"text": "The amino-terminal domain has regions homologous to the oncogene rel and to the developmentally important gene dorsal of Drosophila .", "entity": [{"entity": "oncogene rel", "entity_type": "DNA", "pos": [56, 68]}, {"entity": "dorsal", "entity_type": "DNA", "pos": [111, 117]}, {"entity": "amino-terminal domain", "entity_type": "protein", "pos": [4, 25]}], "task": "NER"}
{"text": "The carboxy-terminal domain contains repeat structures found in a variety of proteins that are involved in cell-cycle control of yeast and in tissue differentiation in Drosophila and Ceanorhabditis elegans , as well as in the putative human oncogene bcl-3 and in the ankyrin protein .", "entity": [{"entity": "carboxy-terminal domain", "entity_type": "protein", "pos": [4, 27]}, {"entity": "ankyrin protein", "entity_type": "protein", "pos": [267, 282]}, {"entity": "putative human oncogene bcl-3", "entity_type": "DNA", "pos": [226, 255]}], "task": "NER"}
{"text": "A truncated form of the product of this gene translated in vitro is a DNA-binding protein which interacts specifically with the kappa B binding site found in many inducible genes , including the enhancer in human immunodeficiency virus .", "entity": [{"entity": "inducible genes", "entity_type": "DNA", "pos": [163, 178]}, {"entity": "kappa B binding site", "entity_type": "DNA", "pos": [128, 148]}, {"entity": "DNA-binding protein", "entity_type": "protein", "pos": [70, 89]}], "task": "NER"}
{"text": "This gene is yet another in a growing list of important regulatory molecules whose expression is transcriptionally induced upon cellular activation .", "entity": [], "task": "NER"}
{"text": "Extrarenal receptor-effector-mechanisms for aldosterone : the sequence of effects on the cellular electrolyte transport in human lymphocytes and their implications for disorders of the water and electrolyte balances .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [129, 140]}, {"entity": "human lymphocytes", "entity_type": "cell type", "pos": [123, 140]}], "task": "NER"}
{"text": "High affinity aldosterone binding sites have not only been described in the classic target tissues such as the renal tubules , but also in non-classic target tissues such as the hippocampus , mammary gland , endothelial cells and, recently, human mononuclear leukocytes .", "entity": [{"entity": "endothelial cells", "entity_type": "cell type", "pos": [208, 225]}, {"entity": "human mononuclear leukocytes", "entity_type": "cell type", "pos": [241, 269]}], "task": "NER"}
{"text": "An in vitro effect of aldosterone on intracellular sodium , potassium and calcium concentrations and cell volume was shown in human mononuclear leukocytes .", "entity": [{"entity": "human mononuclear leukocytes", "entity_type": "cell type", "pos": [126, 154]}], "task": "NER"}
{"text": "In the absence of aldosterone , the intracellular Na+ , K+ and Ca2+ concentrations and the cell volume decreased significantly, but remained constant when aldosterone (1.4 nmol/l) was added to the incubation medium .", "entity": [], "task": "NER"}
{"text": "These effects of aldosterone were blocked by the aldosterone antagonist canrenone (140 nmol/l).", "entity": [], "task": "NER"}
{"text": "The sodium/proton exchanger of the cell membrane could be identified as the primary target of the aldosterone action, possibly non-genomically mediated through membrane receptors .", "entity": [{"entity": "sodium/proton exchanger", "entity_type": "protein", "pos": [4, 27]}, {"entity": "membrane receptors", "entity_type": "protein", "pos": [160, 178]}], "task": "NER"}
{"text": "The clinical significance of this model was underlined by the demonstration of absent or a decreased number of mineralocorticoid receptors and the lack of electrolyte response to aldosterone in human mononuclear leukocytes of patients with pseudohypoaldosteronism and aldosteronism .", "entity": [{"entity": "mineralocorticoid receptors", "entity_type": "protein", "pos": [111, 138]}, {"entity": "human mononuclear leukocytes", "entity_type": "cell type", "pos": [194, 222]}], "task": "NER"}
{"text": "Additionally, an abnormal effector mechanism could be demonstrated in human mononuclear leukocytes from essential hypertensives .", "entity": [{"entity": "human mononuclear leukocytes", "entity_type": "cell type", "pos": [70, 98]}], "task": "NER"}
{"text": "These studies are the first to demonstrate the significance of extrarenal, nonepithelial mineralocorticoid receptors and the related effector mechanism in different disorders of the water and electrolyte balance in man .", "entity": [{"entity": "mineralocorticoid receptors", "entity_type": "protein", "pos": [89, 116]}, {"entity": "extrarenal, nonepithelial mineralocorticoid receptors", "entity_type": "protein", "pos": [63, 116]}], "task": "NER"}
{"text": "Immunohistochemical study of steroid hormones and an estrogen binding assay in malignant soft tissue tumors .", "entity": [{"entity": "malignant soft tissue tumors", "entity_type": "cell type", "pos": [79, 107]}], "task": "NER"}
{"text": "Immunohistochemically, the immunoreaction against 5 steroid hormone anti-sera ( estradiol , estriol , cortisol , progesterone and testosterone ) was examined in 39 cases with the malignant soft tissue tumors ( fibrosarcoma : 8, malignant fibrous histiocytoma : 6, rhabdomyosarcoma : 10, leiomyosarcoma : 10, liposarcoma : 5).", "entity": [{"entity": "malignant soft tissue tumors", "entity_type": "cell type", "pos": [179, 207]}], "task": "NER"}
{"text": "Seventeen cases revealed distinct immunostaining against at least 1 of the 5 steroid hormones .", "entity": [], "task": "NER"}
{"text": "Immunostained tumor cells were more frequently distributed in the area where tumor cell infiltration was more invasive.", "entity": [{"entity": "Immunostained tumor cells", "entity_type": "cell type", "pos": [0, 25]}], "task": "NER"}
{"text": "The majority of the positive cases occurred in female cases.", "entity": [], "task": "NER"}
{"text": "Furthermore, the existence of estrogen receptor (estrogen binding activity) was examined histochemically in 39 cases and it was detected in 8.", "entity": [{"entity": "estrogen receptor", "entity_type": "protein", "pos": [30, 47]}], "task": "NER"}
{"text": "We concluded that steroid hormones might be closely related to tumor cell infiltration of some malignant soft tissue tumors .", "entity": [{"entity": "malignant soft tissue tumors", "entity_type": "cell type", "pos": [95, 123]}], "task": "NER"}
{"text": "Involvement of cyclic AMP-dependent protein kinases in the signal transduction pathway for interleukin-1 .", "entity": [{"entity": "interleukin-1", "entity_type": "protein", "pos": [91, 104]}, {"entity": "cyclic AMP-dependent protein kinases", "entity_type": "protein", "pos": [15, 51]}], "task": "NER"}
{"text": "Expression of a highly specific protein inhibitor for cyclic AMP-dependent protein kinases in interleukin-1 (IL-1)-responsive cells blocked IL-1-induced gene transcription that was driven by the kappa immunoglobulin enhancer or the human immunodeficiency virus long terminal repeat .", "entity": [{"entity": "cyclic AMP-dependent protein kinases", "entity_type": "protein", "pos": [54, 90]}, {"entity": "interleukin-1", "entity_type": "protein", "pos": [94, 107]}, {"entity": "human immunodeficiency virus long terminal repeat", "entity_type": "DNA", "pos": [232, 281]}, {"entity": "kappa immunoglobulin enhancer", "entity_type": "DNA", "pos": [195, 224]}, {"entity": "IL-1-induced gene", "entity_type": "DNA", "pos": [140, 157]}, {"entity": "interleukin-1 (IL-1)-responsive cells", "entity_type": "cell line", "pos": [94, 131]}], "task": "NER"}
{"text": "This inhibitor did not affect protein kinase C -mediated gene transcription , suggesting that cyclic AMP-dependent protein kinases are involved in the signal transduction pathway for IL-1 in a number of responsive cell types .", "entity": [{"entity": "protein kinase C", "entity_type": "protein", "pos": [30, 46]}, {"entity": "cyclic AMP-dependent protein kinases", "entity_type": "protein", "pos": [94, 130]}, {"entity": "IL-1", "entity_type": "protein", "pos": [183, 187]}, {"entity": "responsive cell types", "entity_type": "cell type", "pos": [203, 224]}], "task": "NER"}
{"text": "The Epstein-Barr virus ( EBV ) ORI1yt enhancer is not B-cell specific and does not respond synergistically to the EBV transcription factors R and Z .", "entity": [{"entity": "Epstein-Barr virus ( EBV ) ORI1yt enhancer", "entity_type": "DNA", "pos": [4, 46]}], "task": "NER"}
{"text": "The Epstein-Barr virus DR promoter is located upstream of the PstI repeats , and in addition to the TATA box , it contains an upstream region (positions -69 to -220) responsive to EB1 (Z) (the BZLF1-encoded transcription factor ) and an enhancer with two functionally distinct domains, A and B .", "entity": [{"entity": "PstI repeats", "entity_type": "DNA", "pos": [62, 74]}, {"entity": "B", "entity_type": "DNA", "pos": [12, 13]}, {"entity": "EB1 (Z)", "entity_type": "protein", "pos": [180, 187]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [237, 245]}, {"entity": "TATA box", "entity_type": "DNA", "pos": [100, 108]}, {"entity": "upstream region", "entity_type": "DNA", "pos": [126, 141]}, {"entity": "BZLF1-encoded transcription factor", "entity_type": "protein", "pos": [193, 227]}, {"entity": "A", "entity_type": "DNA", "pos": [101, 102]}, {"entity": "Epstein-Barr virus DR promoter", "entity_type": "DNA", "pos": [4, 34]}], "task": "NER"}
{"text": "Domain B has been described as a B-cell-specific EB1 -responsive element (P.M.Lieberman, J.M.Hardwick, and S.D.Hayward, J.Virol.63:3040-3050, 1989) activated synergistically by EB1 and R , an EBV early product encoded by the open reading frame BRLF1 (M.A. Cox, J.Leahy, and J.M.Hardwick, J.Virol.64:313-321, 1990).", "entity": [{"entity": "EB1", "entity_type": "protein", "pos": [49, 52]}, {"entity": "open reading frame BRLF1", "entity_type": "DNA", "pos": [225, 249]}, {"entity": "EBV early product", "entity_type": "protein", "pos": [192, 209]}, {"entity": "B-cell-specific EB1 -responsive element", "entity_type": "DNA", "pos": [33, 72]}, {"entity": "R", "entity_type": "protein", "pos": [185, 186]}, {"entity": "Domain B", "entity_type": "DNA", "pos": [0, 8]}, {"entity": "EB1", "entity_type": "protein", "pos": [177, 180]}, {"entity": "BRLF1", "entity_type": "DNA", "pos": [244, 249]}], "task": "NER"}
{"text": "We show here that domain B is an R-responsive element in HeLa cells and is therefore not an EB1 -responsive B-cell-specific element .", "entity": [{"entity": "EB1", "entity_type": "protein", "pos": [92, 95]}, {"entity": "R-responsive element", "entity_type": "DNA", "pos": [33, 53]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [57, 67]}, {"entity": "domain B", "entity_type": "DNA", "pos": [18, 26]}, {"entity": "EB1 -responsive B-cell-specific element", "entity_type": "DNA", "pos": [92, 131]}], "task": "NER"}
{"text": "However, there is an EB1 -binding site ( ZRE-B ) located within the R-responsive enhancer region .", "entity": [{"entity": "R-responsive enhancer region", "entity_type": "DNA", "pos": [68, 96]}, {"entity": "EB1 -binding site", "entity_type": "DNA", "pos": [21, 38]}, {"entity": "EB1", "entity_type": "protein", "pos": [21, 24]}, {"entity": "ZRE-B", "entity_type": "DNA", "pos": [41, 46]}], "task": "NER"}
{"text": "ZRE-B can be deleted without affecting the R-dependent enhancer activity .", "entity": [{"entity": "ZRE-B", "entity_type": "DNA", "pos": [0, 5]}], "task": "NER"}
{"text": "Moreover, there is no cooperation or synergy between R and EB1 when activating the B domain ( ZRE-B plus the R-responsive element ) positioned as an enhancer .", "entity": [{"entity": "EB1", "entity_type": "protein", "pos": [59, 62]}, {"entity": "ZRE-B", "entity_type": "DNA", "pos": [94, 99]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [149, 157]}, {"entity": "B domain", "entity_type": "DNA", "pos": [83, 91]}, {"entity": "R", "entity_type": "protein", "pos": [53, 54]}, {"entity": "R-responsive element", "entity_type": "DNA", "pos": [109, 129]}], "task": "NER"}
{"text": "ZRE-B is therefore not part of the R- inducible enhancer .", "entity": [{"entity": "ZRE-B", "entity_type": "DNA", "pos": [0, 5]}, {"entity": "R- inducible enhancer", "entity_type": "DNA", "pos": [35, 56]}], "task": "NER"}
{"text": "We have tested several subregions of the DR enhancer B domain , either alone or in combination, for their capacity to transmit the R-activating signal to the rabbit beta-globin promoter .", "entity": [{"entity": "rabbit beta-globin promoter", "entity_type": "DNA", "pos": [158, 185]}, {"entity": "B domain", "entity_type": "DNA", "pos": [53, 61]}, {"entity": "DR enhancer", "entity_type": "DNA", "pos": [41, 52]}], "task": "NER"}
{"text": "We found that the R-responsive element is composed of four protoenhancers that span the whole B domain .", "entity": [{"entity": "B domain", "entity_type": "DNA", "pos": [94, 102]}, {"entity": "protoenhancers", "entity_type": "DNA", "pos": [59, 73]}, {"entity": "R-responsive element", "entity_type": "DNA", "pos": [18, 38]}], "task": "NER"}
{"text": "These protoenhancers alone are weakly or not responsive to R .", "entity": [{"entity": "protoenhancers", "entity_type": "DNA", "pos": [6, 20]}, {"entity": "R", "entity_type": "protein", "pos": [59, 60]}], "task": "NER"}
{"text": "One of the protoenhancers contains the overlapping palindromes 5'-TTGTCCcgtGGACAAaTGTCC-3' .", "entity": [{"entity": "protoenhancers", "entity_type": "DNA", "pos": [11, 25]}, {"entity": "overlapping palindromes", "entity_type": "DNA", "pos": [39, 62]}], "task": "NER"}
{"text": "However, one palindrome , either alone or duplicated, or the overlapping palindromes did not respond to R.", "entity": [{"entity": "palindrome", "entity_type": "DNA", "pos": [13, 23]}, {"entity": "overlapping palindromes", "entity_type": "DNA", "pos": [61, 84]}], "task": "NER"}
{"text": "Nuclear 3,5,3'-triiodothyronine receptors ( T3R ) of circulating human lymphocytes in hyper- and hypo thyroidism and nonthyroidal diseases .", "entity": [{"entity": "3,5,3'-triiodothyronine receptors", "entity_type": "protein", "pos": [8, 41]}, {"entity": "T3R", "entity_type": "protein", "pos": [44, 47]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [71, 82]}, {"entity": "circulating human lymphocytes", "entity_type": "cell type", "pos": [53, 82]}], "task": "NER"}
{"text": "The clinical implications of nuclear T3R alterations of circulating lymphocytes in hyperthyroidism , hypothyroidism and nonthyroidal diseases were investigated.", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [68, 79]}, {"entity": "T3R", "entity_type": "protein", "pos": [37, 40]}, {"entity": "circulating lymphocytes", "entity_type": "cell type", "pos": [56, 79]}], "task": "NER"}
{"text": "Nuclear T3R in lymphocytes was determined by radio-ligand binding analysis .", "entity": [{"entity": "T3R", "entity_type": "protein", "pos": [8, 11]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [15, 26]}], "task": "NER"}
{"text": "The results showed that in hyper- and hypo thyroid patients the nuclear affinity ( Ka ) for T3 was similar to that of normal subjects .", "entity": [], "task": "NER"}
{"text": "In hyperthyroidism nuclear T3 maximal binding capacity ( MBC ) was unaltered, whereas in hypothyroidism the MBC was significantly increased.", "entity": [], "task": "NER"}
{"text": "In the patients with diabetes mellitus , chronic renal failure and hepatic cirrhosis , the nuclear T3R MBC of lymphocytes was about 1.5-1.6 times of the normal controls .", "entity": [{"entity": "nuclear T3R", "entity_type": "protein", "pos": [91, 102]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [110, 121]}, {"entity": "T3R", "entity_type": "protein", "pos": [99, 102]}], "task": "NER"}
{"text": "It was concluded that there existed hormonal regulation of nuclear T3R , and up-regulation was seen in hypothyroidism and low T3 syndrome .", "entity": [{"entity": "T3R", "entity_type": "protein", "pos": [67, 70]}, {"entity": "nuclear T3R", "entity_type": "protein", "pos": [59, 70]}], "task": "NER"}
{"text": "Lymphocyte cell lines from vitamin D-dependent rickets type II show functional defects in the 1 alpha,25-dihydroxyvitamin D3 receptor .", "entity": [{"entity": "1 alpha,25-dihydroxyvitamin D3 receptor", "entity_type": "protein", "pos": [94, 133]}, {"entity": "Lymphocyte cell lines", "entity_type": "cell line", "pos": [0, 21]}], "task": "NER"}
{"text": "Lymphocyte cell lines were established from five patients with vitamin D-dependent rickets , type II ( VDDR-II ).", "entity": [{"entity": "Lymphocyte cell lines", "entity_type": "cell line", "pos": [0, 21]}], "task": "NER"}
{"text": "These lines were established by infection with human T-lymphotrophic virus type I ( HTLV-I ).", "entity": [], "task": "NER"}
{"text": "Binding of [3H]1 alpha,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) to its receptor in these cell lines was compared to binding studies using a T-lymphocyte cell line ( S-LB1 ) from a normal individual.", "entity": [{"entity": "T-lymphocyte cell line", "entity_type": "cell line", "pos": [138, 160]}, {"entity": "S-LB1", "entity_type": "cell line", "pos": [163, 168]}], "task": "NER"}
{"text": "The 1,25(OH)2D3 receptor of S-LB1 was comparable to the well-characterized chick intestinal 1,25(OH)2D3 receptor in terms of its ligand binding affinity and capacity, its mobility on 5-20% sucrose gradients, and its adsorption to and elution properties from DNA-cellulose .", "entity": [{"entity": "chick intestinal 1,25(OH)2D3 receptor", "entity_type": "protein", "pos": [75, 112]}, {"entity": "S-LB1", "entity_type": "cell line", "pos": [28, 33]}], "task": "NER"}
{"text": "Three cell lines established from patients with VDDR-II ( Rh- VDR , Sh- VDR , and Ab- VDR ) showed no specific binding of 1,25(OH)2D3 to a receptor and treatment of the cultured cells with 1,25(OH)2D3 did not stimulate production of 24,25-dihydroxy-vitamin D3 ( 24,25(OH)2D3 ), a response which is diagnostic of the presence of a functional 1,25(OH)2D3 receptor .", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [62, 65]}, {"entity": "VDR", "entity_type": "protein", "pos": [72, 75]}, {"entity": "cultured cells", "entity_type": "cell line", "pos": [169, 183]}, {"entity": "functional 1,25(OH)2D3 receptor", "entity_type": "protein", "pos": [330, 361]}, {"entity": "cell lines", "entity_type": "cell line", "pos": [6, 16]}, {"entity": "receptor", "entity_type": "protein", "pos": [139, 147]}, {"entity": "VDR", "entity_type": "protein", "pos": [86, 89]}], "task": "NER"}
{"text": "In a fourth cell line , A1-VDR , the receptor for 1,25(OH)2D3 had a low binding capacity and 25(OH)D3-24-hydroxylase activity was not detectable.", "entity": [{"entity": "cell line", "entity_type": "cell line", "pos": [12, 21]}, {"entity": "A1-VDR", "entity_type": "cell line", "pos": [24, 30]}, {"entity": "25(OH)D3-24-hydroxylase", "entity_type": "protein", "pos": [93, 116]}], "task": "NER"}
{"text": "Induction of 24,25-(OH)2D3 synthesis by 1,25(OH)2D3 was observed in the fifth cell line , designated Ro-VDR , although the sensitivity to hormone treatment was lower than in the control cell line from a normal donor .", "entity": [{"entity": "control cell line", "entity_type": "cell line", "pos": [178, 195]}, {"entity": "cell line", "entity_type": "cell line", "pos": [78, 87]}, {"entity": "Ro-VDR", "entity_type": "cell line", "pos": [101, 107]}], "task": "NER"}
{"text": "The capacity of the receptor for 1,25(OH)2D3 was low in Ro-VDR .", "entity": [{"entity": "Ro-VDR", "entity_type": "cell line", "pos": [56, 62]}, {"entity": "receptor", "entity_type": "protein", "pos": [20, 28]}], "task": "NER"}
{"text": "In all cell lines where 1,25(OH)2D3 binding to a receptor was detectable, the receptor had the typical sedimentation coefficient of 3.7 S on sucrose density gradient analysis .", "entity": [{"entity": "receptor", "entity_type": "protein", "pos": [49, 57]}, {"entity": "receptor", "entity_type": "protein", "pos": [78, 86]}, {"entity": "cell lines", "entity_type": "cell line", "pos": [7, 17]}], "task": "NER"}
{"text": "Binding and elution properties to DNA-cellulose , however, differed from normal in both Ro-VDR and A1-VDR cells where elution from DNA-cellulose occurred at a lower salt concentration than is typical of the 1,25(OH)2D3 receptor .", "entity": [{"entity": "receptor", "entity_type": "protein", "pos": [219, 227]}, {"entity": "A1-VDR", "entity_type": "cell line", "pos": [99, 105]}, {"entity": "Ro-VDR", "entity_type": "cell line", "pos": [88, 94]}, {"entity": "A1-VDR cells", "entity_type": "cell line", "pos": [99, 111]}, {"entity": "1,25(OH)2D3 receptor", "entity_type": "protein", "pos": [207, 227]}], "task": "NER"}
{"text": "While Ro-VDR cells showed typical nuclear localization of the unoccupied 1,25(OH)2D3 receptor , neither the unoccupied nor the occupied receptor from A1-VDR cells was completely localized in the nucleus .", "entity": [{"entity": "receptor", "entity_type": "protein", "pos": [85, 93]}, {"entity": "unoccupied 1,25(OH)2D3 receptor", "entity_type": "protein", "pos": [62, 93]}, {"entity": "A1-VDR cells", "entity_type": "cell line", "pos": [150, 162]}, {"entity": "receptor", "entity_type": "protein", "pos": [136, 144]}, {"entity": "Ro-VDR", "entity_type": "cell line", "pos": [6, 12]}, {"entity": "Ro-VDR cells", "entity_type": "cell line", "pos": [6, 18]}, {"entity": "A1-VDR", "entity_type": "cell line", "pos": [150, 156]}], "task": "NER"}
{"text": "In a series of functional studies we found that modulation of the level of the mRNAs coding for both the c-myc oncogene and the growth factor known as granulocyte-monocyte colony stimulating activity by 1,25(OH)2D3 correlated with the 1,25(OH)2D3 receptor status of these cells.", "entity": [{"entity": "mRNAs", "entity_type": "RNA", "pos": [79, 84]}, {"entity": "receptor", "entity_type": "protein", "pos": [247, 255]}, {"entity": "1,25(OH)2D3 receptor", "entity_type": "protein", "pos": [235, 255]}, {"entity": "c-myc oncogene", "entity_type": "DNA", "pos": [105, 119]}], "task": "NER"}
{"text": "Use of these cell lines will facilitate further study of the molecular defect(s) in the receptor for 1,25(OH)2D3 in vitamin D-dependent rickets type II and will allow a correlation with impairment of cellular functions .", "entity": [{"entity": "receptor", "entity_type": "protein", "pos": [88, 96]}, {"entity": "cell lines", "entity_type": "cell line", "pos": [13, 23]}], "task": "NER"}
{"text": "Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells .", "entity": [{"entity": "human myeloid leukemic cells", "entity_type": "cell line", "pos": [108, 136]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [55, 60]}], "task": "NER"}
{"text": "AP-1 , the polypeptide product of c-jun , recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate ( TPA ).", "entity": [{"entity": "AP-1", "entity_type": "protein", "pos": [0, 4]}, {"entity": "specific DNA sequences", "entity_type": "DNA", "pos": [66, 88]}, {"entity": "genes", "entity_type": "DNA", "pos": [121, 126]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [34, 39]}], "task": "NER"}
{"text": "We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation .", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [51, 56]}, {"entity": "HL-60 cells", "entity_type": "cell line", "pos": [76, 87]}], "task": "NER"}
{"text": "Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells , increased significantly by 6 h, and reached near maximal levels by 24 h of exposure to 32 nM TPA .", "entity": [{"entity": "untreated HL-60 leukemic cells", "entity_type": "cell line", "pos": [51, 81]}, {"entity": "c-jun transcripts", "entity_type": "RNA", "pos": [14, 31]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [14, 19]}], "task": "NER"}
{"text": "Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells .", "entity": [{"entity": "human U-937", "entity_type": "cell line", "pos": [60, 71]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [20, 25]}, {"entity": "THP-1 monocytic leukemia cells", "entity_type": "cell line", "pos": [76, 106]}], "task": "NER"}
{"text": "Similar findings were obtained with bryostatin 1 (10 nM), another activator of protein kinase C and inducer of monocytic differentiation .", "entity": [{"entity": "protein kinase C", "entity_type": "protein", "pos": [79, 95]}], "task": "NER"}
{"text": "Furthermore, 1,25-dihydroxyvitamin D3 (0.5 microM), a structurally distinct agent which also induces HL-60 monocytic differentiation , increased c-jun expression .", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [145, 150]}], "task": "NER"}
{"text": "TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts.", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [100, 105]}, {"entity": "HL-60 cells", "entity_type": "cell line", "pos": [17, 28]}], "task": "NER"}
{"text": "Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells , and that exposure to TPA increases this rate 3.3-fold.", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [50, 55]}, {"entity": "HL-60 cells", "entity_type": "cell line", "pos": [88, 99]}, {"entity": "untreated HL-60 cells", "entity_type": "cell line", "pos": [78, 99]}], "task": "NER"}
{"text": "Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription .", "entity": [{"entity": "HL-60 cells", "entity_type": "cell line", "pos": [13, 24]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [87, 92]}], "task": "NER"}
{"text": "The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min.", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [17, 22]}, {"entity": "c-jun RNA", "entity_type": "RNA", "pos": [17, 26]}, {"entity": "HL-60 cells", "entity_type": "cell line", "pos": [53, 64]}], "task": "NER"}
{"text": "In contrast, the half-life of c-jun RNA in TPA -treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h.", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [30, 35]}, {"entity": "HL-60 cells", "entity_type": "cell line", "pos": [56, 67]}, {"entity": "c-jun RNA", "entity_type": "RNA", "pos": [30, 39]}, {"entity": "TPA -treated HL-60 cells", "entity_type": "cell line", "pos": [43, 67]}], "task": "NER"}
{"text": "These findings suggested that the increase in c-jun RNA observed during TPA -induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms .", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [46, 51]}, {"entity": "c-jun RNA", "entity_type": "RNA", "pos": [46, 55]}], "task": "NER"}
{"text": "[ Hormonal interactions and glucocorticoid receptors in patients with the nephrotic syndrome ]", "entity": [{"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [28, 52]}], "task": "NER"}
{"text": "As many as 27 children aged 6 to 15 years with morphologically verified nephropathies were examined.", "entity": [], "task": "NER"}
{"text": "Four variants of changes in the thyroid status , characteristic of children with different variants of nephrotic syndrome were distinguished: 1) biochemical signs of primary hypothyroidism , 2) biochemical signs of secondary hypothyroidism , 3) low content of T3, 4) dysfunction of the hypophyseal and thyroid system .", "entity": [], "task": "NER"}
{"text": "It is shown that the low level of steroid receptors , thyroid hormones that the low level of steroid receptors , thyroid hormones (T3 and T4) and cortisol is typical of children with the signs of renal dysplasia .", "entity": [{"entity": "steroid receptors", "entity_type": "protein", "pos": [34, 51]}, {"entity": "steroid receptors", "entity_type": "protein", "pos": [93, 110]}], "task": "NER"}
{"text": "It is assumed that superaddition under such conditions of immune glomerulopathy ( glomerulonephritis and nephrotic syndrome ) gives rise to the resistance to the treatment with glucocorticoids .", "entity": [], "task": "NER"}
{"text": "Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs .", "entity": [{"entity": "NF-kappa B binding motifs", "entity_type": "DNA", "pos": [91, 116]}, {"entity": "adenovirus early region 3 promoter", "entity_type": "DNA", "pos": [41, 75]}], "task": "NER"}
{"text": "A primary site of infection by human adenoviruses is lymphoid cells .", "entity": [{"entity": "lymphoid cells", "entity_type": "cell type", "pos": [53, 67]}], "task": "NER"}
{"text": "However, analysis of the viral control elements and the cellular factors that regulate adenoviral gene expression in lymphocytes has not been reported.", "entity": [{"entity": "viral control elements", "entity_type": "DNA", "pos": [25, 47]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [117, 128]}, {"entity": "cellular factors", "entity_type": "protein", "pos": [56, 72]}], "task": "NER"}
{"text": "The adenovirus early region 3 ( ES ) gene products are involved in the maintenance of viral persistence by complexing with the class I MHC antigens , thus preventing their cell surface expression with a resultant decrease in host immunologic destruction .", "entity": [{"entity": "class I MHC antigens", "entity_type": "protein", "pos": [127, 147]}, {"entity": "ES", "entity_type": "DNA", "pos": [32, 34]}, {"entity": "adenovirus early region 3", "entity_type": "DNA", "pos": [4, 29]}, {"entity": "adenovirus early region 3 ( ES ) gene products", "entity_type": "protein", "pos": [4, 50]}], "task": "NER"}
{"text": "To determine whether different cellular factors were involved in E3 regulation in lymphocytes as compared with HeLa cells , both DNA binding and transfection analysis with the E3 promoter in both cell types were performed.", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [82, 93]}, {"entity": "E3 promoter", "entity_type": "DNA", "pos": [176, 187]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [111, 121]}, {"entity": "cellular factors", "entity_type": "protein", "pos": [31, 47]}], "task": "NER"}
{"text": "These studies detected two novel domains referred to as L1 and L2 with a variety of lymphoid but not HeLa extracts .", "entity": [{"entity": "L2", "entity_type": "DNA", "pos": [63, 65]}, {"entity": "novel domains", "entity_type": "DNA", "pos": [27, 40]}, {"entity": "L1", "entity_type": "DNA", "pos": [56, 58]}], "task": "NER"}
{"text": "Each of these domains possessed strong homology to motifs previously found to bind the cellular factor NF-kappa B .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [103, 113]}, {"entity": "cellular factor NF-kappa B", "entity_type": "protein", "pos": [87, 113]}], "task": "NER"}
{"text": "Transfections of E3 constructs linked to the chloramphenicol acetyltransferase gene revealed that mutagenesis of the distal NF-kappa B motif ( L2 ) had minimal effects on promoter expression in HeLa cells , but resulted in dramatic decreases in expression by lymphoid cells .", "entity": [{"entity": "lymphoid cells", "entity_type": "cell type", "pos": [259, 273]}, {"entity": "L2", "entity_type": "DNA", "pos": [143, 145]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [194, 204]}, {"entity": "E3 constructs", "entity_type": "DNA", "pos": [17, 30]}, {"entity": "distal NF-kappa B motif", "entity_type": "DNA", "pos": [117, 140]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [124, 134]}, {"entity": "chloramphenicol acetyltransferase gene", "entity_type": "DNA", "pos": [45, 83]}], "task": "NER"}
{"text": "In contrast, mutagenesis of proximal NF-kappa B motif ( L1 ) had minimal effects on gene expression in both HeLa cells and lymphoid cells but resulted in a small, but reproducible, increase in gene expression in lymphoid cells when coupled to the L2 mutation .", "entity": [{"entity": "L2", "entity_type": "DNA", "pos": [247, 249]}, {"entity": "lymphoid cells", "entity_type": "cell type", "pos": [123, 137]}, {"entity": "proximal NF-kappa B motif", "entity_type": "DNA", "pos": [28, 53]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [108, 118]}, {"entity": "lymphoid cells", "entity_type": "cell type", "pos": [212, 226]}, {"entity": "L1", "entity_type": "DNA", "pos": [56, 58]}], "task": "NER"}
{"text": "Reversing the position and subsequent mutagenesis of the L1 and L2 domains indicated that the primary sequence of these motifs rather than their position in the E3 promoter was critical for regulating gene expression .", "entity": [{"entity": "primary sequence", "entity_type": "DNA", "pos": [94, 110]}, {"entity": "L1", "entity_type": "DNA", "pos": [57, 59]}, {"entity": "E3 promoter", "entity_type": "DNA", "pos": [161, 172]}, {"entity": "L2", "entity_type": "DNA", "pos": [64, 66]}, {"entity": "L2 domains", "entity_type": "DNA", "pos": [64, 74]}], "task": "NER"}
{"text": "Characterization of defensin resistance phenotypes associated with mutations in the phoP virulence regulon of Salmonella typhimurium .", "entity": [{"entity": "phoP virulence regulon", "entity_type": "DNA", "pos": [84, 106]}, {"entity": "defensin", "entity_type": "protein", "pos": [20, 28]}], "task": "NER"}
{"text": "The defensin sensitivities of Salmonella typhimurium strains with mutations in the phoP/phoQ two-component virulence regulon were tested by using purified defensins NP-1 and NP-2 .", "entity": [{"entity": "purified defensins", "entity_type": "protein", "pos": [146, 164]}, {"entity": "phoP/phoQ two-component virulence regulon", "entity_type": "DNA", "pos": [83, 124]}, {"entity": "NP-1", "entity_type": "protein", "pos": [165, 169]}, {"entity": "defensin", "entity_type": "protein", "pos": [4, 12]}, {"entity": "NP-2", "entity_type": "protein", "pos": [174, 178]}], "task": "NER"}
{"text": "Strains with mutations in either gene of the regulatory pair ( phoP [ transcriptional activator ] or phoQ [ membrane sensor kinase ]) had increased sensitivities to defensin .", "entity": [{"entity": "phoP", "entity_type": "DNA", "pos": [63, 67]}, {"entity": "defensin", "entity_type": "protein", "pos": [165, 173]}, {"entity": "regulatory pair", "entity_type": "DNA", "pos": [45, 60]}, {"entity": "transcriptional activator", "entity_type": "DNA", "pos": [70, 95]}, {"entity": "phoQ", "entity_type": "DNA", "pos": [101, 105]}, {"entity": "membrane sensor kinase", "entity_type": "protein", "pos": [108, 130]}], "task": "NER"}
{"text": "The predicted periplasmic domain of the PhoQ protein contained a markedly anionic domain that could interact with cationic proteins and that could be responsible for resistance to defensin .", "entity": [{"entity": "periplasmic domain", "entity_type": "protein", "pos": [14, 32]}, {"entity": "PhoQ protein", "entity_type": "protein", "pos": [40, 52]}, {"entity": "cationic proteins", "entity_type": "protein", "pos": [114, 131]}, {"entity": "defensin", "entity_type": "protein", "pos": [180, 188]}], "task": "NER"}
{"text": "Because insertion mutations in phoP are polar on phoQ , we constructed strains that expressed the PhoQ protein in the absence of PhoP to test whether resistance to defensin requires only the phoQ gene product .", "entity": [{"entity": "PhoP", "entity_type": "protein", "pos": [129, 133]}, {"entity": "phoQ", "entity_type": "DNA", "pos": [49, 53]}, {"entity": "PhoQ protein", "entity_type": "protein", "pos": [98, 110]}, {"entity": "phoQ", "entity_type": "DNA", "pos": [191, 195]}, {"entity": "phoP", "entity_type": "DNA", "pos": [31, 35]}, {"entity": "phoQ gene product", "entity_type": "protein", "pos": [191, 208]}], "task": "NER"}
{"text": "We found that resistance to defensin requires the function of both components of this regulatory system , because strains expressing PhoQ without PhoP were still markedly sensitive to defensins .", "entity": [{"entity": "PhoQ", "entity_type": "protein", "pos": [133, 137]}, {"entity": "defensins", "entity_type": "protein", "pos": [184, 193]}, {"entity": "PhoP", "entity_type": "protein", "pos": [146, 150]}], "task": "NER"}
{"text": "This implied that a pag ( phoP -activated gene ) product is responsible for defensin resistance .", "entity": [{"entity": "phoP", "entity_type": "DNA", "pos": [26, 30]}, {"entity": "phoP -activated gene", "entity_type": "DNA", "pos": [26, 46]}, {"entity": "defensin", "entity_type": "protein", "pos": [76, 84]}, {"entity": "pag", "entity_type": "DNA", "pos": [20, 23]}, {"entity": "pag ( phoP -activated gene ) product", "entity_type": "protein", "pos": [20, 56]}], "task": "NER"}
{"text": "We also tested for the ability of defensins NP-1 , NP-5 , and HNP-1 to activate pag expression and found that these peptides have no effect.", "entity": [{"entity": "HNP-1", "entity_type": "protein", "pos": [62, 67]}, {"entity": "pag", "entity_type": "DNA", "pos": [80, 83]}, {"entity": "NP-1", "entity_type": "protein", "pos": [44, 48]}, {"entity": "defensins", "entity_type": "protein", "pos": [34, 43]}, {"entity": "NP-5", "entity_type": "protein", "pos": [51, 55]}], "task": "NER"}
{"text": "Defensin resistance is not the only virulence characteristic controlled by the PhoP -PhoQ regulon because mutations in pagC , as well as ones in the phoP locus that resulted in constitutive pag activation (phenotype PhoPc ), had no effect on defensin resistance , even though they rendered the organism avirulent and deficient in survival within macrophages .", "entity": [{"entity": "phoP locus", "entity_type": "DNA", "pos": [149, 159]}, {"entity": "PhoP", "entity_type": "protein", "pos": [79, 83]}, {"entity": "pag", "entity_type": "DNA", "pos": [119, 122]}, {"entity": "phoP", "entity_type": "DNA", "pos": [149, 153]}, {"entity": "PhoP -PhoQ regulon", "entity_type": "protein", "pos": [79, 97]}, {"entity": "PhoPc", "entity_type": "protein", "pos": [216, 221]}, {"entity": "defensin", "entity_type": "protein", "pos": [242, 250]}, {"entity": "pagC", "entity_type": "DNA", "pos": [119, 123]}, {"entity": "macrophages", "entity_type": "cell type", "pos": [346, 357]}, {"entity": "-PhoQ", "entity_type": "protein", "pos": [84, 89]}], "task": "NER"}
{"text": "The virulence defect conferred by mutations in the phoP -phoQ two-component regulatory system is not completely explained by alterations in resistance to cationic proteins and involves the control of other proteins necessary for S. typhimurium survival within macrophages .", "entity": [{"entity": "-phoQ", "entity_type": "DNA", "pos": [56, 61]}, {"entity": "cationic proteins", "entity_type": "protein", "pos": [154, 171]}, {"entity": "phoP", "entity_type": "DNA", "pos": [51, 55]}, {"entity": "macrophages", "entity_type": "cell type", "pos": [260, 271]}], "task": "NER"}
{"text": "Stimulation of a human T-cell clone with anti-CD3 or tumor necrosis factor induces NF-kappa B translocation but not human immunodeficiency virus 1 enhancer-dependent transcription .", "entity": [{"entity": "anti-CD3", "entity_type": "protein", "pos": [41, 49]}, {"entity": "tumor necrosis factor", "entity_type": "protein", "pos": [53, 74]}, {"entity": "human T-cell clone", "entity_type": "cell line", "pos": [17, 35]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [83, 93]}], "task": "NER"}
{"text": "The expression of transiently transfected expression vectors under the control of the long terminal repeat ( LTR ) of the human immunodeficiency virus ( HIV ) or its enhancer sequence and the translocation of the HIV enhancer-binding protein NF-kappa B were analyzed in two human T-cell clones stimulated through their T-cell receptor complex or by tumor necrosis factor or phorbol 12-myristate 13-acetate .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [242, 252]}, {"entity": "T-cell clones", "entity_type": "cell line", "pos": [280, 293]}, {"entity": "long terminal repeat", "entity_type": "DNA", "pos": [86, 106]}, {"entity": "tumor necrosis factor", "entity_type": "protein", "pos": [349, 370]}, {"entity": "T-cell receptor complex", "entity_type": "protein", "pos": [319, 342]}, {"entity": "HIV enhancer-binding protein", "entity_type": "protein", "pos": [213, 241]}, {"entity": "LTR", "entity_type": "DNA", "pos": [109, 112]}, {"entity": "enhancer sequence", "entity_type": "DNA", "pos": [166, 183]}], "task": "NER"}
{"text": "We found a dissociation of NF-kappa B translocation from transactivation of either the HIV LTR or the HIV enhancer .", "entity": [{"entity": "HIV LTR", "entity_type": "DNA", "pos": [87, 94]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [27, 37]}, {"entity": "HIV enhancer", "entity_type": "DNA", "pos": [102, 114]}], "task": "NER"}
{"text": "Interleukin 2 induced proliferation but not NF-kappa B translocation or LTR transactivation .", "entity": [{"entity": "Interleukin 2", "entity_type": "protein", "pos": [0, 13]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [44, 54]}, {"entity": "LTR", "entity_type": "DNA", "pos": [72, 75]}], "task": "NER"}
{"text": "Phorbol ester or specific antigen recognition induced HIV LTR transactivation , whereas stimulation with tumor necrosis factor or antibody to CD3 did not.", "entity": [{"entity": "CD3", "entity_type": "protein", "pos": [142, 145]}, {"entity": "tumor necrosis factor", "entity_type": "protein", "pos": [105, 126]}, {"entity": "HIV LTR", "entity_type": "DNA", "pos": [54, 61]}], "task": "NER"}
{"text": "The two latter signals were nevertheless able to induce NF-kappa B translocation with a pattern in the band-shift assay indistinguishable from that observed using phorbol ester .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [56, 66]}], "task": "NER"}
{"text": "Our finding that induction of NF-kappa B by tumor necrosis factor or antibody to CD3 is not sufficient to induce HIV enhancer -dependent transcription in cloned T cells contrasts with results obtained in most lymphoblastoid T-cell lines and indicates that normal T lymphocytes differ from tumoral T cells in terms of requirements for HIV LTR activation .", "entity": [{"entity": "antibody to CD3", "entity_type": "protein", "pos": [69, 84]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [263, 276]}, {"entity": "cloned T cells", "entity_type": "cell line", "pos": [154, 168]}, {"entity": "HIV LTR", "entity_type": "DNA", "pos": [334, 341]}, {"entity": "HIV enhancer", "entity_type": "DNA", "pos": [113, 125]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [265, 276]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [30, 40]}, {"entity": "lymphoblastoid T-cell lines", "entity_type": "cell line", "pos": [209, 236]}, {"entity": "tumoral T cells", "entity_type": "cell type", "pos": [289, 304]}, {"entity": "tumor necrosis factor", "entity_type": "protein", "pos": [44, 65]}], "task": "NER"}
{"text": "Furthermore, our results suggest that events linked to T-cell activation , in addition to NF-kappa B translocation per se, induce functional interactions of the NF-kappa B complex with the HIV enhancer .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [90, 100]}, {"entity": "NF-kappa B complex", "entity_type": "protein", "pos": [161, 179]}, {"entity": "HIV enhancer", "entity_type": "DNA", "pos": [189, 201]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [161, 171]}], "task": "NER"}
{"text": "Decreased concentration of 1,25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with X-linked hypophosphatemic rickets : effect of phosphate supplementation .", "entity": [{"entity": "1,25-dihydroxyvitamin D3 receptors", "entity_type": "protein", "pos": [27, 61]}, {"entity": "peripheral mononuclear cells", "entity_type": "cell type", "pos": [65, 93]}], "task": "NER"}
{"text": "Abnormal renal tubular phosphate transport is considered to be the primary defect in X-linked hypophosphatemic rickets ( XLH ).", "entity": [], "task": "NER"}
{"text": "However, the resistance to vitamin D treatment in XLH cannot be explained by hypophosphatemia alone.", "entity": [], "task": "NER"}
{"text": "Since most of the actions of vitamin D are mediated by its receptors ( VDR ), abnormalities of VDR have been postulated in XLH .", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [71, 74]}, {"entity": "VDR", "entity_type": "protein", "pos": [95, 98]}], "task": "NER"}
{"text": "In order to investigate this possibility, we measured the concentration of VDR in PHA-activated peripheral mononuclear cells from 10 XLH patients .", "entity": [{"entity": "PHA-activated peripheral mononuclear cells", "entity_type": "cell line", "pos": [82, 124]}, {"entity": "VDR", "entity_type": "protein", "pos": [75, 78]}, {"entity": "peripheral mononuclear cells", "entity_type": "cell type", "pos": [96, 124]}], "task": "NER"}
{"text": "Patients without phosphate supplementation showed significantly lower concentration (21.7 +/- 5.1 fmol/mg protein, mean +/- SEM) compared to the normal controls (60.7 +/- 4.0).", "entity": [], "task": "NER"}
{"text": "On the contrary, there was no significant difference between the phosphate-supplemented patients (58.3 +/- 2.7) and controls .", "entity": [], "task": "NER"}
{"text": "There was a significant positive correlation between VDR concentration and serum phosphate (P less than 0.05).", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [53, 56]}], "task": "NER"}
{"text": "In two patients , VDR was increased after daily phosphate supplementation was started.", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [18, 21]}], "task": "NER"}
{"text": "These results indicate that a decreased concentration of VDR secondary to persistent hypophosphatemia is one of the causes of vitamin D resistance in XLH .", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [57, 60]}], "task": "NER"}
{"text": "Two distinct forms of active transcription factor CREB ( cAMP response element binding protein ).", "entity": [{"entity": "active transcription factor CREB", "entity_type": "protein", "pos": [22, 54]}, {"entity": "cAMP response element binding protein", "entity_type": "protein", "pos": [57, 94]}], "task": "NER"}
{"text": "Mammalian cells express two distinct forms of transcription factor CREB ( cAMP response element binding protein ) that are apparently the products of alternative splicing of the CREB gene transcript .", "entity": [{"entity": "CREB gene transcript", "entity_type": "RNA", "pos": [178, 198]}, {"entity": "transcription factor CREB", "entity_type": "protein", "pos": [46, 71]}, {"entity": "cAMP response element binding protein", "entity_type": "protein", "pos": [74, 111]}, {"entity": "CREB", "entity_type": "protein", "pos": [67, 71]}, {"entity": "CREB", "entity_type": "protein", "pos": [178, 182]}, {"entity": "Mammalian cells", "entity_type": "cell type", "pos": [0, 15]}], "task": "NER"}
{"text": "The two proteins differ by a 14-amino acid serine-rich insertion present in one of the CREB isoforms .", "entity": [{"entity": "CREB isoforms", "entity_type": "protein", "pos": [87, 100]}, {"entity": "14-amino acid serine-rich insertion", "entity_type": "protein", "pos": [29, 64]}, {"entity": "CREB", "entity_type": "protein", "pos": [87, 91]}], "task": "NER"}
{"text": "We show that both CREB isoforms are expressed in many cell types and mammalian species .", "entity": [{"entity": "CREB", "entity_type": "protein", "pos": [18, 22]}, {"entity": "many cell types", "entity_type": "cell type", "pos": [49, 64]}, {"entity": "CREB isoforms", "entity_type": "protein", "pos": [18, 31]}], "task": "NER"}
{"text": "Both encode proteins that bind specifically to a cAMP response element in vitro .", "entity": [{"entity": "cAMP response element in vitro", "entity_type": "DNA", "pos": [49, 79]}], "task": "NER"}
{"text": "As expected for proteins of this class, the CREB proteins bind DNA as dimers.", "entity": [{"entity": "CREB", "entity_type": "protein", "pos": [44, 48]}, {"entity": "CREB proteins", "entity_type": "protein", "pos": [44, 57]}], "task": "NER"}
{"text": "Both proteins impart cAMP -regulated transcriptional activity to a heterologous DNA-binding domain , showing that cAMP directly modulates the transcriptional stimulatory activity of CREB .", "entity": [{"entity": "CREB", "entity_type": "protein", "pos": [182, 186]}, {"entity": "heterologous DNA-binding domain", "entity_type": "DNA", "pos": [67, 98]}], "task": "NER"}
{"text": "The presence of multiple CREB isoforms with identical DNA-binding specificities but differences in the presumed regulatory domain raises the possibility that CREB proteins may be able to integrate distinct regulatory signals at the level of gene transcription .", "entity": [{"entity": "regulatory domain", "entity_type": "protein", "pos": [112, 129]}, {"entity": "CREB", "entity_type": "protein", "pos": [25, 29]}, {"entity": "CREB isoforms", "entity_type": "protein", "pos": [25, 38]}, {"entity": "CREB proteins", "entity_type": "protein", "pos": [158, 171]}, {"entity": "CREB", "entity_type": "protein", "pos": [158, 162]}], "task": "NER"}
{"text": "Human immunodeficiency virus vpr product is a virion-associated regulatory protein .", "entity": [{"entity": "Human immunodeficiency virus vpr product", "entity_type": "protein", "pos": [0, 40]}, {"entity": "virion-associated regulatory protein", "entity_type": "protein", "pos": [46, 82]}], "task": "NER"}
{"text": "The vpr product of the human immunodeficiency virus type 1 ( HIV-1 ) acts in trans to accelerate virus replication and cytopathic effect in T cells .", "entity": [{"entity": "vpr product", "entity_type": "protein", "pos": [4, 15]}, {"entity": "T cells", "entity_type": "cell type", "pos": [140, 147]}], "task": "NER"}
{"text": "Here it is shown that the HIV-1 viral particle contains multiple copies of the vpr protein .", "entity": [{"entity": "vpr protein", "entity_type": "protein", "pos": [79, 90]}], "task": "NER"}
{"text": "The vpr product is the first regulatory protein of HIV-1 to be found in the virus particle .", "entity": [{"entity": "vpr product", "entity_type": "protein", "pos": [4, 15]}], "task": "NER"}
{"text": "This observation raises the possibility that vpr acts to facilitate the early steps of infection before de novo viral protein synthesis occurs.", "entity": [{"entity": "vpr", "entity_type": "DNA", "pos": [45, 48]}], "task": "NER"}
{"text": "A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation .", "entity": [{"entity": "B-cell lineage-specific transcription factor", "entity_type": "protein", "pos": [8, 52]}, {"entity": "differentiation", "entity_type": "protein", "pos": [93, 108]}], "task": "NER"}
{"text": "A novel B-cell-specific transcription factor , BSAP , was identified as a mammalian homolog of the sea urchin protein TSAP , which interacts with the promoters of four tissue-specific late histone H2A-2 and H2B-2 genes .", "entity": [{"entity": "mammalian homolog", "entity_type": "protein", "pos": [74, 91]}, {"entity": "sea urchin protein", "entity_type": "protein", "pos": [99, 117]}, {"entity": "TSAP", "entity_type": "protein", "pos": [118, 122]}, {"entity": "BSAP", "entity_type": "protein", "pos": [47, 51]}, {"entity": "promoters", "entity_type": "DNA", "pos": [150, 159]}, {"entity": "B-cell-specific transcription factor", "entity_type": "protein", "pos": [8, 44]}], "task": "NER"}
{"text": "As shown by mobility-shift , methylation interference , and mutational analyses , the mammalian protein BSAP recognizes all four sea urchin binding sites in a manner indistinguishable from TSAP ; however, the two proteins differ in molecular weight.", "entity": [{"entity": "TSAP", "entity_type": "protein", "pos": [189, 193]}, {"entity": "mammalian protein", "entity_type": "protein", "pos": [86, 103]}, {"entity": "sea urchin binding sites", "entity_type": "DNA", "pos": [129, 153]}, {"entity": "BSAP", "entity_type": "protein", "pos": [104, 108]}], "task": "NER"}
{"text": "BSAP is exclusively restricted to the B-cell lineage of lymphoid differentiation .", "entity": [{"entity": "BSAP", "entity_type": "protein", "pos": [0, 4]}], "task": "NER"}
{"text": "Its expression appears to be activated during pro-B-cell development , is abundant at the pre-B- and mature B- cell stages , but is absent in terminally differentiated plasma cells .", "entity": [{"entity": "terminally differentiated plasma cells", "entity_type": "cell type", "pos": [142, 180]}], "task": "NER"}
{"text": "Moreover, BSAP is clearly a B-cell-specific transcription factor , as a wild-type but not a mutant TSAP -binding site of the sea urchin functions only in transfected B cells as an upstream promoter element .", "entity": [{"entity": "transfected B cells", "entity_type": "cell line", "pos": [154, 173]}, {"entity": "TSAP", "entity_type": "protein", "pos": [99, 103]}, {"entity": "mutant TSAP -binding site", "entity_type": "DNA", "pos": [92, 117]}, {"entity": "upstream promoter element", "entity_type": "DNA", "pos": [180, 205]}, {"entity": "BSAP", "entity_type": "protein", "pos": [10, 14]}, {"entity": "B-cell-specific transcription factor", "entity_type": "protein", "pos": [28, 64]}, {"entity": "wild-type", "entity_type": "DNA", "pos": [72, 81]}], "task": "NER"}
{"text": "Competition experiments did not reveal any high-affinity binding site for BSAP in known regulatory regions of immunoglobulin and class II major histocompatibility (MHC) genes , suggesting that BSAP is a regulator of a different set of B-lymphoid-specific genes .", "entity": [{"entity": "regulatory regions", "entity_type": "DNA", "pos": [88, 106]}, {"entity": "BSAP", "entity_type": "protein", "pos": [74, 78]}, {"entity": "high-affinity binding site", "entity_type": "DNA", "pos": [43, 69]}, {"entity": "B-lymphoid-specific genes", "entity_type": "DNA", "pos": [235, 260]}, {"entity": "BSAP", "entity_type": "protein", "pos": [193, 197]}], "task": "NER"}
{"text": "Octamer transcription factors and the cell type-specificity of immunoglobulin gene expression .", "entity": [{"entity": "cell type-specificity of immunoglobulin gene", "entity_type": "DNA", "pos": [38, 82]}, {"entity": "Octamer transcription factors", "entity_type": "protein", "pos": [0, 29]}], "task": "NER"}
{"text": "Antibodies are produced exclusively in B lymphocytes .", "entity": [{"entity": "Antibodies", "entity_type": "protein", "pos": [0, 10]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [41, 52]}, {"entity": "B lymphocytes", "entity_type": "cell type", "pos": [39, 52]}], "task": "NER"}
{"text": "The expression of the antibody-encoding genes , the immunoglobulin (Ig) genes , is also restricted to B cells .", "entity": [{"entity": "B cells", "entity_type": "cell type", "pos": [102, 109]}, {"entity": "antibody-encoding genes", "entity_type": "DNA", "pos": [22, 45]}, {"entity": "immunoglobulin (Ig) genes", "entity_type": "DNA", "pos": [52, 77]}], "task": "NER"}
{"text": "The octamer sequence ATGCAAAT is present in the promoter and the enhancer of Ig genes , and plays an important role in its tissue-specific expression .", "entity": [{"entity": "octamer sequence", "entity_type": "DNA", "pos": [4, 20]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [65, 73]}, {"entity": "Ig genes", "entity_type": "DNA", "pos": [77, 85]}, {"entity": "promoter", "entity_type": "DNA", "pos": [48, 56]}], "task": "NER"}
{"text": "This sequence motif is a binding site for nuclear proteins , the so-called octamer transcription factors ( Oct or OTF factors ).", "entity": [{"entity": "OTF factors", "entity_type": "protein", "pos": [114, 125]}, {"entity": "nuclear proteins", "entity_type": "protein", "pos": [42, 58]}, {"entity": "sequence motif", "entity_type": "DNA", "pos": [5, 19]}, {"entity": "octamer transcription factors", "entity_type": "protein", "pos": [75, 104]}, {"entity": "Oct", "entity_type": "protein", "pos": [107, 110]}], "task": "NER"}
{"text": "The Oct-1 protein is present in all cell types analyzed so far, whereas Oct-2A and Oct-2B are found mainly in B lymphocytes .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [112, 123]}, {"entity": "Oct-2B", "entity_type": "protein", "pos": [83, 89]}, {"entity": "B lymphocytes", "entity_type": "cell type", "pos": [110, 123]}, {"entity": "Oct-2A", "entity_type": "protein", "pos": [72, 78]}, {"entity": "Oct-1 protein", "entity_type": "protein", "pos": [4, 17]}], "task": "NER"}
{"text": "All three proteins show the same sequence specificity and binding affinity .", "entity": [], "task": "NER"}
{"text": "It appears that the B cell-specific expression of Ig genes is mediated at least in part by cell type-specific Oct factors , and that there are both quantitative and qualitative differences between Oct-1 and Oct-2 factors .", "entity": [{"entity": "Oct-1", "entity_type": "protein", "pos": [197, 202]}, {"entity": "Oct-2 factors", "entity_type": "protein", "pos": [207, 220]}, {"entity": "type-specific Oct factors", "entity_type": "protein", "pos": [96, 121]}, {"entity": "Ig genes", "entity_type": "DNA", "pos": [50, 58]}], "task": "NER"}
{"text": "Recently, a number of other octamer factor variants were identified.", "entity": [{"entity": "octamer factor variants", "entity_type": "protein", "pos": [28, 51]}], "task": "NER"}
{"text": "Many of these may be created by alternative splicing of a primary transcript of one Oct factor gene and may serve a specific function in the fine tuning of gene expression .", "entity": [{"entity": "primary transcript", "entity_type": "RNA", "pos": [58, 76]}], "task": "NER"}
{"text": "A factor known to bind to endogenous Ig heavy chain enhancer only in lymphocytes is a ubiquitously active transcription factor .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [69, 80]}, {"entity": "endogenous Ig heavy chain enhancer", "entity_type": "DNA", "pos": [26, 60]}, {"entity": "ubiquitously active transcription factor", "entity_type": "protein", "pos": [86, 126]}], "task": "NER"}
{"text": "The transcriptional enhancer located in the first intron of the immunoglobulin heavy chain constant region is a major determinant of B-cell-specific expression of immunoglobulin genes .", "entity": [{"entity": "transcriptional enhancer", "entity_type": "DNA", "pos": [4, 28]}, {"entity": "immunoglobulin genes", "entity_type": "DNA", "pos": [163, 183]}, {"entity": "immunoglobulin heavy chain constant region", "entity_type": "DNA", "pos": [64, 106]}], "task": "NER"}
{"text": "Like other enhancers , the Ig heavy chain enhancer contains several short sequence motifs that bind specific transcription factors .", "entity": [{"entity": "enhancers", "entity_type": "DNA", "pos": [11, 20]}, {"entity": "Ig heavy chain enhancer", "entity_type": "DNA", "pos": [27, 50]}, {"entity": "sequence motifs", "entity_type": "DNA", "pos": [74, 89]}, {"entity": "specific transcription factors", "entity_type": "protein", "pos": [100, 130]}], "task": "NER"}
{"text": "Each binding site contributes to the overall activity of the enhancer , however no single element seems absolutely required for activity.", "entity": [{"entity": "enhancer", "entity_type": "DNA", "pos": [61, 69]}, {"entity": "binding site", "entity_type": "DNA", "pos": [5, 17]}], "task": "NER"}
{"text": "For a better understanding of the Ig heavy chain enhancer components , we have cloned and analyzed individual sequence elements .", "entity": [{"entity": "sequence elements", "entity_type": "DNA", "pos": [110, 127]}, {"entity": "Ig heavy chain enhancer", "entity_type": "DNA", "pos": [34, 57]}, {"entity": "Ig heavy chain enhancer components", "entity_type": "DNA", "pos": [34, 68]}], "task": "NER"}
{"text": "We find that the factor that binds to the E3 enhancer motif , CATGTGGC , is a ubiquitous transcription factor .", "entity": [{"entity": "ubiquitous transcription factor", "entity_type": "protein", "pos": [78, 109]}, {"entity": "E3 enhancer motif", "entity_type": "DNA", "pos": [42, 59]}], "task": "NER"}
{"text": "It is present in an active form in both B cells and non- B cells , where it can mediate transcriptional activation in vitro and in vivo.", "entity": [{"entity": "B cells", "entity_type": "cell type", "pos": [40, 47]}, {"entity": "non- B cells", "entity_type": "cell type", "pos": [52, 64]}, {"entity": "B cells", "entity_type": "cell type", "pos": [57, 64]}], "task": "NER"}
{"text": "However, despite its ability to activate transcription of a transfected reporter gene , the factor is apparently unable to bind to the endogenous Ig heavy chain enhancer in non- lymphoid cells : In previous experiments by others, the characteristic in vivo footprint of this factor, designated NF-muE3 , was detected in B cells but not in non-B cells .", "entity": [{"entity": "NF-muE3", "entity_type": "protein", "pos": [294, 301]}, {"entity": "B cells", "entity_type": "cell type", "pos": [320, 327]}, {"entity": "lymphoid cells", "entity_type": "cell type", "pos": [178, 192]}, {"entity": "transfected reporter gene", "entity_type": "DNA", "pos": [60, 85]}, {"entity": "Ig heavy chain enhancer", "entity_type": "DNA", "pos": [146, 169]}, {"entity": "non- lymphoid cells", "entity_type": "cell type", "pos": [173, 192]}, {"entity": "non-B cells", "entity_type": "cell type", "pos": [339, 350]}, {"entity": "endogenous Ig heavy chain enhancer", "entity_type": "DNA", "pos": [135, 169]}], "task": "NER"}
{"text": "From this and other findings the picture emerges that there are at least three categories of factors which mediate cell-type-specific transcription in B lymphocytes : (a) cell-specific factors such as Oct-2A and Oct-2B that are not expressed in most other cell types: (b) ubiquitous factors such as NF-kappa B that are constitutively active in B cells but are sequestered in an inactive form in other cells; (c) ubiquitously active factors , exemplified by the one binding to the E3 sequence motif .", "entity": [{"entity": "Oct-2B", "entity_type": "protein", "pos": [212, 218]}, {"entity": "B lymphocytes", "entity_type": "cell type", "pos": [151, 164]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [299, 309]}, {"entity": "ubiquitous factors", "entity_type": "protein", "pos": [272, 290]}, {"entity": "B cells", "entity_type": "cell type", "pos": [344, 351]}, {"entity": "ubiquitously active factors", "entity_type": "protein", "pos": [412, 439]}, {"entity": "cell-specific factors", "entity_type": "protein", "pos": [171, 192]}, {"entity": "E3 sequence motif", "entity_type": "DNA", "pos": [480, 497]}, {"entity": "Oct-2A", "entity_type": "protein", "pos": [201, 207]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [153, 164]}], "task": "NER"}
{"text": "This factor is present in an active form in a variety of cell types but is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-B cells , perhaps due to a non-permissive chromatin structure of the Ig heavy chain locus .", "entity": [{"entity": "Ig heavy chain locus", "entity_type": "DNA", "pos": [219, 239]}, {"entity": "chromatin", "entity_type": "DNA", "pos": [192, 201]}, {"entity": "endogenous Ig heavy chain enhancer", "entity_type": "DNA", "pos": [108, 142]}, {"entity": "Ig heavy chain enhancer", "entity_type": "DNA", "pos": [119, 142]}, {"entity": "non-B cells", "entity_type": "cell type", "pos": [146, 157]}], "task": "NER"}
{"text": "[ Endocrine status changes in children with bronchial asthma ]", "entity": [], "task": "NER"}
{"text": "A study was made of adrenocortical function by measuring blood plasma cortisol concentration and amount of glucocorticoid receptors in lymphocytes as well as thyroid function by measuring blood plasma triidothyronine and thyroxine concentration in 58 bronchial asthma children aged 1 to 14 years.", "entity": [{"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [107, 131]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [135, 146]}], "task": "NER"}
{"text": "The authors revealed alterations in the functional activity of the indicated endocrine glands depending on the intensity of bronchial patency disorders and the nature of the therapeutic measures carried out.", "entity": [], "task": "NER"}
{"text": "TAR independent activation of the human immunodeficiency virus in phorbol ester stimulated T lymphocytes .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [91, 104]}, {"entity": "TAR", "entity_type": "DNA", "pos": [0, 3]}], "task": "NER"}
{"text": "Multiple regulatory elements in the human immunodeficiency virus long terminal repeat ( HIV LTR ) are required for activation of HIV gene expression .", "entity": [{"entity": "human immunodeficiency virus long terminal repeat", "entity_type": "DNA", "pos": [36, 85]}, {"entity": "Multiple regulatory elements", "entity_type": "DNA", "pos": [0, 28]}, {"entity": "HIV LTR", "entity_type": "DNA", "pos": [88, 95]}, {"entity": "long terminal repeat", "entity_type": "DNA", "pos": [65, 85]}], "task": "NER"}
{"text": "Previous transfection studies of HIV LTR constructs linked to the chloramphenicol acetyltransferase gene indicated that multiple regulatory regions including the enhancer , SP1 , TATA and TAR regions were important for HIV gene expression .", "entity": [{"entity": "chloramphenicol acetyltransferase gene", "entity_type": "DNA", "pos": [66, 104]}, {"entity": "TAR regions", "entity_type": "DNA", "pos": [188, 199]}, {"entity": "SP1", "entity_type": "DNA", "pos": [173, 176]}, {"entity": "regulatory regions", "entity_type": "DNA", "pos": [129, 147]}, {"entity": "TATA", "entity_type": "DNA", "pos": [179, 183]}, {"entity": "HIV LTR constructs", "entity_type": "DNA", "pos": [33, 51]}, {"entity": "HIV LTR", "entity_type": "DNA", "pos": [33, 40]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [162, 170]}], "task": "NER"}
{"text": "To characterize these regulatory elements further, mutations in these regions were inserted into both the 5' and 3' HIV LTRs and infectious proviral constructs were assembled.", "entity": [{"entity": "HIV LTRs", "entity_type": "DNA", "pos": [116, 124]}, {"entity": "regulatory elements", "entity_type": "DNA", "pos": [22, 41]}], "task": "NER"}
{"text": "These constructs were transfected into either HeLa cells , Jurkat cells or U937 cells in both the presence and absence of phorbol esters which have previously been demonstrated to activate HIV gene expression .", "entity": [{"entity": "HeLa cells", "entity_type": "cell line", "pos": [46, 56]}, {"entity": "U937 cells", "entity_type": "cell line", "pos": [75, 85]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [59, 71]}], "task": "NER"}
{"text": "Viral gene expression was assayed by the level of p24 gag protein released from cultures transfected with the proviral constructs .", "entity": [{"entity": "p24 gag protein", "entity_type": "protein", "pos": [50, 65]}], "task": "NER"}
{"text": "Results in all cell lines indicated that mutations of the SP1 , TATA and the TAR loop and stem secondary structure resulted in marked decreases in gene expression while mutations of the enhancer motif or TAR primary sequence resulted in only slight decreases.", "entity": [{"entity": "TAR primary sequence", "entity_type": "DNA", "pos": [204, 224]}, {"entity": "TAR loop", "entity_type": "DNA", "pos": [77, 85]}, {"entity": "stem secondary structure", "entity_type": "DNA", "pos": [90, 114]}, {"entity": "TATA", "entity_type": "DNA", "pos": [64, 68]}, {"entity": "SP1", "entity_type": "DNA", "pos": [58, 61]}, {"entity": "enhancer motif", "entity_type": "DNA", "pos": [186, 200]}], "task": "NER"}
{"text": "However, viruses containing mutations in either the TAR loop sequences or stem secondary structure which were very defective for gene expression in untreated Jurkat cells , gave nearly wild-type levels of gene expression in phorbol ester -treated Jurkat cells but not in phorbol ester -treated HeLa or U937 cells .", "entity": [{"entity": "Jurkat cells", "entity_type": "cell line", "pos": [158, 170]}, {"entity": "stem secondary structure", "entity_type": "DNA", "pos": [74, 98]}, {"entity": "phorbol ester -treated HeLa", "entity_type": "cell line", "pos": [271, 298]}, {"entity": "U937 cells", "entity_type": "cell line", "pos": [302, 312]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [247, 259]}, {"entity": "phorbol ester -treated Jurkat cells", "entity_type": "cell line", "pos": [224, 259]}, {"entity": "TAR loop sequences", "entity_type": "DNA", "pos": [52, 70]}], "task": "NER"}
{"text": "High level gene expression of these TAR mutant constructs in phorbol ester -treated Jurkat cells was eliminated by second site mutations in the enhancer region or by disruption of the tat gene .", "entity": [{"entity": "TAR mutant constructs", "entity_type": "DNA", "pos": [36, 57]}, {"entity": "tat gene", "entity_type": "DNA", "pos": [184, 192]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [84, 96]}, {"entity": "phorbol ester -treated Jurkat cells", "entity_type": "cell line", "pos": [61, 96]}, {"entity": "enhancer region", "entity_type": "DNA", "pos": [144, 159]}], "task": "NER"}
{"text": "A case of hypersensitivity to thyroid hormones with normally functioning thyroid gland and increased nuclear triiodothyronine receptors .", "entity": [{"entity": "triiodothyronine receptors", "entity_type": "protein", "pos": [109, 135]}], "task": "NER"}
{"text": "A 52-year-old male presented himself with tachycardia crises which appeared first during childhood, increased in frequency without goiter or exophthalmos .", "entity": [], "task": "NER"}
{"text": "Cardiac and adrenergic diseases were excluded.", "entity": [], "task": "NER"}
{"text": "The thyroid function was normal regarding T4 , free T4 and T3 , TBG , radioiodine uptake , TSH and T3 suppressibility ; however the TSH response to TRH was decreased.", "entity": [], "task": "NER"}
{"text": "The lymphocyte nuclear T3 receptor was found with an affinity close to that of normal volunteers (Ka: 1.42 x 10(10) M-1 vs 1.95 +/- 0.35 x 10(10) M-1) and a binding capacity markedly increased (9.9 vs 3.7 +/- 0.4 fmol T3 /100 micrograms DNA).", "entity": [{"entity": "lymphocyte nuclear T3 receptor", "entity_type": "protein", "pos": [4, 34]}], "task": "NER"}
{"text": "Pindolol was inefficient on the dysrhythmia which disappeared with carbimazole and relapsed after withdrawal of the antithyroid drug.", "entity": [], "task": "NER"}
{"text": "Under carbimazole , the plasma T4 markedly decreased (27.7 +/- 3.6 nmol/l) but the patient remained euthyroid .", "entity": [], "task": "NER"}
{"text": "The clinical course and the laboratory data suggest that the tachycardia crises are the consequence of a hypersensitivity of the heart to thyroid hormones , associated with an increased number of T3 nuclear receptor sites in lymphocytes .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [225, 236]}, {"entity": "T3 nuclear receptor", "entity_type": "protein", "pos": [196, 215]}], "task": "NER"}
{"text": "Induction of immediate early response genes by macrophage colony-stimulating factor in normal human monocytes .", "entity": [{"entity": "immediate early response genes", "entity_type": "DNA", "pos": [13, 43]}, {"entity": "normal human monocytes", "entity_type": "cell type", "pos": [87, 109]}, {"entity": "macrophage colony-stimulating factor", "entity_type": "protein", "pos": [47, 83]}], "task": "NER"}
{"text": "A group of coordinately induced protooncogenes , cytoskeletal , and extracellular matrix genes have been termed immediate early response genes , and their induction has been associated with growth factor -stimulated cell proliferation .", "entity": [{"entity": "protooncogenes", "entity_type": "DNA", "pos": [32, 46]}, {"entity": "immediate early response genes", "entity_type": "DNA", "pos": [112, 142]}, {"entity": "growth factor", "entity_type": "protein", "pos": [190, 203]}], "task": "NER"}
{"text": "We have investigated the induction of these genes by macrophage-CSF ( M-CSF ) in human monocytes that do not proliferate in response to M-CSF but require the factor for optimal cell differentiation .", "entity": [{"entity": "macrophage-CSF", "entity_type": "protein", "pos": [53, 67]}, {"entity": "human monocytes", "entity_type": "cell type", "pos": [81, 96]}, {"entity": "M-CSF", "entity_type": "protein", "pos": [70, 75]}, {"entity": "M-CSF", "entity_type": "protein", "pos": [136, 141]}], "task": "NER"}
{"text": "Normal human monocytes were isolated, carefully washed, and incubated for 36 to 48 h in fetal bovine serum-containing medium .", "entity": [{"entity": "human monocytes", "entity_type": "cell type", "pos": [7, 22]}], "task": "NER"}
{"text": "At the end of this incubation the resting cells were stimulated with M-CSF , and RNA was isolated for analysis by Northern blotting .", "entity": [{"entity": "RNA", "entity_type": "RNA", "pos": [81, 84]}, {"entity": "M-CSF", "entity_type": "protein", "pos": [69, 74]}, {"entity": "resting cells", "entity_type": "cell type", "pos": [34, 47]}], "task": "NER"}
{"text": "RNA from control resting cells contained low to undetectable levels of c-jun , fibronectin receptor , and actin mRNA .", "entity": [{"entity": "resting cells", "entity_type": "cell type", "pos": [17, 30]}, {"entity": "RNA", "entity_type": "RNA", "pos": [0, 3]}, {"entity": "fibronectin receptor", "entity_type": "RNA", "pos": [79, 99]}, {"entity": "c-jun", "entity_type": "RNA", "pos": [71, 76]}, {"entity": "actin mRNA", "entity_type": "RNA", "pos": [106, 116]}], "task": "NER"}
{"text": "Within 15 to 30 min of addition of M-CSF , however, there was a dramatic coordinate induction of these genes.", "entity": [{"entity": "M-CSF", "entity_type": "protein", "pos": [35, 40]}], "task": "NER"}
{"text": "The c-jun gene expression was very transient and was not detectable by 60 min after M-CSF addition .", "entity": [{"entity": "M-CSF", "entity_type": "protein", "pos": [84, 89]}, {"entity": "c-jun gene", "entity_type": "DNA", "pos": [4, 14]}], "task": "NER"}
{"text": "In contrast, the expression of actin and fibronectin receptor mRNA was more sustained, and the expression of these genes remained elevated at 24 to 48 h after M-CSF addition .", "entity": [{"entity": "M-CSF", "entity_type": "protein", "pos": [159, 164]}], "task": "NER"}
{"text": "We also observed the induction of the myelomonocytic specific tyrosine kinase hck gene simultaneously with the other immediate early response genes .", "entity": [{"entity": "myelomonocytic specific tyrosine kinase hck gene", "entity_type": "DNA", "pos": [38, 86]}, {"entity": "myelomonocytic specific tyrosine kinase", "entity_type": "protein", "pos": [38, 77]}, {"entity": "immediate early response genes", "entity_type": "DNA", "pos": [117, 147]}], "task": "NER"}
{"text": "The protein synthesis inhibitor cycloheximide did not block the induction of any of these genes, and in fact, super-induced the expression of c-jun and hck .", "entity": [{"entity": "hck", "entity_type": "DNA", "pos": [152, 155]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [142, 147]}], "task": "NER"}
{"text": "Nuclear run on transcription of the c-jun , hck , and actin genes .", "entity": [{"entity": "hck", "entity_type": "DNA", "pos": [44, 47]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [36, 41]}, {"entity": "actin genes", "entity_type": "DNA", "pos": [54, 65]}], "task": "NER"}
{"text": "Therefore, in normal human monocytes M-CSF induces immediate early response genes without inducing cell proliferation.", "entity": [{"entity": "human monocytes", "entity_type": "cell type", "pos": [21, 36]}, {"entity": "normal human monocytes", "entity_type": "cell type", "pos": [14, 36]}, {"entity": "M-CSF", "entity_type": "protein", "pos": [37, 42]}, {"entity": "immediate early response genes", "entity_type": "DNA", "pos": [51, 81]}], "task": "NER"}
{"text": "These genes may then play a role in altering the physiologic status of the cells in response to CSF .", "entity": [{"entity": "CSF", "entity_type": "protein", "pos": [96, 99]}], "task": "NER"}
{"text": "Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner .", "entity": [{"entity": "nuclear factor", "entity_type": "protein", "pos": [10, 24]}, {"entity": "T cells", "entity_type": "cell type", "pos": [105, 112]}, {"entity": "kappa B elements", "entity_type": "DNA", "pos": [40, 56]}, {"entity": "human immunodeficiency virus enhancer", "entity_type": "DNA", "pos": [64, 101]}], "task": "NER"}
{"text": "Cyclosporin A ( CsA ) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of lymphokine genes which are induced upon T-cell activation , among them the gene coding for interleukin-2 .", "entity": [{"entity": "lymphokine genes", "entity_type": "DNA", "pos": [122, 138]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [213, 226]}], "task": "NER"}
{"text": "In addition, the activation of the human immunodeficiency virus ( HIV ) is partially suppressed.", "entity": [], "task": "NER"}
{"text": "To better understand the molecular mechanisms underlying suppression by CsA , we have investigated the effects of this drug on transcription factors in T cells .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [127, 148]}, {"entity": "T cells", "entity_type": "cell type", "pos": [152, 159]}], "task": "NER"}
{"text": "Here we report that the formation of two distinct mitogen-inducible DNA-binding complexes , the kappa B complex within the HIV enhancer and the NFAT-1 complex within the interleukin-2 enhancer , is inhibited in the presence of CsA .", "entity": [{"entity": "NFAT-1 complex", "entity_type": "protein", "pos": [144, 158]}, {"entity": "mitogen-inducible DNA-binding complexes", "entity_type": "protein", "pos": [50, 89]}, {"entity": "kappa B complex", "entity_type": "protein", "pos": [96, 111]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [170, 183]}, {"entity": "interleukin-2 enhancer", "entity_type": "DNA", "pos": [170, 192]}, {"entity": "HIV enhancer", "entity_type": "DNA", "pos": [123, 135]}], "task": "NER"}
{"text": "The kappa B-binding activity with the HIV enhancer is inhibited only if it is activated via the mitogen phytohemagglutinin whereas phorbol myristate acetate -mediated activation is completely insensitive to the drug.", "entity": [{"entity": "phytohemagglutinin", "entity_type": "protein", "pos": [104, 122]}, {"entity": "HIV enhancer", "entity_type": "DNA", "pos": [38, 50]}, {"entity": "mitogen", "entity_type": "protein", "pos": [96, 103]}], "task": "NER"}
{"text": "This suggests a model in which functionally indistinguishable kappa B complexes can be activated via two separate pathways of signal transduction distinguishable by CsA .", "entity": [{"entity": "kappa B complexes", "entity_type": "protein", "pos": [62, 79]}], "task": "NER"}
{"text": "Purification of TCF-1 alpha , a T-cell-specific transcription factor that activates the T-cell receptor C alpha gene enhancer in a context-dependent manner.", "entity": [{"entity": "T-cell receptor C alpha gene enhancer", "entity_type": "DNA", "pos": [88, 125]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [16, 27]}, {"entity": "T-cell-specific transcription factor", "entity_type": "protein", "pos": [32, 68]}], "task": "NER"}
{"text": "The differentiation of T cells into functionally diverse subpopulations is controlled in part, by transcriptional activation and silencing ; however, little is known in detail about the proteins that influence this developmental process .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [23, 30]}], "task": "NER"}
{"text": "We have purified a new T-cell-specific factor , TCF-1 alpha , that is implicated in the activation of genes encoding a major component of the human T-cell receptor ( TCR ).", "entity": [{"entity": "T-cell-specific factor", "entity_type": "protein", "pos": [23, 45]}, {"entity": "TCR", "entity_type": "protein", "pos": [166, 169]}, {"entity": "human T-cell receptor", "entity_type": "protein", "pos": [142, 163]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [48, 59]}], "task": "NER"}
{"text": "TCF-1 alpha , originally identified and purified through its binding sites on the HIV-1 promoter , was found to bind to the TCR alpha enhancer and to promoters for several genes expressed at significantly earlier stages of T-cell development than the TCR alpha gene (e.g., p56lck and CD3 delta ).", "entity": [{"entity": "TCR", "entity_type": "protein", "pos": [124, 127]}, {"entity": "TCR", "entity_type": "protein", "pos": [251, 254]}, {"entity": "genes", "entity_type": "DNA", "pos": [172, 177]}, {"entity": "CD3 delta", "entity_type": "DNA", "pos": [284, 293]}, {"entity": "p56lck", "entity_type": "DNA", "pos": [273, 279]}, {"entity": "HIV-1 promoter", "entity_type": "DNA", "pos": [82, 96]}, {"entity": "promoters", "entity_type": "DNA", "pos": [150, 159]}, {"entity": "TCR alpha enhancer", "entity_type": "DNA", "pos": [124, 142]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [0, 11]}, {"entity": "TCR alpha gene", "entity_type": "DNA", "pos": [251, 265]}], "task": "NER"}
{"text": "Sequences related to the TCF-1 alpha binding motif ( 5'-GGCACCCTTTGA-3' ) are also found in the human TCR delta (and possibly TCR beta ) enhancers .", "entity": [{"entity": "TCR beta", "entity_type": "DNA", "pos": [126, 134]}, {"entity": "TCF-1 alpha binding motif", "entity_type": "DNA", "pos": [25, 50]}, {"entity": "TCR", "entity_type": "protein", "pos": [102, 105]}, {"entity": "TCR delta", "entity_type": "DNA", "pos": [102, 111]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [25, 36]}, {"entity": "enhancers", "entity_type": "DNA", "pos": [137, 146]}, {"entity": "human TCR delta", "entity_type": "DNA", "pos": [96, 111]}, {"entity": "TCR", "entity_type": "protein", "pos": [126, 129]}], "task": "NER"}
{"text": "Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that TCF-1 alpha activity is derived from a family of 57- to 53-kD proteins that are abundantly expressed in mature and immature T-cell lines ( Jurkat , CCRF-CEM ) and not in mature B cells ( JY , Namalwa ) or nonlymphoid (HeLa) cell lines .", "entity": [{"entity": "CCRF-CEM", "entity_type": "cell line", "pos": [251, 259]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [103, 114]}, {"entity": "nonlymphoid (HeLa) cell lines", "entity_type": "cell line", "pos": [308, 337]}, {"entity": "mature B cells", "entity_type": "cell line", "pos": [273, 287]}, {"entity": "JY", "entity_type": "cell line", "pos": [290, 292]}, {"entity": "Namalwa", "entity_type": "cell line", "pos": [295, 302]}, {"entity": "57- to 53-kD proteins", "entity_type": "protein", "pos": [152, 173]}, {"entity": "Jurkat", "entity_type": "cell line", "pos": [242, 248]}], "task": "NER"}
{"text": "A small 95-bp fragment of the TCR alpha control region that contains the TCF-1 alpha binding site juxtaposed between a cAMP-response element (the CRE or T alpha 1 motif ) and the binding site for a distinct lymphoid-specific protein ( TCF-2 alpha ) behaved as a potent T-cell-specific enhancer in vivo.", "entity": [{"entity": "TCF-1 alpha binding site", "entity_type": "DNA", "pos": [73, 97]}, {"entity": "CRE", "entity_type": "DNA", "pos": [146, 149]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [73, 84]}, {"entity": "TCR alpha control region", "entity_type": "DNA", "pos": [30, 54]}, {"entity": "T alpha 1 motif", "entity_type": "DNA", "pos": [153, 168]}, {"entity": "binding site", "entity_type": "DNA", "pos": [85, 97]}, {"entity": "TCF-2 alpha", "entity_type": "protein", "pos": [235, 246]}, {"entity": "TCR", "entity_type": "protein", "pos": [30, 33]}, {"entity": "T-cell-specific enhancer", "entity_type": "DNA", "pos": [269, 293]}, {"entity": "cAMP-response element", "entity_type": "DNA", "pos": [119, 140]}, {"entity": "lymphoid-specific protein", "entity_type": "protein", "pos": [207, 232]}], "task": "NER"}
{"text": "Tandem copies of this enhancer functioned synergistically in mature (Jurkat) T-cell lines as well as resting and activated immature (CCRF-CEM) T-cell lines .", "entity": [{"entity": "mature (Jurkat) T-cell lines", "entity_type": "cell line", "pos": [61, 89]}, {"entity": "immature (CCRF-CEM) T-cell lines", "entity_type": "cell line", "pos": [123, 155]}], "task": "NER"}
{"text": "Mutation of the TCF-1 alpha binding site diminished enhancer activity and disrupted the synergism observed in vivo between tandem enhancer repeats .", "entity": [{"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [16, 27]}, {"entity": "tandem enhancer repeats", "entity_type": "DNA", "pos": [123, 146]}, {"entity": "TCF-1 alpha binding site", "entity_type": "DNA", "pos": [16, 40]}], "task": "NER"}
{"text": "The TCF-1 alpha binding site was also required for TCR alpha enhancer activity in transcriptionally active extracts from Jurkat but not HeLa cells , confirming that TCF-1 alpha is a T-cell-specific transcription factor .", "entity": [{"entity": "Jurkat", "entity_type": "cell line", "pos": [121, 127]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [4, 15]}, {"entity": "TCR", "entity_type": "protein", "pos": [51, 54]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [165, 176]}, {"entity": "T-cell-specific transcription factor", "entity_type": "protein", "pos": [182, 218]}, {"entity": "TCF-1 alpha binding site", "entity_type": "DNA", "pos": [4, 28]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [136, 146]}], "task": "NER"}
{"text": "Curiously, the TCF-1 alpha binding element was inactive in vivo when removed from its neighboring elements on the TCR alpha enhancer and positioned in one or more copies upstream of a heterologous promoter .", "entity": [{"entity": "TCR alpha enhancer", "entity_type": "DNA", "pos": [114, 132]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [15, 26]}, {"entity": "TCR", "entity_type": "protein", "pos": [114, 117]}, {"entity": "heterologous promoter", "entity_type": "DNA", "pos": [184, 205]}], "task": "NER"}
{"text": "Thus, the transcriptional activity of TCF-1 alpha appears to depend on the TCF-2 alpha and T alpha 1 ( CREB ) transcription factors and the context of its binding site within the TCR alpha enhancer .", "entity": [{"entity": "TCF-2 alpha", "entity_type": "protein", "pos": [75, 86]}, {"entity": "TCR alpha enhancer", "entity_type": "DNA", "pos": [179, 197]}, {"entity": "CREB", "entity_type": "protein", "pos": [103, 107]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [110, 131]}, {"entity": "T alpha 1", "entity_type": "protein", "pos": [91, 100]}, {"entity": "TCR", "entity_type": "protein", "pos": [179, 182]}, {"entity": "TCF-1 alpha", "entity_type": "protein", "pos": [38, 49]}], "task": "NER"}
{"text": "Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells .", "entity": [{"entity": "human beta-globin dominant control region", "entity_type": "DNA", "pos": [37, 78]}, {"entity": "erythroid cells", "entity_type": "cell type", "pos": [116, 131]}, {"entity": "inducible enhancer", "entity_type": "DNA", "pos": [94, 112]}, {"entity": "Tandem AP-1-binding sites", "entity_type": "DNA", "pos": [0, 25]}], "task": "NER"}
{"text": "A powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5' to the human epsilon-globin gene within the dominant control or locus-activating region .", "entity": [{"entity": "18-bp DNA segment", "entity_type": "DNA", "pos": [42, 59]}, {"entity": "human epsilon-globin gene", "entity_type": "DNA", "pos": [84, 109]}, {"entity": "locus-activating region", "entity_type": "DNA", "pos": [141, 164]}, {"entity": "dominant control", "entity_type": "DNA", "pos": [121, 137]}], "task": "NER"}
{"text": "This enhancer is inducible in K562 human erythroleukemia cells , increasing linked gamma-globin promoter /luciferase gene expression to 170-fold over an enhancerless construct .", "entity": [{"entity": "enhancer", "entity_type": "DNA", "pos": [5, 13]}, {"entity": "enhancerless construct", "entity_type": "DNA", "pos": [153, 175]}, {"entity": "/luciferase", "entity_type": "protein", "pos": [105, 116]}, {"entity": "K562 human erythroleukemia cells", "entity_type": "cell line", "pos": [30, 62]}, {"entity": "gamma-globin promoter", "entity_type": "DNA", "pos": [83, 104]}], "task": "NER"}
{"text": "The enhancer consists of tandem AP-1-binding sites , phased 10 bp apart, which are both required for full activity.", "entity": [{"entity": "tandem AP-1-binding sites", "entity_type": "DNA", "pos": [25, 50]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [4, 12]}], "task": "NER"}
{"text": "DNA-protein binding assays with nuclear extracts from induced cells demonstrate a high molecular weight complex on the enhancer .", "entity": [{"entity": "enhancer", "entity_type": "DNA", "pos": [119, 127]}, {"entity": "high molecular weight complex", "entity_type": "protein", "pos": [82, 111]}], "task": "NER"}
{"text": "The formation of this complex also requires both AP-1 sites and correlates with maximal enhancer activity .", "entity": [{"entity": "enhancer", "entity_type": "DNA", "pos": [88, 96]}, {"entity": "AP-1 sites", "entity_type": "DNA", "pos": [49, 59]}], "task": "NER"}
{"text": "Induction of the enhancer may have a role in the increase in globin gene transcription that characterizes erythroid maturation .", "entity": [{"entity": "globin gene", "entity_type": "DNA", "pos": [61, 72]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [17, 25]}], "task": "NER"}
{"text": "Enhancer activity appears to be mediated by the binding of a complex of proteins from the jun and fos families to tandem AP-1 consensus sequences .", "entity": [{"entity": "jun and fos families", "entity_type": "DNA", "pos": [90, 110]}, {"entity": "tandem AP-1 consensus sequences", "entity_type": "DNA", "pos": [114, 145]}], "task": "NER"}
{"text": "Identification of a novel factor that interacts with an immunoglobulin heavy-chain promoter and stimulates transcription in conjunction with the lymphoid cell-specific factor OTF2 .", "entity": [{"entity": "immunoglobulin heavy-chain promoter", "entity_type": "DNA", "pos": [56, 91]}, {"entity": "lymphoid cell-specific factor", "entity_type": "protein", "pos": [145, 174]}, {"entity": "OTF2", "entity_type": "protein", "pos": [175, 179]}, {"entity": "novel factor", "entity_type": "protein", "pos": [20, 32]}], "task": "NER"}
{"text": "The tissue-specific expression of the MOPC 141 immunoglobulin heavy-chain gene was studied by using in vitro transcription .", "entity": [{"entity": "MOPC 141 immunoglobulin heavy-chain gene", "entity_type": "DNA", "pos": [38, 78]}], "task": "NER"}
{"text": "B-cell-specific transcription of this gene was dependent on the octamer element 5'-ATGCAAAG-3' , located in the upstream region of this promoter and in the promoters of all other immunoglobulin heavy- and light- chain genes .", "entity": [{"entity": "upstream region", "entity_type": "DNA", "pos": [112, 127]}, {"entity": "octamer element", "entity_type": "DNA", "pos": [64, 79]}, {"entity": "promoters", "entity_type": "DNA", "pos": [156, 165]}, {"entity": "promoter", "entity_type": "DNA", "pos": [136, 144]}], "task": "NER"}
{"text": "The interaction of purified octamer transcription factors 1 and 2 ( OTF1 and OTF2 ) with the MOPC 141 promoter was studied by using electrophoretic mobility shift assays and DNase I footprinting .", "entity": [{"entity": "DNase I", "entity_type": "protein", "pos": [174, 181]}, {"entity": "MOPC 141 promoter", "entity_type": "DNA", "pos": [93, 110]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [36, 57]}, {"entity": "octamer transcription factors", "entity_type": "protein", "pos": [28, 57]}, {"entity": "OTF2", "entity_type": "protein", "pos": [77, 81]}, {"entity": "OTF1", "entity_type": "protein", "pos": [68, 72]}], "task": "NER"}
{"text": "Purified OTF1 from HeLa cells and OTF1 and OTF2 from B cells bound to identical sequences within the heavy-chain promoter .", "entity": [{"entity": "OTF1", "entity_type": "protein", "pos": [9, 13]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [19, 29]}, {"entity": "B cells", "entity_type": "cell type", "pos": [53, 60]}, {"entity": "heavy-chain promoter", "entity_type": "DNA", "pos": [101, 121]}, {"entity": "OTF2", "entity_type": "protein", "pos": [43, 47]}, {"entity": "OTF1", "entity_type": "protein", "pos": [34, 38]}], "task": "NER"}
{"text": "The OTF interactions we observed extended over the heptamer element 5'-CTCAGGA-3' , and it seems likely that the binding of the purified factors involves cooperation between octamer and heptamer sites in this promoter .", "entity": [{"entity": "heptamer element", "entity_type": "DNA", "pos": [51, 67]}, {"entity": "promoter", "entity_type": "DNA", "pos": [209, 217]}, {"entity": "purified factors", "entity_type": "protein", "pos": [128, 144]}], "task": "NER"}
{"text": "In addition to these elements, we identified a second regulatory element , the N element with the sequence 5'-GGAACCTCCCCC-3' .", "entity": [{"entity": "N element", "entity_type": "DNA", "pos": [79, 88]}, {"entity": "regulatory element", "entity_type": "DNA", "pos": [54, 72]}], "task": "NER"}
{"text": "The N element could independently mediate low levels of transcription in both B-cell and HeLa-cell extracts , and, in conjunction with the octamer element , it can promote high levels of transcription in B-cell extracts .", "entity": [{"entity": "N element", "entity_type": "DNA", "pos": [4, 13]}, {"entity": "octamer element", "entity_type": "DNA", "pos": [139, 154]}], "task": "NER"}
{"text": "The N element bound a transcription factor , NTF , that is ubiquitous in cell-type distribution , and NTF was distinct from any of the previously described proteins that bind to similar sequences.", "entity": [{"entity": "cell-type distribution", "entity_type": "protein", "pos": [73, 95]}, {"entity": "previously described proteins", "entity_type": "protein", "pos": [135, 164]}, {"entity": "N element", "entity_type": "DNA", "pos": [4, 13]}, {"entity": "NTF", "entity_type": "protein", "pos": [45, 48]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [22, 42]}, {"entity": "NTF", "entity_type": "protein", "pos": [102, 105]}], "task": "NER"}
{"text": "Based on these results, we propose that NTF and OTF2 interactions (both with their cognate DNA elements and possibly at the protein-protein level ) may be critical to B-cell-specific expression and that these interactions provide additional pathways for regulating gene expression .", "entity": [{"entity": "OTF2", "entity_type": "protein", "pos": [48, 52]}, {"entity": "cognate DNA elements", "entity_type": "DNA", "pos": [83, 103]}, {"entity": "NTF", "entity_type": "protein", "pos": [40, 43]}], "task": "NER"}
{"text": "NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene .", "entity": [{"entity": "transcriptional activator", "entity_type": "protein", "pos": [24, 49]}, {"entity": "granulocyte-macrophage colony-stimulating factor gene", "entity_type": "DNA", "pos": [57, 110]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [0, 10]}], "task": "NER"}
{"text": "The expression of the gene encoding the granulocyte- macrophage colony-stimulating factor ( GM-CSF ) is induced upon activation of T cells with phytohemagglutinin and active phorbolester and upon expression of tax1 , a transactivating protein of the human T-cell leukemia virus type I .", "entity": [{"entity": "tax1", "entity_type": "protein", "pos": [210, 214]}, {"entity": "transactivating protein", "entity_type": "protein", "pos": [219, 242]}, {"entity": "T cells", "entity_type": "cell type", "pos": [131, 138]}, {"entity": "macrophage colony-stimulating factor", "entity_type": "protein", "pos": [53, 89]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [92, 98]}, {"entity": "granulocyte- macrophage colony-stimulating factor", "entity_type": "protein", "pos": [40, 89]}, {"entity": "phytohemagglutinin", "entity_type": "protein", "pos": [144, 162]}], "task": "NER"}
{"text": "The same agents induce transcription from the interleukin-2 receptor alpha-chain and interleukin-2 genes , depending on promoter elements that bind the inducible transcription factor NF-kappa B (or an NF-kappa B -like factor ).", "entity": [{"entity": "promoter elements", "entity_type": "DNA", "pos": [120, 137]}, {"entity": "inducible transcription factor", "entity_type": "protein", "pos": [152, 182]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [183, 193]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [201, 211]}, {"entity": "NF-kappa B -like factor", "entity_type": "protein", "pos": [201, 224]}], "task": "NER"}
{"text": "We therefore tested the possibility that the GM-CSF gene is also regulated by a cognate motif for the NF-kappa B transcription factor .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [102, 112]}, {"entity": "GM-CSF gene", "entity_type": "DNA", "pos": [45, 56]}, {"entity": "NF-kappa B transcription factor", "entity_type": "protein", "pos": [102, 133]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [45, 51]}], "task": "NER"}
{"text": "A recent functional analysis by Miyatake et al. (S. Miyatake, M. Seiki, M. Yoshida, and K. Arai, Mol. Cell. Biol. 8:5581-5587, 1988) described a short promoter region in the GM-CSF gene that conferred strong inducibility by T-cell-activating signals and tax1 , but no NF-kappa B -binding motifs were identified.", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [268, 278]}, {"entity": "short promoter region", "entity_type": "DNA", "pos": [145, 166]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [174, 180]}, {"entity": "NF-kappa B -binding motifs", "entity_type": "DNA", "pos": [268, 294]}, {"entity": "tax1", "entity_type": "protein", "pos": [254, 258]}, {"entity": "GM-CSF gene", "entity_type": "DNA", "pos": [174, 185]}], "task": "NER"}
{"text": "Using electrophoretic mobility shift assays , we showed binding of purified human NF-kappa B and of the NF-kappa B activated in Jurkat T cells to an oligonucleotide comprising the GM-CSF promoter element responsible for mediating responsiveness to T-cell-activating signals and tax1 .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [82, 92]}, {"entity": "T cells", "entity_type": "cell type", "pos": [135, 142]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [180, 186]}, {"entity": "Jurkat T cells", "entity_type": "cell line", "pos": [128, 142]}, {"entity": "human NF-kappa B", "entity_type": "protein", "pos": [76, 92]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [104, 114]}, {"entity": "tax1", "entity_type": "protein", "pos": [278, 282]}, {"entity": "GM-CSF promoter element", "entity_type": "DNA", "pos": [180, 203]}], "task": "NER"}
{"text": "As shown by a methylation interference analysis and oligonucleotide competition experiments, purified NF-kappa B binds at positions -82 to -91 ( GGGAACTACC ) of the GM-CSF promoter sequence with an affinity similar to that with which it binds to the biologically functional kappa B motif in the beta interferon promoter ( GGGAAATTCC ).", "entity": [{"entity": "positions -82 to -91", "entity_type": "DNA", "pos": [122, 142]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [165, 171]}, {"entity": "GM-CSF promoter", "entity_type": "DNA", "pos": [165, 180]}, {"entity": "beta interferon promoter", "entity_type": "DNA", "pos": [295, 319]}, {"entity": "biologically functional kappa B motif", "entity_type": "DNA", "pos": [250, 287]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [102, 112]}], "task": "NER"}
{"text": "Two kappa B-like motifs at positions -98 to -108 of the GM-CSF promoter were also recognized but with much lower affinities.", "entity": [{"entity": "positions -98 to -108", "entity_type": "DNA", "pos": [27, 48]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [56, 62]}, {"entity": "kappa B-like motifs", "entity_type": "DNA", "pos": [4, 23]}, {"entity": "GM-CSF promoter", "entity_type": "DNA", "pos": [56, 71]}], "task": "NER"}
{"text": "Our data provide strong evidence that the expression of the GM-CSF gene following T-cell activation is controlled by binding of the NF-kappa B transcription factor to a high-affinity binding site in the GM-CSF promoter .", "entity": [{"entity": "GM-CSF", "entity_type": "protein", "pos": [60, 66]}, {"entity": "high-affinity binding site", "entity_type": "DNA", "pos": [169, 195]}, {"entity": "GM-CSF gene", "entity_type": "DNA", "pos": [60, 71]}, {"entity": "NF-kappa B transcription factor", "entity_type": "protein", "pos": [132, 163]}, {"entity": "GM-CSF promoter", "entity_type": "DNA", "pos": [203, 218]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [132, 142]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [203, 209]}], "task": "NER"}
{"text": "Effects of mitogenic agents upon glucocorticoid action in human tonsillar T- lymphocytes .", "entity": [{"entity": "human tonsillar T- lymphocytes", "entity_type": "cell type", "pos": [58, 88]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [77, 88]}], "task": "NER"}
{"text": "The treatment of human tonsillar T- lymphocytes with 4-phorbol 12-myristate 13-acetate ( PMA ), resulted in about two fold increase in glucocorticoid receptor ( GR ) number , without any significant change in the receptor affinity .", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [161, 163]}, {"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [135, 158]}, {"entity": "human tonsillar T- lymphocytes", "entity_type": "cell type", "pos": [17, 47]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [36, 47]}], "task": "NER"}
{"text": "This increase disappeared in the presence of cycloheximide .", "entity": [], "task": "NER"}
{"text": "Alone, PMA and calcium ionophore A23187 did not affect, but together stimulated, like phytohaemagglutinin ( PHA ), leucine and, in particular, thymidine incorporation .", "entity": [{"entity": "PHA", "entity_type": "protein", "pos": [108, 111]}, {"entity": "phytohaemagglutinin", "entity_type": "protein", "pos": [86, 105]}], "task": "NER"}
{"text": "PMA enhanced slightly the stimulatory effect of PHA .", "entity": [{"entity": "PHA", "entity_type": "protein", "pos": [48, 51]}], "task": "NER"}
{"text": "Alone, these agents failed to alter the suppressive effect of dexamethasone on thymidine and leucine incorporation ; however, PMA -A23187 and PMA -PHA combinations appeared to antagonize the suppression by dexamethasone .", "entity": [{"entity": "-PHA", "entity_type": "protein", "pos": [146, 150]}], "task": "NER"}
{"text": "To be or not to be a responder in T-cell responses : ubiquitous oligopeptides in all proteins.", "entity": [], "task": "NER"}
{"text": "Amino acid sequences of all proteins are essays written in the same language.", "entity": [], "task": "NER"}
{"text": "Accordingly, the same set of words and phrases ( oligopeptides ) appear in totally unrelated proteins .", "entity": [{"entity": "unrelated proteins", "entity_type": "protein", "pos": [83, 101]}], "task": "NER"}
{"text": "The reason that only certain individuals of particular major histocompatibility complex (MHC) haplotypes can mount T-cell responses against a given antigen of pathogens is found in the fact that T-cell receptors are designed to recognize 18-20 residue-long peptide fragments sandwiched between two alpha-helices of class I or class II MHC molecules .", "entity": [{"entity": "class II MHC molecules", "entity_type": "protein", "pos": [326, 348]}, {"entity": "alpha-helices", "entity_type": "protein", "pos": [298, 311]}, {"entity": "T-cell receptors", "entity_type": "protein", "pos": [195, 211]}, {"entity": "major histocompatibility complex (MHC) haplotypes", "entity_type": "protein", "pos": [55, 104]}, {"entity": "class I", "entity_type": "protein", "pos": [315, 322]}], "task": "NER"}
{"text": "At this range of peptide lengths , most would appear as self, while nonselfness of the remainders are destined to be quite ambiguous, hence creating responders and nonresponders.", "entity": [], "task": "NER"}
{"text": "Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [45, 58]}, {"entity": "immunophilin", "entity_type": "protein", "pos": [104, 116]}], "task": "NER"}
{"text": "Proliferation and immunologic function of T lymphocytes are initiated by signals from the antigen receptor that are inhibited by the immunosuppressant FK506 but not by its structural analog, rapamycin .", "entity": [{"entity": "antigen receptor", "entity_type": "protein", "pos": [90, 106]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [42, 55]}], "task": "NER"}
{"text": "On the other hand, interleukin 2 ( IL-2 )-induced signals are blocked by rapamycin but not by FK506 .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [35, 39]}, {"entity": "interleukin 2", "entity_type": "protein", "pos": [19, 32]}], "task": "NER"}
{"text": "Remarkably, these two drugs inhibit each other's actions, raising the possibility that both act by means of a common immunophilin ( immunosuppressant binding protein ).", "entity": [{"entity": "immunosuppressant binding protein", "entity_type": "protein", "pos": [132, 165]}, {"entity": "immunophilin", "entity_type": "protein", "pos": [117, 129]}], "task": "NER"}
{"text": "We find that the dissociation constant of rapamycin to the FK506 binding protein FKBP (Kd = 0.2 nM) is close to the dissociation constant of FK506 to FKBP (Kd = 0.4 nM) and to their effective biologic inhibitory concentrations .", "entity": [{"entity": "FKBP", "entity_type": "protein", "pos": [81, 85]}, {"entity": "FK506 binding protein", "entity_type": "protein", "pos": [59, 80]}, {"entity": "FKBP", "entity_type": "protein", "pos": [150, 154]}], "task": "NER"}
{"text": "However, an excess of rapamycin is needed to revert FK506 -mediated inhibition of IL-2 production , apoptosis , and transcriptional activation of NF-AT , a T-cell-specific transcription factor necessary for IL-2 gene activation .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [82, 86]}, {"entity": "IL-2", "entity_type": "protein", "pos": [207, 211]}, {"entity": "T-cell-specific transcription factor", "entity_type": "protein", "pos": [156, 192]}, {"entity": "IL-2 gene", "entity_type": "DNA", "pos": [207, 216]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [146, 151]}], "task": "NER"}
{"text": "Similarly, an excess of FK506 is needed to revert rapamycin -mediated inhibition of IL-2 -induced proliferation .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [84, 88]}], "task": "NER"}
{"text": "The drug concentrations required for antagonism may be explained by the relative affinity of the drugs to, and by the abundance of, the immunophilin FKBP .", "entity": [{"entity": "FKBP", "entity_type": "protein", "pos": [149, 153]}, {"entity": "immunophilin", "entity_type": "protein", "pos": [136, 148]}], "task": "NER"}
{"text": "FKBP has been shown to catalyze the interconversion of the cis- and trans- rotamers of the peptidyl-prolyl amide bond of peptide substrates ; here we show that rapamycin , like FK506 , is a potent inhibitor of the rotamase activity of FKBP (Ki = 0.2 nM).", "entity": [{"entity": "peptidyl-prolyl amide bond", "entity_type": "protein", "pos": [91, 117]}, {"entity": "FKBP", "entity_type": "protein", "pos": [0, 4]}, {"entity": "FKBP", "entity_type": "protein", "pos": [235, 239]}], "task": "NER"}
{"text": "Neither FKBP binding nor inhibition of rotamase activity of FKBP alone is sufficient to explain the biologic actions of these drugs.", "entity": [{"entity": "FKBP", "entity_type": "protein", "pos": [8, 12]}, {"entity": "FKBP", "entity_type": "protein", "pos": [60, 64]}], "task": "NER"}
{"text": "Rather, these findings suggest that immunophilin bound to FK506 interferes with antigen receptor -induced signals , while rapamycin bound to the immunophilin interferes with IL-2 -induced signals .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [174, 178]}, {"entity": "immunophilin", "entity_type": "protein", "pos": [36, 48]}, {"entity": "immunophilin", "entity_type": "protein", "pos": [145, 157]}, {"entity": "antigen receptor", "entity_type": "protein", "pos": [80, 96]}], "task": "NER"}
{"text": "Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos , c-jun , and EGR2 mRNA .", "entity": [{"entity": "human monocyte PDGF(B) mRNA", "entity_type": "RNA", "pos": [32, 59]}], "task": "NER"}
{"text": "Adherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage .", "entity": [{"entity": "circulating monocyte", "entity_type": "cell type", "pos": [62, 82]}, {"entity": "tissue macrophage", "entity_type": "cell type", "pos": [88, 105]}], "task": "NER"}
{"text": "This differentiation is accompanied by an augmented capacity to generate growth factors .", "entity": [{"entity": "growth factors", "entity_type": "protein", "pos": [73, 87]}], "task": "NER"}
{"text": "We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit ( PDGF[B] ) and transforming growth factor-beta ( TGF-beta ).", "entity": [{"entity": "PDGF[B]", "entity_type": "protein", "pos": [230, 237]}, {"entity": "transforming growth factor-beta", "entity_type": "protein", "pos": [244, 275]}, {"entity": "platelet-derived growth factor B subunit", "entity_type": "protein", "pos": [187, 227]}, {"entity": "growth factors", "entity_type": "protein", "pos": [164, 178]}, {"entity": "TGF-beta", "entity_type": "protein", "pos": [278, 286]}, {"entity": "mRNA", "entity_type": "RNA", "pos": [138, 142]}], "task": "NER"}
{"text": "After in vitro adherence, human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d.", "entity": [{"entity": "PDGF(B) mRNA", "entity_type": "RNA", "pos": [69, 81]}, {"entity": "PDGF(B)", "entity_type": "protein", "pos": [69, 76]}], "task": "NER"}
{"text": "No increase in TGF-beta mRNA was observed.", "entity": [{"entity": "TGF-beta mRNA", "entity_type": "RNA", "pos": [15, 28]}, {"entity": "TGF-beta", "entity_type": "protein", "pos": [15, 23]}], "task": "NER"}
{"text": "The 6-h increase in PDGF(B) mRNA was adherence dependent, and in addition, was abrogated when the cytoskeletal integrity was compromised by cytochalasin D .", "entity": [{"entity": "PDGF(B)", "entity_type": "protein", "pos": [20, 27]}, {"entity": "PDGF(B) mRNA", "entity_type": "RNA", "pos": [20, 32]}], "task": "NER"}
{"text": "The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide .", "entity": [{"entity": "PDGF(B) mRNA", "entity_type": "RNA", "pos": [20, 32]}, {"entity": "PDGF(B)", "entity_type": "protein", "pos": [20, 27]}], "task": "NER"}
{"text": "Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation .", "entity": [{"entity": "PDGF(B) mRNA", "entity_type": "RNA", "pos": [91, 103]}, {"entity": "PDGF(B)", "entity_type": "protein", "pos": [91, 98]}], "task": "NER"}
{"text": "The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos (maximal at 20 min), c-jun, and EGR2 (maximal at 6-24 h).", "entity": [{"entity": "PDGF(B)", "entity_type": "protein", "pos": [14, 21]}, {"entity": "early growth response genes", "entity_type": "DNA", "pos": [103, 130]}, {"entity": "mRNAs", "entity_type": "RNA", "pos": [90, 95]}, {"entity": "PDGF(B) mRNA", "entity_type": "RNA", "pos": [14, 26]}, {"entity": "c-fos", "entity_type": "DNA", "pos": [131, 136]}, {"entity": "adherent monocytes", "entity_type": "cell type", "pos": [39, 57]}], "task": "NER"}
{"text": "The increase in c-jun and EGR2, but not c-fos , mRNA was also abrogated by cytochalasin D .", "entity": [{"entity": "c-fos", "entity_type": "DNA", "pos": [40, 45]}], "task": "NER"}
{"text": "These observations suggest that adherence results in increases of c-fos , c-jun , EGR2 , and PDGF(B) mRNA .", "entity": [], "task": "NER"}
{"text": "In addition, the increases in c-jun , EGR2 , and PDGF(B) may depend on cytoskeletal rearrangement .", "entity": [{"entity": "PDGF(B)", "entity_type": "protein", "pos": [49, 56]}, {"entity": "EGR2", "entity_type": "DNA", "pos": [38, 42]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [30, 35]}], "task": "NER"}
{"text": "Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished.", "entity": [], "task": "NER"}
{"text": "Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor .", "entity": [{"entity": "transcription factor", "entity_type": "protein", "pos": [23, 43]}, {"entity": "T-cell antigen receptor", "entity_type": "protein", "pos": [121, 144]}], "task": "NER"}
{"text": "Stimulation of T lymphocytes through their antigen receptor leads to the appearance of several transcription factors , including NF-AT and NF-kappa B , which are involved in regulating genes required for immunologic activation.", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [139, 149]}, {"entity": "antigen receptor", "entity_type": "protein", "pos": [43, 59]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [95, 116]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [15, 28]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [129, 134]}], "task": "NER"}
{"text": "To investigate the activity of a single transcription factor in individual viable cells , we have applied an assay that uses the fluorescence-activated cell sorter to quantitate beta-galactosidase ( beta-gal ).", "entity": [{"entity": "individual viable cells", "entity_type": "cell type", "pos": [64, 87]}, {"entity": "beta-gal", "entity_type": "protein", "pos": [178, 186]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [40, 60]}, {"entity": "beta-galactosidase", "entity_type": "protein", "pos": [178, 196]}], "task": "NER"}
{"text": "We have analyzed the distribution of NF-AT transcriptional activity among T cells undergoing activation by using a construct in which three tandem copies of the NF-AT -binding site directs transcription of the lacZ gene .", "entity": [{"entity": "lacZ gene", "entity_type": "DNA", "pos": [210, 219]}, {"entity": "NF-AT -binding site", "entity_type": "DNA", "pos": [161, 180]}, {"entity": "T cells", "entity_type": "cell type", "pos": [74, 81]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [37, 42]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [161, 166]}], "task": "NER"}
{"text": "Unexpectedly, stimulation of cloned stably transfected Jurkat T cells leads to a bimodal pattern of beta-gal expression in which some cells express no beta-gal and others express high levels.", "entity": [{"entity": "beta-gal", "entity_type": "protein", "pos": [100, 108]}, {"entity": "T cells", "entity_type": "cell type", "pos": [62, 69]}, {"entity": "cloned stably transfected Jurkat T cells", "entity_type": "cell line", "pos": [29, 69]}], "task": "NER"}
{"text": "This expression pattern cannot be accounted for by cell-cycle position or heritable variation.", "entity": [], "task": "NER"}
{"text": "Further results, in which beta-gal activity is correlated with NF-AT -binding activity , indicate that the concentration of NF-AT must exceed a critical threshold before transcription initiates.", "entity": [{"entity": "NF-AT", "entity_type": "protein", "pos": [63, 68]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [124, 129]}, {"entity": "beta-gal", "entity_type": "protein", "pos": [26, 34]}], "task": "NER"}
{"text": "This threshold likely reflects the NF-AT concentration-dependent assembly of transcription complexes at the promoter .", "entity": [{"entity": "promoter", "entity_type": "DNA", "pos": [108, 116]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [35, 40]}, {"entity": "transcription complexes", "entity_type": "protein", "pos": [77, 100]}], "task": "NER"}
{"text": "Similar constructs controlled by NF-kappa B or the entire interleukin-2 enhancer show bimodal expression patterns during induction, suggesting that thresholds set by the concentration of transcription factors may be a common property of inducible genes .", "entity": [{"entity": "inducible genes", "entity_type": "DNA", "pos": [237, 252]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [33, 43]}, {"entity": "interleukin-2 enhancer", "entity_type": "DNA", "pos": [58, 80]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [187, 208]}], "task": "NER"}
{"text": "The Epstein-Barr virus ( EBV ) BMRF1 promoter for early antigen ( EA-D ) is regulated by the EBV transactivators , BRLF1 and BZLF1 , in a cell-specific manner .", "entity": [{"entity": "BRLF1", "entity_type": "protein", "pos": [115, 120]}, {"entity": "EA-D", "entity_type": "protein", "pos": [66, 70]}, {"entity": "EBV transactivators", "entity_type": "protein", "pos": [93, 112]}, {"entity": "early antigen", "entity_type": "protein", "pos": [50, 63]}, {"entity": "BZLF1", "entity_type": "protein", "pos": [125, 130]}, {"entity": "Epstein-Barr virus ( EBV ) BMRF1 promoter", "entity_type": "DNA", "pos": [4, 45]}], "task": "NER"}
{"text": "The Epstein-Barr virus early antigen diffuse component ( EA-D ) is essential for Epstein-Barr virus DNA polymerase activity , and its activity is suppressed during latent infection.", "entity": [{"entity": "Epstein-Barr virus early antigen diffuse component", "entity_type": "protein", "pos": [4, 54]}, {"entity": "EA-D", "entity_type": "protein", "pos": [57, 61]}, {"entity": "early antigen", "entity_type": "protein", "pos": [23, 36]}, {"entity": "virus DNA", "entity_type": "DNA", "pos": [94, 103]}], "task": "NER"}
{"text": "We investigated the regulation of the promoter ( BMRF1 ) for this early gene by studying its responsiveness in vitro to two immediate-early viral transactivators , BZLF1 ( Z ) and BRLF1 ( R ), focusing on the differences in response in lymphoid cells and epithelial cells .", "entity": [{"entity": "Z", "entity_type": "protein", "pos": [165, 166]}, {"entity": "R", "entity_type": "protein", "pos": [51, 52]}, {"entity": "lymphoid cells", "entity_type": "cell type", "pos": [236, 250]}, {"entity": "BMRF1", "entity_type": "DNA", "pos": [49, 54]}, {"entity": "BRLF1", "entity_type": "protein", "pos": [180, 185]}, {"entity": "BZLF1", "entity_type": "protein", "pos": [164, 169]}, {"entity": "immediate-early viral transactivators", "entity_type": "protein", "pos": [124, 161]}, {"entity": "epithelial cells", "entity_type": "cell type", "pos": [255, 271]}, {"entity": "promoter", "entity_type": "DNA", "pos": [38, 46]}], "task": "NER"}
{"text": "In lymphoid cells , Z or R alone produced only small increases in EA-D promoter activity , whereas both transactivators together produced a large stimulatory effect.", "entity": [{"entity": "transactivators", "entity_type": "protein", "pos": [104, 119]}, {"entity": "lymphoid cells", "entity_type": "cell type", "pos": [3, 17]}, {"entity": "EA-D promoter", "entity_type": "DNA", "pos": [66, 79]}, {"entity": "EA-D", "entity_type": "protein", "pos": [66, 70]}, {"entity": "R", "entity_type": "protein", "pos": [25, 26]}, {"entity": "Z", "entity_type": "protein", "pos": [20, 21]}], "task": "NER"}
{"text": "In epithelial cells , the Z transactivator alone produced maximal stimulation of the EA-D promoter ; the effect of R and Z together was no greater than that of Z alone.", "entity": [{"entity": "Z transactivator", "entity_type": "protein", "pos": [26, 42]}, {"entity": "EA-D", "entity_type": "protein", "pos": [85, 89]}, {"entity": "Z", "entity_type": "protein", "pos": [26, 27]}, {"entity": "EA-D promoter", "entity_type": "DNA", "pos": [85, 98]}, {"entity": "epithelial cells", "entity_type": "cell type", "pos": [3, 19]}, {"entity": "R", "entity_type": "protein", "pos": [115, 116]}, {"entity": "Z", "entity_type": "protein", "pos": [121, 122]}], "task": "NER"}
{"text": "Deletional analysis and site-directed mutagenesis of the EA-D promoter demonstrated that in epithelial cells the potential AP-1 binding site plays an essential role in Z responsiveness, although sequences further upstream are also important.", "entity": [{"entity": "Z", "entity_type": "protein", "pos": [168, 169]}, {"entity": "EA-D", "entity_type": "protein", "pos": [57, 61]}, {"entity": "AP-1 binding site", "entity_type": "DNA", "pos": [123, 140]}, {"entity": "EA-D promoter", "entity_type": "DNA", "pos": [57, 70]}, {"entity": "epithelial cells", "entity_type": "cell type", "pos": [92, 108]}], "task": "NER"}
{"text": "In lymphoid cells , only the upstream sequences are required for transactivation by the Z/R combination, and the AP-1 site is dispensable.", "entity": [{"entity": "upstream sequences", "entity_type": "DNA", "pos": [29, 47]}, {"entity": "lymphoid cells", "entity_type": "cell type", "pos": [3, 17]}, {"entity": "Z/R", "entity_type": "protein", "pos": [88, 91]}, {"entity": "AP-1 site", "entity_type": "protein", "pos": [113, 122]}], "task": "NER"}
{"text": "These data suggest that EA-D ( BMRF1 ) promoter regulation by Z and R is cell type specific and appears to involve different mechanisms in each cell type.", "entity": [{"entity": "R", "entity_type": "protein", "pos": [33, 34]}, {"entity": "Z", "entity_type": "protein", "pos": [62, 63]}, {"entity": "EA-D ( BMRF1 ) promoter", "entity_type": "DNA", "pos": [24, 47]}, {"entity": "EA-D", "entity_type": "protein", "pos": [24, 28]}, {"entity": "BMRF1", "entity_type": "DNA", "pos": [31, 36]}], "task": "NER"}
{"text": "Complementary DNA encoding the human T-cell FK506 -binding protein , a peptidylprolyl cis-trans isomerase distinct from cyclophilin .", "entity": [{"entity": "cyclophilin", "entity_type": "protein", "pos": [120, 131]}, {"entity": "human T-cell FK506 -binding protein", "entity_type": "protein", "pos": [31, 66]}, {"entity": "peptidylprolyl cis-trans isomerase", "entity_type": "protein", "pos": [71, 105]}, {"entity": "Complementary DNA", "entity_type": "DNA", "pos": [0, 17]}], "task": "NER"}
{"text": "The recently discovered macrolide FK506 has been demonstrated to have potent immunosuppressive activity at concentrations 100-fold lower than cyclosporin A , a cyclic undecapeptide that is used to prevent rejection after transplantation of bone marrow and organs , such as kidney , heart , and liver .", "entity": [], "task": "NER"}
{"text": "After the recent discovery that the cyclosporin A -binding protein cyclophilin is identical to peptidylprolyl cis-trans isomerase , a cellular binding protein for FK506 was found to be distinct from cyclophilin but to have the same enzymatic activity .", "entity": [{"entity": "cyclophilin", "entity_type": "protein", "pos": [67, 78]}, {"entity": "cyclosporin A -binding protein", "entity_type": "protein", "pos": [36, 66]}, {"entity": "cellular binding protein", "entity_type": "protein", "pos": [134, 158]}, {"entity": "peptidylprolyl cis-trans isomerase", "entity_type": "protein", "pos": [95, 129]}, {"entity": "cyclophilin", "entity_type": "protein", "pos": [199, 210]}], "task": "NER"}
{"text": "In this study, we isolated a cDNA coding for FK506 -binding protein ( FKBP ) from human peripheral blood T cells by using mixed 20-mer oligonucleotide probes synthesized on the basis of the sequence, Glu-Asp-Gly-Lys-Lys-Phe-Asp , reported for bovine FKBP .", "entity": [{"entity": "FKBP", "entity_type": "protein", "pos": [70, 74]}, {"entity": "FKBP", "entity_type": "protein", "pos": [250, 254]}, {"entity": "bovine FKBP", "entity_type": "protein", "pos": [243, 254]}, {"entity": "cDNA", "entity_type": "DNA", "pos": [29, 33]}, {"entity": "T cells", "entity_type": "cell type", "pos": [105, 112]}], "task": "NER"}
{"text": "The DNA isolated contained an open reading frame encoding 108 amino acid residues .", "entity": [], "task": "NER"}
{"text": "The first 40 residues of the deduced amino acid sequence were identical to those of the reported amino-terminal sequence of bovine FKBP , indicating that the DNA sequence isolated represents the gene coding for FKBP .", "entity": [{"entity": "FKBP", "entity_type": "protein", "pos": [131, 135]}, {"entity": "amino acid sequence", "entity_type": "protein", "pos": [37, 56]}, {"entity": "FKBP", "entity_type": "protein", "pos": [211, 215]}], "task": "NER"}
{"text": "Computer-assisted analysis of the deduced amino acid sequence indicates that FKBP exhibits no internal homology and does not have significant sequence similarity to any other amino acid sequences of known proteins, including cyclophilin .", "entity": [{"entity": "FKBP", "entity_type": "protein", "pos": [77, 81]}, {"entity": "cyclophilin", "entity_type": "protein", "pos": [225, 236]}], "task": "NER"}
{"text": "This result suggests that two catalytically similar proteins, cyclophilin and FKBP , evolved independently.", "entity": [{"entity": "cyclophilin", "entity_type": "protein", "pos": [62, 73]}, {"entity": "FKBP", "entity_type": "protein", "pos": [78, 82]}], "task": "NER"}
{"text": "In Northern blot analysis , mRNA species of approximately 1.8 kilobases that hybridized with human FKBP cDNA were detected in poly(A)+ RNAs from brain , lung , liver , and placental cells and leukocytes .", "entity": [{"entity": "human FKBP cDNA", "entity_type": "DNA", "pos": [93, 108]}, {"entity": "mRNA species", "entity_type": "RNA", "pos": [28, 40]}, {"entity": "FKBP", "entity_type": "protein", "pos": [99, 103]}, {"entity": "placental cells", "entity_type": "cell type", "pos": [172, 187]}, {"entity": "leukocytes", "entity_type": "cell type", "pos": [192, 202]}, {"entity": "poly(A)+ RNAs", "entity_type": "RNA", "pos": [126, 139]}], "task": "NER"}
{"text": "Induction of Jurkat leukemic T cells with phorbol 12-myristate 13-acetate and ionomycin did not affect the level of FKBP mRNA .", "entity": [{"entity": "FKBP mRNA", "entity_type": "RNA", "pos": [116, 125]}, {"entity": "Jurkat leukemic T cells", "entity_type": "cell line", "pos": [13, 36]}, {"entity": "T cells", "entity_type": "cell type", "pos": [29, 36]}, {"entity": "FKBP", "entity_type": "protein", "pos": [116, 120]}], "task": "NER"}
{"text": "Southern blot analysis of human genomic DNA digested with different restriction enzymes suggests the existence of only a few copies of the DNA sequence encoding FKBP .", "entity": [{"entity": "FKBP", "entity_type": "protein", "pos": [161, 165]}, {"entity": "human genomic DNA", "entity_type": "DNA", "pos": [26, 43]}, {"entity": "restriction enzymes", "entity_type": "protein", "pos": [68, 87]}], "task": "NER"}
{"text": "This is in contrast to the result that as many as 20 copies of the cyclophilin gene and possible pseudogenes may be present in the mammalian genome .", "entity": [{"entity": "cyclophilin", "entity_type": "protein", "pos": [67, 78]}, {"entity": "mammalian genome", "entity_type": "DNA", "pos": [131, 147]}, {"entity": "cyclophilin gene", "entity_type": "DNA", "pos": [67, 83]}], "task": "NER"}
{"text": "Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression .", "entity": [{"entity": "immunoglobulin heavy-chain gene", "entity_type": "DNA", "pos": [80, 111]}, {"entity": "lymphoid-specific enhancer element", "entity_type": "DNA", "pos": [24, 58]}], "task": "NER"}
{"text": "To determine whether enhancer elements in addition to the highly conserved octamer (OCTA)-nucleotide motif are important for lymphoid-specific expression of the immunoglobulin heavy-chain (IgH) gene , we have investigated the effect of mutating the binding site for a putative additional lymphoid-specific transcription factor , designated NF-microB , in the murine IgH enhancer .", "entity": [{"entity": "murine IgH enhancer", "entity_type": "DNA", "pos": [359, 378]}, {"entity": "putative additional lymphoid-specific transcription factor", "entity_type": "protein", "pos": [268, 326]}, {"entity": "octamer (OCTA)-nucleotide motif", "entity_type": "DNA", "pos": [75, 106]}, {"entity": "NF-microB", "entity_type": "protein", "pos": [340, 349]}, {"entity": "enhancer elements", "entity_type": "DNA", "pos": [21, 38]}, {"entity": "immunoglobulin heavy-chain (IgH) gene", "entity_type": "DNA", "pos": [161, 198]}, {"entity": "binding site", "entity_type": "DNA", "pos": [249, 261]}], "task": "NER"}
{"text": "We demonstrate that the NF-microB-binding site plays a critical role in the IgH enhancer , because mutation of the microB DNA motif decreased transcriptional activity of the IgH enhancer in cells of the B-cell lineage but not in nonlymphoid cells .", "entity": [{"entity": "IgH enhancer", "entity_type": "DNA", "pos": [76, 88]}, {"entity": "NF-microB-binding site", "entity_type": "DNA", "pos": [24, 46]}, {"entity": "nonlymphoid cells", "entity_type": "cell type", "pos": [229, 246]}, {"entity": "IgH enhancer", "entity_type": "DNA", "pos": [174, 186]}, {"entity": "B-cell lineage", "entity_type": "cell type", "pos": [203, 217]}], "task": "NER"}
{"text": "This effect was comparable to or even stronger than the effect of a mutation in the OCTA site .", "entity": [{"entity": "OCTA site", "entity_type": "DNA", "pos": [84, 93]}], "task": "NER"}
{"text": "Moreover, combined mutation of both microB and OCTA sites further reduced enhancer activity in lymphoid cells .", "entity": [{"entity": "microB", "entity_type": "DNA", "pos": [36, 42]}, {"entity": "OCTA sites", "entity_type": "DNA", "pos": [47, 57]}, {"entity": "lymphoid cells", "entity_type": "cell type", "pos": [95, 109]}], "task": "NER"}
{"text": "Interestingly, alteration of either the microB or E3 site in a 70-base-pair fragment of the IgH enhancer that lacks the binding site for OCTA abolished enhancer activity in lymphoid cells completely.", "entity": [{"entity": "lymphoid cells", "entity_type": "cell type", "pos": [173, 187]}, {"entity": "E3 site", "entity_type": "DNA", "pos": [50, 57]}, {"entity": "IgH enhancer", "entity_type": "DNA", "pos": [92, 104]}, {"entity": "70-base-pair fragment", "entity_type": "DNA", "pos": [63, 84]}, {"entity": "microB", "entity_type": "DNA", "pos": [40, 46]}], "task": "NER"}
{"text": "Nevertheless, a multimer of the microB motif alone showed no enhancer activity .", "entity": [{"entity": "microB motif", "entity_type": "DNA", "pos": [32, 44]}, {"entity": "microB", "entity_type": "DNA", "pos": [32, 38]}], "task": "NER"}
{"text": "DNase footprinting analysis corroborated the functional data showing that a lymphoid-specific protein binds to the microB DNA motif .", "entity": [{"entity": "microB", "entity_type": "DNA", "pos": [115, 121]}, {"entity": "microB DNA motif", "entity_type": "DNA", "pos": [115, 131]}, {"entity": "lymphoid-specific protein", "entity_type": "protein", "pos": [76, 101]}], "task": "NER"}
{"text": "Our results suggest that the microB element is a new crucial element important for lymphoid-specific expression of the IgH gene but that interaction with another enhancer element is essential for its activity.", "entity": [{"entity": "microB element", "entity_type": "DNA", "pos": [29, 43]}, {"entity": "enhancer element", "entity_type": "DNA", "pos": [162, 178]}, {"entity": "microB", "entity_type": "DNA", "pos": [29, 35]}], "task": "NER"}
{"text": "Stimulation of the human immunodeficiency virus type 2 ( HIV-2 ) gene expression by the cytomegalovirus and HIV-2 transactivator gene .", "entity": [{"entity": "HIV-2 transactivator gene", "entity_type": "DNA", "pos": [108, 133]}], "task": "NER"}
{"text": "Human immunodeficiency virus ( HIV ) often causes latent infection.", "entity": [], "task": "NER"}
{"text": "Transactivation by some DNA viruses has been implicated in inducing HIV-1 replication and pathogenesis.", "entity": [], "task": "NER"}
{"text": "The transactivator (IE-2) gene of the human cytomegalovirus ( CMV ) can enhance HIV-2 as well as HIV-1 gene expression in vitro.", "entity": [{"entity": "transactivator (IE-2) gene", "entity_type": "DNA", "pos": [4, 30]}], "task": "NER"}
{"text": "This inducer can act in concert with the HIV-2 tat gene and T-cell activation in enhancing gene expression in human CD4+ lymphocytes .", "entity": [{"entity": "human CD4+ lymphocytes", "entity_type": "cell type", "pos": [110, 132]}, {"entity": "HIV-2 tat gene", "entity_type": "DNA", "pos": [41, 55]}], "task": "NER"}
{"text": "While the HIV-2 and HIV-1 tat genes and T-cell activators apparently employ independent modes of action, the CMV transactivator in combination with the HIV-2 tat or T-cell activators may employ a gene activation pathway with some common and some distinct components.", "entity": [{"entity": "HIV-2 tat", "entity_type": "DNA", "pos": [152, 161]}, {"entity": "HIV-1 tat genes", "entity_type": "DNA", "pos": [20, 35]}, {"entity": "T-cell activators", "entity_type": "protein", "pos": [40, 57]}, {"entity": "T-cell activators", "entity_type": "protein", "pos": [165, 182]}, {"entity": "CMV transactivator", "entity_type": "DNA", "pos": [109, 127]}], "task": "NER"}
{"text": "Both HIV-2 and CMV transactivators enhance HIV-2 gene expression by transcriptional activation involving transcript initiation as well as elongation , with CMV transactivator affecting elongation more than the initiation .", "entity": [{"entity": "CMV transactivators", "entity_type": "DNA", "pos": [15, 34]}, {"entity": "transactivators", "entity_type": "protein", "pos": [19, 34]}, {"entity": "transactivator", "entity_type": "protein", "pos": [19, 33]}, {"entity": "CMV transactivator", "entity_type": "DNA", "pos": [15, 33]}], "task": "NER"}
{"text": "A significant proportion of transcripts appear to terminate prematurely in the absence of transactivators .", "entity": [{"entity": "transcripts", "entity_type": "RNA", "pos": [28, 39]}, {"entity": "transactivators", "entity_type": "protein", "pos": [90, 105]}], "task": "NER"}
{"text": "Deletion mutation analysis of the HIV-2 long terminal repeat ( LTR ) suggests that the element that responds to CMV transactivation in human CD4+ lymphocytes is either a diffuse one or located downstream of the HIV-2 enhancer element .", "entity": [{"entity": "LTR", "entity_type": "DNA", "pos": [63, 66]}, {"entity": "human CD4+ lymphocytes", "entity_type": "cell type", "pos": [135, 157]}, {"entity": "HIV-2 enhancer element", "entity_type": "DNA", "pos": [211, 233]}, {"entity": "HIV-2 long terminal repeat", "entity_type": "DNA", "pos": [34, 60]}], "task": "NER"}
{"text": "Quantitative immunohistochemical analysis of mononuclear infiltrates in breast carcinomas --correlation with tumour differentiation .", "entity": [{"entity": "mononuclear infiltrates", "entity_type": "cell type", "pos": [45, 68]}], "task": "NER"}
{"text": "Inflammatory infiltrates were analysed in tissue sections of 76 breast carcinomas by counting the percentage of macrophages , IgA+ and IgG+ plasma cells , T cells with their subpopulations, and natural killer cells , and by measuring postcapillary venules ( PCVs , found in 12 cases) within the infiltrates.", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [155, 162]}, {"entity": "natural killer cells", "entity_type": "cell type", "pos": [194, 214]}, {"entity": "Inflammatory infiltrates", "entity_type": "cell type", "pos": [0, 24]}, {"entity": "macrophages", "entity_type": "cell type", "pos": [112, 123]}], "task": "NER"}
{"text": "These parameters were correlated with nuclear grade and biochemically determined hormone receptor status , known markers of tumour differentiation .", "entity": [], "task": "NER"}
{"text": "A direct correlation was found between the extent of inflammation and nuclear grade (P less than 0.0001), and an inverse correlation between inflammation and oestrogen receptor ( OR ) positivity (P less than 0.05) as well as inflammation and progesterone receptor ( PR ) positivity (P less than 0.05).", "entity": [{"entity": "OR", "entity_type": "protein", "pos": [179, 181]}, {"entity": "progesterone receptor", "entity_type": "protein", "pos": [242, 263]}, {"entity": "oestrogen receptor", "entity_type": "protein", "pos": [158, 176]}, {"entity": "PR", "entity_type": "protein", "pos": [266, 268]}], "task": "NER"}
{"text": "The percentage of the OKT8+ suppressor/cytotoxic T cells increased when the inflammation expanded from scanty to moderate (P less than 0.02).", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [49, 56]}, {"entity": "OKT8+ suppressor/cytotoxic T cells", "entity_type": "cell line", "pos": [22, 56]}], "task": "NER"}
{"text": "The diameter of the PCVs also increased with increasing inflammatory infiltrate (P less than 0.02).", "entity": [], "task": "NER"}
{"text": "In addition, a direct correlation exists between the diameter of the PCVs and both the percentage of the OKT8+ T cells (P less than 0.04) and the Leu-7+ natural killer cells (P less than 0.03).", "entity": [{"entity": "natural killer cells", "entity_type": "cell type", "pos": [153, 173]}, {"entity": "T cells", "entity_type": "cell type", "pos": [111, 118]}, {"entity": "OKT8+ T cells", "entity_type": "cell line", "pos": [105, 118]}], "task": "NER"}
{"text": "Reactivity of lymphocytes to a progesterone receptor-specific monoclonal antibody .", "entity": [{"entity": "progesterone receptor-specific monoclonal antibody", "entity_type": "protein", "pos": [31, 81]}, {"entity": "lymphocytes", "entity_type": "cell line", "pos": [14, 25]}], "task": "NER"}
{"text": "In this study we present evidence for reactivity of pregnancy lymphocytes , but not nonpregnancy lymphocytes , with the progesterone receptor-specific monoclonal antibody mPRI .", "entity": [{"entity": "lymphocytes", "entity_type": "cell line", "pos": [62, 73]}, {"entity": "lymphocytes", "entity_type": "cell line", "pos": [97, 108]}, {"entity": "pregnancy lymphocytes", "entity_type": "cell type", "pos": [52, 73]}, {"entity": "progesterone receptor-specific monoclonal antibody", "entity_type": "protein", "pos": [120, 170]}, {"entity": "nonpregnancy lymphocytes", "entity_type": "cell type", "pos": [84, 108]}, {"entity": "mPRI", "entity_type": "protein", "pos": [171, 175]}], "task": "NER"}
{"text": "Using an avidin -biotin peroxidase detection system , we found a nuclear staining in 14.6 +/- 3.7% (mean +/- SEM, N = 27) of pregnancy lymphocytes , while only 0.47 +/- 0.33% (mean +/- SEM, N = 15) of nonpregnancy lymphocytes reacted with the antibody.", "entity": [{"entity": "lymphocytes", "entity_type": "cell line", "pos": [135, 146]}, {"entity": "nonpregnancy lymphocytes", "entity_type": "cell type", "pos": [201, 225]}, {"entity": "lymphocytes", "entity_type": "cell line", "pos": [214, 225]}, {"entity": "-biotin peroxidase", "entity_type": "protein", "pos": [16, 34]}, {"entity": "avidin", "entity_type": "protein", "pos": [9, 15]}, {"entity": "pregnancy lymphocytes", "entity_type": "cell type", "pos": [125, 146]}], "task": "NER"}
{"text": "To characterize the receptor-bearing subset, CD8+ and CD4+ cells were depleted by complement-dependent lysis.", "entity": [], "task": "NER"}
{"text": "Depletion of CD8+ cells was accompanied by 62 +/- 18% loss of progesterone receptor -bearing cells , while depletion of CD4+ cells resulted in a twofold increase in the number of positively staining lymphocytes .", "entity": [{"entity": "progesterone receptor", "entity_type": "protein", "pos": [62, 83]}, {"entity": "CD8+ cells", "entity_type": "cell line", "pos": [13, 23]}, {"entity": "lymphocytes", "entity_type": "cell line", "pos": [199, 210]}, {"entity": "progesterone receptor -bearing cells", "entity_type": "cell line", "pos": [62, 98]}, {"entity": "CD4+ cells", "entity_type": "cell line", "pos": [120, 130]}], "task": "NER"}
{"text": "In nonpregnancy lymphocytes a 3-day PHA treatment , as well as allogeneic stimulation, resulted in a significant increase in the number of receptor-containing cells .", "entity": [{"entity": "PHA", "entity_type": "protein", "pos": [36, 39]}, {"entity": "lymphocytes", "entity_type": "cell line", "pos": [16, 27]}, {"entity": "receptor-containing cells", "entity_type": "cell type", "pos": [139, 164]}, {"entity": "nonpregnancy lymphocytes", "entity_type": "cell line", "pos": [3, 27]}], "task": "NER"}
{"text": "These results suggest that pregnancy , but not nonpregnancy , lymphocytes contain progesterone binding structures , and that these are inducible by mitogenic or alloantigenic stimuli .", "entity": [{"entity": "progesterone binding structures", "entity_type": "protein", "pos": [82, 113]}, {"entity": "lymphocytes", "entity_type": "cell line", "pos": [62, 73]}], "task": "NER"}
{"text": "Activation of human CD4 T lymphocytes .", "entity": [{"entity": "human CD4 T lymphocytes", "entity_type": "cell line", "pos": [14, 37]}], "task": "NER"}
{"text": "Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor .", "entity": [{"entity": "VLA-5 receptor", "entity_type": "protein", "pos": [32, 46]}, {"entity": "AP-1 transcription factor", "entity_type": "protein", "pos": [72, 97]}, {"entity": "CD4 cells", "entity_type": "cell line", "pos": [50, 59]}, {"entity": "fibronectin", "entity_type": "protein", "pos": [15, 26]}], "task": "NER"}
{"text": "Fibronectin synergized with anti-CD3 antibody to promote CD4 cell proliferation in a serum-free culture system whereas no proliferation was observed when CD4 cells were cultured with anti-CD3 alone or fibronectin alone.", "entity": [{"entity": "fibronectin", "entity_type": "protein", "pos": [201, 212]}, {"entity": "anti-CD3 antibody", "entity_type": "protein", "pos": [28, 45]}, {"entity": "anti-CD3", "entity_type": "protein", "pos": [28, 36]}, {"entity": "CD4 cells", "entity_type": "cell line", "pos": [154, 163]}, {"entity": "CD4", "entity_type": "protein", "pos": [57, 60]}, {"entity": "Fibronectin", "entity_type": "protein", "pos": [0, 11]}], "task": "NER"}
{"text": "In addition, anti-CD29 ( integrin beta 1 ) as well as anti-VLA-5 ( human fibronectin receptor ) antibodies blocked this CD4 cell activation in this system.", "entity": [{"entity": "anti-CD29", "entity_type": "protein", "pos": [13, 22]}, {"entity": "fibronectin", "entity_type": "protein", "pos": [73, 84]}, {"entity": "anti-VLA-5", "entity_type": "protein", "pos": [54, 64]}, {"entity": "CD4 cell", "entity_type": "cell line", "pos": [120, 128]}, {"entity": "integrin beta 1", "entity_type": "protein", "pos": [25, 40]}, {"entity": "human fibronectin receptor", "entity_type": "protein", "pos": [67, 93]}], "task": "NER"}
{"text": "Although anti-CD3 alone or fibronectin alone cannot induce IL-2 message by CD4 cells , the combination of anti-CD3 plus fibronectin induced IL-2 message by CD4 cells .", "entity": [{"entity": "anti-CD3", "entity_type": "protein", "pos": [9, 17]}, {"entity": "fibronectin", "entity_type": "protein", "pos": [27, 38]}, {"entity": "anti-CD3", "entity_type": "protein", "pos": [106, 114]}, {"entity": "CD4 cells", "entity_type": "cell line", "pos": [75, 84]}, {"entity": "CD4 cells", "entity_type": "cell line", "pos": [156, 165]}, {"entity": "IL-2", "entity_type": "protein", "pos": [59, 63]}, {"entity": "fibronectin", "entity_type": "protein", "pos": [120, 131]}, {"entity": "IL-2", "entity_type": "protein", "pos": [140, 144]}], "task": "NER"}
{"text": "In an analysis of the molecular mechanism by which IL-2 message was generated, we showed that a fibronectin -VLA-5 fibronectin receptor interaction may contribute an independent signal distinct from the CD3 pathway of activation by the induction of an AP-1 transcriptional factor .", "entity": [{"entity": "fibronectin receptor", "entity_type": "protein", "pos": [115, 135]}, {"entity": "IL-2", "entity_type": "protein", "pos": [51, 55]}, {"entity": "fibronectin", "entity_type": "protein", "pos": [96, 107]}, {"entity": "AP-1 transcriptional factor", "entity_type": "protein", "pos": [252, 279]}, {"entity": "fibronectin", "entity_type": "protein", "pos": [115, 126]}, {"entity": "CD3", "entity_type": "protein", "pos": [203, 206]}], "task": "NER"}
{"text": "Thus the VLA-5 fibronectin receptor on CD4 cells can play a complementary role in CD3 - TCR -mediated signal transduction through its interaction with fibronectin .", "entity": [{"entity": "CD3", "entity_type": "protein", "pos": [82, 85]}, {"entity": "TCR", "entity_type": "protein", "pos": [88, 91]}, {"entity": "VLA-5 fibronectin receptor", "entity_type": "protein", "pos": [9, 35]}, {"entity": "fibronectin", "entity_type": "protein", "pos": [15, 26]}, {"entity": "CD4 cells", "entity_type": "cell line", "pos": [39, 48]}, {"entity": "fibronectin", "entity_type": "protein", "pos": [151, 162]}], "task": "NER"}
{"text": "Glucocorticoid receptors on mononuclear leukocytes in Alzheimer's disease .", "entity": [{"entity": "Glucocorticoid receptors", "entity_type": "protein", "pos": [0, 24]}, {"entity": "mononuclear leukocytes", "entity_type": "cell type", "pos": [28, 50]}], "task": "NER"}
{"text": "Several lines of evidence suggest disturbances of the hypothalamic-pituitary-adrenal ( HPA ) system in Alzheimer's disease ( AD ).", "entity": [], "task": "NER"}
{"text": "In an exploration of the potential role of the glucocorticoid receptor (GR) in AD , GR density and affinity were assessed on mononuclear leukocytes of 12 AD patients and 12 healthy controls .", "entity": [{"entity": "mononuclear leukocytes", "entity_type": "cell type", "pos": [125, 147]}], "task": "NER"}
{"text": "GR binding characteristics did not differ between patients and controls or between patients subdivided according to diagnosis or associated clinical features.", "entity": [], "task": "NER"}
{"text": "These data suggest that the abnormalities of the HPA system in AD are not related to a GR deficiency .", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [87, 89]}], "task": "NER"}
{"text": "Oncogene amplification correlates with dense lymphocyte infiltration in human breast cancers : a role for hematopoietic growth factor release by tumor cells ?", "entity": [{"entity": "tumor cells", "entity_type": "cell type", "pos": [145, 156]}, {"entity": "hematopoietic growth factor", "entity_type": "protein", "pos": [106, 133]}], "task": "NER"}
{"text": "One hundred six primary breast cancer samples were analysed for c-erbB2 , int-2 , and c-myc gene amplification .", "entity": [], "task": "NER"}
{"text": "Surgically confirmed nodal involvement was observed in 42%.", "entity": [], "task": "NER"}
{"text": "Level of gene amplification was studied by Southern and/or slot blot techniques .", "entity": [], "task": "NER"}
{"text": "Amplified c-erbB2 gene sequences were present in 21.5% of all samples.", "entity": [{"entity": "c-erbB2 gene sequences", "entity_type": "DNA", "pos": [10, 32]}], "task": "NER"}
{"text": "Int-2 was amplified in 13.1% and c-myc was amplified in 10.3%.", "entity": [{"entity": "c-myc", "entity_type": "DNA", "pos": [33, 38]}, {"entity": "Int-2", "entity_type": "DNA", "pos": [0, 5]}], "task": "NER"}
{"text": "In a non-parametric test (Kruskal-Wallis) a strong negative association was found between high levels of c-erbB2 amplification and absence of estrogen receptor (ER) (P = .0009) or progesterone receptor ( PR ) (P = .011) expression.", "entity": [{"entity": "progesterone receptor", "entity_type": "protein", "pos": [180, 201]}, {"entity": "PR", "entity_type": "protein", "pos": [204, 206]}, {"entity": "c-erbB2", "entity_type": "DNA", "pos": [105, 112]}], "task": "NER"}
{"text": "No correlations were found between all or high levels of amplification of each oncogene separately or combined with T, N, grade, multifocality of tumor , or associated carcinoma in situ.", "entity": [], "task": "NER"}
{"text": "There was a trend approaching statistical significance for patients with c-erbB2 amplifications to have positive lymph nodes at surgery (P = 0.09).", "entity": [{"entity": "c-erbB2", "entity_type": "DNA", "pos": [73, 80]}], "task": "NER"}
{"text": "A somewhat surprising finding however was a very strong association between oncogene amplification and dense lymphocyte infiltration of the tumor (P = .05). This correlation is even stronger when only high levels of amplification are considered, either for each oncogene separately (P = .0048) or in combination (P = .0007).", "entity": [{"entity": "oncogene", "entity_type": "DNA", "pos": [76, 84]}], "task": "NER"}
{"text": "We propose that malignant cell cytokine production may help explain this observation.", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [31, 39]}], "task": "NER"}
{"text": "Suppression of signals required for activation of transcription factor NF-kappa B in cells constitutively expressing the HTLV-I Tax protein .", "entity": [{"entity": "transcription factor NF-kappa B", "entity_type": "protein", "pos": [50, 81]}, {"entity": "HTLV-I Tax protein", "entity_type": "protein", "pos": [121, 139]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [71, 81]}], "task": "NER"}
{"text": "Transient short-term expression of the Tax protein of human T-cell leukemia virus type-I ( HTLV-I ) leads to activation of the pleiotropic transcription factor NF-kappa B .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [160, 170]}, {"entity": "Tax protein", "entity_type": "protein", "pos": [39, 50]}, {"entity": "transcription factor NF-kappa B", "entity_type": "protein", "pos": [139, 170]}], "task": "NER"}
{"text": "Consistent with findings obtained with transient expression assays , we observed marked accumulation of the transcription factor NF-kappa B in the nucleus of Namalwa B lymphoid cells , which constitutively express Tax .", "entity": [{"entity": "Namalwa B lymphoid cells", "entity_type": "cell line", "pos": [158, 182]}, {"entity": "transcription factor NF-kappa B", "entity_type": "protein", "pos": [108, 139]}, {"entity": "Tax", "entity_type": "protein", "pos": [214, 217]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [129, 139]}], "task": "NER"}
{"text": "In contrast, NF-kappa B activity was not detected in the nucleus following long-term expression of Tax in Jurkat T lymphocytes .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [13, 23]}, {"entity": "Jurkat T lymphocytes", "entity_type": "cell line", "pos": [106, 126]}, {"entity": "Tax", "entity_type": "protein", "pos": [99, 102]}], "task": "NER"}
{"text": "The ability of both mitogens and cytokines to activate NF-kappa B was also blocked in Jurkat cells constitutively expressing Tax .", "entity": [{"entity": "cytokines", "entity_type": "protein", "pos": [33, 42]}, {"entity": "Tax", "entity_type": "protein", "pos": [125, 128]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [86, 98]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [55, 65]}], "task": "NER"}
{"text": "However, the activation of other mitogen-inducible transcription factors , such as Fos and Jun , was unaffected.", "entity": [{"entity": "Jun", "entity_type": "protein", "pos": [91, 94]}, {"entity": "Fos", "entity_type": "protein", "pos": [83, 86]}, {"entity": "mitogen-inducible transcription factors", "entity_type": "protein", "pos": [33, 72]}], "task": "NER"}
{"text": "Thus, depending on the cellular environment , the short- and long-term effects of Tax expression can be quite different.", "entity": [{"entity": "Tax", "entity_type": "protein", "pos": [82, 85]}], "task": "NER"}
{"text": "Consequently, one function of Tax in cells infected with HTLV-I might involve cell-type-specific suppression , as opposed to activation, of distinct signal pathways .", "entity": [{"entity": "Tax", "entity_type": "protein", "pos": [30, 33]}], "task": "NER"}
{"text": "The cells lines described here should be useful for the delineation of signaling pathways utilized in the selective regulation of gene expression .", "entity": [], "task": "NER"}
{"text": "Interferon-gamma and the sexual dimorphism of autoimmunity .", "entity": [{"entity": "Interferon-gamma", "entity_type": "protein", "pos": [0, 16]}], "task": "NER"}
{"text": "The sexual difference in the incidence of autoimmune diseases has remained an enigma for many years.", "entity": [], "task": "NER"}
{"text": "In the examination of the induction of autoimmunity in transgenic mice , evidence has been obtained further implicating the lymphokine interferon-gamma in the etiology of autoimmunity .", "entity": [{"entity": "interferon-gamma", "entity_type": "protein", "pos": [135, 151]}, {"entity": "lymphokine", "entity_type": "protein", "pos": [124, 134]}], "task": "NER"}
{"text": "Sex steroid regulation of the production of this molecule, as well as other cytokines , may help explain the gender-specific differences in the immune system , including autoimmunity .", "entity": [{"entity": "cytokines", "entity_type": "protein", "pos": [76, 85]}], "task": "NER"}
{"text": "Cloning of a transcriptionally active human TATA binding factor .", "entity": [{"entity": "transcriptionally active human TATA binding factor", "entity_type": "protein", "pos": [13, 63]}, {"entity": "human TATA binding factor", "entity_type": "protein", "pos": [38, 63]}], "task": "NER"}
{"text": "Transcription factor IID ( TFIID ) binds to the TATA box promoter element and regulates the expression of most eukaryotic genes transcribed by RNA polymerase II .", "entity": [{"entity": "RNA polymerase II", "entity_type": "protein", "pos": [143, 160]}, {"entity": "eukaryotic genes", "entity_type": "DNA", "pos": [111, 127]}, {"entity": "Transcription factor IID", "entity_type": "protein", "pos": [0, 24]}, {"entity": "TATA box promoter element", "entity_type": "DNA", "pos": [48, 73]}, {"entity": "TFIID", "entity_type": "protein", "pos": [27, 32]}], "task": "NER"}
{"text": "Complementary DNA ( cDNA ) encoding a human TFIID protein has been cloned.", "entity": [{"entity": "TFIID", "entity_type": "protein", "pos": [44, 49]}, {"entity": "Complementary DNA", "entity_type": "DNA", "pos": [0, 17]}, {"entity": "cDNA", "entity_type": "DNA", "pos": [20, 24]}, {"entity": "human TFIID protein", "entity_type": "protein", "pos": [38, 57]}], "task": "NER"}
{"text": "The human TFIID polypeptide has 339 amino acids and a molecular size of 37,745 daltons .", "entity": [{"entity": "TFIID", "entity_type": "protein", "pos": [10, 15]}, {"entity": "human TFIID polypeptide", "entity_type": "protein", "pos": [4, 27]}], "task": "NER"}
{"text": "The carboxyl-terminal 181 amino acids of the human TFIID protein shares 80% identity with the TFIID protein from Saccharomyces cerevisiae .", "entity": [{"entity": "human TFIID protein", "entity_type": "protein", "pos": [45, 64]}, {"entity": "TFIID", "entity_type": "protein", "pos": [51, 56]}, {"entity": "carboxyl-terminal 181 amino acids", "entity_type": "protein", "pos": [4, 37]}, {"entity": "TFIID", "entity_type": "protein", "pos": [94, 99]}], "task": "NER"}
{"text": "The amino terminus contains an unusual repeat of 38 consecutive glutamine residues and an X-Thr-Pro repeat .", "entity": [{"entity": "amino terminus", "entity_type": "protein", "pos": [4, 18]}, {"entity": "X-Thr-Pro repeat", "entity_type": "protein", "pos": [90, 106]}], "task": "NER"}
{"text": "Expression of DNA in reticulocyte lysates or in Escherichia coli yielded a protein that was competent for both DNA binding and transcription activation .", "entity": [{"entity": "DNA", "entity_type": "DNA", "pos": [14, 17]}], "task": "NER"}
{"text": "A novel T-cell trans-activator that recognizes a phorbol ester-inducible element of the interleukin-2 promoter .", "entity": [{"entity": "interleukin-2", "entity_type": "protein", "pos": [88, 101]}, {"entity": "interleukin-2 promoter", "entity_type": "DNA", "pos": [88, 110]}, {"entity": "T-cell trans-activator", "entity_type": "protein", "pos": [8, 30]}, {"entity": "phorbol ester-inducible element", "entity_type": "DNA", "pos": [49, 80]}], "task": "NER"}
{"text": "The interleukin 2 ( IL-2 ) gene promoter is recognized by several cell-type-specific and ubiquitous transcriptional regulators that integrate information transmitted by various signaling systems leading to IL-2 production and T-cell activation .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [20, 24]}, {"entity": "interleukin 2", "entity_type": "protein", "pos": [4, 17]}, {"entity": "interleukin 2 ( IL-2 ) gene promoter", "entity_type": "DNA", "pos": [4, 40]}, {"entity": "IL-2", "entity_type": "protein", "pos": [206, 210]}, {"entity": "T-cell", "entity_type": "cell type", "pos": [226, 232]}], "task": "NER"}
{"text": "Using a combination of transfection , protein-DNA binding, and in vitro transcription methods , we have discovered the novel T-cell-specific transcriptional activator TCF-1 (for T-Cell Factor-1 ), which recognizes a T-cell-specific response element ( TCE ) located within the IL-2 promoter .", "entity": [{"entity": "TCF-1", "entity_type": "protein", "pos": [167, 172]}, {"entity": "T-Cell Factor-1", "entity_type": "protein", "pos": [178, 193]}, {"entity": "novel T-cell-specific transcriptional activator", "entity_type": "protein", "pos": [119, 166]}, {"entity": "IL-2 promoter", "entity_type": "DNA", "pos": [276, 289]}, {"entity": "T-cell-specific response element", "entity_type": "DNA", "pos": [216, 248]}, {"entity": "IL-2", "entity_type": "protein", "pos": [276, 280]}, {"entity": "TCE", "entity_type": "DNA", "pos": [251, 254]}], "task": "NER"}
{"text": "Although the TCE is similar in sequence to a consensus NF kappa B site , several criteria indicate that TCF-1 is distinct from NF kappa B .", "entity": [{"entity": "NF kappa B", "entity_type": "protein", "pos": [55, 65]}, {"entity": "TCF-1", "entity_type": "protein", "pos": [104, 109]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [127, 137]}, {"entity": "NF kappa B site", "entity_type": "DNA", "pos": [55, 70]}, {"entity": "consensus NF kappa B site", "entity_type": "DNA", "pos": [45, 70]}, {"entity": "TCE", "entity_type": "DNA", "pos": [13, 16]}], "task": "NER"}
{"text": "However, like NF kappa B , TCF-1 activity is induced by phorbol esters and other T-cell activators .", "entity": [{"entity": "TCF-1", "entity_type": "protein", "pos": [27, 32]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [14, 24]}], "task": "NER"}
{"text": "Risk factors for breast recurrence in premenopausal and postmenopausal patients with ductal cancers treated by conservation therapy .", "entity": [], "task": "NER"}
{"text": "Risk factors for local failure were evaluated for 496 clinical Stage I-II patients with infiltrating ductal carcinomas (median follow-up, 71 months) treated by conservative surgery and radiotherapy .", "entity": [], "task": "NER"}
{"text": "Monofactorial analysis identified the following factors to be correlated with increased risk: moderate/marked mononuclear cell reaction ( MCR ), high histologic grade (G), extensive intraductal component ( EIC ), tumor necrosis , macroscopic multiplicity , estrogen receptor negativity , anatomic tumor size , age younger than 40 years, and vascular invasion .", "entity": [{"entity": "estrogen receptor", "entity_type": "protein", "pos": [257, 274]}], "task": "NER"}
{"text": "Only MCR , G , and EIC proved significant in Cox multivariate analysis .", "entity": [], "task": "NER"}
{"text": "These risk factors were highly age dependent, with EIC markedly more prevalent in women younger than 50, MCR and G in women younger than 40.", "entity": [], "task": "NER"}
{"text": "Separate Cox analysis for premenopausal patients showed that MCR /EIC determined risk independent of resection margins: tumors with MCR had a 28%, and with EIC a 22% probability of recurring locally by 5 years.", "entity": [], "task": "NER"}
{"text": "Premenopausal patients with neither risk factor had a very low failure rate (2.6% at 5 years), regardless of age.", "entity": [], "task": "NER"}
{"text": "For postmenopausal patients risk of breast recurrence was determined both by adequacy of resection margins and grade, with a high local failure rate for patients having G3 tumors with positive or indeterminate margins (31% at 5 years).", "entity": [], "task": "NER"}
{"text": "The authors conclude that the microscopic examination is the only useful tool for assessing the risk of local failure, which is quite low for the majority of patients treated with breast conservation .", "entity": [], "task": "NER"}
{"text": "High-risk patients can be recognized morphologically.", "entity": [], "task": "NER"}
{"text": "The age dependence of morphologic risk factors appears to explain the high local failure rate seen in patients younger than 40.", "entity": [], "task": "NER"}
{"text": "Tax -independent binding of multiple cellular factors to Tax -response element DNA of HTLV-I .", "entity": [{"entity": "cellular factors", "entity_type": "protein", "pos": [37, 53]}, {"entity": "Tax", "entity_type": "protein", "pos": [0, 3]}, {"entity": "Tax -response element DNA", "entity_type": "DNA", "pos": [57, 82]}, {"entity": "Tax", "entity_type": "protein", "pos": [57, 60]}], "task": "NER"}
{"text": "The human T-cell leukemia virus type I ( HTLV-I ) promoter contains three copies of imperfect repeats of a 21-base pair sequence designated here as TRE ( Tax -response element ) that is responsive to the virally encoded transactivator protein Tax .", "entity": [{"entity": "virally encoded transactivator protein", "entity_type": "protein", "pos": [204, 242]}, {"entity": "Tax -response element", "entity_type": "DNA", "pos": [154, 175]}, {"entity": "TRE", "entity_type": "DNA", "pos": [148, 151]}, {"entity": "human T-cell leukemia virus type I ( HTLV-I ) promoter", "entity_type": "DNA", "pos": [4, 58]}, {"entity": "Tax", "entity_type": "protein", "pos": [154, 157]}, {"entity": "Tax", "entity_type": "protein", "pos": [243, 246]}], "task": "NER"}
{"text": "We have identified and separated four nuclear proteins from C81-66-45 cells, an HTLV-I immortalized Tax -expressing human T-lymphocyte line (Salahuddin et al., 1983), that interact with the TRE -DNA , none of which are identical with the Tax -protein .", "entity": [{"entity": "TRE", "entity_type": "DNA", "pos": [190, 193]}, {"entity": "Tax", "entity_type": "protein", "pos": [100, 103]}, {"entity": "Tax -protein", "entity_type": "protein", "pos": [238, 250]}, {"entity": "nuclear proteins", "entity_type": "protein", "pos": [38, 54]}, {"entity": "TRE -DNA", "entity_type": "DNA", "pos": [190, 198]}, {"entity": "HTLV-I immortalized Tax -expressing human T-lymphocyte line", "entity_type": "cell line", "pos": [80, 139]}, {"entity": "Tax", "entity_type": "protein", "pos": [238, 241]}], "task": "NER"}
{"text": "The proteins identified have molecular weights of about 32, 36 to 42, 50 and 110 kD.", "entity": [], "task": "NER"}
{"text": "Four different methods were used to identify the proteins.", "entity": [], "task": "NER"}
{"text": "First, from different cell lines three or all four of the nuclear proteins were specifically cross-linked by UV irradiation to the radioactively labeled TRE -DNA fragment .", "entity": [{"entity": "TRE -DNA fragment", "entity_type": "DNA", "pos": [153, 170]}, {"entity": "nuclear proteins", "entity_type": "protein", "pos": [58, 74]}, {"entity": "TRE", "entity_type": "DNA", "pos": [153, 156]}], "task": "NER"}
{"text": "Second, TRE -DNA binding proteins sedimented through a glycerol density gradient at rates corresponding to proteins of native molecular weights of 35 to 50 kD and 110 kD.", "entity": [{"entity": "TRE -DNA binding proteins", "entity_type": "protein", "pos": [8, 33]}, {"entity": "TRE", "entity_type": "DNA", "pos": [8, 11]}], "task": "NER"}
{"text": "Third, only the 50 kD protein was retained on a biotinylated DNA-streptavidin matrix when the DNA fragment contained the TRE -DNA .", "entity": [{"entity": "TRE", "entity_type": "DNA", "pos": [121, 124]}, {"entity": "50 kD protein", "entity_type": "protein", "pos": [16, 29]}, {"entity": "TRE -DNA", "entity_type": "DNA", "pos": [121, 129]}], "task": "NER"}
{"text": "Fourth, extensive purification by several cycles of TRE -DNA affinity chromatography resulted in the 32 , 36 to 42 and 110 kD proteins and to less extent the 50 kD factor .", "entity": [{"entity": "50 kD factor", "entity_type": "protein", "pos": [158, 170]}, {"entity": "TRE", "entity_type": "DNA", "pos": [52, 55]}], "task": "NER"}
{"text": "Two abundant proteins of 75 and 80 kD were competed out by poly[d(I-C)] in all reactions.", "entity": [], "task": "NER"}
{"text": "The cAMP-response element CRE , TGACGTCA , present in the 21 base-pair sequence , appears to be essential for specific protein- TRE -DNA interactions because mutation of the two G 's destroys this complex.", "entity": [{"entity": "21 base-pair sequence", "entity_type": "DNA", "pos": [58, 79]}, {"entity": "CRE", "entity_type": "DNA", "pos": [26, 29]}, {"entity": "cAMP-response element", "entity_type": "DNA", "pos": [4, 25]}, {"entity": "TRE", "entity_type": "DNA", "pos": [128, 131]}], "task": "NER"}
{"text": "This result suggests that the cAMP response element binding protein , CREB , is involved in the protein- TRE -DNA complex and in mediating the Tax response .", "entity": [{"entity": "TRE", "entity_type": "DNA", "pos": [105, 108]}, {"entity": "Tax", "entity_type": "protein", "pos": [143, 146]}, {"entity": "protein- TRE -DNA complex", "entity_type": "protein", "pos": [96, 121]}, {"entity": "cAMP response element binding protein", "entity_type": "protein", "pos": [30, 67]}, {"entity": "CREB", "entity_type": "protein", "pos": [70, 74]}], "task": "NER"}
{"text": "Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif .", "entity": [{"entity": "microE5/kappa 2 motif", "entity_type": "DNA", "pos": [73, 94]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [13, 34]}, {"entity": "immunoglobulin enhancer", "entity_type": "DNA", "pos": [49, 72]}], "task": "NER"}
{"text": "Activity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of ubiquitous and developmentally regulated proteins .", "entity": [{"entity": "ubiquitous and developmentally regulated proteins", "entity_type": "protein", "pos": [108, 157]}, {"entity": "ubiquitous", "entity_type": "protein", "pos": [108, 118]}, {"entity": "developmentally regulated proteins", "entity_type": "protein", "pos": [123, 157]}], "task": "NER"}
{"text": "Two complementary DNAs were isolated that encode proteins, denoted ITF-1 and ITF-2 , that are expressed in a variety of cell types and bind the microE5/kappa 2 motif found in both heavy and kappa light chain enhancers .", "entity": [{"entity": "microE5/kappa 2 motif", "entity_type": "DNA", "pos": [144, 165]}, {"entity": "ITF-1", "entity_type": "protein", "pos": [67, 72]}, {"entity": "complementary DNAs", "entity_type": "DNA", "pos": [4, 22]}, {"entity": "ITF-2", "entity_type": "protein", "pos": [77, 82]}], "task": "NER"}
{"text": "The complementary DNAs are the products of distinct genes, yet both ITF-1 and ITF-2 are structurally and functionally similar.", "entity": [{"entity": "complementary DNAs", "entity_type": "DNA", "pos": [4, 22]}, {"entity": "ITF-2", "entity_type": "protein", "pos": [78, 83]}, {"entity": "ITF-1", "entity_type": "protein", "pos": [68, 73]}], "task": "NER"}
{"text": "The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation .", "entity": [{"entity": "helix-loop-helix motifs", "entity_type": "protein", "pos": [66, 89]}], "task": "NER"}
{"text": "Elevated glucocorticoid receptor concentrations before and after glucocorticoid therapy in peripheral mononuclear leukocytes of patients with atopic dermatitis .", "entity": [{"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [9, 32]}, {"entity": "peripheral mononuclear leukocytes", "entity_type": "cell type", "pos": [91, 124]}], "task": "NER"}
{"text": "The number and affinity of glucocorticoid binding sites in peripheral mononuclear leukocytes of patients with atopic dermatitis ( AD ) and healthy controls were determined under baseline conditions and after a defined oral glucocorticoid treatment .", "entity": [{"entity": "peripheral mononuclear leukocytes", "entity_type": "cell type", "pos": [59, 92]}], "task": "NER"}
{"text": "Patients with AD (n = 15) exhibited significantly more glucocorticoid receptors ( GR ) per cell than the control group (n = 22), while the GR affinity did not differ.", "entity": [{"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [55, 79]}, {"entity": "GR", "entity_type": "protein", "pos": [82, 84]}, {"entity": "GR", "entity_type": "protein", "pos": [139, 141]}], "task": "NER"}
{"text": "Methylprednisolone treatment resulted in a significant reduction of the GR sites per cell in the steroid-treated control group (n = 10) in contrast to the patients .", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [72, 74]}], "task": "NER"}
{"text": "The dissociation constant was not affected by methylprednisolone treatment in either group.", "entity": [], "task": "NER"}
{"text": "In view of the therapeutic efficiency of glucocorticoids in AD and findings of abnormal cAMP and cAMP-phosphodiesterase activity , the elevated GR concentrations in AD lend support to the hypothesis of a compensatory GR upregulation due to an insufficient action of endogenous cortisol or to altered cAMP -induced GR expression .", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [144, 146]}, {"entity": "GR", "entity_type": "protein", "pos": [217, 219]}, {"entity": "GR", "entity_type": "protein", "pos": [314, 316]}], "task": "NER"}
{"text": "The actions of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [81, 94]}], "task": "NER"}
{"text": "Cyclosporin A and FK506 are immunosuppressive compounds that have similar inhibitory effects on the expression of several lymphokines produced by T lymphocytes .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [146, 159]}, {"entity": "lymphokines", "entity_type": "protein", "pos": [122, 133]}], "task": "NER"}
{"text": "Despite their similar effects the drugs bind to two different cytosolic protein , cyclophilin and FKBP respectively, which raises the possibility that they have different modes of action.", "entity": [{"entity": "cyclophilin", "entity_type": "protein", "pos": [82, 93]}, {"entity": "FKBP", "entity_type": "protein", "pos": [98, 102]}, {"entity": "cytosolic protein", "entity_type": "protein", "pos": [62, 79]}], "task": "NER"}
{"text": "Using constructs in which mRNA production controlled by a specific transcription factor could be readily measured we found that both cyclosporin A and FK506 completely inhibited transcription activated by NF-AT , NFIL2 A , NFIL2 B and partially inhibited transcription activated by NF kappa B .", "entity": [{"entity": "NFIL2 B", "entity_type": "protein", "pos": [223, 230]}, {"entity": "NFIL2 A", "entity_type": "protein", "pos": [213, 220]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [67, 87]}, {"entity": "mRNA", "entity_type": "RNA", "pos": [26, 30]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [205, 210]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [282, 292]}], "task": "NER"}
{"text": "Cyclosporin A and FK506 inhibited only transcriptional activation that was dependent on Ca2+ mobilization .", "entity": [], "task": "NER"}
{"text": "However, cyclosporin A and FK506 did not inhibit Ca2+ mobilization dependent expression of c-fos mRNA indicating that only a subset of signalling pathways regulated by Ca2+ is sensitive to these drugs.", "entity": [{"entity": "c-fos mRNA", "entity_type": "RNA", "pos": [91, 101]}], "task": "NER"}
{"text": "Furthermore, we did not observe any qualitative differences between the effect of cyclosporin A and FK506 on six different transcription factors which suggests that these drugs may interfere with the activity of a novel Ca2+ dependent step that regulates several transcription factors .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [123, 144]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [263, 284]}], "task": "NER"}
{"text": "The internal methionine codons of human T-cell leukemia virus type II rex gene are not required for p24rex production or virus replication and transformation .", "entity": [{"entity": "human T-cell leukemia virus type II rex gene", "entity_type": "DNA", "pos": [34, 78]}, {"entity": "p24rex", "entity_type": "protein", "pos": [100, 106]}], "task": "NER"}
{"text": "Human T-cell leukemia virus types I ( HTLV-I ) and II ( HTLV-II ) have two nonstructural trans-acting regulatory genes , tax and rex , located in the 3' region of the viral genome .", "entity": [{"entity": "rex", "entity_type": "DNA", "pos": [129, 132]}, {"entity": "3' region", "entity_type": "DNA", "pos": [150, 159]}, {"entity": "viral genome", "entity_type": "DNA", "pos": [167, 179]}, {"entity": "tax", "entity_type": "DNA", "pos": [121, 124]}, {"entity": "nonstructural trans-acting regulatory genes", "entity_type": "DNA", "pos": [75, 118]}], "task": "NER"}
{"text": "The tax gene product ( HTLV-I p40tax and HTLV-II p37tax ) is the transcriptional activator of the viral long terminal repeat .", "entity": [{"entity": "HTLV-I p40tax", "entity_type": "protein", "pos": [23, 36]}, {"entity": "tax", "entity_type": "DNA", "pos": [4, 7]}, {"entity": "viral long terminal repeat", "entity_type": "DNA", "pos": [98, 124]}, {"entity": "p40tax", "entity_type": "DNA", "pos": [30, 36]}, {"entity": "HTLV-II p37tax", "entity_type": "protein", "pos": [41, 55]}, {"entity": "p37tax", "entity_type": "DNA", "pos": [49, 55]}, {"entity": "tax gene product", "entity_type": "protein", "pos": [4, 20]}], "task": "NER"}
{"text": "The rex gene encodes two protein products, p27rex /p21rex and p26rex /p24rex in HTLV-I and HTLV-II , respectively.", "entity": [{"entity": "p26rex /p24rex", "entity_type": "protein", "pos": [62, 76]}, {"entity": "p26rex", "entity_type": "protein", "pos": [62, 68]}, {"entity": "p27rex /p21rex", "entity_type": "protein", "pos": [43, 57]}, {"entity": "/p21rex", "entity_type": "protein", "pos": [50, 57]}, {"entity": "p27rex", "entity_type": "protein", "pos": [43, 49]}, {"entity": "rex gene", "entity_type": "DNA", "pos": [4, 12]}, {"entity": "/p24rex", "entity_type": "protein", "pos": [69, 76]}], "task": "NER"}
{"text": "Rex acts posttranscriptionally to facilitate accumulation of full-length gag/pol and singly spliced env mRNA in the cytoplasm of HTLV-infected cells .", "entity": [{"entity": "Rex", "entity_type": "protein", "pos": [0, 3]}, {"entity": "HTLV-infected cells", "entity_type": "cell type", "pos": [129, 148]}, {"entity": "gag/pol", "entity_type": "protein", "pos": [73, 80]}, {"entity": "env mRNA", "entity_type": "RNA", "pos": [100, 108]}], "task": "NER"}
{"text": "Previous studies showed that the first ATG of the rex gene is critical for Rex production and function.", "entity": [{"entity": "Rex", "entity_type": "protein", "pos": [75, 78]}, {"entity": "rex", "entity_type": "DNA", "pos": [50, 53]}, {"entity": "rex gene", "entity_type": "DNA", "pos": [50, 58]}], "task": "NER"}
{"text": "The importance of the internal ATGs to Rex function is not known.", "entity": [{"entity": "Rex", "entity_type": "protein", "pos": [39, 42]}], "task": "NER"}
{"text": "However, in vitro mutagenesis of the HTLV-I rex gene has provided indirect evidence which suggests that p21rex , and by analogy HTLV-II p24rex , results from initiation at an internal AUG of the tax /rex mRNA .", "entity": [{"entity": "p24rex", "entity_type": "protein", "pos": [136, 142]}, {"entity": "tax", "entity_type": "DNA", "pos": [195, 198]}, {"entity": "rex gene", "entity_type": "DNA", "pos": [44, 52]}, {"entity": "tax /rex mRNA", "entity_type": "RNA", "pos": [195, 208]}, {"entity": "rex", "entity_type": "DNA", "pos": [44, 47]}, {"entity": "/rex", "entity_type": "DNA", "pos": [199, 203]}, {"entity": "p21rex", "entity_type": "protein", "pos": [104, 110]}], "task": "NER"}
{"text": "By using an infectious molecular clone of HTLV-II , we investigated the importance of the internal ATGs of the rex gene on Rex protein production and function.", "entity": [{"entity": "rex", "entity_type": "DNA", "pos": [111, 114]}, {"entity": "Rex", "entity_type": "protein", "pos": [123, 126]}, {"entity": "rex gene", "entity_type": "DNA", "pos": [111, 119]}], "task": "NER"}
{"text": "Our results indicate that p24rex of HTLV-II is not initiated at an internal AUG and that the internal methionine codons are not crucial to the function of the rex gene and, ultimately, the transforming properties of the virus .", "entity": [{"entity": "p24rex", "entity_type": "protein", "pos": [26, 32]}, {"entity": "rex gene", "entity_type": "DNA", "pos": [159, 167]}], "task": "NER"}
{"text": "Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins .", "entity": [{"entity": "B cell type Oct-2 proteins", "entity_type": "protein", "pos": [116, 142]}, {"entity": "ubiquitous Oct-1", "entity_type": "protein", "pos": [95, 111]}, {"entity": "Astrocytes", "entity_type": "cell type", "pos": [0, 10]}, {"entity": "glioblastoma cells", "entity_type": "cell type", "pos": [15, 33]}, {"entity": "octamer-DNA binding proteins", "entity_type": "protein", "pos": [48, 76]}, {"entity": "ubiquitous Oct-1 and B cell type Oct-2 proteins", "entity_type": "protein", "pos": [95, 142]}], "task": "NER"}
{"text": "The 'octamer' sequence , ATGCAAAT or its complement ATTTGCAT , is a key element for the transcriptional regulation of immunoglobulin genes in B-lymphocytes as well as a number of housekeeping genes in all cell types.", "entity": [{"entity": "'octamer' sequence", "entity_type": "DNA", "pos": [4, 22]}, {"entity": "immunoglobulin genes", "entity_type": "DNA", "pos": [118, 138]}, {"entity": "B-lymphocytes", "entity_type": "cell type", "pos": [142, 155]}, {"entity": "housekeeping genes", "entity_type": "DNA", "pos": [179, 197]}], "task": "NER"}
{"text": "In lymphocytes , the octamer-binding protein Oct-2A and variants thereof are thought to contribute to the B-cell specific gene expression , while the ubiquitous protein Oct-1 seems to control general octamer site -dependent transcription .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [3, 14]}, {"entity": "B-cell specific gene", "entity_type": "DNA", "pos": [106, 126]}, {"entity": "Oct-2A", "entity_type": "protein", "pos": [45, 51]}, {"entity": "octamer-binding protein", "entity_type": "protein", "pos": [21, 44]}, {"entity": "octamer site", "entity_type": "DNA", "pos": [200, 212]}], "task": "NER"}
{"text": "Various other genes, for example interleukin-1 and MHC class II genes , contain an octamer sequence in the promoter and are expressed in cells of both the immune and nervous systems .", "entity": [{"entity": "promoter", "entity_type": "DNA", "pos": [107, 115]}, {"entity": "octamer sequence", "entity_type": "DNA", "pos": [83, 99]}], "task": "NER"}
{"text": "This prompted us to analyze the octamer-binding proteins in the latter cells.", "entity": [{"entity": "octamer-binding proteins", "entity_type": "protein", "pos": [32, 56]}], "task": "NER"}
{"text": "Using the electrophoretic mobility shift assay , at least six novel octamer binding proteins were detected in nuclear extracts of cultured mouse astrocytes .", "entity": [{"entity": "cultured mouse astrocytes", "entity_type": "cell type", "pos": [130, 155]}, {"entity": "octamer binding proteins", "entity_type": "protein", "pos": [68, 92]}], "task": "NER"}
{"text": "These proteins are differentially expressed in human glioblastoma and neuroblastoma cell lines .", "entity": [], "task": "NER"}
{"text": "The nervous system-derived (N-Oct) proteins bound to the octamer DNA sequence in a manner which is indistinguishable from the Oct-1 and Oct-2A proteins .", "entity": [{"entity": "nervous system-derived (N-Oct) proteins", "entity_type": "protein", "pos": [4, 43]}, {"entity": "Oct-2A proteins", "entity_type": "protein", "pos": [136, 151]}, {"entity": "octamer DNA sequence", "entity_type": "DNA", "pos": [57, 77]}, {"entity": "Oct-1", "entity_type": "protein", "pos": [126, 131]}], "task": "NER"}
{"text": "The relationship of the N-Oct proteins to Oct-1 and Oct-2A was analyzed by proteolytic clipping bandshift assays and by their reactivity towards antisera raised against recombinant Oct-1 and Oct-2A proteins.", "entity": [{"entity": "Oct-2A", "entity_type": "protein", "pos": [52, 58]}, {"entity": "Oct-2A", "entity_type": "protein", "pos": [191, 197]}, {"entity": "Oct-1", "entity_type": "protein", "pos": [42, 47]}, {"entity": "N-Oct proteins", "entity_type": "protein", "pos": [24, 38]}, {"entity": "Oct-1", "entity_type": "protein", "pos": [181, 186]}], "task": "NER"}
{"text": "On the basis of these assays, all N-Oct-factors were found to be distinct from the ubiquitous Oct-1 and the lymphoid-specific Oct-2A proteins.", "entity": [{"entity": "ubiquitous Oct-1", "entity_type": "protein", "pos": [83, 99]}, {"entity": "Oct-1", "entity_type": "protein", "pos": [94, 99]}, {"entity": "Oct-2A", "entity_type": "protein", "pos": [126, 132]}, {"entity": "lymphoid-specific Oct-2A", "entity_type": "protein", "pos": [108, 132]}, {"entity": "N-Oct-factors", "entity_type": "protein", "pos": [34, 47]}], "task": "NER"}
{"text": "In melanoma cells that contain the N-Oct-3 factor , a transfected lymphocyte-specific promoter was neither activated nor was it repressed upon contransfection with an Oct-2A expression vector .", "entity": [{"entity": "Oct-2A expression vector", "entity_type": "DNA", "pos": [167, 191]}, {"entity": "Oct-2A", "entity_type": "protein", "pos": [167, 173]}, {"entity": "N-Oct-3 factor", "entity_type": "protein", "pos": [35, 49]}, {"entity": "melanoma cells", "entity_type": "cell type", "pos": [3, 17]}], "task": "NER"}
{"text": "We therefore speculate that N-Oct-3 and other N-Oct factors have a specific role in gene expression in cells of the nervous system .", "entity": [{"entity": "N-Oct factors", "entity_type": "protein", "pos": [46, 59]}, {"entity": "N-Oct-3", "entity_type": "protein", "pos": [28, 35]}], "task": "NER"}
{"text": "Detection in non-erythroid cells of a factor with the binding characteristics of the erythroid cell transcription factor EF1 .", "entity": [{"entity": "erythroid cell transcription factor", "entity_type": "protein", "pos": [85, 120]}, {"entity": "non-erythroid cells", "entity_type": "cell type", "pos": [13, 32]}, {"entity": "EF1", "entity_type": "protein", "pos": [121, 124]}], "task": "NER"}
{"text": "The erythroid transcription factor erythroid factor-1 ( EF1 ) plays a critical role in the transcription of erythroid-specific genes .", "entity": [{"entity": "erythroid transcription factor", "entity_type": "protein", "pos": [4, 34]}, {"entity": "EF1", "entity_type": "protein", "pos": [56, 59]}, {"entity": "erythroid-specific genes", "entity_type": "DNA", "pos": [108, 132]}, {"entity": "erythroid factor-1", "entity_type": "protein", "pos": [35, 53]}], "task": "NER"}
{"text": "Here we report the presence of a factor with the mobility and sequence-specific DNA-binding characteristics of EF1 at low abundance in a wide variety of non-erythroid cell types .", "entity": [{"entity": "EF1", "entity_type": "protein", "pos": [111, 114]}, {"entity": "non-erythroid cell types", "entity_type": "cell type", "pos": [153, 177]}], "task": "NER"}
{"text": "This is the first report of an EF1 -like activity in non-erythroid cells and indicates that this factor may play a role in the regulation of genes expressed in such cells.", "entity": [{"entity": "non-erythroid cells", "entity_type": "cell type", "pos": [53, 72]}, {"entity": "genes", "entity_type": "DNA", "pos": [141, 146]}, {"entity": "EF1", "entity_type": "protein", "pos": [31, 34]}], "task": "NER"}
{"text": "Protein kinase inhibitor H-7 blocks accumulation of unspliced mRNA of human T-cell leukemia virus type I ( HTLV-I ).", "entity": [{"entity": "unspliced mRNA", "entity_type": "RNA", "pos": [52, 66]}], "task": "NER"}
{"text": "Rex , the post-transcriptional regulator of human T-cell leukemia virus type I ( HTLV-I ), is known to induce accumulation of the unspliced viral gag-pol mRNA .", "entity": [{"entity": "post-transcriptional regulator", "entity_type": "protein", "pos": [10, 40]}, {"entity": "Rex", "entity_type": "protein", "pos": [0, 3]}, {"entity": "unspliced viral gag-pol mRNA", "entity_type": "RNA", "pos": [130, 158]}], "task": "NER"}
{"text": "Rex is a phosphoprotein found in the cell nucleolus , whose function may be regulated by its localization and phosphorylation .", "entity": [{"entity": "Rex", "entity_type": "protein", "pos": [0, 3]}, {"entity": "phosphoprotein", "entity_type": "protein", "pos": [9, 23]}], "task": "NER"}
{"text": "We have examined the role of phosphorylation on Rex function by using a protein kinase inhibitor , H-7 [ 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine ].", "entity": [{"entity": "Rex", "entity_type": "protein", "pos": [48, 51]}], "task": "NER"}
{"text": "Treatment of an HTLV-I infected human T-cell line with H-7 blocked specifically accumulation of the unspliced gag-pol mRNA , resulting in the decreased Gag protein synthesis that corresponds with the decreased in vivo phosphorylation of Rex .", "entity": [{"entity": "Gag protein", "entity_type": "protein", "pos": [152, 163]}, {"entity": "Rex", "entity_type": "protein", "pos": [237, 240]}, {"entity": "HTLV-I infected human T-cell line", "entity_type": "cell line", "pos": [16, 49]}, {"entity": "unspliced gag-pol mRNA", "entity_type": "RNA", "pos": [100, 122]}], "task": "NER"}
{"text": "In contrast, other viral and cellular products have not been influenced by the level of H-7 used.", "entity": [], "task": "NER"}
{"text": "Therefore, the phosphorylation of Rex is required for the viral RNA partition of HTLV-I .", "entity": [{"entity": "Rex", "entity_type": "protein", "pos": [34, 37]}], "task": "NER"}
{"text": "Increased glucocorticoid responsiveness of CD4+ T-cell clonal lines grown in serum-free media .", "entity": [{"entity": "CD4+ T-cell clonal lines", "entity_type": "cell line", "pos": [43, 67]}], "task": "NER"}
{"text": "CEM-C7 , a human leukemic CD4+ T-lymphocyte cell line and three of its subclones, CEM-4R4 , CEM-3R43 , and ICR-27 , previously cultured in a medium supplemented with 5 to 10% fetal bovine serum , have been adapted to serum-free media .", "entity": [{"entity": "ICR-27", "entity_type": "cell line", "pos": [107, 113]}, {"entity": "CEM-3R43", "entity_type": "cell line", "pos": [92, 100]}, {"entity": "CEM-4R4", "entity_type": "cell line", "pos": [82, 89]}, {"entity": "human leukemic CD4+ T-lymphocyte cell line", "entity_type": "cell line", "pos": [11, 53]}, {"entity": "CEM-C7", "entity_type": "cell line", "pos": [0, 6]}], "task": "NER"}
{"text": "The best medium of those tested was RPMI 1640 supplemented with 5 micrograms/ml each transferrin and insulin + 5 ng/ml sodium selenite +/- 0.1% bovine serum albumin .", "entity": [{"entity": "transferrin", "entity_type": "protein", "pos": [85, 96]}, {"entity": "insulin", "entity_type": "protein", "pos": [101, 108]}, {"entity": "bovine serum albumin", "entity_type": "protein", "pos": [144, 164]}], "task": "NER"}
{"text": "While growing either with or without albumin, the several clonal lines of CEM cells displayed growth similar to serum-supplemented cultures.", "entity": [{"entity": "clonal lines", "entity_type": "cell line", "pos": [58, 70]}, {"entity": "CEM", "entity_type": "cell line", "pos": [74, 77]}], "task": "NER"}
{"text": "Cell proliferation of CEM-C7 cells cultured in both serum-free media has been sustained for 3 mo.", "entity": [{"entity": "CEM-C7", "entity_type": "cell line", "pos": [22, 28]}], "task": "NER"}
{"text": "with culture doubling times of about 25 h for both serum-supplemented and serum-free cultures (viability greater than or equal to 90%).", "entity": [], "task": "NER"}
{"text": "Cell morphology remained essentially the same in serum-free or serum containing media .", "entity": [], "task": "NER"}
{"text": "The expression of CD4 , a marker for T-derived lymphoid cells , was not significantly different in serum-free medium .", "entity": [{"entity": "CD4", "entity_type": "protein", "pos": [18, 21]}, {"entity": "T-derived lymphoid cells", "entity_type": "cell type", "pos": [37, 61]}], "task": "NER"}
{"text": "When grown in serum-free medium, CEM-C7 cells exhibited increased steroid responsiveness as evidenced by increased glucocorticoid receptor binding sites , increased induction of glutamine synthetase , and cell lysis at lower concentrations of steroid .", "entity": [{"entity": "glutamine synthetase", "entity_type": "protein", "pos": [178, 198]}, {"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [115, 138]}, {"entity": "CEM-C7", "entity_type": "cell line", "pos": [33, 39]}], "task": "NER"}
{"text": "Receptor mutant subclones of CEM-C7 , which are proven to be completely unresponsive to micromolar concentrations of dexamethasone when grown in serum-supplemented medium , become partially sensitive to the hormone after growth in defined medium.", "entity": [{"entity": "CEM-C7", "entity_type": "cell line", "pos": [29, 35]}], "task": "NER"}
{"text": "The increased sensitivity of CEM-C7 cells and its subclones to dexamethasone in serum-free medium returned to previous levels when these cells were recultured in serum-containing medium .", "entity": [{"entity": "CEM-C7", "entity_type": "cell line", "pos": [29, 35]}, {"entity": "CEM-C7 cells", "entity_type": "cell line", "pos": [29, 41]}], "task": "NER"}
{"text": "Our results suggest that substances in serum influence steroid effects on these cells and that the molecular details of glucocorticoid hormone action may be pursued more precisely in a clearly defined culture medium.", "entity": [], "task": "NER"}
{"text": "[ Glucocorticoid receptors on human peripheral mononuclear and polymorphonuclear leucocytes : changes in patients with yang-deficiency ]", "entity": [{"entity": "Glucocorticoid receptors", "entity_type": "protein", "pos": [2, 26]}], "task": "NER"}
{"text": "It was found that, in former works, the glucocorticoid receptors ( GCR ) on peripheral mixed leucocytes in patients with Yang-deficiency were decreased.", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [67, 70]}, {"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [40, 64]}, {"entity": "peripheral mixed leucocytes", "entity_type": "cell type", "pos": [76, 103]}], "task": "NER"}
{"text": "In this work, the mixed leucocytes were further separated into mononuclear (MNL) and polymorphonuclear (PML) leucocytes , and GCR were determined in each part of leucocytes .", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [126, 129]}, {"entity": "mixed leucocytes", "entity_type": "cell type", "pos": [18, 34]}, {"entity": "leucocytes", "entity_type": "cell type", "pos": [24, 34]}], "task": "NER"}
{"text": "GCR on MNL and PML in 6 Yang deficient patients were 3473 +/- 413 and 4433 +/- 651 sites/cell respectively, statistically significant from the normal control group (4462 +/- 962 and 5622 +/- 782 sites/cell respectively, P less than 0.05).", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [0, 3]}, {"entity": "MNL", "entity_type": "cell type", "pos": [7, 10]}, {"entity": "PML", "entity_type": "cell type", "pos": [15, 18]}], "task": "NER"}
{"text": "GCR on MNL , PML and mixed leucocytes in 5 patients were determined simultaneously, and all lowered from the control group .", "entity": [{"entity": "mixed leucocytes", "entity_type": "cell type", "pos": [21, 37]}, {"entity": "GCR", "entity_type": "protein", "pos": [0, 3]}, {"entity": "MNL", "entity_type": "cell type", "pos": [7, 10]}, {"entity": "PML", "entity_type": "cell type", "pos": [13, 16]}], "task": "NER"}
{"text": "The results were 3369 +/- 370, 4986 +/- 419 and 4524 +/- 852 sites/cell respectively, with the lowest GCR on MNL and highest on PML .", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [102, 105]}, {"entity": "MNL", "entity_type": "cell type", "pos": [109, 112]}, {"entity": "PML", "entity_type": "cell type", "pos": [128, 131]}], "task": "NER"}
{"text": "The ubiquitous octamer-binding protein (s) is sufficient for transcription of immunoglobulin genes .", "entity": [{"entity": "ubiquitous octamer-binding protein", "entity_type": "protein", "pos": [4, 38]}, {"entity": "immunoglobulin genes", "entity_type": "DNA", "pos": [78, 98]}], "task": "NER"}
{"text": "All immunoglobulin genes contain a conserved octanucleotide promoter element , ATGCAAAT , which has been shown to be required for their normal B-cell-specific transcription .", "entity": [{"entity": "immunoglobulin genes", "entity_type": "DNA", "pos": [4, 24]}, {"entity": "octanucleotide promoter element", "entity_type": "DNA", "pos": [45, 76]}], "task": "NER"}
{"text": "Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned.", "entity": [{"entity": "octamer-binding proteins", "entity_type": "protein", "pos": [71, 95]}, {"entity": "cDNAs", "entity_type": "DNA", "pos": [56, 61]}], "task": "NER"}
{"text": "Some of these proteins (referred to as OTF-2 ) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1 ), is found ubiquitously in all cell types.", "entity": [{"entity": "OTF-1", "entity_type": "protein", "pos": [132, 137]}, {"entity": "OTF-2", "entity_type": "protein", "pos": [39, 44]}], "task": "NER"}
{"text": "The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear.", "entity": [{"entity": "immunoglobulin genes", "entity_type": "DNA", "pos": [90, 110]}], "task": "NER"}
{"text": "We have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro.", "entity": [{"entity": "OTF-2", "entity_type": "protein", "pos": [83, 88]}, {"entity": "immunoglobulin gene", "entity_type": "DNA", "pos": [205, 224]}, {"entity": "steady-state immunoglobulin heavy-chain mRNA", "entity_type": "RNA", "pos": [122, 166]}, {"entity": "human pre-B-cell lines", "entity_type": "cell line", "pos": [23, 45]}, {"entity": "immunoglobulin heavy-chain", "entity_type": "protein", "pos": [135, 161]}], "task": "NER"}
{"text": "Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene .", "entity": [{"entity": "OTF-1", "entity_type": "protein", "pos": [45, 50]}, {"entity": "pre-B cells", "entity_type": "cell line", "pos": [74, 85]}, {"entity": "immunoglobulin gene", "entity_type": "DNA", "pos": [158, 177]}, {"entity": "HeLa cells", "entity_type": "cell line", "pos": [94, 104]}], "task": "NER"}
{"text": "Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity.", "entity": [{"entity": "OTF-2", "entity_type": "protein", "pos": [86, 91]}], "task": "NER"}
{"text": "These results suggest that OTF-1 , without OTF-2 , is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression .", "entity": [{"entity": "immunoglobulin genes", "entity_type": "DNA", "pos": [86, 106]}, {"entity": "OTF-1", "entity_type": "protein", "pos": [27, 32]}, {"entity": "OTF-2", "entity_type": "protein", "pos": [43, 48]}, {"entity": "immunoglobulin gene", "entity_type": "DNA", "pos": [86, 105]}, {"entity": "OTF-2", "entity_type": "protein", "pos": [116, 121]}], "task": "NER"}
{"text": "Effects of aldosterone on intralymphocytic sodium and potassium in patients with essential hypertension .", "entity": [], "task": "NER"}
{"text": "In vitro binding of aldosterone to mineralocorticoid receptors on human mononuclear leukocytes ( HML ) and its effects on the intracellular sodium and potassium concentrations of HML have already been described.", "entity": [{"entity": "HML", "entity_type": "cell type", "pos": [97, 100]}, {"entity": "mineralocorticoid receptors", "entity_type": "protein", "pos": [35, 62]}, {"entity": "HML", "entity_type": "cell type", "pos": [179, 182]}, {"entity": "human mononuclear leukocytes", "entity_type": "cell type", "pos": [66, 94]}], "task": "NER"}
{"text": "In the present paper this easily accessible human cell model was investigated in 13 patients with essential hypertension .", "entity": [], "task": "NER"}
{"text": "In only four patients sodium in HML without incubation was elevated compared with the range for normal persons .", "entity": [{"entity": "HML", "entity_type": "cell type", "pos": [32, 35]}], "task": "NER"}
{"text": "A decrease of intracellular sodium or potassium occurred during incubation without aldosterone (P less than 0.02).", "entity": [], "task": "NER"}
{"text": "The addition of 1.4 nM aldosterone did not prevent this loss of electrolytes as observed in normal persons .", "entity": [], "task": "NER"}
{"text": "Plasma renin activity and aldosterone were not correlated with the electrolyte response and were within the normal limits.", "entity": [{"entity": "Plasma renin", "entity_type": "protein", "pos": [0, 12]}], "task": "NER"}
{"text": "The number of mineralocorticoid receptors /cell were within or close to the normal range (n = 9).", "entity": [{"entity": "mineralocorticoid receptors", "entity_type": "protein", "pos": [14, 41]}], "task": "NER"}
{"text": "The independence of intracellular electrolytes from aldosterone despite a normal number of mineralocorticoid receptors may reflect an impairment of the mineralocorticoid effector mechanism in the HML of patients with essential hypertension .", "entity": [{"entity": "mineralocorticoid receptors", "entity_type": "protein", "pos": [91, 118]}, {"entity": "HML", "entity_type": "cell type", "pos": [196, 199]}], "task": "NER"}
{"text": "[Differential diagnostic value of receptors of 1,25-dihydroxyvitamin D3 ( calcitriol ) determination in lymphocytes of children with rickets and rickets -like diseases ]", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [104, 115]}], "task": "NER"}
{"text": "The authors provide the results of studying 1,25-dihydroxyvitamin D3 ( calcitriol ) in lymphocytes of children with rickets and rickets -like diseases .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [87, 98]}], "task": "NER"}
{"text": "It is proposed that the character of their expression under the influence of vitamin D may be used with differential diagnostic purposes in view.", "entity": [], "task": "NER"}
{"text": "Regulation of gene expression with double-stranded phosphorothioate oligonucleotides .", "entity": [], "task": "NER"}
{"text": "Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation .", "entity": [{"entity": "transcriptional regulatory proteins", "entity_type": "protein", "pos": [59, 94]}], "task": "NER"}
{"text": "The functions of these proteins can be antagonized by several methods, each with specific limitations.", "entity": [], "task": "NER"}
{"text": "Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences .", "entity": [{"entity": "sequence-specific DNA-binding proteins", "entity_type": "protein", "pos": [14, 52]}], "task": "NER"}
{"text": "The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappa B .", "entity": [{"entity": "nuclear factor (NF)-kappa B", "entity_type": "protein", "pos": [96, 123]}, {"entity": "octamer transcription factor", "entity_type": "protein", "pos": [64, 92]}], "task": "NER"}
{"text": "The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner.", "entity": [], "task": "NER"}
{"text": "Octamer-dependent activation of a reporter plasmid or NF-kappa B -dependent activation of the human immunodeficiency virus ( HIV ) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line .", "entity": [{"entity": "human immunodeficiency virus ( HIV ) enhancer", "entity_type": "DNA", "pos": [94, 139]}, {"entity": "transiently transfected B cell line", "entity_type": "cell line", "pos": [223, 258]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [54, 64]}, {"entity": "reporter plasmid", "entity_type": "DNA", "pos": [34, 50]}], "task": "NER"}
{"text": "Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 ( IL-2 ) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer .", "entity": [{"entity": "interleukin-2", "entity_type": "protein", "pos": [120, 133]}, {"entity": "IL-2 enhancer", "entity_type": "DNA", "pos": [225, 238]}, {"entity": "octamer consensus", "entity_type": "DNA", "pos": [65, 82]}, {"entity": "Jurkat T leukemia cells", "entity_type": "cell line", "pos": [86, 109]}, {"entity": "mutated octamer site", "entity_type": "DNA", "pos": [197, 217]}, {"entity": "IL-2", "entity_type": "protein", "pos": [136, 140]}], "task": "NER"}
{"text": "The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral , immunosuppressive , or other therapeutic effects .", "entity": [], "task": "NER"}
{"text": "[Effect of the regimen of kidney-tonifying and qi-invigorating on aging changes of glucocorticoid receptor ]", "entity": [{"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [83, 106]}], "task": "NER"}
{"text": "The plasma cortisol concentration and the sites of glucocorticoid receptor ( GCR ) in the peripheral lymphocytes were measured in 32 healthy aged persons and 13 young adults .", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [77, 80]}, {"entity": "peripheral lymphocytes", "entity_type": "cell type", "pos": [90, 112]}, {"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [51, 74]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [101, 112]}], "task": "NER"}
{"text": "In animal experiment , GCR of spleen lymphocytic cell was also measured in 18 aged rats and 9 young rats .", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [23, 26]}, {"entity": "spleen lymphocytic cell", "entity_type": "cell type", "pos": [30, 53]}], "task": "NER"}
{"text": "The results showed that GCR was significantly lower in the aged persons or rats than that in the young while the plasma cortisol level didn't change with aging.", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [24, 27]}], "task": "NER"}
{"text": "So we think that GCR is more sensitive than the plasma cortisol level to reflect the aging change of the adrenal cortex function .", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [17, 20]}], "task": "NER"}
{"text": "After the treatment with the regimen of Kidney-tonifying and Qi-invigorating , the GCR of the aged persons and rats was enhanced, and in this way, the function of the aged adrenal cortex was improved.", "entity": [{"entity": "GCR", "entity_type": "protein", "pos": [83, 86]}], "task": "NER"}
{"text": "Interferon affects nuclear proteins in cells of clinically sensitive chronic myelogenous leukemia patients .", "entity": [{"entity": "nuclear proteins", "entity_type": "protein", "pos": [19, 35]}], "task": "NER"}
{"text": "Cytoplasmic protein extracts from chronic myelogenous leukemia ( CML ) cells contained an activity that altered the electrophoretic mobility of complexes formed between nuclear proteins and the transcriptional enhancers of interferon (IFN)-inducible genes.", "entity": [{"entity": "nuclear proteins", "entity_type": "protein", "pos": [169, 185]}, {"entity": "chronic myelogenous leukemia ( CML ) cells", "entity_type": "cell type", "pos": [34, 76]}], "task": "NER"}
{"text": "Exposure of CML cells to IFN-alpha diminished the effect of the CML cytoplasmic proteins on these nuclear protein-DNA complexes .", "entity": [{"entity": "CML cells", "entity_type": "cell type", "pos": [12, 21]}, {"entity": "IFN-alpha", "entity_type": "protein", "pos": [25, 34]}, {"entity": "CML cytoplasmic proteins", "entity_type": "protein", "pos": [64, 88]}, {"entity": "nuclear protein-DNA complexes", "entity_type": "protein", "pos": [98, 127]}], "task": "NER"}
{"text": "The presence of clinical responsiveness to IFN-alpha correlated with the sensitivity to the IFN -induced change in the electrophoretic mobility of nuclear protein-DNA complexes .", "entity": [{"entity": "IFN", "entity_type": "protein", "pos": [43, 46]}, {"entity": "IFN-alpha", "entity_type": "protein", "pos": [43, 52]}, {"entity": "nuclear protein-DNA complexes", "entity_type": "protein", "pos": [147, 176]}], "task": "NER"}
{"text": "These data suggest that the action of IFN-alpha in CML may be linked to a pathway that can result in posttranslational modification of nuclear proteins .", "entity": [{"entity": "IFN-alpha", "entity_type": "protein", "pos": [38, 47]}, {"entity": "nuclear proteins", "entity_type": "protein", "pos": [135, 151]}], "task": "NER"}
{"text": "Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1 .", "entity": [{"entity": "Epstein-Barr virus nuclear antigen 2", "entity_type": "protein", "pos": [0, 36]}, {"entity": "latent membrane protein", "entity_type": "protein", "pos": [52, 75]}, {"entity": "LMP1", "entity_type": "protein", "pos": [76, 80]}], "task": "NER"}
{"text": "Several lines of evidence are compatible with the hypothesis that Epstein-Barr virus ( EBV ) nuclear antigen 2 ( EBNA-2 ) or leader protein ( EBNA-LP ) affects expression of the EBV latent infection membrane protein LMP1 .", "entity": [{"entity": "Epstein-Barr virus ( EBV ) nuclear antigen 2", "entity_type": "protein", "pos": [66, 110]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [113, 119]}, {"entity": "leader protein", "entity_type": "protein", "pos": [125, 139]}, {"entity": "EBNA-LP", "entity_type": "protein", "pos": [142, 149]}, {"entity": "EBV latent infection membrane protein", "entity_type": "protein", "pos": [178, 215]}, {"entity": "LMP1", "entity_type": "protein", "pos": [216, 220]}], "task": "NER"}
{"text": "We now demonstrate the following.", "entity": [], "task": "NER"}
{"text": "(i) Acute transfection and expression of EBNA-2 under control of simian virus 40 or Moloney murine leukemia virus promoters resulted in increased LMP1 expression in P3HR-1-infected Burkitt's lymphoma cells and the P3HR-1 or Daudi cell line .", "entity": [{"entity": "LMP1", "entity_type": "protein", "pos": [146, 150]}, {"entity": "P3HR-1", "entity_type": "cell line", "pos": [165, 171]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [41, 47]}, {"entity": "P3HR-1-infected Burkitt's lymphoma cells", "entity_type": "cell line", "pos": [165, 205]}, {"entity": "Daudi cell line", "entity_type": "cell line", "pos": [224, 239]}], "task": "NER"}
{"text": "(ii) Transfection and expression of EBNA-LP alone had no effect on LMP1 expression and did not act synergistically with EBNA-2 to affect LMP1 expression .", "entity": [{"entity": "EBNA-LP", "entity_type": "protein", "pos": [36, 43]}, {"entity": "LMP1", "entity_type": "protein", "pos": [67, 71]}, {"entity": "LMP1", "entity_type": "protein", "pos": [137, 141]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [120, 126]}], "task": "NER"}
{"text": "(iii) LMP1 expression in Daudi and P3HR-1-infected cells was controlled at the mRNA level , and EBNA-2 expression in Daudi cells increased LMP1 mRNA .", "entity": [{"entity": "LMP1 mRNA", "entity_type": "RNA", "pos": [139, 148]}, {"entity": "LMP1", "entity_type": "protein", "pos": [6, 10]}, {"entity": "Daudi", "entity_type": "cell line", "pos": [25, 30]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [96, 102]}, {"entity": "P3HR-1-infected cells", "entity_type": "cell line", "pos": [35, 56]}, {"entity": "mRNA", "entity_type": "RNA", "pos": [79, 83]}, {"entity": "LMP1", "entity_type": "protein", "pos": [139, 143]}, {"entity": "Daudi cells", "entity_type": "cell line", "pos": [117, 128]}], "task": "NER"}
{"text": "(iv) No other EBV genes were required for EBNA-2 transactivation of LMP1 since cotransfection of recombinant EBNA-2 expression vectors and genomic LMP1 DNA fragments enhanced LMP1 expression in the EBV-negative B-lymphoma cell lines BJAB , Louckes , and BL30 .", "entity": [{"entity": "LMP1", "entity_type": "protein", "pos": [68, 72]}, {"entity": "LMP1", "entity_type": "protein", "pos": [147, 151]}, {"entity": "BJAB", "entity_type": "cell line", "pos": [233, 237]}, {"entity": "EBV genes", "entity_type": "DNA", "pos": [14, 23]}, {"entity": "Louckes", "entity_type": "cell line", "pos": [240, 247]}, {"entity": "recombinant EBNA-2 expression vectors", "entity_type": "DNA", "pos": [97, 134]}, {"entity": "EBV-negative B-lymphoma cell lines", "entity_type": "cell line", "pos": [198, 232]}, {"entity": "LMP1", "entity_type": "protein", "pos": [175, 179]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [42, 48]}, {"entity": "BL30", "entity_type": "cell line", "pos": [254, 258]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [109, 115]}, {"entity": "LMP1 DNA fragments", "entity_type": "DNA", "pos": [147, 165]}], "task": "NER"}
{"text": "(v) An EBNA-2 -responsive element was found within the -512 to +40 LMP1 DNA since this DNA linked to a chloramphenicol acetyltransferase reporter gene was transactivated by cotransfection with an EBNA-2 expression vector .", "entity": [{"entity": "EBNA-2", "entity_type": "protein", "pos": [7, 13]}, {"entity": "LMP1", "entity_type": "protein", "pos": [67, 71]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [196, 202]}, {"entity": "LMP1 DNA", "entity_type": "DNA", "pos": [67, 75]}, {"entity": "chloramphenicol acetyltransferase", "entity_type": "protein", "pos": [103, 136]}, {"entity": "EBNA-2 expression vector", "entity_type": "DNA", "pos": [196, 220]}, {"entity": "-512 to +40 LMP1 DNA", "entity_type": "DNA", "pos": [55, 75]}, {"entity": "EBNA-2 -responsive element", "entity_type": "DNA", "pos": [7, 33]}, {"entity": "chloramphenicol acetyltransferase reporter gene", "entity_type": "DNA", "pos": [103, 150]}], "task": "NER"}
{"text": "(vi) The EBV type 2 EBNA-2 transactivated LMP1 as well as the EBV type 1 EBNA-2 .", "entity": [{"entity": "LMP1", "entity_type": "protein", "pos": [42, 46]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [20, 26]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [73, 79]}, {"entity": "EBV type 1 EBNA-2", "entity_type": "protein", "pos": [62, 79]}], "task": "NER"}
{"text": "(vii) Two deletions within the EBNA-2 gene which rendered EBV transformation incompetent did not transactivate LMP1 , whereas a transformation-competent EBNA-2 deletion mutant did transactivate LMP1 .", "entity": [{"entity": "EBNA-2", "entity_type": "protein", "pos": [31, 37]}, {"entity": "transformation-competent EBNA-2 deletion mutant", "entity_type": "DNA", "pos": [128, 175]}, {"entity": "LMP1", "entity_type": "protein", "pos": [111, 115]}, {"entity": "LMP1", "entity_type": "protein", "pos": [194, 198]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [153, 159]}], "task": "NER"}
{"text": "LMP1 is a potent effector of B-lymphocyte activation and can act synergistically with EBNA-2 to induce cellular CD23 gene expression .", "entity": [{"entity": "LMP1", "entity_type": "protein", "pos": [0, 4]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [86, 92]}], "task": "NER"}
{"text": "Thus, EBNA-2 transactivation of LMP1 amplifies the biological impact of EBNA-2 and underscores its central role in EBV-induced growth transformation .", "entity": [{"entity": "EBNA-2", "entity_type": "protein", "pos": [6, 12]}, {"entity": "EBNA-2", "entity_type": "protein", "pos": [72, 78]}, {"entity": "LMP1", "entity_type": "protein", "pos": [32, 36]}], "task": "NER"}
{"text": "The expression of c-fos , c-jun , and c-myc genes is regulated by heat shock in human lymphoid cells .", "entity": [{"entity": "c-fos", "entity_type": "DNA", "pos": [18, 23]}, {"entity": "human lymphoid cells", "entity_type": "cell type", "pos": [80, 100]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [26, 31]}, {"entity": "c-myc genes", "entity_type": "DNA", "pos": [38, 49]}], "task": "NER"}
{"text": "The effect of heat shock on the expression of the nuclear protooncogenes c-fos , c-jun , and c-myc was studied in human lymphoid cells .", "entity": [{"entity": "c-fos", "entity_type": "DNA", "pos": [73, 78]}, {"entity": "nuclear protooncogenes", "entity_type": "DNA", "pos": [50, 72]}, {"entity": "human lymphoid cells", "entity_type": "cell type", "pos": [114, 134]}, {"entity": "c-myc", "entity_type": "DNA", "pos": [93, 98]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [81, 86]}], "task": "NER"}
{"text": "Heat shock caused an increase in c-fos and c-jun mRNA levels and a decrease in c-myc mRNA levels in pre-B (Hyon) and T (DND-41) cell lines as well as in freshly isolated normal human thymocytes.", "entity": [{"entity": "c-myc", "entity_type": "DNA", "pos": [79, 84]}, {"entity": "c-myc mRNA", "entity_type": "RNA", "pos": [79, 89]}], "task": "NER"}
{"text": "The changes in the mRNA levels of these protooncogenes in Hyon cells were most pronounced at 42 and 43 degrees C; kinetic analysis demonstrated that the changes could be detected within 30 min of heat shock .", "entity": [{"entity": "protooncogenes", "entity_type": "DNA", "pos": [40, 54]}, {"entity": "Hyon cells", "entity_type": "cell line", "pos": [58, 68]}], "task": "NER"}
{"text": "Altered transcription of c-fos and c-myc genes was the primary effect of heat shock .", "entity": [{"entity": "c-myc", "entity_type": "DNA", "pos": [35, 40]}, {"entity": "c-fos", "entity_type": "DNA", "pos": [25, 30]}, {"entity": "c-myc genes", "entity_type": "DNA", "pos": [35, 46]}], "task": "NER"}
{"text": "Secondarily, heat shock of Hyon cells stabilized the c-myc mRNA level by increasing its half-life from 24 to 45 min.", "entity": [{"entity": "Hyon cells", "entity_type": "cell line", "pos": [27, 37]}, {"entity": "c-myc mRNA", "entity_type": "RNA", "pos": [53, 63]}, {"entity": "c-myc", "entity_type": "DNA", "pos": [53, 58]}], "task": "NER"}
{"text": "The overall effect of heat shock on c-myc mRNA level , however, was a marked inhibition of its transcription .", "entity": [{"entity": "c-myc mRNA", "entity_type": "RNA", "pos": [36, 46]}, {"entity": "c-myc", "entity_type": "DNA", "pos": [36, 41]}], "task": "NER"}
{"text": "These results demonstrate that the transcription of nuclear protooncogenes is regulated by heat shock indicating a role for nuclear protooncogenes in the stress response of lymphoid cells .", "entity": [{"entity": "lymphoid cells", "entity_type": "cell type", "pos": [173, 187]}, {"entity": "protooncogenes", "entity_type": "DNA", "pos": [60, 74]}, {"entity": "nuclear protooncogenes", "entity_type": "DNA", "pos": [52, 74]}, {"entity": "nuclear protooncogenes", "entity_type": "DNA", "pos": [124, 146]}, {"entity": "protooncogenes", "entity_type": "DNA", "pos": [132, 146]}], "task": "NER"}
{"text": "Mapping of B-cell epitopes of the human hepatitis B virus X protein .", "entity": [{"entity": "human hepatitis B virus X protein", "entity_type": "protein", "pos": [34, 67]}, {"entity": "B-cell epitopes", "entity_type": "protein", "pos": [11, 26]}], "task": "NER"}
{"text": "The immune response to the X protein of human hepatitis B virus ( HBV ) was studied by epitope mapping by using a set of MS2-HBx fusion proteins and synthetic peptides .", "entity": [{"entity": "MS2-HBx fusion proteins", "entity_type": "protein", "pos": [121, 144]}, {"entity": "X protein", "entity_type": "protein", "pos": [27, 36]}], "task": "NER"}
{"text": "Antibodies in sera of patients with acute and chronic HBV infection showed a multispecific immune response .", "entity": [], "task": "NER"}
{"text": "Each serum contained antibodies to a different set of epitopes , which taken together cover most of the HBx sequence .", "entity": [{"entity": "HBx sequence", "entity_type": "protein", "pos": [104, 116]}, {"entity": "epitopes", "entity_type": "protein", "pos": [54, 62]}, {"entity": "antibodies", "entity_type": "protein", "pos": [21, 31]}], "task": "NER"}
{"text": "Some of the epitopes were detectable only by immunoblotting with fusion proteins ; others were detectable only by an enzyme-linked immunosorbent assay ( ELISA ) with synthetic peptides .", "entity": [{"entity": "fusion proteins", "entity_type": "protein", "pos": [65, 80]}], "task": "NER"}
{"text": "The carboxy-terminal half of the HBx protein was preferentially recognized by antibodies from patients with chronic hepatitis and contained a short immunodominant antigenic region with at least two major nonoverlapping epitopes .", "entity": [{"entity": "carboxy-terminal half", "entity_type": "protein", "pos": [4, 25]}, {"entity": "HBx protein", "entity_type": "protein", "pos": [33, 44]}, {"entity": "immunodominant antigenic region", "entity_type": "protein", "pos": [148, 179]}, {"entity": "nonoverlapping epitopes", "entity_type": "protein", "pos": [204, 227]}, {"entity": "antibodies", "entity_type": "protein", "pos": [78, 88]}, {"entity": "HBx", "entity_type": "protein", "pos": [33, 36]}], "task": "NER"}
{"text": "Anti- HBx antibody titers as revealed by peptide ELISAs were highest and most frequent in patients with chronic hepatitis and usually low in acutely infected patients and asymptomatic carriers .", "entity": [{"entity": "HBx", "entity_type": "protein", "pos": [6, 9]}], "task": "NER"}
{"text": "The data demonstrate a remarkable qualitative and quantitative heterogeneity of the humoral HBx immune response which can be monitored by HBx -specific peptide ELISAs .", "entity": [{"entity": "HBx", "entity_type": "protein", "pos": [92, 95]}, {"entity": "HBx", "entity_type": "protein", "pos": [138, 141]}], "task": "NER"}
{"text": "Such tests may become useful diagnostic tools .", "entity": [], "task": "NER"}
{"text": "[The inhibitory effect of hydrocortisone on the chemotactic migration of human leukocytes ]", "entity": [{"entity": "human leukocytes", "entity_type": "cell type", "pos": [73, 89]}], "task": "NER"}
{"text": "Random migration ( RM ) and chemotactic migration ( ChtM ) of human leukocytes to yeast activated serum were studied with the modified Boyden chamber method .", "entity": [{"entity": "human leukocytes", "entity_type": "cell type", "pos": [62, 78]}], "task": "NER"}
{"text": "Both RM and ChtM showed circadian rhythm .", "entity": [], "task": "NER"}
{"text": "Leukocytes migrated most rapidly at night.", "entity": [{"entity": "Leukocytes", "entity_type": "cell type", "pos": [0, 10]}], "task": "NER"}
{"text": "The difference between the peak (0:00) and trough values (8:00) of RM and ChtM was significant statistically (P less than 0.01).", "entity": [], "task": "NER"}
{"text": "ChtM was inhibited by hydrocortisone (F) of physiological concentration (10(-9)-10(-7) mol/L) which was dose-dependent and completely antagonized by the competitive antagonist , RU38486 .", "entity": [], "task": "NER"}
{"text": "The inhibitory effect was much more evident with higher dose (more than 10(-5) mol/L) and it was also reversed by RU38486 , but only partially.", "entity": [], "task": "NER"}
{"text": "It is suggested that glucocorticoids ( GC ) may be a physiological regulator of the activity of leukocytes and its inhibitory action on ChtM may be involved in antiinflammatory mechanisms of GC of pharmacological doses .", "entity": [{"entity": "leukocytes", "entity_type": "cell type", "pos": [96, 106]}], "task": "NER"}
{"text": "The action of physiological and pharmacological concentration of GC may be mediated by low affinity specific binding sites of glucocorticoid receptors .", "entity": [{"entity": "low affinity specific binding sites", "entity_type": "protein", "pos": [87, 122]}, {"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [126, 150]}], "task": "NER"}
{"text": "Heterogeneity of antigen molecules recognized by anti-tax1 monoclonal antibody Lt-4 in cell lines bearing human T cell leukemia virus type I and related retroviruses .", "entity": [{"entity": "antigen molecules", "entity_type": "protein", "pos": [17, 34]}, {"entity": "anti-tax1 monoclonal antibody", "entity_type": "protein", "pos": [49, 78]}, {"entity": "Lt-4", "entity_type": "protein", "pos": [79, 83]}], "task": "NER"}
{"text": "Using a monoclonal antibody , Lt-4 , directed against human T cell leukemia virus type I ( HTLV-I ) trans-activator ( tax1 ) antigen , we examined the expression of tax1 and related antigens in a variety of T cell lines bearing HTLV-I and related retroviruses , simian T cell leukemia virus type I ( STLV-I ) and HTLV-II , by immunofluorescence and immunoblot assays .", "entity": [{"entity": "human T cell leukemia virus type I ( HTLV-I ) trans-activator ( tax1 ) antigen", "entity_type": "protein", "pos": [54, 132]}, {"entity": "antigens", "entity_type": "protein", "pos": [182, 190]}, {"entity": "tax1", "entity_type": "protein", "pos": [118, 122]}, {"entity": "monoclonal antibody", "entity_type": "protein", "pos": [8, 27]}, {"entity": "Lt-4", "entity_type": "protein", "pos": [30, 34]}, {"entity": "human T cell leukemia virus type I ( HTLV-I ) trans-activator", "entity_type": "protein", "pos": [54, 115]}, {"entity": "tax1", "entity_type": "protein", "pos": [165, 169]}, {"entity": "T cell lines", "entity_type": "cell line", "pos": [207, 219]}], "task": "NER"}
{"text": "Lt-4 reacted with all HTLV-I -bearing cell lines tested and five out of eight simian cell lines bearing STLV-I , but not with an HTLV-II -bearing cell line .", "entity": [{"entity": "HTLV-II -bearing cell line", "entity_type": "cell line", "pos": [129, 155]}, {"entity": "Lt-4", "entity_type": "protein", "pos": [0, 4]}, {"entity": "simian cell lines", "entity_type": "cell line", "pos": [78, 95]}, {"entity": "HTLV-I -bearing cell lines", "entity_type": "cell line", "pos": [22, 48]}], "task": "NER"}
{"text": "Lt-4 detected 40 kd tax1 antigen molecules in most HTLV-I -bearing cell lines except one cell line that expressed 39 kd tax1 antigen .", "entity": [{"entity": "39 kd tax1 antigen", "entity_type": "protein", "pos": [114, 132]}, {"entity": "Lt-4", "entity_type": "protein", "pos": [0, 4]}, {"entity": "tax1", "entity_type": "protein", "pos": [20, 24]}, {"entity": "tax1", "entity_type": "protein", "pos": [120, 124]}, {"entity": "HTLV-I -bearing cell lines", "entity_type": "cell line", "pos": [51, 77]}, {"entity": "tax1 antigen molecules", "entity_type": "protein", "pos": [20, 42]}], "task": "NER"}
{"text": "In the STLV-I -bearing T cell lines , tax1 -related antigen molecules detected by Lt-4 were heterogeneous, having molecular weights in the range of 36-41 kd.", "entity": [{"entity": "STLV-I -bearing T cell lines", "entity_type": "cell line", "pos": [7, 35]}, {"entity": "tax1 -related antigen molecules", "entity_type": "protein", "pos": [38, 69]}, {"entity": "Lt-4", "entity_type": "protein", "pos": [82, 86]}, {"entity": "T cell lines", "entity_type": "cell line", "pos": [23, 35]}, {"entity": "tax1", "entity_type": "protein", "pos": [38, 42]}], "task": "NER"}
{"text": "Characterization of the human immunodeficiency virus type 1 enhancer -binding proteins from the human T-cell line Jurkat .", "entity": [{"entity": "Jurkat", "entity_type": "cell line", "pos": [114, 120]}, {"entity": "human immunodeficiency virus type 1 enhancer -binding proteins", "entity_type": "protein", "pos": [24, 86]}, {"entity": "human T-cell line", "entity_type": "cell line", "pos": [96, 113]}, {"entity": "human immunodeficiency virus type 1 enhancer", "entity_type": "DNA", "pos": [24, 68]}], "task": "NER"}
{"text": "The transcription of the human immunodeficiency virus type 1 ( HIV-1 ) is under the control of cellular proteins that bind to the viral long terminal repeat ( LTR ).", "entity": [{"entity": "cellular proteins", "entity_type": "protein", "pos": [95, 112]}, {"entity": "viral long terminal repeat", "entity_type": "DNA", "pos": [130, 156]}, {"entity": "LTR", "entity_type": "DNA", "pos": [159, 162]}], "task": "NER"}
{"text": "Among the protein-binding regions of the HIV-1 LTR is the transcription-enhancer region .", "entity": [{"entity": "HIV-1 LTR", "entity_type": "DNA", "pos": [41, 50]}, {"entity": "transcription-enhancer region", "entity_type": "DNA", "pos": [58, 87]}], "task": "NER"}
{"text": "We show that at least one inducible , C1 , and one constitutive, C2 , protein can bind to the HIV enhancer in Jurkat cells .", "entity": [{"entity": "inducible", "entity_type": "protein", "pos": [26, 35]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [110, 122]}, {"entity": "C1", "entity_type": "protein", "pos": [38, 40]}, {"entity": "HIV enhancer", "entity_type": "DNA", "pos": [94, 106]}, {"entity": "C2", "entity_type": "protein", "pos": [65, 67]}, {"entity": "constitutive, C2 , protein", "entity_type": "protein", "pos": [51, 77]}], "task": "NER"}
{"text": "The two proteins differ in their surface charge , since they are separable by anion-exchange chromatography .", "entity": [], "task": "NER"}
{"text": "Bivalent cations such as Mg2+ and Zn2+ differentially affect their binding to oligonucleotides which contain the HIV-enhancer domain .", "entity": [{"entity": "HIV-enhancer domain", "entity_type": "DNA", "pos": [113, 132]}], "task": "NER"}
{"text": "Both C1 and C2 proteins also bind to a similar sequence found in the interleukin-2 -receptor alpha-subunit enhancer .", "entity": [{"entity": "C1", "entity_type": "protein", "pos": [5, 7]}, {"entity": "interleukin-2 -receptor alpha-subunit", "entity_type": "protein", "pos": [69, 106]}, {"entity": "C2 proteins", "entity_type": "protein", "pos": [12, 23]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [69, 82]}, {"entity": "interleukin-2 -receptor alpha-subunit enhancer", "entity_type": "DNA", "pos": [69, 115]}], "task": "NER"}
{"text": "The inducible C1 protein was partially purified by three chromatographic steps and characterized by u.v. cross-linking as a 47 kDa protein .", "entity": [{"entity": "C1", "entity_type": "protein", "pos": [14, 16]}, {"entity": "inducible C1 protein", "entity_type": "protein", "pos": [4, 24]}, {"entity": "47 kDa protein", "entity_type": "protein", "pos": [124, 138]}], "task": "NER"}
{"text": "Differences in transcriptional enhancers of HIV-1 and HIV-2 .", "entity": [{"entity": "transcriptional enhancers", "entity_type": "DNA", "pos": [15, 40]}], "task": "NER"}
{"text": "Response to T cell activation signals .", "entity": [{"entity": "T cell", "entity_type": "cell type", "pos": [12, 18]}], "task": "NER"}
{"text": "T cell activation results in high levels of HIV replication and is thought to be one mechanism leading to the conversion from latent to active viral infection .", "entity": [{"entity": "T cell", "entity_type": "cell type", "pos": [0, 6]}], "task": "NER"}
{"text": "In HIV-1 , the sequences that respond to these signaling events are found in the long terminal repeat ( LTR ) and comprise the transcriptional enhancer , which contains two conserved binding sites for the nuclear factor kappa B ( NF kappa B ).", "entity": [{"entity": "conserved binding sites", "entity_type": "DNA", "pos": [173, 196]}, {"entity": "nuclear factor kappa B", "entity_type": "protein", "pos": [205, 227]}, {"entity": "long terminal repeat", "entity_type": "DNA", "pos": [81, 101]}, {"entity": "LTR", "entity_type": "DNA", "pos": [104, 107]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [230, 240]}, {"entity": "transcriptional enhancer", "entity_type": "DNA", "pos": [127, 151]}], "task": "NER"}
{"text": "The corresponding region in the second AIDS retrovirus , HIV-2 , contains a conserved and a divergent NF kappa B binding site .", "entity": [{"entity": "NF kappa B", "entity_type": "protein", "pos": [102, 112]}, {"entity": "NF kappa B binding site", "entity_type": "DNA", "pos": [102, 125]}], "task": "NER"}
{"text": "We demonstrate that the HIV-1 LTR responds better than the HIV-2 LTR to T cell activation signals.", "entity": [{"entity": "HIV-2 LTR", "entity_type": "DNA", "pos": [59, 68]}, {"entity": "HIV-1 LTR", "entity_type": "DNA", "pos": [24, 33]}], "task": "NER"}
{"text": "These qualitative differences in the response to T cell activation are reproduced not only when HIV-1 or HIV-2 enhancers are placed upstream of a heterologous promoter but also when these enhancers are switched between their respective LTR .", "entity": [{"entity": "LTR", "entity_type": "DNA", "pos": [236, 239]}, {"entity": "heterologous promoter", "entity_type": "DNA", "pos": [146, 167]}, {"entity": "enhancers", "entity_type": "DNA", "pos": [111, 120]}, {"entity": "T cell", "entity_type": "cell type", "pos": [49, 55]}], "task": "NER"}
{"text": "In electrophoretic mobility shift assays, NF kappa B binds to both conserved sites in the HIV-1 transcriptional enhancer and only to the single conserved site in the HIV-2 transcriptional enhancer .", "entity": [{"entity": "HIV-2 transcriptional enhancer", "entity_type": "DNA", "pos": [166, 196]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [42, 52]}, {"entity": "HIV-1 transcriptional enhancer", "entity_type": "DNA", "pos": [90, 120]}], "task": "NER"}
{"text": "Instead of NF kappa B , the activator protein 3 binds to the divergent site in HIV-2 .", "entity": [{"entity": "activator protein 3", "entity_type": "protein", "pos": [28, 47]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [11, 21]}], "task": "NER"}
{"text": "In conclusion, HIV-1 and HIV-2 are differentially regulated by T cell activation signals, and this difference may account for the longer period of viral latency observed with HIV-2 than with HIV-1 infection .", "entity": [], "task": "NER"}
{"text": "NF-X2 that binds to the DRA X2-box is activator protein 1 .", "entity": [{"entity": "DRA X2-box", "entity_type": "DNA", "pos": [24, 34]}, {"entity": "activator protein 1", "entity_type": "protein", "pos": [38, 57]}, {"entity": "NF-X2", "entity_type": "protein", "pos": [0, 5]}], "task": "NER"}
{"text": "Expression cloning of c-Jun .", "entity": [{"entity": "c-Jun", "entity_type": "protein", "pos": [22, 27]}], "task": "NER"}
{"text": "Human class II MHC Ag are a family of cell surface glycoproteins .", "entity": [{"entity": "cell surface glycoproteins", "entity_type": "protein", "pos": [38, 64]}, {"entity": "Human class II MHC Ag", "entity_type": "protein", "pos": [0, 21]}], "task": "NER"}
{"text": "Their constitutive expression is limited to B lymphocytes and thymic epithelial cells .", "entity": [{"entity": "B lymphocytes", "entity_type": "cell type", "pos": [44, 57]}, {"entity": "thymic epithelial cells", "entity_type": "cell type", "pos": [62, 85]}], "task": "NER"}
{"text": "In many other cells their expression can be induced by IFN-gamma .", "entity": [{"entity": "IFN-gamma", "entity_type": "protein", "pos": [55, 64]}], "task": "NER"}
{"text": "Conserved upstream promoter sequences regulate this tissue-specific expression of class II genes .", "entity": [{"entity": "class II genes", "entity_type": "DNA", "pos": [82, 96]}], "task": "NER"}
{"text": "In the DRA promoter , one of these cis-acting regulatory motifs is the X2-box to which nuclear factor X2 ( NF-X2 ) binds.", "entity": [{"entity": "nuclear factor X2", "entity_type": "protein", "pos": [87, 104]}, {"entity": "DRA promoter", "entity_type": "DNA", "pos": [7, 19]}, {"entity": "cis-acting regulatory motifs", "entity_type": "DNA", "pos": [35, 63]}, {"entity": "NF-X2", "entity_type": "protein", "pos": [107, 112]}, {"entity": "X2-box", "entity_type": "DNA", "pos": [71, 77]}], "task": "NER"}
{"text": "Here, we present the isolation and characterization of the full-length cDNA clone encoding NF-X2 .", "entity": [{"entity": "full-length cDNA clone", "entity_type": "DNA", "pos": [59, 81]}, {"entity": "NF-X2", "entity_type": "protein", "pos": [91, 96]}], "task": "NER"}
{"text": "This cDNA clone was isolated by expression cDNA cloning , and encodes the human c-Jun protein , which together with c-Fos forms the heterodimeric activator protein-1 transcription complex .", "entity": [{"entity": "c-Jun", "entity_type": "protein", "pos": [80, 85]}, {"entity": "heterodimeric activator protein-1 transcription complex", "entity_type": "protein", "pos": [132, 187]}, {"entity": "c-Fos", "entity_type": "protein", "pos": [116, 121]}, {"entity": "cDNA", "entity_type": "DNA", "pos": [5, 9]}, {"entity": "human c-Jun protein", "entity_type": "protein", "pos": [74, 93]}, {"entity": "cDNA clone", "entity_type": "DNA", "pos": [5, 15]}], "task": "NER"}
{"text": "Whereas c-Fos /c-Jun heterodimers do not exist in B cells , they form and bind to the X2-box in class II nonexpressing cells .", "entity": [{"entity": "c-Fos /c-Jun heterodimers", "entity_type": "protein", "pos": [8, 33]}, {"entity": "X2-box", "entity_type": "DNA", "pos": [86, 92]}, {"entity": "class II nonexpressing cells", "entity_type": "cell line", "pos": [96, 124]}, {"entity": "c-Fos", "entity_type": "protein", "pos": [8, 13]}, {"entity": "/c-Jun", "entity_type": "protein", "pos": [14, 20]}, {"entity": "B cells", "entity_type": "cell line", "pos": [50, 57]}], "task": "NER"}
{"text": "Thus, c-Fos /c-Jun heterodimers might contribute to the repression of DRA gene expression .", "entity": [{"entity": "c-Fos", "entity_type": "protein", "pos": [6, 11]}, {"entity": "c-Fos /c-Jun heterodimers", "entity_type": "protein", "pos": [6, 31]}, {"entity": "DRA gene", "entity_type": "DNA", "pos": [70, 78]}, {"entity": "/c-Jun", "entity_type": "protein", "pos": [12, 18]}], "task": "NER"}
{"text": "Synthesis of 4,19-disubstituted derivatives of DOC .", "entity": [], "task": "NER"}
{"text": "Radioreceptor assay of some corticosteroid derivatives in human mononuclear leukocytes .", "entity": [{"entity": "human mononuclear leukocytes", "entity_type": "cell type", "pos": [58, 86]}], "task": "NER"}
{"text": "Several new 4,19-substituted steroids and previously synthesized corticosteroids were assayed for affinity to type 1 receptors in human mononuclear leukocytes .", "entity": [{"entity": "human mononuclear leukocytes", "entity_type": "cell type", "pos": [130, 158]}, {"entity": "type 1 receptors", "entity_type": "protein", "pos": [110, 126]}], "task": "NER"}
{"text": "11 beta,19-epoxy-4,21-dihydroxypregn-4-ene-3,20-dione (2) was hydrogenated with Pd-C to yield a mixture of all four dihydro derivatives 5, accompanied by 4,21-diacetoxy-11 beta,19-epoxy-3-hydroxypregnan-20-one (6) and 21-acetoxy-11 beta,19-epoxy-4-hydroxypregnane-3,20-dione (7).", "entity": [], "task": "NER"}
{"text": "With hot acetic + p-toluenesulfonic acid 5 underwent rearrangement to 21-acetoxy-11 beta,19-epoxypregn-5-ene-4,20-dione (8) Pd-C hydrogenation of 3,21-diacetoxy-5 beta,19-cyclopregna-2,9(11)-diene-4,20-dione (10) gave 3,21-diacetoxy-5 beta,19-cyclopregn-5-ene-4,20-dione (11) and the 9,11-dihydro derivative of the latter.", "entity": [], "task": "NER"}
{"text": "Treatment of 10 with warm HCl furnished 19-chloro-4,21-dihydroxypregna-4,9(11)-diene-3,20-dione (13).", "entity": [], "task": "NER"}
{"text": "Pd-C hydrogenation of its diacetate 14 afforded the 4,5-dihydro derivative 18, 19-chloro-21-acetoxypregn-9(11)-en-20-one (15), its 4-acetoxy derivative 16 and the 3,4-diacetoxy derivative 17.", "entity": [], "task": "NER"}
{"text": "When tested in a radioreceptor assay in human mononuclear leukocytes the synthesized compounds showed only low relative binding affinities ( RBA ) to type 1 receptor , the highest being 0.72% for 13 ( aldosterone = 100%).", "entity": [{"entity": "human mononuclear leukocytes", "entity_type": "cell type", "pos": [40, 68]}, {"entity": "type 1 receptor", "entity_type": "protein", "pos": [150, 165]}], "task": "NER"}
{"text": "For comparison, other RBA in this system were: 19-noraldosterone , 20%; 18-deoxyaldosterone , 5.8%; 18-deoxy-19-noraldosterone , 4.7%; 18,21-anhydroaldosterone , 0.37%; 17-isoaldosterone , 7.6% and apoaldosterone , 4.3%", "entity": [], "task": "NER"}
{"text": "Cell type specificity and activation requirements for NFAT-1 ( nuclear factor of activated T-cells ) transcriptional activity determined by a new method using transgenic mice to assay transcriptional activity of an individual nuclear factor .", "entity": [{"entity": "NFAT-1", "entity_type": "protein", "pos": [54, 60]}, {"entity": "nuclear factor", "entity_type": "protein", "pos": [63, 77]}, {"entity": "nuclear factor", "entity_type": "protein", "pos": [226, 240]}, {"entity": "activated T-cells", "entity_type": "cell type", "pos": [81, 98]}], "task": "NER"}
{"text": "Nuclear factor of activated T-cells ( NFAT-1 ) is a transcription factor which is considered to be an important regulator in early T-cell activation .", "entity": [{"entity": "Nuclear factor", "entity_type": "protein", "pos": [0, 14]}, {"entity": "activated T-cells", "entity_type": "cell type", "pos": [18, 35]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [52, 72]}, {"entity": "NFAT-1", "entity_type": "protein", "pos": [38, 44]}], "task": "NER"}
{"text": "We have developed a system to monitor the transcriptional activity of NFAT-1 at the single cell level in whole animals .", "entity": [{"entity": "NFAT-1", "entity_type": "protein", "pos": [70, 76]}], "task": "NER"}
{"text": "The system is based on the use of an oligomerized NFAT-1 binding motif that directs transcription of SV40 T-antigen in transgenic mice .", "entity": [{"entity": "transcription of SV40 T-antigen", "entity_type": "protein", "pos": [84, 115]}, {"entity": "NFAT-1", "entity_type": "protein", "pos": [50, 56]}], "task": "NER"}
{"text": "This report represents the first demonstration that a multimerized short binding motif can function appropriately in transgenic mice .", "entity": [], "task": "NER"}
{"text": "NFAT-1 activity had previously been thought to be confined to activated T-lymphocytes upon release of intracellular calcium .", "entity": [{"entity": "intracellular calcium", "entity_type": "cell type", "pos": [102, 123]}, {"entity": "activated T-lymphocytes", "entity_type": "cell type", "pos": [62, 85]}, {"entity": "NFAT-1", "entity_type": "protein", "pos": [0, 6]}], "task": "NER"}
{"text": "By targeting NFAT-1 -dependent gene expression in transgenic mice we discovered new sites of NFAT-1 activity .", "entity": [{"entity": "NFAT-1", "entity_type": "protein", "pos": [13, 19]}, {"entity": "NFAT-1", "entity_type": "protein", "pos": [93, 99]}], "task": "NER"}
{"text": "Besides in T-lymphocytes NFAT-1 activity could also be induced in T-lymphocyte-depleted spleen cells and purified B-lymphocytes and requires agents that both release intracellular calcium and activate protein kinase C .", "entity": [{"entity": "T-lymphocytes", "entity_type": "cell type", "pos": [11, 24]}, {"entity": "purified B-lymphocytes", "entity_type": "cell type", "pos": [105, 127]}, {"entity": "T-lymphocyte-depleted spleen cells", "entity_type": "cell type", "pos": [66, 100]}, {"entity": "protein kinase C", "entity_type": "protein", "pos": [201, 217]}, {"entity": "NFAT-1", "entity_type": "protein", "pos": [25, 31]}], "task": "NER"}
{"text": "A difference in the time course of appearance of NFAT-1 activity between T-lymphocytes and non-T-lymphocytes was revealed.", "entity": [{"entity": "NFAT-1", "entity_type": "protein", "pos": [49, 55]}, {"entity": "non-T-lymphocytes", "entity_type": "cell type", "pos": [91, 108]}, {"entity": "T-lymphocytes", "entity_type": "cell type", "pos": [73, 86]}], "task": "NER"}
{"text": "Constitutive expression was observed in a small population of cells in the dermis and some mice have developed skin lesions .", "entity": [], "task": "NER"}
{"text": "Interestingly, the tissue pattern of expression of the NFAT-1 activity resembles the expression pattern described for HIV-LTR/tat transgenic mice (Vogel, J., Hinrichs, S. H., Reynolds, R. K., Luciw, P. A., and Jay, G. (1988) Nature 335, 606-611).", "entity": [{"entity": "NFAT-1", "entity_type": "protein", "pos": [55, 61]}], "task": "NER"}
{"text": "This similarity in expression and the fact that NFAT-1 has been shown to bind functional sequences in HIV-LTR suggest a role for NFAT-1 in dermal activation of the HIV-LTR .", "entity": [{"entity": "HIV-LTR", "entity_type": "DNA", "pos": [102, 109]}, {"entity": "functional sequences", "entity_type": "DNA", "pos": [78, 98]}, {"entity": "NFAT-1", "entity_type": "protein", "pos": [48, 54]}, {"entity": "HIV-LTR", "entity_type": "DNA", "pos": [164, 171]}, {"entity": "NFAT-1", "entity_type": "protein", "pos": [129, 135]}], "task": "NER"}
{"text": "A novel T-cell protein which recognizes a palindromic sequence in the negative regulatory element of the human immunodeficiency virus long terminal repeat .", "entity": [{"entity": "human immunodeficiency virus long terminal repeat", "entity_type": "DNA", "pos": [105, 154]}, {"entity": "T-cell protein", "entity_type": "protein", "pos": [8, 22]}, {"entity": "palindromic sequence", "entity_type": "DNA", "pos": [42, 62]}, {"entity": "negative regulatory element", "entity_type": "DNA", "pos": [70, 97]}], "task": "NER"}
{"text": "Two major protein-binding sites within the negative regulatory element of the human immunodeficiency virus type 1 long terminal repeat have been identified.", "entity": [{"entity": "human immunodeficiency virus type 1 long terminal repeat", "entity_type": "DNA", "pos": [78, 134]}, {"entity": "negative regulatory element", "entity_type": "DNA", "pos": [43, 70]}, {"entity": "major protein-binding sites", "entity_type": "DNA", "pos": [4, 31]}], "task": "NER"}
{"text": "One ( site B ) contained a palindromic sequence with homology to steroid/thyroid hormone response elements but was distinct from previously described binding sites of this class.", "entity": [{"entity": "palindromic sequence", "entity_type": "DNA", "pos": [27, 47]}, {"entity": "site B", "entity_type": "DNA", "pos": [6, 12]}, {"entity": "steroid/thyroid hormone response elements", "entity_type": "DNA", "pos": [65, 106]}], "task": "NER"}
{"text": "A novel T-cell protein recognized the palindromic sequence within site B and also bound estrogen- or thyroid hormone- response elements with lower affinity.", "entity": [{"entity": "site B", "entity_type": "DNA", "pos": [66, 72]}, {"entity": "T-cell protein", "entity_type": "protein", "pos": [8, 22]}, {"entity": "palindromic sequence", "entity_type": "DNA", "pos": [38, 58]}], "task": "NER"}
{"text": "A 7-base-pair mutation in the site B palindrome , which destroyed protein binding, resulted in increased expression from the human immunodeficiency virus type 1 long terminal repeat in T cells .", "entity": [{"entity": "site B palindrome", "entity_type": "DNA", "pos": [30, 47]}, {"entity": "human immunodeficiency virus type 1 long terminal repeat", "entity_type": "DNA", "pos": [125, 181]}, {"entity": "site B", "entity_type": "DNA", "pos": [30, 36]}, {"entity": "T cells", "entity_type": "cell type", "pos": [185, 192]}], "task": "NER"}
{"text": "Progesterone suppression of pregnancy lymphocytes is not mediated by glucocorticoid effect.", "entity": [{"entity": "pregnancy lymphocytes", "entity_type": "cell type", "pos": [28, 49]}], "task": "NER"}
{"text": "This study investigated whether the suppressive effect of progesterone on pregnancy lymphocytes is mediated by specific progesterone receptors .", "entity": [{"entity": "pregnancy lymphocytes", "entity_type": "cell type", "pos": [74, 95]}, {"entity": "progesterone receptors", "entity_type": "protein", "pos": [120, 142]}], "task": "NER"}
{"text": "The effects of a competitive progesterone antagonist ( RU486 ) and a specific glucocorticoid receptor blocker ( RU43044 ) were tested on the release of a blocking factor by progesterone -treated pregnancy lymphocytes .", "entity": [{"entity": "blocking factor", "entity_type": "protein", "pos": [154, 169]}, {"entity": "pregnancy lymphocytes", "entity_type": "cell type", "pos": [195, 216]}, {"entity": "progesterone -treated pregnancy lymphocytes", "entity_type": "cell line", "pos": [173, 216]}, {"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [78, 101]}], "task": "NER"}
{"text": "RU 486 tested at an equal concentration as progesterone significantly inhibited the production of the blocking factor , while RU 43044 was without effect.", "entity": [{"entity": "blocking factor", "entity_type": "protein", "pos": [102, 117]}], "task": "NER"}
{"text": "These data suggest that in pregnancy, lymphocyte progesterone acts on specific progesterone receptors and glucocorticoid binding sites are not involved.", "entity": [{"entity": "progesterone receptors", "entity_type": "protein", "pos": [79, 101]}, {"entity": "glucocorticoid binding sites", "entity_type": "protein", "pos": [106, 134]}], "task": "NER"}
{"text": "The 56-59-kilodalton protein identified in untransformed steroid receptor complexes is a unique protein that exists in cytosol in a complex with both the 70- and 90- kilodalton heat shock proteins .", "entity": [{"entity": "untransformed steroid receptor complexes", "entity_type": "protein", "pos": [43, 83]}, {"entity": "56-59-kilodalton protein", "entity_type": "protein", "pos": [4, 28]}, {"entity": "unique protein", "entity_type": "protein", "pos": [89, 103]}], "task": "NER"}
{"text": "It has previously been shown that 9S , untransformed progestin , estrogen , androgen , and glucocorticoid receptor complexes in rabbit uterine and liver cytosols contain a 59-kDa protein [Tai, P.K., Maeda, Y., Nakao, K., Wakim, N.G., Duhring, J.L., & Faber, L.E.(1986) Biochemistry 25, 5269-5275].", "entity": [{"entity": "59-kDa protein", "entity_type": "protein", "pos": [172, 186]}, {"entity": "9S", "entity_type": "protein", "pos": [34, 36]}], "task": "NER"}
{"text": "In this work we show that the monoclonal antibody KN 382/EC1 raised against the rabbit 59-kDa protein reacts with 9S , untransformed glucocorticoid receptor complexes in cytosol prepared from human IM-9 lymphocytes but not with 4S salt-transformed receptors .", "entity": [{"entity": "rabbit 59-kDa protein", "entity_type": "protein", "pos": [80, 101]}, {"entity": "untransformed glucocorticoid receptor complexes", "entity_type": "protein", "pos": [119, 166]}, {"entity": "monoclonal antibody KN 382/EC1", "entity_type": "protein", "pos": [30, 60]}, {"entity": "human IM-9 lymphocytes", "entity_type": "cell line", "pos": [192, 214]}, {"entity": "4S salt-transformed receptors", "entity_type": "protein", "pos": [228, 257]}, {"entity": "9S", "entity_type": "protein", "pos": [114, 116]}], "task": "NER"}
{"text": "The human protein recognized by the EC1 antibody is a 56-kDa protein ( p56 ) of moderate abundance located predominantly in the cytoplasm by indirect immunofluorescence .", "entity": [{"entity": "56-kDa protein", "entity_type": "protein", "pos": [54, 68]}, {"entity": "p56", "entity_type": "protein", "pos": [71, 74]}, {"entity": "EC1 antibody", "entity_type": "protein", "pos": [36, 48]}], "task": "NER"}
{"text": "There are at least six isomorphs of p56 by two-dimensional gel analysis .", "entity": [{"entity": "isomorphs", "entity_type": "protein", "pos": [23, 32]}, {"entity": "p56", "entity_type": "protein", "pos": [36, 39]}], "task": "NER"}
{"text": "N-Terminal sequencing ( 20 amino acids ) shows that p56 is a unique human protein .", "entity": [{"entity": "p56", "entity_type": "protein", "pos": [52, 55]}, {"entity": "unique human protein", "entity_type": "protein", "pos": [61, 81]}], "task": "NER"}
{"text": "When p56 is immunoadsorbed from IM-9 cell cytosol , both the 70- and 90- kDa heat shock proteins are coadsorbed in an immune-specific manner .", "entity": [{"entity": "p56", "entity_type": "protein", "pos": [5, 8]}, {"entity": "IM-9 cell", "entity_type": "cell line", "pos": [32, 41]}], "task": "NER"}
{"text": "Neither heat shock protein reacts directly with the EC1 antibody .", "entity": [{"entity": "EC1 antibody", "entity_type": "protein", "pos": [52, 64]}, {"entity": "heat shock protein", "entity_type": "protein", "pos": [8, 26]}], "task": "NER"}
{"text": "We conclude that p56 exists in cytosol in a higher order complex containing hsp70 and hsp90 , both of which in turn have been found to be associated with untransformed steroid receptors .", "entity": [{"entity": "hsp70", "entity_type": "protein", "pos": [76, 81]}, {"entity": "untransformed steroid receptors", "entity_type": "protein", "pos": [154, 185]}, {"entity": "hsp90", "entity_type": "protein", "pos": [86, 91]}, {"entity": "p56", "entity_type": "protein", "pos": [17, 20]}], "task": "NER"}
{"text": "Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus .", "entity": [{"entity": "ets-1", "entity_type": "protein", "pos": [55, 60]}, {"entity": "transcriptional activator sequence", "entity_type": "DNA", "pos": [71, 105]}, {"entity": "long terminal repeat", "entity_type": "DNA", "pos": [117, 137]}, {"entity": "proto-oncoprotein", "entity_type": "protein", "pos": [37, 54]}], "task": "NER"}
{"text": "The ets proto-oncogene family is a group of sequence-related genes whose normal cellular function is unknown.", "entity": [{"entity": "ets proto-oncogene family", "entity_type": "DNA", "pos": [4, 29]}, {"entity": "sequence-related genes", "entity_type": "DNA", "pos": [44, 66]}], "task": "NER"}
{"text": "In a study of cellular proteins involved in the transcriptional regulation of murine retroviruses in T lymphocytes , we have discovered that a member of the ets gene family encodes a sequence-specific DNA-binding protein .", "entity": [{"entity": "cellular proteins", "entity_type": "protein", "pos": [14, 31]}, {"entity": "sequence-specific DNA-binding protein", "entity_type": "protein", "pos": [183, 220]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [101, 114]}, {"entity": "ets gene family", "entity_type": "DNA", "pos": [157, 172]}], "task": "NER"}
{"text": "A mouse ets-1 cDNA clone was obtained by screening a mouse thymus cDNA expression library with a double-stranded oligonucleotide probe representing 20 bp of the Moloney murine sarcoma virus ( MSV ) long terminal repeat ( LTR ).", "entity": [{"entity": "ets-1", "entity_type": "protein", "pos": [8, 13]}, {"entity": "long terminal repeat", "entity_type": "DNA", "pos": [198, 218]}, {"entity": "double-stranded oligonucleotide probe", "entity_type": "DNA", "pos": [97, 134]}, {"entity": "mouse thymus cDNA expression library", "entity_type": "DNA", "pos": [53, 89]}, {"entity": "mouse ets-1 cDNA clone", "entity_type": "DNA", "pos": [2, 24]}, {"entity": "LTR", "entity_type": "DNA", "pos": [221, 224]}], "task": "NER"}
{"text": "The cDNA sequence has an 813-bp open reading frame ( ORF ) whose predicted amino acid sequence is 97.6% identical to the 272 carboxy-terminal amino acids of the human ets-1 protein .", "entity": [{"entity": "ORF", "entity_type": "DNA", "pos": [53, 56]}, {"entity": "272 carboxy-terminal amino acids", "entity_type": "protein", "pos": [121, 153]}, {"entity": "ets-1", "entity_type": "protein", "pos": [167, 172]}, {"entity": "human ets-1 protein", "entity_type": "protein", "pos": [161, 180]}, {"entity": "813-bp open reading frame", "entity_type": "DNA", "pos": [25, 50]}, {"entity": "cDNA sequence", "entity_type": "DNA", "pos": [4, 17]}, {"entity": "amino acid sequence", "entity_type": "protein", "pos": [75, 94]}], "task": "NER"}
{"text": "The ORF was expressed in bacteria , and the 30-kD protein product was shown to bind DNA in a sequence-specific manner by mobility-shift assays , Southwestern blot analysis , and methylation interference .", "entity": [{"entity": "30-kD protein product", "entity_type": "protein", "pos": [44, 65]}, {"entity": "DNA", "entity_type": "DNA", "pos": [84, 87]}, {"entity": "ORF", "entity_type": "DNA", "pos": [4, 7]}], "task": "NER"}
{"text": "A mutant LTR containing four base pair substitutions in the ets-1 binding site was constructed and was shown to have reduced binding in vitro.", "entity": [{"entity": "mutant LTR", "entity_type": "DNA", "pos": [2, 12]}, {"entity": "ets-1", "entity_type": "protein", "pos": [60, 65]}, {"entity": "ets-1 binding site", "entity_type": "DNA", "pos": [60, 78]}], "task": "NER"}
{"text": "Transcriptional efficiency of the MSV LTR promoter containing this disrupted ets-1 binding site was compared to the activity of a wild-type promoter in mouse T lymphocytes in culture, and 15- to 20-fold reduction in expression of a reporter gene was observed.", "entity": [{"entity": "ets-1", "entity_type": "protein", "pos": [77, 82]}, {"entity": "wild-type promoter", "entity_type": "DNA", "pos": [130, 148]}, {"entity": "reporter gene", "entity_type": "DNA", "pos": [232, 245]}, {"entity": "mouse T lymphocytes", "entity_type": "cell type", "pos": [152, 171]}, {"entity": "ets-1 binding site", "entity_type": "DNA", "pos": [77, 95]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [158, 171]}, {"entity": "MSV LTR promoter", "entity_type": "DNA", "pos": [34, 50]}], "task": "NER"}
{"text": "We propose that ets-1 functions as a transcriptional activator of mammalian type-C retroviruses and speculate that ets-related genes constitute a new group of eukaryotic DNA-binding proteins .", "entity": [{"entity": "eukaryotic DNA-binding proteins", "entity_type": "protein", "pos": [159, 190]}, {"entity": "ets-related genes", "entity_type": "DNA", "pos": [115, 132]}, {"entity": "ets-1", "entity_type": "protein", "pos": [16, 21]}], "task": "NER"}
{"text": "Type II estrogen binding sites in human peripheral blood mononuclear cells : variations during the menstrual cycle .", "entity": [{"entity": "human peripheral blood mononuclear cells", "entity_type": "cell type", "pos": [34, 74]}, {"entity": "Type II estrogen binding sites", "entity_type": "protein", "pos": [0, 30]}], "task": "NER"}
{"text": "We have previously reported that human peripheral blood mononuclear cells ( PBMC ) contain type II estrogen binding sites ( type II EBS ).", "entity": [{"entity": "type II EBS", "entity_type": "protein", "pos": [124, 135]}, {"entity": "II estrogen binding sites", "entity_type": "protein", "pos": [96, 121]}, {"entity": "human peripheral blood mononuclear cells", "entity_type": "cell type", "pos": [33, 73]}, {"entity": "PBMC", "entity_type": "cell type", "pos": [76, 80]}], "task": "NER"}
{"text": "In this study, the fluctuations of type II EBS during the menstrual cycle were analyzed in 6 normally menstruating women .", "entity": [{"entity": "type II EBS", "entity_type": "protein", "pos": [35, 46]}], "task": "NER"}
{"text": "Approximately 3 times higher levels of type II EBS were found in the periovulatory period with respect to both follicular and luteal phases .", "entity": [{"entity": "type II EBS", "entity_type": "protein", "pos": [39, 50]}], "task": "NER"}
{"text": "In postmenopausal women the mean type II EBS levels were similar to those observed in the follicular phase of the cycle.", "entity": [{"entity": "type II EBS", "entity_type": "protein", "pos": [33, 44]}], "task": "NER"}
{"text": "However, in 3 postmenopausal patients a short course of estrogen or tamoxifen resulted in a marked increase of type II EBS levels.", "entity": [{"entity": "type II EBS", "entity_type": "protein", "pos": [111, 122]}], "task": "NER"}
{"text": "Tamoxifen was also found to compete with 17 beta-estradiol for type II EBS in PBMC , although to a lesser extent than diethylstilbestrol .", "entity": [{"entity": "PBMC", "entity_type": "cell type", "pos": [78, 82]}, {"entity": "type II EBS", "entity_type": "protein", "pos": [63, 74]}], "task": "NER"}
{"text": "Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression .", "entity": [{"entity": "Mononuclear leukocyte", "entity_type": "cell type", "pos": [0, 21]}, {"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [22, 45]}], "task": "NER"}
{"text": "Some patients with major depressive disorder ( MDD ) have elevated plasma cortisol concentrations and show failure to suppress cortisol secretion upon administration of dexamethasone ( DEX ), yet they do not have Cushingoid features .", "entity": [], "task": "NER"}
{"text": "To study whether this represents glucocorticoid ( GC ) resistance , [3H]-DEX-binding assays were used to measure, in vitro, the GC receptor affinity (1/Kd) and number ( Bmax ) in mononuclear leukocytes of 11 MDD patients and 15 control subjects .", "entity": [{"entity": "GC receptor", "entity_type": "protein", "pos": [128, 139]}, {"entity": "mononuclear leukocytes", "entity_type": "cell type", "pos": [179, 201]}], "task": "NER"}
{"text": "No receptor abnormalities were detected in the MDD group; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients , if present, probably lies beyond the initial receptor binding .", "entity": [], "task": "NER"}
{"text": "DEX (1.0 mg orally) was administered to study in vivo GC receptor down-regulation .", "entity": [{"entity": "vivo GC receptor", "entity_type": "protein", "pos": [49, 65]}], "task": "NER"}
{"text": "Compared to the control group , fewer depressed subjects down-regulated Bmax after DEX .", "entity": [], "task": "NER"}
{"text": "By paired t-test , Bmax decreased significantly in the control group but not in the depressed group .", "entity": [], "task": "NER"}
{"text": "Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation , severity of depression or cortisol concentrations across all the subjects.", "entity": [], "task": "NER"}
{"text": "These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality , and they emphasize the importance of considering receptor studies in the context of GC -mediated cell processes in order to identify the exact cellular defect(s) leading to GC resistance .", "entity": [], "task": "NER"}
{"text": "Ras-related GTP-binding proteins and leukocyte signal transduction .", "entity": [{"entity": "leukocyte", "entity_type": "cell type", "pos": [37, 46]}, {"entity": "Ras-related GTP-binding proteins", "entity_type": "protein", "pos": [0, 32]}], "task": "NER"}
{"text": "Many aspects of leukocyte function are regulated by both heterotrimeric and Ras-related GTP-binding proteins , but there is little definite information about their roles in the specialized processes utilized by leukocytes for cell killing.", "entity": [{"entity": "leukocyte", "entity_type": "cell type", "pos": [16, 25]}, {"entity": "leukocytes", "entity_type": "cell type", "pos": [211, 221]}, {"entity": "heterotrimeric", "entity_type": "protein", "pos": [57, 71]}, {"entity": "Ras-related GTP-binding proteins", "entity_type": "protein", "pos": [76, 108]}], "task": "NER"}
{"text": "Recent progress in understanding the regulation of the phagocyte NADPH oxidase by the Rac GTP-binding proteins provides a basis for defining the operational characteristics of one such phagocyte system .", "entity": [{"entity": "phagocyte NADPH oxidase", "entity_type": "protein", "pos": [55, 78]}, {"entity": "Rac GTP-binding proteins", "entity_type": "protein", "pos": [86, 110]}], "task": "NER"}
{"text": "It is clear from various studies that the activity of the NADPH oxidase can be modulated through the regulation of the GTP-GDP state of Rac .", "entity": [{"entity": "GTP-GDP state", "entity_type": "protein", "pos": [119, 132]}, {"entity": "Rac", "entity_type": "protein", "pos": [136, 139]}, {"entity": "NADPH oxidase", "entity_type": "protein", "pos": [58, 71]}], "task": "NER"}
{"text": "Proteins exist in leukocytes able to modify GTP-binding protein function in this manner, and their activity may be regulated by signals generated on phagocyte stimulation .", "entity": [{"entity": "leukocytes", "entity_type": "cell type", "pos": [18, 28]}, {"entity": "GTP-binding protein", "entity_type": "protein", "pos": [44, 63]}], "task": "NER"}
{"text": "Proteins of the Ras superfamily are likely to be involved in a variety of normal phagocyte functions through their ability to modulate the assembly of actin filaments , direct vesicle trafficking and fusion, and so forth.", "entity": [{"entity": "Ras superfamily", "entity_type": "protein", "pos": [16, 31]}, {"entity": "actin filaments", "entity_type": "protein", "pos": [151, 166]}], "task": "NER"}
{"text": "BSAP : a key regulator of B-cell development and differentiation .", "entity": [{"entity": "BSAP", "entity_type": "protein", "pos": [0, 4]}, {"entity": "B-cell", "entity_type": "cell type", "pos": [26, 32]}], "task": "NER"}
{"text": "B-cell-specific activator protein ( BSAP ) is a recently identified member of the Pax-gene family of transcription factors ; in the lymphoid system , BSAP is produced only in B cells .", "entity": [{"entity": "B cells", "entity_type": "cell type", "pos": [175, 182]}, {"entity": "BSAP", "entity_type": "protein", "pos": [36, 40]}, {"entity": "Pax-gene family", "entity_type": "DNA", "pos": [82, 97]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [101, 122]}, {"entity": "BSAP", "entity_type": "protein", "pos": [150, 154]}, {"entity": "B-cell-specific activator protein", "entity_type": "protein", "pos": [0, 33]}], "task": "NER"}
{"text": "Here, Markus Neurath, Eckhard Stuber and Warren Strober describe the molecular structure of BSAP and focus on the ability of this protein to regulate the expression of B-cell-specific genes .", "entity": [{"entity": "B-cell-specific genes", "entity_type": "DNA", "pos": [168, 189]}, {"entity": "BSAP", "entity_type": "protein", "pos": [92, 96]}], "task": "NER"}
{"text": "They propose that BSAP is a key protein of B cells and that it not only influence B-cell development but also influences the balance between B-cell proliferation and immunoglobulin secretion at later stages of B-cell differentiation .", "entity": [{"entity": "immunoglobulin", "entity_type": "protein", "pos": [166, 180]}, {"entity": "key protein", "entity_type": "protein", "pos": [28, 39]}, {"entity": "BSAP", "entity_type": "protein", "pos": [18, 22]}, {"entity": "B cells", "entity_type": "cell type", "pos": [43, 50]}], "task": "NER"}
{"text": "Down-regulation of NF-kappa B protein levels in activated human lymphocytes by 1,25-dihydroxyvitamin D3 [published erratum appears in Proc Natl Acad Sci U S A 1996 Jan 9;93(1):524]", "entity": [{"entity": "NF-kappa B protein", "entity_type": "protein", "pos": [19, 37]}], "task": "NER"}
{"text": "The effect of 1,25-dihydroxyvitamin D3 [ 1,25(OH)2)D3 ], a steroid hormone with immunomodulating properties, on nuclear factor kappa B ( NF-kappa B ) proteins was examined in in vitro activated normal human lymphocytes by Western blot analysis .", "entity": [{"entity": "human lymphocytes", "entity_type": "cell type", "pos": [201, 218]}, {"entity": "in vitro activated normal human lymphocytes", "entity_type": "cell line", "pos": [175, 218]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [137, 147]}, {"entity": "nuclear factor kappa B", "entity_type": "protein", "pos": [112, 134]}], "task": "NER"}
{"text": "Over a 72-hr period of activation, the expression of the 50-kDa NF-kappa B , p50 , and its precursor, p105 , was increased progressively.", "entity": [{"entity": "p105", "entity_type": "protein", "pos": [102, 106]}, {"entity": "p50", "entity_type": "protein", "pos": [77, 80]}, {"entity": "50-kDa NF-kappa B", "entity_type": "protein", "pos": [57, 74]}], "task": "NER"}
{"text": "When cells were activated in the presence of 1,25(OH)2D3 , the levels of the mature protein as well as its precursor were decreased.", "entity": [], "task": "NER"}
{"text": "The effect of the hormone on the levels of p50 was demonstrable in the cytosolic and nuclear compartments ; it required between 4 and 8 hr and was specific, as 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were ineffective.", "entity": [{"entity": "p50", "entity_type": "protein", "pos": [43, 46]}], "task": "NER"}
{"text": "Besides p50 , 1,25(OH)2D3 decreased the levels of another NF-kappa B protein , namely c-rel .", "entity": [{"entity": "NF-kappa B protein", "entity_type": "protein", "pos": [58, 76]}, {"entity": "c-rel", "entity_type": "protein", "pos": [86, 91]}, {"entity": "p50", "entity_type": "protein", "pos": [8, 11]}], "task": "NER"}
{"text": "In addition, 1,25(OH)2D3 decreased the abundance of a specific DNA-protein complex formed upon incubation of nuclear extracts from activated lymphocytes with a labeled NF-kappa B DNA binding motif .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [168, 178]}, {"entity": "specific DNA-protein complex", "entity_type": "protein", "pos": [54, 82]}, {"entity": "NF-kappa B DNA binding motif", "entity_type": "protein", "pos": [168, 196]}], "task": "NER"}
{"text": "Further, 1,25(OH)2D3 inhibited the transcriptional activity of NF-kappa B in Jurkat cells transiently transfected with a construct containing four tandem repeats of the NF-kappa B binding sequence of the immunoglobulin kappa light chain gene linked to the chloramphenicol acetyltransferase reporter gene .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [63, 73]}, {"entity": "immunoglobulin kappa light chain gene", "entity_type": "DNA", "pos": [204, 241]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [169, 179]}, {"entity": "NF-kappa B binding sequence", "entity_type": "DNA", "pos": [169, 196]}, {"entity": "tandem repeats", "entity_type": "DNA", "pos": [147, 161]}, {"entity": "chloramphenicol acetyltransferase", "entity_type": "protein", "pos": [256, 289]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [77, 89]}, {"entity": "chloramphenicol acetyltransferase reporter gene", "entity_type": "DNA", "pos": [256, 303]}, {"entity": "construct", "entity_type": "DNA", "pos": [121, 130]}], "task": "NER"}
{"text": "These observations demonstrate directly that there is de novo synthesis of NF-kappa B during human lymphocyte activation and suggest that this process is hormonally regulated.", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [75, 85]}], "task": "NER"}
{"text": "The myeloid zinc finger gene , MZF-1 , regulates the CD34 promoter in vitro.", "entity": [{"entity": "CD34 promoter", "entity_type": "DNA", "pos": [53, 66]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [31, 36]}, {"entity": "myeloid zinc finger gene", "entity_type": "DNA", "pos": [4, 28]}], "task": "NER"}
{"text": "MZF-1 is a C2H2 zinc finger gene encoding a putative transcriptional regulator of myeloid differentiation .", "entity": [{"entity": "C2H2 zinc finger gene", "entity_type": "DNA", "pos": [11, 32]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [0, 5]}, {"entity": "putative transcriptional regulator", "entity_type": "protein", "pos": [44, 78]}], "task": "NER"}
{"text": "The MZF-1 protein contains 13 C2H2 zinc fingers arranged in bipartite DNA binding domains containing zinc fingers through 4 and, in the carboxy-terminus , 5 through 13.", "entity": [{"entity": "carboxy-terminus", "entity_type": "protein", "pos": [136, 152]}, {"entity": "DNA binding domains", "entity_type": "protein", "pos": [70, 89]}, {"entity": "C2H2 zinc fingers", "entity_type": "protein", "pos": [30, 47]}, {"entity": "zinc fingers", "entity_type": "protein", "pos": [35, 47]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [4, 9]}], "task": "NER"}
{"text": "We previously identified the DNA consensus binding site recognized by the two DNA binding domains .", "entity": [{"entity": "DNA binding domains", "entity_type": "protein", "pos": [78, 97]}, {"entity": "DNA consensus binding site", "entity_type": "DNA", "pos": [29, 55]}], "task": "NER"}
{"text": "To assess the transcription regulatory function of MZF-1 , the full-length MZF-1 coding region was fused to the DNA binding domain of the yeast transactivator GAL4 .", "entity": [{"entity": "MZF-1", "entity_type": "DNA", "pos": [51, 56]}, {"entity": "DNA binding domain", "entity_type": "protein", "pos": [112, 130]}, {"entity": "yeast transactivator GAL4", "entity_type": "protein", "pos": [138, 163]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [75, 80]}, {"entity": "GAL4", "entity_type": "protein", "pos": [159, 163]}], "task": "NER"}
{"text": "The expression vector was cotransfected with the chloramphenicol acetyl transferase (CAT) reporter gene regulated by the thymidine kinase promoter containing GAL4 DNA binding sites into NIH 3T3 , 293 , K562 , and Jurkat cell lines .", "entity": [{"entity": "chloramphenicol acetyl transferase (CAT) reporter gene", "entity_type": "DNA", "pos": [49, 103]}, {"entity": "NIH 3T3", "entity_type": "cell line", "pos": [186, 193]}, {"entity": "GAL4", "entity_type": "protein", "pos": [158, 162]}, {"entity": "293", "entity_type": "cell line", "pos": [196, 199]}, {"entity": "thymidine kinase", "entity_type": "protein", "pos": [121, 137]}, {"entity": "chloramphenicol acetyl transferase", "entity_type": "protein", "pos": [49, 83]}, {"entity": "thymidine kinase promoter", "entity_type": "DNA", "pos": [121, 146]}, {"entity": "K562", "entity_type": "cell line", "pos": [202, 206]}, {"entity": "GAL4 DNA binding sites", "entity_type": "DNA", "pos": [158, 180]}, {"entity": "Jurkat cell lines", "entity_type": "cell line", "pos": [213, 230]}], "task": "NER"}
{"text": "MZF-1 represses CAT reporter gene expression via GAL4 binding sites in the nonhematopoietic cell lines NIH 3T3 and 293 .", "entity": [{"entity": "CAT reporter gene", "entity_type": "DNA", "pos": [16, 33]}, {"entity": "nonhematopoietic cell lines", "entity_type": "cell line", "pos": [75, 102]}, {"entity": "NIH 3T3", "entity_type": "cell line", "pos": [103, 110]}, {"entity": "GAL4", "entity_type": "protein", "pos": [49, 53]}, {"entity": "293", "entity_type": "cell line", "pos": [115, 118]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [0, 5]}], "task": "NER"}
{"text": "In contrast, MZF-1 activates CAT reporter gene expression in the hematopoietic cell lines K562 and Jurkat .", "entity": [{"entity": "Jurkat", "entity_type": "cell line", "pos": [99, 105]}, {"entity": "CAT reporter gene", "entity_type": "DNA", "pos": [29, 46]}, {"entity": "hematopoietic cell lines", "entity_type": "cell line", "pos": [65, 89]}, {"entity": "K562", "entity_type": "cell line", "pos": [90, 94]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [13, 18]}], "task": "NER"}
{"text": "The MZF-1 binding sites are present in the promoters of several genes expressed during myeloid differentiation , including the CD34 promoter .", "entity": [{"entity": "genes", "entity_type": "DNA", "pos": [64, 69]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [4, 9]}, {"entity": "CD34 promoter", "entity_type": "DNA", "pos": [127, 140]}, {"entity": "promoters", "entity_type": "DNA", "pos": [43, 52]}, {"entity": "MZF-1 binding sites", "entity_type": "DNA", "pos": [4, 23]}], "task": "NER"}
{"text": "MZF-1 transcriptional regulation of this physiologically relevant promoter was assessed in both hematopoietic and nonhematopoietic cell lines .", "entity": [{"entity": "nonhematopoietic cell lines", "entity_type": "cell line", "pos": [114, 141]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [0, 5]}, {"entity": "hematopoietic", "entity_type": "cell line", "pos": [96, 109]}, {"entity": "physiologically relevant promoter", "entity_type": "DNA", "pos": [41, 74]}], "task": "NER"}
{"text": "Recombinant MZF-1 protein specifically binds to the consensus binding sites in the CD34 promoter in mobility shift assays .", "entity": [{"entity": "Recombinant MZF-1 protein", "entity_type": "protein", "pos": [0, 25]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [12, 17]}, {"entity": "consensus binding sites", "entity_type": "DNA", "pos": [52, 75]}, {"entity": "CD34 promoter", "entity_type": "DNA", "pos": [83, 96]}], "task": "NER"}
{"text": "MZF-1 expression vectors were cotransfected with the luciferase reporter plasmids regulated by the CD34 promoter into both nonhematopoietic and hematopoietic cell lines .", "entity": [{"entity": "CD34 promoter", "entity_type": "DNA", "pos": [99, 112]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [0, 5]}, {"entity": "luciferase reporter plasmids", "entity_type": "DNA", "pos": [53, 81]}], "task": "NER"}
{"text": "As with the heterologous DNA binding domain , MZF-1 represses reporter gene expression in nonhematopoietic cell lines and activates expression in hematopoietic cell lines .", "entity": [{"entity": "hematopoietic cell lines", "entity_type": "cell line", "pos": [93, 117]}, {"entity": "nonhematopoietic cell lines", "entity_type": "cell line", "pos": [90, 117]}, {"entity": "DNA binding domain", "entity_type": "protein", "pos": [25, 43]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [46, 51]}, {"entity": "reporter gene", "entity_type": "DNA", "pos": [62, 75]}], "task": "NER"}
{"text": "Activation of CD34 expression in hematopoietic cell lines is dependent on the presence of intact MZF-1 binding sites .", "entity": [{"entity": "hematopoietic cell lines", "entity_type": "cell line", "pos": [33, 57]}, {"entity": "MZF-1 binding sites", "entity_type": "DNA", "pos": [97, 116]}, {"entity": "CD34", "entity_type": "protein", "pos": [14, 18]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [97, 102]}], "task": "NER"}
{"text": "The cell type-specific regulation of the CD34 promoter by MZF-1 suggests the presence of tissue-specific regulators/adapters or differential MZF-1 modifications that determine MZF-1 transcriptional regulatory function .", "entity": [{"entity": "MZF-1", "entity_type": "DNA", "pos": [58, 63]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [141, 146]}, {"entity": "CD34 promoter", "entity_type": "DNA", "pos": [41, 54]}, {"entity": "MZF-1", "entity_type": "DNA", "pos": [176, 181]}], "task": "NER"}
{"text": "The murine BCL6 gene is induced in activated lymphocytes as an immediate early gene .", "entity": [{"entity": "BCL6 gene", "entity_type": "DNA", "pos": [11, 20]}, {"entity": "activated lymphocytes", "entity_type": "cell type", "pos": [35, 56]}, {"entity": "immediate early gene", "entity_type": "DNA", "pos": [63, 83]}], "task": "NER"}
{"text": "The chromosomal translocation involving 3q27 is often detected in human B-cell lymphomas , especially diffuse lymphomas with a large-cell component .", "entity": [{"entity": "3q27", "entity_type": "DNA", "pos": [40, 44]}, {"entity": "human B-cell lymphomas", "entity_type": "cell type", "pos": [66, 88]}], "task": "NER"}
{"text": "The BCL6 gene has been isolated from the chromosomal breakpoint in these lymphomas .", "entity": [{"entity": "BCL6 gene", "entity_type": "DNA", "pos": [4, 13]}], "task": "NER"}
{"text": "Here we cloned the murine BCL6 (mBCL6) cDNA from the muscle cDNA library using the human BCL6 (hBCL6) cDNA as a probe.", "entity": [{"entity": "human BCL6", "entity_type": "protein", "pos": [83, 93]}, {"entity": "murine BCL6 (mBCL6) cDNA", "entity_type": "DNA", "pos": [19, 43]}, {"entity": "murine BCL6", "entity_type": "protein", "pos": [19, 30]}, {"entity": "human BCL6 (hBCL6) cDNA", "entity_type": "DNA", "pos": [83, 106]}, {"entity": "muscle cDNA library", "entity_type": "DNA", "pos": [53, 72]}], "task": "NER"}
{"text": "The predicted amino acid sequence was 95% identical to that of hBCL6 .", "entity": [{"entity": "hBCL6", "entity_type": "protein", "pos": [63, 68]}], "task": "NER"}
{"text": "It contains six repeats of the Kruppel-like zinc-finger motif that are completely identical to those of hBCL6 , indicating that the BCL6 gene is well conserved between humans and mice .", "entity": [{"entity": "hBCL6", "entity_type": "protein", "pos": [104, 109]}, {"entity": "BCL6 gene", "entity_type": "DNA", "pos": [132, 141]}, {"entity": "Kruppel-like zinc-finger motif", "entity_type": "protein", "pos": [31, 61]}], "task": "NER"}
{"text": "Expression of the mBCL6 gene was ubiquitously detected in adult mouse tissues including lymphatic organs .", "entity": [{"entity": "mBCL6 gene", "entity_type": "DNA", "pos": [18, 28]}], "task": "NER"}
{"text": "Furthermore, it was induced in lymphocytes activated with phorbol ester and Ca2+ ionophore within 30 min after stimulation.", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [31, 42]}], "task": "NER"}
{"text": "This induction was not inhibited by treatment of the cells with a protein synthesis inhibitor , cycloheximide .", "entity": [], "task": "NER"}
{"text": "These results suggest that BCL6 plays a role in activated lymphocytes as an immediate early gene.", "entity": [{"entity": "activated lymphocytes", "entity_type": "cell type", "pos": [48, 69]}, {"entity": "BCL6", "entity_type": "protein", "pos": [27, 31]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [58, 69]}], "task": "NER"}
{"text": "The role of BSAP ( Pax-5 ) in B-cell development .", "entity": [{"entity": "BSAP", "entity_type": "protein", "pos": [12, 16]}, {"entity": "Pax-5", "entity_type": "protein", "pos": [19, 24]}], "task": "NER"}
{"text": "The hierarchy of transcriptional control in B-cell development has recently been analyzed by targeted gene inactivation in the mouse .", "entity": [], "task": "NER"}
{"text": "In this manner, the paired box containing gene Pax-5 , encoding the B cell specific transcription factor BSAP , has been shown to play a key role in early B lymphopoiesis .", "entity": [{"entity": "BSAP", "entity_type": "protein", "pos": [105, 109]}, {"entity": "Pax-5", "entity_type": "DNA", "pos": [47, 52]}, {"entity": "paired box containing gene", "entity_type": "DNA", "pos": [20, 46]}, {"entity": "B cell specific transcription factor", "entity_type": "protein", "pos": [68, 104]}], "task": "NER"}
{"text": "Other experimental strategies have implicated BSAP in the control of cell proliferation , isotype switching and transcription of the immunoglobulin heavy-chain gene at late stages of B-cell differentiation .", "entity": [{"entity": "BSAP", "entity_type": "protein", "pos": [46, 50]}, {"entity": "immunoglobulin heavy-chain", "entity_type": "protein", "pos": [133, 159]}, {"entity": "immunoglobulin heavy-chain gene", "entity_type": "DNA", "pos": [133, 164]}], "task": "NER"}
{"text": "The DNA-binding properties of two heat shock factors , HSF1 and HSF3 , are induced in the avian erythroblast cell line HD6 .", "entity": [{"entity": "two heat shock factors", "entity_type": "protein", "pos": [30, 52]}, {"entity": "HD6", "entity_type": "cell line", "pos": [119, 122]}, {"entity": "HSF3", "entity_type": "protein", "pos": [64, 68]}, {"entity": "avian erythroblast cell line", "entity_type": "cell line", "pos": [90, 118]}, {"entity": "HSF1", "entity_type": "protein", "pos": [55, 59]}], "task": "NER"}
{"text": "Avian cells express three heat shock transcription factor ( HSF ) genes corresponding to a novel factor , HSF3 , and homologs of mouse and human HSF1 and HSF2 .", "entity": [{"entity": "HSF", "entity_type": "protein", "pos": [60, 63]}, {"entity": "HSF3", "entity_type": "protein", "pos": [106, 110]}, {"entity": "HSF2", "entity_type": "protein", "pos": [154, 158]}, {"entity": "heat shock transcription factor", "entity_type": "protein", "pos": [26, 57]}, {"entity": "novel factor", "entity_type": "protein", "pos": [91, 103]}, {"entity": "HSF1", "entity_type": "protein", "pos": [145, 149]}, {"entity": "heat shock transcription factor ( HSF ) genes", "entity_type": "DNA", "pos": [26, 71]}], "task": "NER"}
{"text": "Analysis of the biochemical and cell biological properties of these HSFs reveals that HSF3 has properties in common with both HSF1 and HSF2 and yet has features which are distinct from both.", "entity": [{"entity": "HSF2", "entity_type": "protein", "pos": [135, 139]}, {"entity": "HSF3", "entity_type": "protein", "pos": [86, 90]}, {"entity": "HSFs", "entity_type": "protein", "pos": [68, 72]}, {"entity": "HSF1", "entity_type": "protein", "pos": [126, 130]}], "task": "NER"}
{"text": "HSF3 is constitutively expressed in the erythroblast cell line HD6 , the lymphoblast cell line MSB , and embryo fibroblasts , and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock.", "entity": [{"entity": "embryo fibroblasts", "entity_type": "cell line", "pos": [105, 123]}, {"entity": "lymphoblast cell line MSB", "entity_type": "cell line", "pos": [73, 98]}, {"entity": "HSF3", "entity_type": "protein", "pos": [0, 4]}, {"entity": "erythroblast cell line HD6", "entity_type": "cell line", "pos": [40, 66]}], "task": "NER"}
{"text": "Acquisition of HSF3 DNA-binding activity in HD6 cells is accompanied by oligomerization from a non-DNA-binding dimer to a DNA-binding trimer , whereas the effect of heat shock on HSF1 is oligomerization of an inert monomer to a DNA-binding trimer .", "entity": [{"entity": "non-DNA-binding dimer", "entity_type": "protein", "pos": [95, 116]}, {"entity": "DNA-binding trimer", "entity_type": "protein", "pos": [122, 140]}, {"entity": "DNA-binding trimer", "entity_type": "protein", "pos": [228, 246]}, {"entity": "HSF3", "entity_type": "protein", "pos": [15, 19]}, {"entity": "HD6 cells", "entity_type": "cell line", "pos": [44, 53]}, {"entity": "HSF1", "entity_type": "protein", "pos": [179, 183]}, {"entity": "inert monomer", "entity_type": "protein", "pos": [209, 222]}], "task": "NER"}
{"text": "Induction of HSF3 DNA-binding activity is delayed compared with that of HSF1 .", "entity": [{"entity": "HSF1", "entity_type": "protein", "pos": [72, 76]}, {"entity": "HSF3", "entity_type": "protein", "pos": [13, 17]}], "task": "NER"}
{"text": "As occurs for HSF1 , heat shock leads to the translocation of HSF3 to the nucleus.", "entity": [{"entity": "HSF3", "entity_type": "protein", "pos": [62, 66]}, {"entity": "HSF1", "entity_type": "protein", "pos": [14, 18]}], "task": "NER"}
{"text": "HSF exhibits the properties of a transcriptional activator , as judged from the stimulatory activity of transiently overexpressed HSF3 measured by using a heat shock element-containing reporter construct and as independently assayed by the activity of a chimeric GAL4 -HSF3 protein on a GAL4 reporter construct .", "entity": [{"entity": "transcriptional activator", "entity_type": "protein", "pos": [33, 58]}, {"entity": "heat shock element-containing reporter construct", "entity_type": "DNA", "pos": [155, 203]}, {"entity": "GAL4", "entity_type": "protein", "pos": [263, 267]}, {"entity": "GAL4 reporter construct", "entity_type": "DNA", "pos": [287, 310]}, {"entity": "chimeric GAL4 -HSF3 protein", "entity_type": "protein", "pos": [254, 281]}, {"entity": "-HSF3", "entity_type": "protein", "pos": [268, 273]}, {"entity": "transiently overexpressed HSF3", "entity_type": "protein", "pos": [104, 134]}, {"entity": "GAL4", "entity_type": "protein", "pos": [287, 291]}, {"entity": "HSF3", "entity_type": "protein", "pos": [130, 134]}], "task": "NER"}
{"text": "These results reveal that HSF3 is negatively regulated in avian cells and acquires DNA-binding activity in certain cells upon heat shock .", "entity": [{"entity": "avian cells", "entity_type": "cell type", "pos": [58, 69]}, {"entity": "HSF3", "entity_type": "protein", "pos": [26, 30]}], "task": "NER"}
{"text": "Direct demonstration of NFATp dephosphorylation and nuclear localization in activated HT-2 cells using a specific NFATp polyclonal antibody .", "entity": [{"entity": "HT-2 cells", "entity_type": "cell line", "pos": [86, 96]}, {"entity": "NFATp", "entity_type": "protein", "pos": [24, 29]}, {"entity": "activated HT-2 cells", "entity_type": "cell line", "pos": [76, 96]}, {"entity": "NFATp polyclonal antibody", "entity_type": "protein", "pos": [114, 139]}, {"entity": "NFATp", "entity_type": "protein", "pos": [114, 119]}], "task": "NER"}
{"text": "Nuclear factor of activated T cells ( NFAT ) regulates transcription of a number of cytokine genes , and NFAT DNA binding activity is stimulated following T cell activation .", "entity": [{"entity": "cytokine genes", "entity_type": "protein", "pos": [84, 98]}, {"entity": "NFAT", "entity_type": "protein", "pos": [38, 42]}, {"entity": "NFAT", "entity_type": "protein", "pos": [105, 109]}, {"entity": "Nuclear factor of activated T cells", "entity_type": "protein", "pos": [0, 35]}], "task": "NER"}
{"text": "Several lines of evidence have suggested that NFAT is a substrate for calcineurin , a serine/threonine phosphatase .", "entity": [{"entity": "NFAT", "entity_type": "protein", "pos": [46, 50]}, {"entity": "calcineurin", "entity_type": "protein", "pos": [70, 81]}, {"entity": "serine/threonine phosphatase", "entity_type": "protein", "pos": [86, 114]}], "task": "NER"}
{"text": "Using a polyclonal antibody to murine NFATp , Western blot analysis of various mouse tissues demonstrated that the 110-130-kDa NFATp protein was highly expressed in thymus and spleen .", "entity": [{"entity": "murine NFATp", "entity_type": "protein", "pos": [31, 43]}, {"entity": "NFATp protein", "entity_type": "protein", "pos": [127, 140]}, {"entity": "NFATp", "entity_type": "protein", "pos": [38, 43]}, {"entity": "NFATp", "entity_type": "protein", "pos": [127, 132]}], "task": "NER"}
{"text": "Treatment of immunoprecipitated NFATp from untreated HT-2 cells with calcineurin resulted in the dephosphorylation of NFATp , demonstrating that NFATp is an in vitro substrate for calcineurin .", "entity": [{"entity": "NFATp", "entity_type": "protein", "pos": [32, 37]}, {"entity": "calcineurin", "entity_type": "protein", "pos": [69, 80]}, {"entity": "calcineurin", "entity_type": "protein", "pos": [180, 191]}, {"entity": "HT-2 cells", "entity_type": "cell line", "pos": [53, 63]}, {"entity": "NFATp", "entity_type": "protein", "pos": [118, 123]}, {"entity": "NFATp", "entity_type": "protein", "pos": [145, 150]}], "task": "NER"}
{"text": "NFATp immunoprecipitated from 32P-labeled HT-2 cells migrated as an approximately 120-kDa protein that was localized to the cytosol of the cells.", "entity": [{"entity": "NFATp", "entity_type": "protein", "pos": [0, 5]}, {"entity": "HT-2 cells", "entity_type": "cell line", "pos": [42, 52]}, {"entity": "32P-labeled HT-2 cells", "entity_type": "cell line", "pos": [30, 52]}], "task": "NER"}
{"text": "Treatment of the cells with ionomycin resulted in a decrease in the molecular weight of NFATp and a loss of 32P , consistent with NFATp dephosphorylation .", "entity": [{"entity": "NFATp", "entity_type": "protein", "pos": [88, 93]}, {"entity": "NFATp", "entity_type": "protein", "pos": [130, 135]}], "task": "NER"}
{"text": "The dephosphorylation of NFATp was accompanied by localization of the protein to the nuclear fraction .", "entity": [{"entity": "NFATp", "entity_type": "protein", "pos": [25, 30]}], "task": "NER"}
{"text": "Both of these events were blocked by preincubation of the cells with FK506 , a calcineurin inhibitor , consistent with the hypothesis that NFATp is a calcineurin substrate in cells.", "entity": [{"entity": "calcineurin", "entity_type": "protein", "pos": [79, 90]}, {"entity": "NFATp", "entity_type": "protein", "pos": [139, 144]}, {"entity": "calcineurin", "entity_type": "protein", "pos": [150, 161]}], "task": "NER"}
{"text": "Activation and expression of the nuclear factors of activated T cells , NFATp and NFATc , in human natural killer cells : regulation upon CD16 ligand binding .", "entity": [{"entity": "NFATp", "entity_type": "protein", "pos": [72, 77]}, {"entity": "nuclear factors", "entity_type": "protein", "pos": [33, 48]}, {"entity": "human natural killer cells", "entity_type": "cell type", "pos": [93, 119]}, {"entity": "activated T cells", "entity_type": "cell type", "pos": [52, 69]}, {"entity": "NFATc", "entity_type": "protein", "pos": [82, 87]}, {"entity": "CD16", "entity_type": "protein", "pos": [138, 142]}], "task": "NER"}
{"text": "The putative factors that couple the signal transduction from surface receptors to the activation of cytokine synthesis in natural killer (NK) cells have not been elucidated.", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [101, 109]}, {"entity": "natural killer (NK) cells", "entity_type": "cell type", "pos": [123, 148]}], "task": "NER"}
{"text": "We report here that the nuclear factor of activated T cells ( NFATp ), a cyclosporin A ( CsA )-sensitive factor that regulates the transcription of several cytokines , mediates CD16 -induced activation of cytokine genes in human NK cells .", "entity": [{"entity": "CD16", "entity_type": "protein", "pos": [177, 181]}, {"entity": "activated T cells", "entity_type": "cell type", "pos": [42, 59]}, {"entity": "human NK cells", "entity_type": "cell type", "pos": [223, 237]}, {"entity": "NFATp", "entity_type": "protein", "pos": [62, 67]}, {"entity": "cyclosporin A ( CsA )-sensitive factor", "entity_type": "protein", "pos": [73, 111]}, {"entity": "cytokines", "entity_type": "protein", "pos": [156, 165]}, {"entity": "cytokine genes", "entity_type": "protein", "pos": [205, 219]}, {"entity": "nuclear factor", "entity_type": "protein", "pos": [24, 38]}], "task": "NER"}
{"text": "CD16 ( Fc gamma RIIIA )-induced expression of cytokine mRNA in NK cells occurs via a CsA -sensitive and Ca(2+)-dependent mechanism .", "entity": [{"entity": "NK cells", "entity_type": "cell type", "pos": [63, 71]}, {"entity": "cytokine mRNA", "entity_type": "RNA", "pos": [46, 59]}, {"entity": "Fc gamma RIIIA", "entity_type": "protein", "pos": [7, 21]}, {"entity": "CD16", "entity_type": "protein", "pos": [0, 4]}], "task": "NER"}
{"text": "Stimulation of NK cells with CD16 ligands induces NFAT -like DNA binding activity in the nuclear extracts from these cells, as detected in electrophoretic mobility shift assays .", "entity": [{"entity": "CD16", "entity_type": "protein", "pos": [29, 33]}, {"entity": "NFAT", "entity_type": "protein", "pos": [50, 54]}, {"entity": "NK cells", "entity_type": "cell type", "pos": [15, 23]}], "task": "NER"}
{"text": "This occurs with fast kinetics after stimulation, via a CsA -sensitive and Ca(2+)-dependent mechanism that does not require de novo protein synthesis.", "entity": [], "task": "NER"}
{"text": "NK cell NFAT is present in the cytosol of nonstimulated cells , migrates to the nucleus upon stimulation, and can associate with AP-1 .", "entity": [{"entity": "NK cell NFAT", "entity_type": "protein", "pos": [0, 12]}, {"entity": "AP-1", "entity_type": "protein", "pos": [129, 133]}, {"entity": "nonstimulated cells", "entity_type": "cell type", "pos": [42, 61]}], "task": "NER"}
{"text": "Two distinct molecules, NFATp and NFATc , have been reported to mediate NFAT activity .", "entity": [{"entity": "NFAT", "entity_type": "protein", "pos": [24, 28]}, {"entity": "NFATc", "entity_type": "protein", "pos": [34, 39]}, {"entity": "NFATp", "entity_type": "protein", "pos": [24, 29]}], "task": "NER"}
{"text": "The results of supershift assays using NFATp- and NFATc- specific antibodies indicate that NK cell activation early after CD16 ligand binding involves primarily, if not exclusively, NFATp , and Western blot analysis shows that this has the same electrophoretic mobility (approximately 120 kD) as that of T lymphocytes .", "entity": [{"entity": "CD16", "entity_type": "protein", "pos": [122, 126]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [304, 317]}, {"entity": "NFATp", "entity_type": "protein", "pos": [39, 44]}], "task": "NER"}
{"text": "NK cells do not express NFATc constitutively, but NFATc mRNA accumulation is induced in these cells within 2 h of stimulation with CD16 ligands .", "entity": [{"entity": "NFATc", "entity_type": "protein", "pos": [24, 29]}, {"entity": "NK cells", "entity_type": "cell type", "pos": [0, 8]}, {"entity": "NFATc", "entity_type": "protein", "pos": [50, 55]}, {"entity": "NFATc mRNA", "entity_type": "RNA", "pos": [50, 60]}], "task": "NER"}
{"text": "However, supershift assays using the available mAb recognizing the T cell NFATc revealed no detectable NFATc protein in nuclear and cytoplasmic extracts from CD16- or phorbol ester -stimulated cells at any time tested, up to 4 h.", "entity": [{"entity": "T cell NFATc", "entity_type": "protein", "pos": [67, 79]}, {"entity": "NFATc", "entity_type": "protein", "pos": [74, 79]}, {"entity": "phorbol ester -stimulated cells", "entity_type": "cell line", "pos": [167, 198]}, {"entity": "NFATc", "entity_type": "protein", "pos": [103, 108]}, {"entity": "mAb", "entity_type": "protein", "pos": [47, 50]}], "task": "NER"}
{"text": "These results provide the first direct evidence that both CsA -sensitive transcription factors , NFATp and NFATc , are expressed in human NK cells , and that their activation and/or expression can be regulated in primary cells by a single stimulus, that, in the case of CD16 in NK cells , results in early activation of NFATp and subsequently induced expression of NFATc mRNA .", "entity": [{"entity": "CsA -sensitive transcription factors", "entity_type": "protein", "pos": [58, 94]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [73, 94]}, {"entity": "NFATc", "entity_type": "protein", "pos": [107, 112]}, {"entity": "NK cells", "entity_type": "cell type", "pos": [138, 146]}, {"entity": "NFATc mRNA", "entity_type": "RNA", "pos": [365, 375]}, {"entity": "NFATp", "entity_type": "protein", "pos": [97, 102]}, {"entity": "NFATp", "entity_type": "protein", "pos": [320, 325]}, {"entity": "NFATc", "entity_type": "protein", "pos": [365, 370]}, {"entity": "NK cells", "entity_type": "cell type", "pos": [278, 286]}], "task": "NER"}
{"text": "Interleukin 2 signaling involves the phosphorylation of Stat proteins .", "entity": [{"entity": "Stat proteins", "entity_type": "protein", "pos": [56, 69]}], "task": "NER"}
{"text": "One of the most important cytokines involved in immune response regulation is interleukin 2 (IL-2), a potent activator of the proliferation and function of T lymphocytes and natural killer cells .", "entity": [{"entity": "natural killer cells", "entity_type": "cell type", "pos": [174, 194]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [156, 169]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [158, 169]}, {"entity": "cytokines", "entity_type": "protein", "pos": [26, 35]}], "task": "NER"}
{"text": "The mechanisms by which the effects of IL-2 are propagated within cells are not understood.", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [39, 43]}], "task": "NER"}
{"text": "While the binding of IL-2 to its receptor was recently shown to lead to the activation of two kinases , Jak-1 and Jak-3 , subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized.", "entity": [{"entity": "Jak-1", "entity_type": "protein", "pos": [104, 109]}, {"entity": "IL-2", "entity_type": "protein", "pos": [21, 25]}, {"entity": "Jak-3", "entity_type": "protein", "pos": [114, 119]}, {"entity": "kinases", "entity_type": "protein", "pos": [94, 101]}], "task": "NER"}
{"text": "Since many cytokines that activate Jak kinases also lead to the tyrosine phosphorylation and activation of members of the Stat family of transcription factors , the ability of IL-2 to trigger Stat phosphorylation was examined.", "entity": [{"entity": "Jak kinases", "entity_type": "protein", "pos": [35, 46]}, {"entity": "kinases", "entity_type": "protein", "pos": [39, 46]}, {"entity": "Stat family", "entity_type": "protein", "pos": [122, 133]}, {"entity": "IL-2", "entity_type": "protein", "pos": [176, 180]}, {"entity": "cytokines", "entity_type": "protein", "pos": [11, 20]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [137, 158]}], "task": "NER"}
{"text": "Exposure of activated human T lymphocytes or of a natural killer cell line ( NKL ) to IL-2 leads to the phosphorylation of Stat1 alpha , Stat1 beta , and Stat3 , as well as of two Stat-related proteins , p94 and p95 .", "entity": [{"entity": "natural killer cell line", "entity_type": "cell line", "pos": [50, 74]}, {"entity": "natural killer cell", "entity_type": "cell type", "pos": [50, 69]}, {"entity": "Stat1 alpha", "entity_type": "protein", "pos": [123, 134]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [28, 41]}, {"entity": "p94", "entity_type": "protein", "pos": [204, 207]}, {"entity": "human T lymphocytes", "entity_type": "cell type", "pos": [22, 41]}, {"entity": "Stat3", "entity_type": "protein", "pos": [154, 159]}, {"entity": "p95", "entity_type": "protein", "pos": [212, 215]}, {"entity": "IL-2", "entity_type": "protein", "pos": [86, 90]}, {"entity": "NKL", "entity_type": "cell line", "pos": [77, 80]}, {"entity": "Stat-related proteins", "entity_type": "protein", "pos": [180, 201]}, {"entity": "Stat1 beta", "entity_type": "protein", "pos": [137, 147]}], "task": "NER"}
{"text": "p94 and p95 share homology with Stat1 at the phosphorylation site and in the Src homology 2 (SH2) domain , but otherwise are immunologically distinct from Stat1 .", "entity": [{"entity": "Stat1", "entity_type": "protein", "pos": [32, 37]}, {"entity": "phosphorylation site", "entity_type": "protein", "pos": [45, 65]}, {"entity": "Src homology 2 (SH2) domain", "entity_type": "protein", "pos": [77, 104]}, {"entity": "Stat1", "entity_type": "protein", "pos": [155, 160]}, {"entity": "p94", "entity_type": "protein", "pos": [0, 3]}, {"entity": "p95", "entity_type": "protein", "pos": [8, 11]}], "task": "NER"}
{"text": "These Stat proteins were found to translocate to the nucleus and to bind to a specific DNA sequence .", "entity": [{"entity": "Stat proteins", "entity_type": "protein", "pos": [6, 19]}, {"entity": "specific DNA sequence", "entity_type": "DNA", "pos": [78, 99]}], "task": "NER"}
{"text": "These findings suggest a mechanism by which IL-2 binding to its receptor may activate specific genes involved in immune cell function .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [44, 48]}, {"entity": "specific genes", "entity_type": "DNA", "pos": [86, 100]}], "task": "NER"}
{"text": "Expression of c-fos correlates with IFN-alpha responsiveness in Philadelphia chromosome positive chronic myelogenous leukemia .", "entity": [{"entity": "IFN-alpha", "entity_type": "protein", "pos": [36, 45]}, {"entity": "c-fos", "entity_type": "DNA", "pos": [14, 19]}], "task": "NER"}
{"text": "This study evaluates (i) constitutive levels of oncogene and p53 transcripts in chronic phase CML patients and (ii) their modulations subsequent to in vivo therapy with rIFN-alpha 2c .", "entity": [{"entity": "rIFN-alpha 2c", "entity_type": "protein", "pos": [169, 182]}, {"entity": "oncogene", "entity_type": "DNA", "pos": [48, 56]}, {"entity": "p53 transcripts", "entity_type": "RNA", "pos": [61, 76]}], "task": "NER"}
{"text": "Peripheral blood mononuclear cells ( pbmc ) and bone marrow cells of 26 patients were examined for c-fos , c-myc , p53 and the hybrid bcr/abl mRNA levels .", "entity": [{"entity": "Peripheral blood mononuclear cells", "entity_type": "cell type", "pos": [0, 34]}, {"entity": "pbmc", "entity_type": "cell type", "pos": [37, 41]}, {"entity": "bone marrow cells", "entity_type": "cell type", "pos": [48, 65]}], "task": "NER"}
{"text": "Results indicated that (i) constitutive c-fos transcript levels are significantly higher in patients subsequently responding to IFN-alpha therapy (p < 0.01) and positively correlated with the proportion of lymphocytes (r = 0.6895, p < 0.01) and negatively with the proportion of immature cells (r = -0.568, p < 0.01) contained in the pbmc preparations tested, (ii) constitutive mRNA levels of the hybrid bcr/abl , c-myc and p53 are positively correlated with each other, but failed to relate to disease parameters, and (iii) acute and chronic in vivo exposure to IFN-alpha is accompanied by upregulation of c-fos and downregulation of c-myc mRNA levels in responder patients .", "entity": [{"entity": "pbmc", "entity_type": "cell type", "pos": [334, 338]}, {"entity": "p53", "entity_type": "DNA", "pos": [424, 427]}, {"entity": "hybrid bcr/abl", "entity_type": "DNA", "pos": [397, 411]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [206, 217]}, {"entity": "IFN-alpha", "entity_type": "protein", "pos": [128, 137]}, {"entity": "IFN-alpha", "entity_type": "protein", "pos": [563, 572]}, {"entity": "c-fos", "entity_type": "DNA", "pos": [40, 45]}, {"entity": "c-myc", "entity_type": "DNA", "pos": [414, 419]}, {"entity": "c-myc mRNA", "entity_type": "RNA", "pos": [635, 645]}, {"entity": "constitutive mRNA", "entity_type": "RNA", "pos": [365, 382]}, {"entity": "c-fos transcript", "entity_type": "RNA", "pos": [40, 56]}, {"entity": "immature cells", "entity_type": "cell type", "pos": [279, 293]}], "task": "NER"}
{"text": "Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of estrogen receptors in human peripheral monocytes .", "entity": [{"entity": "human peripheral monocytes", "entity_type": "cell type", "pos": [144, 170]}, {"entity": "estrogen receptors", "entity_type": "protein", "pos": [122, 140]}], "task": "NER"}
{"text": "PROBLEM: The clinical significance of the differential expression of estrogen receptor ( ER ) in human monocytes was evaluated.", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [89, 91]}, {"entity": "human monocytes", "entity_type": "cell type", "pos": [97, 112]}, {"entity": "estrogen receptor", "entity_type": "protein", "pos": [69, 86]}], "task": "NER"}
{"text": "METHOD: Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy .", "entity": [], "task": "NER"}
{"text": "In addition, the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine.", "entity": [], "task": "NER"}
{"text": "RESULTS: During menopause there is a significant decrease in the percentage of ER positive monocytes , and an increase in blood monocyte number , which declines following estrogen replacement therapy to values of the young.", "entity": [{"entity": "monocyte", "entity_type": "cell type", "pos": [91, 99]}, {"entity": "blood monocyte", "entity_type": "cell type", "pos": [122, 136]}, {"entity": "ER", "entity_type": "protein", "pos": [79, 81]}, {"entity": "ER positive monocytes", "entity_type": "cell type", "pos": [79, 100]}], "task": "NER"}
{"text": "CONCLUSIONS: These findings suggest that estrogen modulates the monocyte numbers and its effects may be mediated through the ER in the monocytes .", "entity": [{"entity": "monocyte", "entity_type": "cell type", "pos": [64, 72]}, {"entity": "monocytes", "entity_type": "cell type", "pos": [135, 144]}, {"entity": "ER", "entity_type": "protein", "pos": [125, 127]}], "task": "NER"}
{"text": "Staphylococcal enterotoxins modulate interleukin 2 receptor expression and ligand-induced tyrosine phosphorylation of the Janus protein- tyrosine kinase 3 ( Jak3 ) and signal transducers and activators of transcription ( Stat proteins ).", "entity": [{"entity": "Jak3", "entity_type": "protein", "pos": [157, 161]}, {"entity": "Janus protein- tyrosine kinase 3", "entity_type": "protein", "pos": [122, 154]}, {"entity": "signal transducers and activators of transcription", "entity_type": "protein", "pos": [168, 218]}, {"entity": "Stat proteins", "entity_type": "protein", "pos": [221, 234]}, {"entity": "interleukin 2 receptor", "entity_type": "protein", "pos": [37, 59]}, {"entity": "Staphylococcal enterotoxins", "entity_type": "protein", "pos": [0, 27]}], "task": "NER"}
{"text": "Staphylococcal enterotoxins ( SE ) stimulate T cells expressing the appropriate variable region beta chain of ( V beta ) T-cell receptors and have been implicated in the pathogenesis of several autoimmune diseases .", "entity": [{"entity": "variable region beta chain", "entity_type": "protein", "pos": [80, 106]}, {"entity": "Staphylococcal enterotoxins", "entity_type": "protein", "pos": [0, 27]}, {"entity": "V beta", "entity_type": "protein", "pos": [112, 118]}, {"entity": "variable region beta chain of ( V beta ) T-cell receptors", "entity_type": "protein", "pos": [80, 137]}, {"entity": "T cells", "entity_type": "cell type", "pos": [45, 52]}, {"entity": "SE", "entity_type": "protein", "pos": [30, 32]}], "task": "NER"}
{"text": "Depending on costimulatory signals , SE induce either proliferation or anergy in T cells .", "entity": [{"entity": "SE", "entity_type": "protein", "pos": [37, 39]}, {"entity": "T cells", "entity_type": "cell type", "pos": [81, 88]}], "task": "NER"}
{"text": "In addition, SE can induce an interleukin-2 ( IL-2 ) nonresponsive state and apoptosis .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [46, 50]}, {"entity": "SE", "entity_type": "protein", "pos": [13, 15]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [30, 43]}], "task": "NER"}
{"text": "Here, we show that SE induce dynamic changes in the expression of and signal transduction through the IL-2 receptor (IL-2R) beta and gamma chains ( IL-2R beta and IL-2R gamma ) in human antigen-specific CD4+ T-cell lines .", "entity": [{"entity": "human antigen-specific CD4+ T-cell lines", "entity_type": "cell line", "pos": [180, 220]}, {"entity": "IL-2R gamma", "entity_type": "protein", "pos": [163, 174]}, {"entity": "SE", "entity_type": "protein", "pos": [19, 21]}, {"entity": "IL-2R beta", "entity_type": "protein", "pos": [148, 158]}], "task": "NER"}
{"text": "Thus, after 4 hr of exposure to SEA and SEB , the expression of IL-2R beta was down-regulated, IL-2R gamma was slightly up-regulated, while IL-2R alpha remained largely unaffected.", "entity": [{"entity": "IL-2R alpha", "entity_type": "protein", "pos": [140, 151]}, {"entity": "SEA", "entity_type": "protein", "pos": [32, 35]}, {"entity": "IL-2R gamma", "entity_type": "protein", "pos": [95, 106]}, {"entity": "SEB", "entity_type": "protein", "pos": [40, 43]}, {"entity": "IL-2R beta", "entity_type": "protein", "pos": [64, 74]}], "task": "NER"}
{"text": "The changes in the composition of IL-2Rs were accompanied by inhibition of IL-2 -induced tyrosine phosphorylation of the Janus protein- tyrosine kinase 3 ( Jak3 ) and signal transducers and activators of transcription called Stat3 and Stat5 .", "entity": [{"entity": "IL-2Rs", "entity_type": "protein", "pos": [34, 40]}, {"entity": "Jak3", "entity_type": "protein", "pos": [156, 160]}, {"entity": "Stat3", "entity_type": "protein", "pos": [225, 230]}, {"entity": "Stat5", "entity_type": "protein", "pos": [235, 240]}, {"entity": "Janus protein- tyrosine kinase 3", "entity_type": "protein", "pos": [121, 153]}, {"entity": "signal transducers and activators of transcription", "entity_type": "protein", "pos": [167, 217]}, {"entity": "IL-2", "entity_type": "protein", "pos": [34, 38]}], "task": "NER"}
{"text": "In parallel experiments, IL-2 -driven proliferation was inhibited significantly.", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [25, 29]}], "task": "NER"}
{"text": "After 16 hr of exposure to SE , the expression of IL-2R beta remained low, while that of IL2R alpha and IL2R gamma was further up-regulated, and ligand-induced tyrosine phosphorylation of Jak3 and Stat proteins was partly normalized.", "entity": [{"entity": "IL2R alpha", "entity_type": "protein", "pos": [89, 99]}, {"entity": "IL2R gamma", "entity_type": "protein", "pos": [104, 114]}, {"entity": "SE", "entity_type": "protein", "pos": [27, 29]}, {"entity": "Stat proteins", "entity_type": "protein", "pos": [197, 210]}, {"entity": "Jak3", "entity_type": "protein", "pos": [188, 192]}, {"entity": "IL-2R beta", "entity_type": "protein", "pos": [50, 60]}], "task": "NER"}
{"text": "Yet, IL-2 -driven proliferation remained profoundly inhibited, suggesting that signaling events other than Jak3 /Stat activation had also been changed following SE stimulation .", "entity": [{"entity": "/Stat", "entity_type": "protein", "pos": [112, 117]}, {"entity": "Jak3", "entity_type": "protein", "pos": [107, 111]}, {"entity": "SE", "entity_type": "protein", "pos": [161, 163]}, {"entity": "IL-2", "entity_type": "protein", "pos": [5, 9]}], "task": "NER"}
{"text": "In conclusion, our data suggest that SE can modulate IL-2R expression and signal transduction involving the Jak/Stat pathway in CD4+ T-cell lines .", "entity": [{"entity": "Jak/Stat", "entity_type": "protein", "pos": [108, 116]}, {"entity": "CD4+ T-cell lines", "entity_type": "cell line", "pos": [128, 145]}, {"entity": "SE", "entity_type": "protein", "pos": [37, 39]}, {"entity": "IL-2R", "entity_type": "protein", "pos": [53, 58]}], "task": "NER"}
{"text": "Constitutive NF-kappa B activation , enhanced granulopoiesis , and neonatal lethality in I kappa B alpha -deficient mice .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [13, 23]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [89, 104]}], "task": "NER"}
{"text": "Transcription factors belonging to the NF-kappa B family are controlled by inhibitory I kappa B proteins , mainly I kappa B alpha and I kappa B beta .", "entity": [{"entity": "NF-kappa B family", "entity_type": "protein", "pos": [39, 56]}, {"entity": "Transcription factors", "entity_type": "protein", "pos": [0, 21]}, {"entity": "I kappa B beta", "entity_type": "protein", "pos": [134, 148]}, {"entity": "inhibitory I kappa B proteins", "entity_type": "protein", "pos": [75, 104]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [114, 129]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [39, 49]}], "task": "NER"}
{"text": "Apparently normal at birth, I kappa B alpha -/- mice exhibit severe runting, skin defects , and extensive granulopoiesis postnatally, typically dying by 8 days.", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [28, 43]}], "task": "NER"}
{"text": "Hematopoietic tissues from these mice display elevated levels of both nuclear NF-kappa B and mRNAs of some, but not all, genes thought to be regulated by NF-kappa B .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [78, 88]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [154, 164]}, {"entity": "mRNAs", "entity_type": "RNA", "pos": [93, 98]}, {"entity": "nuclear NF-kappa B", "entity_type": "protein", "pos": [70, 88]}], "task": "NER"}
{"text": "NF-kappa B elevation results in these phenotypic abnormalities because mice lacking both I kappa B alpha and the p50 subunit of NF-kappa B show a dramatically delayed onset of abnormalities .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [0, 10]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [128, 138]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [89, 104]}, {"entity": "p50 subunit", "entity_type": "protein", "pos": [113, 124]}], "task": "NER"}
{"text": "In contrast to hematopoietic cells , I kappa B alpha -/- embryonic fibroblasts show minimal constitutive NF-kappa B , as well as normal signal-dependent NF-kappa B activation that is concomitant with I kappa B beta degradation .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [105, 115]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [153, 163]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [37, 52]}, {"entity": "constitutive NF-kappa B", "entity_type": "protein", "pos": [92, 115]}, {"entity": "I kappa B alpha -/- embryonic fibroblasts", "entity_type": "cell line", "pos": [37, 78]}, {"entity": "I kappa B beta", "entity_type": "protein", "pos": [200, 214]}, {"entity": "hematopoietic cells", "entity_type": "cell type", "pos": [15, 34]}], "task": "NER"}
{"text": "Our results indicate that I kappa b beta, but not I kappa B alpha , is required for the signal-dependent activation of NF-kappa B in fibroblasts .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [50, 65]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [119, 129]}, {"entity": "fibroblasts", "entity_type": "cell type", "pos": [133, 144]}], "task": "NER"}
{"text": "However, I kappa B alpha is required for the postinduction repression of NF-kappa B in fibroblasts .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [9, 24]}, {"entity": "fibroblasts", "entity_type": "cell type", "pos": [87, 98]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [73, 83]}], "task": "NER"}
{"text": "These results define distinct roles for the two forms of I kappa B and demonstrate the necessity for stringent control of NF-kappa B .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [122, 132]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [57, 66]}], "task": "NER"}
{"text": "Interleukin-7 can induce the activation of Jak 1 , Jak 3 and STAT 5 proteins in murine T cells .", "entity": [{"entity": "Jak 1", "entity_type": "protein", "pos": [43, 48]}, {"entity": "Interleukin-7", "entity_type": "protein", "pos": [0, 13]}, {"entity": "STAT 5 proteins", "entity_type": "protein", "pos": [61, 76]}, {"entity": "Jak 3", "entity_type": "protein", "pos": [51, 56]}, {"entity": "T cells", "entity_type": "cell type", "pos": [87, 94]}], "task": "NER"}
{"text": "The activation of Janus protein tyrosine kinases ( Jak ) and STAT ( signal transducer and activator of transcription ) proteins has recently been linked to the signal transduction mechanism of several cytokines .", "entity": [{"entity": "STAT ( signal transducer and activator of transcription ) proteins", "entity_type": "protein", "pos": [61, 127]}, {"entity": "cytokines", "entity_type": "protein", "pos": [201, 210]}, {"entity": "Janus protein tyrosine kinases", "entity_type": "protein", "pos": [18, 48]}, {"entity": "STAT", "entity_type": "protein", "pos": [61, 65]}, {"entity": "Jak", "entity_type": "protein", "pos": [51, 54]}, {"entity": "signal transducer and activator of transcription", "entity_type": "protein", "pos": [68, 116]}], "task": "NER"}
{"text": "IL-7 was observed to induce a rapid and dose-dependent tyrosine phosphorylation of Jak 1 and Jak 3 and concomitantly, the tyrosine phosphorylation and DNA binding activity of multiple STAT proteins .", "entity": [{"entity": "Jak 3", "entity_type": "protein", "pos": [93, 98]}, {"entity": "STAT proteins", "entity_type": "protein", "pos": [184, 197]}, {"entity": "Jak 1", "entity_type": "protein", "pos": [83, 88]}, {"entity": "IL-7", "entity_type": "protein", "pos": [0, 4]}], "task": "NER"}
{"text": "The STAT proteins utilized by IL-7 were identical to those induced by IL-2 and could be identified as various STAT 5 isoforms .", "entity": [{"entity": "STAT proteins", "entity_type": "protein", "pos": [4, 17]}, {"entity": "STAT 5 isoforms", "entity_type": "protein", "pos": [110, 125]}, {"entity": "IL-7", "entity_type": "protein", "pos": [30, 34]}, {"entity": "IL-2", "entity_type": "protein", "pos": [70, 74]}], "task": "NER"}
{"text": "Moreover, the induction of both Jak 1 and 3 , and STAT 5 activity strongly correlated with the growth-promoting effects of IL-7 , suggesting that this signal transduction mechanism may play a key role in IL-7 -induced proliferation .", "entity": [{"entity": "IL-7", "entity_type": "protein", "pos": [123, 127]}, {"entity": "STAT 5", "entity_type": "protein", "pos": [50, 56]}, {"entity": "IL-7", "entity_type": "protein", "pos": [204, 208]}], "task": "NER"}
{"text": "Cytokine -modulating activity of tepoxalin , a new potential antirheumatic .", "entity": [{"entity": "Cytokine", "entity_type": "protein", "pos": [0, 8]}], "task": "NER"}
{"text": "Tepoxalin is a new dual cyclooxygenase/5-lipoxygenase anti-inflammatory compound currently under clinical investigation.", "entity": [], "task": "NER"}
{"text": "It has been shown to possess anti-inflammatory activity in a variety of animal models and more recently to inhibit IL-2 induced signal transduction .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [115, 119]}], "task": "NER"}
{"text": "The current study was conducted to evaluate the cytokine modulating activity of tepoxalin and the role of iron in these effects.", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [48, 56]}], "task": "NER"}
{"text": "In human peripheral blood mononuclear cells ( PBMC ) stimulated with OKT3/PMA , tepoxalin inhibited lymphocyte proliferation with an IC50 of 6 microM.", "entity": [{"entity": "human peripheral blood mononuclear cells", "entity_type": "cell type", "pos": [3, 43]}, {"entity": "PBMC", "entity_type": "cell type", "pos": [46, 50]}, {"entity": "lymphocyte", "entity_type": "cell type", "pos": [100, 110]}], "task": "NER"}
{"text": "Additionally, it inhibited the production of LTB4 (IC50 = 0.5 microM) and the cytokines IL-2 , IL-6 and TNF alpha (IC50 = 10-12 microM).", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [88, 92]}, {"entity": "IL-6", "entity_type": "protein", "pos": [95, 99]}, {"entity": "TNF alpha", "entity_type": "protein", "pos": [104, 113]}, {"entity": "LTB4", "entity_type": "protein", "pos": [45, 49]}, {"entity": "cytokines", "entity_type": "protein", "pos": [78, 87]}], "task": "NER"}
{"text": "Cytotoxicity was not demonstrated at these concentrations.", "entity": [], "task": "NER"}
{"text": "Add-back experiments with either cytokines ( IL-2 or IL-6 ), LTB4 or conditioned media failed to restore the proliferative response in the presence of tepoxalin .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [45, 49]}, {"entity": "LTB4", "entity_type": "protein", "pos": [61, 65]}, {"entity": "IL-6", "entity_type": "protein", "pos": [53, 57]}, {"entity": "cytokines", "entity_type": "protein", "pos": [33, 42]}], "task": "NER"}
{"text": "However, the concurrent addition of iron (in the form of ferrous or ferric chloride and other iron salts ) reversed the inhibition of proliferation caused by tepoxalin .", "entity": [], "task": "NER"}
{"text": "Tepoxalin also inhibits the activation of NF kappa B , a transcription factor which acts on several cytokine genes .", "entity": [{"entity": "cytokine genes", "entity_type": "DNA", "pos": [100, 114]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [42, 52]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [57, 77]}], "task": "NER"}
{"text": "Tepoxalin 's effect on NF kappa B is also reversed by the addition of iron salts .", "entity": [{"entity": "NF kappa B", "entity_type": "protein", "pos": [23, 33]}], "task": "NER"}
{"text": "These data suggest that the action of tepoxalin to inhibit proliferation in PBMC may be at least in part due to its ability to reduce the amount of available iron resulting in decreased activation of NF kappa B and subsequent inhibition of cytokine production .", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [240, 248]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [200, 210]}, {"entity": "PBMC", "entity_type": "cell type", "pos": [76, 80]}], "task": "NER"}
{"text": "N- and C-terminal sequences control degradation of MAD3/ I kappa B alpha in response to inducers of NF-kappa B activity .", "entity": [{"entity": "MAD3/ I kappa B alpha", "entity_type": "protein", "pos": [51, 72]}, {"entity": "N- and C-terminal sequences", "entity_type": "protein", "pos": [0, 27]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [57, 72]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [100, 110]}], "task": "NER"}
{"text": "The proteolytic degradation of the inhibitory protein MAD3/ I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [186, 196]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [165, 185]}, {"entity": "MAD3/ I kappa B alpha", "entity_type": "protein", "pos": [54, 75]}, {"entity": "inhibitory protein", "entity_type": "protein", "pos": [35, 53]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [60, 75]}], "task": "NER"}
{"text": "Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity , such as phorbol myristate acetate or lipopolysaccharide .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [220, 230]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [36, 51]}, {"entity": "human I kappa B alpha protein", "entity_type": "protein", "pos": [30, 59]}, {"entity": "mouse 70Z/3 cells", "entity_type": "cell line", "pos": [87, 104]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [165, 180]}], "task": "NER"}
{"text": "In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [227, 242]}, {"entity": "proteasome", "entity_type": "protein", "pos": [48, 58]}, {"entity": "human I kappa B alpha protein", "entity_type": "protein", "pos": [221, 250]}], "task": "NER"}
{"text": "By expressing mutant forms of the human protein in this cell line , we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha .", "entity": [{"entity": "cell line", "entity_type": "cell line", "pos": [56, 65]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [192, 207]}], "task": "NER"}
{"text": "Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation .", "entity": [{"entity": "amino acid 279", "entity_type": "protein", "pos": [87, 101]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [56, 71]}, {"entity": "C terminus", "entity_type": "protein", "pos": [38, 48]}], "task": "NER"}
{"text": "Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein.", "entity": [{"entity": "N terminus", "entity_type": "protein", "pos": [106, 116]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [63, 78]}], "task": "NER"}
{"text": "Microtubules mediate cellular 25-hydroxyvitamin D3 trafficking and the genomic response to 1,25-dihydroxyvitamin D3 in normal human monocytes .", "entity": [{"entity": "Microtubules", "entity_type": "protein", "pos": [0, 12]}, {"entity": "human monocytes", "entity_type": "cell type", "pos": [126, 141]}], "task": "NER"}
{"text": "The genomic actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the intracellular vitamin D receptor ( VDR ).", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [117, 120]}, {"entity": "vitamin D receptor", "entity_type": "protein", "pos": [96, 114]}], "task": "NER"}
{"text": "Although immunocytochemistry has shown that disruption of microtubular assembly prevents nuclear access of the sterol- VDR complex , the role of microtubules in the response to 1,25(OH)2D3 has not been studied in viable cells .", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [119, 122]}, {"entity": "viable cells", "entity_type": "cell type", "pos": [213, 225]}, {"entity": "microtubules", "entity_type": "protein", "pos": [145, 157]}, {"entity": "sterol- VDR complex", "entity_type": "protein", "pos": [111, 130]}], "task": "NER"}
{"text": "Our studies examined this interaction in normal human monocytes .", "entity": [{"entity": "human monocytes", "entity_type": "cell type", "pos": [48, 63]}], "task": "NER"}
{"text": "Monocytes convert 25(OH)D3 to 1,25(OH)2D3 and to 24-hydroxylated metabolites more polar than 1,25(OH)2D3 .", "entity": [], "task": "NER"}
{"text": "Microtubule disruption totally abolished the ability of exogenous 1,25(OH)2D3 to suppress its own synthesis and to induce 24-hydroxylase mRNA and activity, without affecting either total 1,25(OH)2D3 uptake or maximal 1,25(OH)2D3 -VDR binding .", "entity": [{"entity": "24-hydroxylase mRNA", "entity_type": "RNA", "pos": [122, 141]}, {"entity": "-VDR", "entity_type": "protein", "pos": [229, 233]}], "task": "NER"}
{"text": "Thus, intact microtubules are essential for 1,25(OH)2D3 -dependent modulation of gene transcription .", "entity": [{"entity": "microtubules", "entity_type": "protein", "pos": [13, 25]}], "task": "NER"}
{"text": "Interestingly, microtubule disruption also decreased monocyte 1,25(OH)2D3 synthesis , not by decreasing the Vmax of monocyte mitochondrial 1 alpha-hydroxylase but through an increase in the Km for 25(OH)2D3 .", "entity": [{"entity": "monocyte mitochondrial 1 alpha-hydroxylase", "entity_type": "protein", "pos": [116, 158]}, {"entity": "monocyte", "entity_type": "cell type", "pos": [53, 61]}, {"entity": "microtubule", "entity_type": "protein", "pos": [15, 26]}, {"entity": "monocyte", "entity_type": "cell type", "pos": [116, 124]}], "task": "NER"}
{"text": "We examined 25(OH)D3 transport .", "entity": [], "task": "NER"}
{"text": "Microtubule disruption did not affect total cellular 25(OH)D3 uptake but reduced its intracellular trafficking to the mitochondria .", "entity": [], "task": "NER"}
{"text": "Thus, microtubules participate in intracellular 25(OH)D3 transport , and their integrity determines normal 1,25(OH)2D3 synthesis .", "entity": [{"entity": "microtubules", "entity_type": "protein", "pos": [6, 18]}], "task": "NER"}
{"text": "Relationship between Rap1 protein phosphorylation and regulation of Ca2+ transport in platelets : a new approach.", "entity": [{"entity": "platelets", "entity_type": "cell type", "pos": [86, 95]}, {"entity": "Rap1 protein", "entity_type": "protein", "pos": [21, 33]}], "task": "NER"}
{"text": "Although the interrelationship between the two messengers Ca2+ and cyclic AMP in platelet function is well documented, its mechanism of action still remains to be established.", "entity": [], "task": "NER"}
{"text": "We investigated here the question of the regulation of platelet Ca(2+)-ATPases by cyclic AMP through the phosphorylation of the Rap1 protein using a pathological model .", "entity": [{"entity": "Rap1 protein", "entity_type": "protein", "pos": [128, 140]}, {"entity": "platelet Ca(2+)-ATPases", "entity_type": "protein", "pos": [55, 78]}], "task": "NER"}
{"text": "We first found experimental conditions where Ca(2+)-transport by platelet membrane vesicles appeared to be dependent on the phosphorylation of the Rap1 protein .", "entity": [{"entity": "Rap1 protein", "entity_type": "protein", "pos": [147, 159]}], "task": "NER"}
{"text": "Then, we studied platelets of patients with congestive heart failure for their expression of the potential 97 kDa Ca(2+)-ATPase target of regulation through the Rap1 protein as well as the phosphorylation of the Rap1 protein using the catalytic subunit of the cyclic AMP -dependent protein kinase ( C. Sub. ).", "entity": [{"entity": "C. Sub.", "entity_type": "protein", "pos": [299, 306]}, {"entity": "cyclic AMP -dependent protein kinase", "entity_type": "protein", "pos": [260, 296]}, {"entity": "97 kDa Ca(2+)-ATPase target", "entity_type": "protein", "pos": [107, 134]}, {"entity": "Ca(2+)-ATPase", "entity_type": "protein", "pos": [114, 127]}, {"entity": "Rap1 protein", "entity_type": "protein", "pos": [161, 173]}, {"entity": "Rap1 protein", "entity_type": "protein", "pos": [212, 224]}, {"entity": "catalytic subunit", "entity_type": "protein", "pos": [235, 252]}, {"entity": "platelets", "entity_type": "cell type", "pos": [17, 26]}], "task": "NER"}
{"text": "In the first patients studied, we found no significant modification in the expression of the 97 kDa Ca(2+)-ATPase by Western blotting using the PL/IM 430 monoclonal antibody which specifically recognized this isoform.", "entity": [{"entity": "97 kDa Ca(2+)-ATPase", "entity_type": "protein", "pos": [93, 113]}, {"entity": "PL/IM 430 monoclonal antibody", "entity_type": "protein", "pos": [144, 173]}], "task": "NER"}
{"text": "In contrast, the Rap1 protein was differentially phosphorylated when using 15 micrograms/ml of the C. Sub.", "entity": [{"entity": "Rap1 protein", "entity_type": "protein", "pos": [17, 29]}, {"entity": "C. Sub.", "entity_type": "protein", "pos": [99, 106]}], "task": "NER"}
{"text": "These results allowed us to use these pathological platelets to study the relationship between the expression of Rap1 protein and the regulation of Ca2+ transport by selecting a patient with severe heart failure .", "entity": [{"entity": "platelets", "entity_type": "cell type", "pos": [51, 60]}, {"entity": "Rap1 protein", "entity_type": "protein", "pos": [113, 125]}], "task": "NER"}
{"text": "We could show a decrease in the expression as well as in the phosphorylation of Rap1 protein and demonstrate a lower effect of C. Sub. on Ca2+ transport .", "entity": [{"entity": "Rap1 protein", "entity_type": "protein", "pos": [80, 92]}, {"entity": "C. Sub.", "entity_type": "protein", "pos": [127, 134]}], "task": "NER"}
{"text": "Finally, by studying a further series of patients , we could confirm that the decrease in Rap1 protein expression in heart failure, whatever its extent, was variable, and could strictly correlate the expression of Rap1 protein with the stimulatory effect of C. Sub. on Ca2+ transport .", "entity": [{"entity": "Rap1 protein", "entity_type": "protein", "pos": [90, 102]}, {"entity": "C. Sub.", "entity_type": "protein", "pos": [258, 265]}, {"entity": "Rap1 protein", "entity_type": "protein", "pos": [214, 226]}], "task": "NER"}
{"text": "Besides the evidence for regulation of the expression of the Rap1 protein in platelets from patients with heart failure , these findings constitute a new approach in favour of the regulation of platelet Ca2+ transport through the phosphorylation of the Rap1 protein .", "entity": [{"entity": "platelets", "entity_type": "cell type", "pos": [77, 86]}, {"entity": "Rap1 protein", "entity_type": "protein", "pos": [61, 73]}, {"entity": "Rap1 protein", "entity_type": "protein", "pos": [253, 265]}], "task": "NER"}
{"text": "An IRF-1 -dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes .", "entity": [{"entity": "mitogen-activated T lymphocytes", "entity_type": "cell line", "pos": [63, 94]}, {"entity": "IRF-1", "entity_type": "protein", "pos": [3, 8]}], "task": "NER"}
{"text": "Lymphocytes are particularly susceptible to DNA damage-induced apoptosis , a response which may serve as a form of ' altruistic suicide ' to counter their intrinsic high potential for mutation and clonal expansion .", "entity": [{"entity": "Lymphocytes", "entity_type": "cell line", "pos": [0, 11]}], "task": "NER"}
{"text": "The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes , but an as yet unknown, p53 -independent pathway (s) appears to mediate the same event in mitogen-activated mature T lymphocytes .", "entity": [{"entity": "thymocytes", "entity_type": "cell type", "pos": [79, 89]}, {"entity": "p53", "entity_type": "protein", "pos": [22, 25]}, {"entity": "mitogen-activated mature T lymphocytes", "entity_type": "cell line", "pos": [181, 219]}, {"entity": "tumour suppressor p53", "entity_type": "protein", "pos": [4, 25]}], "task": "NER"}
{"text": "Here we show DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor (IRF)-1 .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [51, 64]}, {"entity": "antioncogenic transcription factor interferon regulatory factor", "entity_type": "protein", "pos": [85, 148]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [99, 119]}, {"entity": "(IRF)-1", "entity_type": "protein", "pos": [149, 156]}], "task": "NER"}
{"text": "Thus two different anti-onco-genic transcription factors , p53 and IRF-1 , are required for distinct apoptotic pathways in T lymphocytes .", "entity": [{"entity": "IRF-1", "entity_type": "protein", "pos": [67, 72]}, {"entity": "p53", "entity_type": "protein", "pos": [59, 62]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [123, 136]}, {"entity": "anti-onco-genic transcription factors", "entity_type": "protein", "pos": [19, 56]}], "task": "NER"}
{"text": "We also show that mitogen induction of the interleukin-1 beta converting enzyme ( ICE ) gene , a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3 , is IRF-1 -dependent .", "entity": [{"entity": "ICE", "entity_type": "protein", "pos": [82, 85]}, {"entity": "interleukin-1 beta converting enzyme", "entity_type": "protein", "pos": [43, 79]}, {"entity": "interleukin-1 beta converting enzyme ( ICE ) gene", "entity_type": "DNA", "pos": [43, 92]}, {"entity": "ced-3", "entity_type": "DNA", "pos": [163, 168]}, {"entity": "mammalian homologue", "entity_type": "protein", "pos": [97, 116]}, {"entity": "Caenorhabditis elegans cell death gene", "entity_type": "DNA", "pos": [124, 162]}, {"entity": "IRF-1", "entity_type": "protein", "pos": [174, 179]}], "task": "NER"}
{"text": "Ectopic overexpression of IRF-1 results in the activation of the endogenous gene for ICE and enhances the sensitivity of cells to radiation-induced apoptosis .", "entity": [{"entity": "endogenous gene", "entity_type": "DNA", "pos": [65, 80]}, {"entity": "ICE", "entity_type": "protein", "pos": [85, 88]}, {"entity": "IRF-1", "entity_type": "protein", "pos": [26, 31]}], "task": "NER"}
{"text": "Circadian rhythm of glucocorticoid receptors in human peripheral leukocytes and their reactivity to glucocorticoids .", "entity": [{"entity": "human peripheral leukocytes", "entity_type": "cell type", "pos": [48, 75]}, {"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [20, 44]}], "task": "NER"}
{"text": "1) There exists a CR of GR in human leukocytes , PMN , and monocytes with the peak values from 0400 to 0800 hr and the trough values between 2300 and 0000 hr.", "entity": [{"entity": "PMN", "entity_type": "cell type", "pos": [49, 52]}, {"entity": "GR", "entity_type": "protein", "pos": [24, 26]}, {"entity": "human leukocytes", "entity_type": "cell type", "pos": [30, 46]}, {"entity": "monocytes", "entity_type": "cell type", "pos": [59, 68]}], "task": "NER"}
{"text": "The difference between them was significant statistically.", "entity": [], "task": "NER"}
{"text": "2) The FI of the chemotactic migration rate of PMN by cortisol also showed diurnal changes which were synchronous with that of GR .", "entity": [{"entity": "PMN", "entity_type": "cell type", "pos": [47, 50]}, {"entity": "GR", "entity_type": "protein", "pos": [127, 129]}], "task": "NER"}
{"text": "This indicates that the CR of GR may be of functional significance.", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [30, 32]}], "task": "NER"}
{"text": "3) In Cushing's syndrome , the CR of GR was normal in spite of the fact that the CR of plasma cortisol was disturbed.", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [37, 39]}], "task": "NER"}
{"text": "This indicates the independency of the CR of GR from that of cortisol .", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [45, 47]}], "task": "NER"}
{"text": "4) In apoplexy caused by brain ischemia , the CR of GR was abolished in patients with basal lesions but preserved when the lesions were located in the cerebral cortex .", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [52, 54]}], "task": "NER"}
{"text": "These results strongly suggest that the main \" circadian pacemaker \" of GR is located in the basal brain , most probably in the suprachiasmatic nuclei as has been suggested for rodents .", "entity": [{"entity": "GR", "entity_type": "protein", "pos": [72, 74]}], "task": "NER"}
{"text": "B-lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus .", "entity": [{"entity": "B-lymphoblastoid cell lines", "entity_type": "cell line", "pos": [0, 27]}], "task": "NER"}
{"text": "On several occasions we have observed retrovirus-like particles ( RVLPs ) by transmission electron microscopy ( EM ) of cultured T cells from a patient with MS .", "entity": [{"entity": "cultured T cells", "entity_type": "cell line", "pos": [120, 136]}], "task": "NER"}
{"text": "Later we established spontaneously formed B-lymphoblastoid cell lines ( LCLs ) from a patient with an MS -like disease and from another patient with MS who had a reactivated Epstein-Barr virus (EBV) infection .", "entity": [{"entity": "B-lymphoblastoid cell lines", "entity_type": "cell line", "pos": [42, 69]}, {"entity": "LCLs", "entity_type": "cell line", "pos": [72, 76]}], "task": "NER"}
{"text": "Both LCLs were found by EM to produce RVLP and EBV particles .", "entity": [{"entity": "LCLs", "entity_type": "cell line", "pos": [5, 9]}], "task": "NER"}
{"text": "Reverse transcriptase (RT) assays were positive in purified viral material from both LCLs .", "entity": [{"entity": "LCLs", "entity_type": "cell line", "pos": [85, 89]}], "task": "NER"}
{"text": "To substantiate these findings we initiated an intensified culturing procedure and were able to establish LCLs from 5 out of 21 consecutive MS patients and 1 out of 13 consecutive healthy controls .", "entity": [{"entity": "LCLs", "entity_type": "cell line", "pos": [106, 110]}], "task": "NER"}
{"text": "All LCLs were found to produce both RVLP and EBV particles by EM .", "entity": [{"entity": "LCLs", "entity_type": "cell line", "pos": [4, 8]}], "task": "NER"}
{"text": "Whether the putative new retrovirus (es) and EBV have any causal relationship to MS is still not known, but the findings support this possibility.", "entity": [], "task": "NER"}
{"text": "Identification of an ionomycin /cyclosporin A -responsive element within the human T cell receptor gamma enhancer .", "entity": [{"entity": "human T cell receptor gamma enhancer", "entity_type": "DNA", "pos": [77, 113]}, {"entity": "ionomycin /cyclosporin A -responsive element", "entity_type": "DNA", "pos": [21, 65]}], "task": "NER"}
{"text": "Activation through the Ca2+ / calcineurin pathway is essential to the transcription of many cytokine genes .", "entity": [{"entity": "calcineurin", "entity_type": "protein", "pos": [30, 41]}, {"entity": "cytokine genes", "entity_type": "DNA", "pos": [92, 106]}], "task": "NER"}
{"text": "The conserved cis-acting sequence , GGAAAA , and transcription factors binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [49, 70]}, {"entity": "conserved cis-acting sequence", "entity_type": "DNA", "pos": [4, 33]}], "task": "NER"}
{"text": "Here we report the identification and importance of the same sequence in a non-cytokine gene , the human T cell receptor gamma ( TCRG ) enhancer .", "entity": [{"entity": "non-cytokine gene", "entity_type": "DNA", "pos": [75, 92]}, {"entity": "human T cell receptor gamma ( TCRG ) enhancer", "entity_type": "DNA", "pos": [99, 144]}, {"entity": "human T cell", "entity_type": "cell type", "pos": [99, 111]}, {"entity": "TCRG", "entity_type": "protein", "pos": [129, 133]}, {"entity": "human T cell receptor gamma", "entity_type": "protein", "pos": [99, 126]}], "task": "NER"}
{"text": "Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin -induced activation of the TCRG enhancer .", "entity": [{"entity": "TCRG enhancer", "entity_type": "DNA", "pos": [165, 178]}], "task": "NER"}
{"text": "Our studies provide an explanation for a previous observation that TCRG mRNA levels , but not mRNA levels for T cell receptor alpha and -beta , are increased by ionomycin treatment .", "entity": [{"entity": "TCRG mRNA", "entity_type": "RNA", "pos": [67, 76]}], "task": "NER"}
{"text": "Coexpression of NF-kappa B /Rel and Sp1 transcription factors in human immunodeficiency virus 1 -induced, dendritic cell-T-cell syncytia .", "entity": [{"entity": "Sp1", "entity_type": "protein", "pos": [36, 39]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [16, 26]}, {"entity": "NF-kappa B /Rel", "entity_type": "protein", "pos": [16, 31]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [40, 61]}], "task": "NER"}
{"text": "Productive infection of T cells with human immunodeficiency virus 1 ( HIV-1 ) typically requires that the T cells be stimulated with antigens or mitogens .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [24, 31]}, {"entity": "T cells", "entity_type": "cell type", "pos": [106, 113]}], "task": "NER"}
{"text": "This requirement has been attributed to the activation of the transcription factor NF-kappa B , which synergizes with the constitutive transcription factor Sp1 to drive the HIV-1 promoter .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [83, 93]}, {"entity": "Sp1", "entity_type": "protein", "pos": [156, 159]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [62, 82]}, {"entity": "HIV-1 promoter", "entity_type": "DNA", "pos": [173, 187]}, {"entity": "constitutive transcription factor", "entity_type": "protein", "pos": [122, 155]}], "task": "NER"}
{"text": "Recently, we have found that vigorous replication of HIV-1 takes place in nonactivated memory T cells after syncytium formation with dendritic cells ( DCs ).", "entity": [{"entity": "dendritic cells", "entity_type": "cell type", "pos": [133, 148]}, {"entity": "memory T cells", "entity_type": "cell type", "pos": [87, 101]}, {"entity": "DCs", "entity_type": "cell type", "pos": [151, 154]}, {"entity": "T cells", "entity_type": "cell type", "pos": [94, 101]}], "task": "NER"}
{"text": "These syncytia lack activated cells as determined by an absence of staining for Ki-67 cell cycle antigen.", "entity": [{"entity": "activated cells", "entity_type": "cell type", "pos": [20, 35]}], "task": "NER"}
{"text": "The expression and activity of NF-kappa B and Sp1 were, therefore, analyzed in isolated T cells and DCs from humans and mice .", "entity": [{"entity": "Sp1", "entity_type": "protein", "pos": [46, 49]}, {"entity": "DCs", "entity_type": "cell type", "pos": [100, 103]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [31, 41]}, {"entity": "T cells", "entity_type": "cell type", "pos": [88, 95]}], "task": "NER"}
{"text": "We have used immunolabeling , Western blot analysis , and electrophoretic mobility shift and supershift assays .", "entity": [], "task": "NER"}
{"text": "T cells lack active NF-kappa B but express Sp1 as expected.", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [20, 30]}, {"entity": "T cells", "entity_type": "cell type", "pos": [0, 7]}, {"entity": "Sp1", "entity_type": "protein", "pos": [43, 46]}], "task": "NER"}
{"text": "DCs express high levels of all known NF-kappa B and Rel proteins , with activity residing primarily within RelB , p50 , and p65 .", "entity": [{"entity": "RelB", "entity_type": "protein", "pos": [107, 111]}, {"entity": "p50", "entity_type": "protein", "pos": [114, 117]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [37, 47]}, {"entity": "p65", "entity_type": "protein", "pos": [124, 127]}, {"entity": "Rel proteins", "entity_type": "protein", "pos": [52, 64]}, {"entity": "DCs", "entity_type": "cell type", "pos": [0, 3]}], "task": "NER"}
{"text": "However, DCs lack Sp1 , which may explain the failure of HIV-1 to replicate in purified DCs .", "entity": [{"entity": "DCs", "entity_type": "cell type", "pos": [9, 12]}, {"entity": "Sp1", "entity_type": "protein", "pos": [18, 21]}, {"entity": "DCs", "entity_type": "cell type", "pos": [88, 91]}], "task": "NER"}
{"text": "Coexpression of NF-kappa B and Sp1 occurs in the heterologous DC-T-cell syncytia that are induced by HIV-1 .", "entity": [{"entity": "heterologous DC-T-cell syncytia", "entity_type": "cell type", "pos": [49, 80]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [16, 26]}, {"entity": "Sp1", "entity_type": "protein", "pos": [31, 34]}], "task": "NER"}
{"text": "Therefore, HIV-1 -induced cell fusion brings together factors that upregulate virus transcription .", "entity": [], "task": "NER"}
{"text": "Since DCs and memory T cells frequently traffic together in situ, these unusual heterologous syncytia could develop in infected individuals and lead to chronic HIV-1 replication without ostensible immune stimulation .", "entity": [{"entity": "DCs", "entity_type": "cell type", "pos": [6, 9]}, {"entity": "heterologous syncytia", "entity_type": "cell type", "pos": [80, 101]}, {"entity": "T cells", "entity_type": "cell type", "pos": [21, 28]}], "task": "NER"}
{"text": "Cupric ion blocks NF kappa B activation through inhibiting the signal-induced phosphorylation of I kappa B alpha .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [97, 112]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [18, 28]}], "task": "NER"}
{"text": "A transcription factor NF kappa B , which regulates expression of various cellular genes involved in immune responses and viral genes including HIV , is sequestered in the cytoplasm as a complex with an inhibitory protein I kappa B .", "entity": [{"entity": "inhibitory protein I kappa B", "entity_type": "protein", "pos": [203, 231]}, {"entity": "viral genes", "entity_type": "DNA", "pos": [122, 133]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [23, 33]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [2, 22]}], "task": "NER"}
{"text": "Various extracellular signals induce phosphorylation and rapid degradation of I kappa B alpha to release NF kappa B .", "entity": [{"entity": "NF kappa B", "entity_type": "protein", "pos": [105, 115]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [78, 93]}], "task": "NER"}
{"text": "Cu2+ was found to inhibit the activation of NF kappa B induced by TNF-alpha , TPA , or H2O2 .", "entity": [{"entity": "NF kappa B", "entity_type": "protein", "pos": [44, 54]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [66, 75]}], "task": "NER"}
{"text": "Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by TNF-alpha in the presence of Cu2+ resulted in the release of NF kappa B from I kappa B alpha , indicating that Cu2+ interferes with the dissociation of the NF kappa B -I kappa B complex .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [161, 176]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [145, 155]}, {"entity": "NF kappa B -I kappa B complex", "entity_type": "protein", "pos": [240, 269]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [84, 93]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [240, 250]}], "task": "NER"}
{"text": "Neither phosphorylation nor degradation of I kappa B alpha was observed upon TNF-alpha stimulation in the presence of Cu2+ .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [43, 58]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [77, 86]}], "task": "NER"}
{"text": "These results indicate that Cu2+ inhibits the release of NF kappa B by blockade of a signal leading to the phosphorylation of I kappa B alpha .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [126, 141]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [57, 67]}], "task": "NER"}
{"text": "Cloning a cDNA from human NK/ T cells which codes for a protein with high proline content .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [30, 37]}, {"entity": "cDNA", "entity_type": "DNA", "pos": [10, 14]}, {"entity": "NK/ T cells", "entity_type": "cell type", "pos": [26, 37]}], "task": "NER"}
{"text": "A cDNA clone , B4-2 , was isolated from a natural killer (NK) minus T cell subtractive library .", "entity": [{"entity": "natural killer (NK) minus T cell subtractive library", "entity_type": "DNA", "pos": [42, 94]}, {"entity": "cDNA clone", "entity_type": "DNA", "pos": [2, 12]}, {"entity": "B4-2", "entity_type": "DNA", "pos": [15, 19]}], "task": "NER"}
{"text": "The B4-2 clone coded for an mRNA of 2061 bp in length.", "entity": [{"entity": "mRNA", "entity_type": "RNA", "pos": [28, 32]}, {"entity": "B4-2", "entity_type": "DNA", "pos": [4, 8]}], "task": "NER"}
{"text": "It encodes a deduced 327 aa protein with a calculated molecular mass of 35.2 kDa.", "entity": [{"entity": "327 aa protein", "entity_type": "protein", "pos": [21, 35]}], "task": "NER"}
{"text": "Searching of B4-2 DNA and protein sequences against various databases revealed no high homology to other sequences.", "entity": [{"entity": "B4-2", "entity_type": "DNA", "pos": [13, 17]}, {"entity": "B4-2 DNA", "entity_type": "DNA", "pos": [13, 21]}], "task": "NER"}
{"text": "However, B4-2 has an unusually high proline content (13%), contains a putative nuclear targeting sequence , and has several SPXX motifs which are frequently found in gene regulatory proteins .", "entity": [{"entity": "SPXX motifs", "entity_type": "protein", "pos": [124, 135]}, {"entity": "nuclear targeting sequence", "entity_type": "protein", "pos": [79, 105]}, {"entity": "gene regulatory proteins", "entity_type": "protein", "pos": [166, 190]}, {"entity": "B4-2", "entity_type": "DNA", "pos": [9, 13]}], "task": "NER"}
{"text": "One of the stretches of prolines in B4-2 closely resembles the ligand for proteins with SH3 domains .", "entity": [{"entity": "B4-2", "entity_type": "DNA", "pos": [36, 40]}, {"entity": "SH3 domains", "entity_type": "protein", "pos": [88, 99]}], "task": "NER"}
{"text": "Northern hybridization data showed that B4-2 is not a lymphoid specific gene and is expressed in a hepatoma cell line and also weakly transcribed or absent in a variety of other cells.", "entity": [{"entity": "B4-2", "entity_type": "DNA", "pos": [40, 44]}, {"entity": "lymphoid specific gene", "entity_type": "DNA", "pos": [54, 76]}, {"entity": "hepatoma cell line", "entity_type": "cell line", "pos": [99, 117]}], "task": "NER"}
{"text": "A polyclonal antiserum raised against recombinant B4-2 recognizes a 32-34 kDa protein in lymphocytes .", "entity": [{"entity": "32-34 kDa protein", "entity_type": "protein", "pos": [68, 85]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [89, 100]}, {"entity": "B4-2", "entity_type": "DNA", "pos": [50, 54]}, {"entity": "recombinant B4-2", "entity_type": "protein", "pos": [38, 54]}], "task": "NER"}
{"text": "Activation of JAK3 , but not JAK1 , is critical for IL-2 -induced proliferation and STAT5 recruitment by a COOH-terminal region of the IL-2 receptor beta-chain .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [52, 56]}, {"entity": "JAK1", "entity_type": "protein", "pos": [29, 33]}, {"entity": "JAK3", "entity_type": "protein", "pos": [14, 18]}, {"entity": "STAT5", "entity_type": "protein", "pos": [84, 89]}, {"entity": "IL-2 receptor beta-chain", "entity_type": "protein", "pos": [135, 159]}, {"entity": "COOH-terminal region", "entity_type": "protein", "pos": [107, 127]}], "task": "NER"}
{"text": "A number of cytokines and growth factors use the JAK -STAT pathway to signal from the cell membrane to the nucleus .", "entity": [{"entity": "growth factors", "entity_type": "protein", "pos": [26, 40]}, {"entity": "-STAT", "entity_type": "protein", "pos": [53, 58]}, {"entity": "JAK", "entity_type": "protein", "pos": [49, 52]}, {"entity": "cytokines", "entity_type": "protein", "pos": [12, 21]}], "task": "NER"}
{"text": "While homodimerizing cytokine receptors may transmit signal via a single form of JAK (i.e. growth hormone receptors ), several multicomponent cytokine receptors have been shown to require simultaneous activation of pairs of different JAK kinases (i.e. interferon receptors ).", "entity": [{"entity": "JAK kinases", "entity_type": "protein", "pos": [234, 245]}, {"entity": "JAK", "entity_type": "protein", "pos": [81, 84]}, {"entity": "multicomponent cytokine receptors", "entity_type": "protein", "pos": [127, 160]}, {"entity": "interferon receptors", "entity_type": "protein", "pos": [252, 272]}, {"entity": "homodimerizing cytokine receptors", "entity_type": "protein", "pos": [6, 39]}, {"entity": "growth hormone receptors", "entity_type": "protein", "pos": [91, 115]}], "task": "NER"}
{"text": "Recent evidence for a preferential coupling of JAK3 to interleukin-2 receptor-gamma ( IL-2R gamma ) and JAK1 to IL-2R beta supports the concept of heterotrans-activation of JAK1 and JAK3 caused by IL-2 -induced heterodimerization of their receptor partners .", "entity": [{"entity": "IL-2R beta", "entity_type": "protein", "pos": [112, 122]}, {"entity": "IL-2R gamma", "entity_type": "protein", "pos": [86, 97]}, {"entity": "JAK3", "entity_type": "protein", "pos": [47, 51]}, {"entity": "JAK1", "entity_type": "protein", "pos": [104, 108]}, {"entity": "interleukin-2 receptor-gamma", "entity_type": "protein", "pos": [55, 83]}, {"entity": "IL-2", "entity_type": "protein", "pos": [86, 90]}, {"entity": "JAK1", "entity_type": "protein", "pos": [173, 177]}, {"entity": "JAK3", "entity_type": "protein", "pos": [182, 186]}], "task": "NER"}
{"text": "The present study verified the ability of IL-2 to cause tyrosine phosphorylation and activation of JAK1 and JAK3 , but demonstrated that IL-2 stimulated JAK3 to a significantly larger extent than JAK1 in human T lymphocytes and the YT cell line .", "entity": [{"entity": "JAK3", "entity_type": "protein", "pos": [108, 112]}, {"entity": "JAK3", "entity_type": "protein", "pos": [153, 157]}, {"entity": "JAK1", "entity_type": "protein", "pos": [99, 103]}, {"entity": "IL-2", "entity_type": "protein", "pos": [42, 46]}, {"entity": "IL-2", "entity_type": "protein", "pos": [137, 141]}, {"entity": "human T lymphocytes", "entity_type": "cell type", "pos": [204, 223]}, {"entity": "JAK1", "entity_type": "protein", "pos": [196, 200]}, {"entity": "YT cell line", "entity_type": "cell line", "pos": [232, 244]}], "task": "NER"}
{"text": "This conclusion was based upon several independent criteria, including more vigorous tyrosine phosphorylation of JAK3 , more marked enzymatic activation of JAK3 as well as higher abundance of JAK3 in activated IL-2 receptor complexes .", "entity": [{"entity": "IL-2 receptor complexes", "entity_type": "protein", "pos": [210, 233]}, {"entity": "JAK3", "entity_type": "protein", "pos": [113, 117]}, {"entity": "JAK3", "entity_type": "protein", "pos": [156, 160]}, {"entity": "JAK3", "entity_type": "protein", "pos": [192, 196]}], "task": "NER"}
{"text": "Furthermore, when human IL-2R beta was stably expressed in murine BA/F3 cells , robust IL-2 -induced proliferation and JAK3 activation occurred without detectable involvement of either JAK1 , JAK2 or TYK2 .", "entity": [{"entity": "JAK1", "entity_type": "protein", "pos": [185, 189]}, {"entity": "JAK2", "entity_type": "protein", "pos": [192, 196]}, {"entity": "IL-2R", "entity_type": "protein", "pos": [24, 29]}, {"entity": "murine BA/F3 cells", "entity_type": "cell line", "pos": [59, 77]}, {"entity": "IL-2", "entity_type": "protein", "pos": [24, 28]}, {"entity": "JAK3", "entity_type": "protein", "pos": [119, 123]}, {"entity": "TYK2", "entity_type": "protein", "pos": [200, 204]}, {"entity": "human IL-2R beta", "entity_type": "protein", "pos": [18, 34]}], "task": "NER"}
{"text": "We therefore propose that IL-2 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL-2 -induced heterodimerization of IL-2R beta and IL-2R gamma .", "entity": [{"entity": "IL-2R", "entity_type": "protein", "pos": [171, 176]}, {"entity": "IL-2", "entity_type": "protein", "pos": [26, 30]}, {"entity": "IL-2R gamma", "entity_type": "protein", "pos": [186, 197]}, {"entity": "JAK3", "entity_type": "protein", "pos": [120, 124]}, {"entity": "IL-2 receptor", "entity_type": "protein", "pos": [26, 39]}, {"entity": "IL-2", "entity_type": "protein", "pos": [135, 139]}, {"entity": "JAK1", "entity_type": "protein", "pos": [111, 115]}, {"entity": "IL-2R beta", "entity_type": "protein", "pos": [171, 181]}], "task": "NER"}
{"text": "Nonetheless, a membrane-proximal region of human IL-2R beta ( Asn240-Leu335 ) was critical for JAK3 activation, and the amount of JAK3 present in activated IL-2 receptor complexes increased with time, suggesting that stabilization of JAK3 binding to the receptor complex relies on both IL-2R beta and IL-2R gamma .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [49, 53]}, {"entity": "membrane-proximal region", "entity_type": "protein", "pos": [15, 39]}, {"entity": "IL-2R beta", "entity_type": "protein", "pos": [49, 59]}, {"entity": "JAK3", "entity_type": "protein", "pos": [95, 99]}, {"entity": "receptor complex", "entity_type": "protein", "pos": [161, 177]}, {"entity": "Asn240-Leu335", "entity_type": "protein", "pos": [62, 75]}, {"entity": "JAK3", "entity_type": "protein", "pos": [130, 134]}, {"entity": "IL-2 receptor complexes", "entity_type": "protein", "pos": [156, 179]}, {"entity": "IL-2R beta", "entity_type": "protein", "pos": [286, 296]}, {"entity": "IL-2R gamma", "entity_type": "protein", "pos": [301, 312]}, {"entity": "JAK3", "entity_type": "protein", "pos": [234, 238]}], "task": "NER"}
{"text": "Moreover, STAT5 was found to be the predominant STAT transcription factor used by IL-2 in human T cells , and specifically required a COOH-terminal region of IL-2R beta ( Ser386-Val525 ), while STAT5 recruitment was not correlated to activation of IL-2R gamma or JAK3 .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [82, 86]}, {"entity": "T cells", "entity_type": "cell type", "pos": [96, 103]}, {"entity": "COOH-terminal region", "entity_type": "protein", "pos": [134, 154]}, {"entity": "human T cells", "entity_type": "cell type", "pos": [90, 103]}, {"entity": "Ser386-Val525", "entity_type": "protein", "pos": [171, 184]}, {"entity": "JAK3", "entity_type": "protein", "pos": [263, 267]}, {"entity": "STAT transcription factor", "entity_type": "protein", "pos": [48, 73]}, {"entity": "STAT5", "entity_type": "protein", "pos": [10, 15]}, {"entity": "STAT5", "entity_type": "protein", "pos": [194, 199]}, {"entity": "IL-2R beta", "entity_type": "protein", "pos": [158, 168]}, {"entity": "IL-2R gamma", "entity_type": "protein", "pos": [248, 259]}], "task": "NER"}
{"text": "Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human T lymphocytes .", "entity": [{"entity": "human T lymphocytes", "entity_type": "cell type", "pos": [110, 129]}], "task": "NER"}
{"text": "Although evidence indicates that dehydroepiandrosterone ( DHEA ) exerts direct physiological effects , its mechanism of action remains unknown.", "entity": [], "task": "NER"}
{"text": "DHEA binding sites were examined using a whole-cell binding assay in a human T lymphoid cell line , PEER , revealing that a single class of high-affinity binding sites for DHEA (dissociation constant = 7.4 +/- 0.53 nmol/L, mean +/- SE, n = 4) was greatly increased when treated with DHEA , phorbol-12-myristate-13-acetate , and the Ca2+ ionophore A23187.", "entity": [{"entity": "human T lymphoid cell line", "entity_type": "cell line", "pos": [71, 97]}, {"entity": "PEER", "entity_type": "cell line", "pos": [100, 104]}], "task": "NER"}
{"text": "Bound [3H] DHEA was displaced sensitively by DHEA and secondarily by dihydrotestosterone , but not effectively by other steroids , including DHEA sulfate .", "entity": [], "task": "NER"}
{"text": "These results not only indicate the existence of a DHEA receptor , but also suggest that T cells become susceptible to regulation by DHEA during the process of signal-induced activation .", "entity": [{"entity": "DHEA receptor", "entity_type": "protein", "pos": [51, 64]}, {"entity": "T cells", "entity_type": "cell type", "pos": [89, 96]}], "task": "NER"}
{"text": "Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105 .", "entity": [{"entity": "transcriptional activator precursor", "entity_type": "protein", "pos": [44, 79]}, {"entity": "p105", "entity_type": "protein", "pos": [80, 84]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [33, 43]}], "task": "NER"}
{"text": "Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein , E2 , and a novel ubiquitin-protein ligase , E3 , involved in conjugation.", "entity": [{"entity": "ubiquitin-carrier protein", "entity_type": "protein", "pos": [63, 88]}, {"entity": "E2", "entity_type": "protein", "pos": [91, 93]}, {"entity": "ubiquitin-protein ligase", "entity_type": "protein", "pos": [108, 132]}, {"entity": "E3", "entity_type": "protein", "pos": [135, 137]}], "task": "NER"}
{"text": "In most cases, the transcriptional factor NF-kappa B is a heterodimer consisting of two subunits, p50 and p65 , which are encoded by two distinct genes of the Rel family .", "entity": [{"entity": "heterodimer", "entity_type": "protein", "pos": [58, 69]}, {"entity": "p65", "entity_type": "protein", "pos": [106, 109]}, {"entity": "Rel family", "entity_type": "DNA", "pos": [159, 169]}, {"entity": "p50", "entity_type": "protein", "pos": [98, 101]}, {"entity": "transcriptional factor", "entity_type": "protein", "pos": [19, 41]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [42, 52]}], "task": "NER"}
{"text": "p50 is translated as a precursor of 105 kDa .", "entity": [{"entity": "105 kDa", "entity_type": "protein", "pos": [36, 43]}, {"entity": "p50", "entity_type": "protein", "pos": [0, 3]}], "task": "NER"}
{"text": "The C-terminal domain of the precursor is rapidly degraded, forming the mature p50 subunit consisted of the N-terminal region of the molecule.", "entity": [{"entity": "mature p50 subunit", "entity_type": "protein", "pos": [72, 90]}, {"entity": "N-terminal region", "entity_type": "protein", "pos": [108, 125]}, {"entity": "C-terminal domain", "entity_type": "protein", "pos": [4, 21]}], "task": "NER"}
{"text": "The mechanism of generation of p50 is not known.", "entity": [{"entity": "p50", "entity_type": "protein", "pos": [31, 34]}], "task": "NER"}
{"text": "It has been suggested that the ubiquitin -proteasome system is involved in the process; however, the specific enzymes involved and the mechanism of limited proteolysis , in which half of the molecule is spared, have been obscure.", "entity": [{"entity": "enzymes", "entity_type": "protein", "pos": [110, 117]}, {"entity": "ubiquitin", "entity_type": "protein", "pos": [31, 40]}, {"entity": "-proteasome", "entity_type": "protein", "pos": [41, 52]}], "task": "NER"}
{"text": "Palombella and colleagues (Palombella, V.J., Rando, O.J., Goldberg, A.L., and Maniatis, T.(1994) Cell 78, 773-785) have shown that ubiquitin is required for the processing in a cell-free system of a truncated, artificially constructed, 60-kDa precursor .", "entity": [{"entity": "60-kDa precursor", "entity_type": "protein", "pos": [236, 252]}, {"entity": "ubiquitin", "entity_type": "protein", "pos": [131, 140]}], "task": "NER"}
{"text": "They have also shown that proteasome inhibitors block the processing both in vitro and in vivo.", "entity": [{"entity": "proteasome", "entity_type": "protein", "pos": [26, 36]}], "task": "NER"}
{"text": "In this study, we demonstrate reconstitution of a cell-free processing system and demonstrate directly that: (a) the ubiquitin -proteasome system is involved in processing of the intact p105 precursor, (b) conjugation of ubiquitin to the precursor is an essential intermediate step in the processing, (c) the recently discovered novel species of the ubiquitin -carrier protein , E2-F1 , that is involved in the conjugation and degradation of p53 , is also required for the limited processing of the p105 precursor , and (d) a novel, approximately 320-kDa species of ubiquitin -protein ligase , is involved in the process.", "entity": [{"entity": "ubiquitin", "entity_type": "protein", "pos": [117, 126]}, {"entity": "ubiquitin", "entity_type": "protein", "pos": [221, 230]}, {"entity": "p105 precursor", "entity_type": "protein", "pos": [186, 200]}, {"entity": "ubiquitin", "entity_type": "protein", "pos": [350, 359]}, {"entity": "E2-F1", "entity_type": "protein", "pos": [379, 384]}, {"entity": "-proteasome", "entity_type": "protein", "pos": [127, 138]}, {"entity": "ubiquitin -carrier protein", "entity_type": "protein", "pos": [350, 376]}, {"entity": "p53", "entity_type": "protein", "pos": [442, 445]}, {"entity": "ubiquitin -protein ligase", "entity_type": "protein", "pos": [566, 591]}, {"entity": "320-kDa species", "entity_type": "protein", "pos": [547, 562]}, {"entity": "ubiquitin", "entity_type": "protein", "pos": [566, 575]}, {"entity": "p105", "entity_type": "protein", "pos": [186, 190]}], "task": "NER"}
{"text": "This novel enzyme is distinct from E6-AP , the p53 -conjugating ligase , and from E3 alpha , the \"N-end rule\" ligase .", "entity": [{"entity": "\"N-end rule\" ligase", "entity_type": "protein", "pos": [97, 116]}, {"entity": "E3", "entity_type": "protein", "pos": [82, 84]}, {"entity": "E6-AP", "entity_type": "protein", "pos": [35, 40]}, {"entity": "p53", "entity_type": "protein", "pos": [47, 50]}, {"entity": "E3 alpha", "entity_type": "protein", "pos": [82, 90]}, {"entity": "p53 -conjugating ligase", "entity_type": "protein", "pos": [47, 70]}], "task": "NER"}
{"text": "Flutamide in the treatment of hirsutism : long-term clinical effects , endocrine changes , and androgen receptor behavior .", "entity": [{"entity": "androgen receptor", "entity_type": "protein", "pos": [95, 112]}], "task": "NER"}
{"text": "OBJECTIVE: To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters , as well as on the androgen receptor status, in hirsute women .", "entity": [{"entity": "androgen receptor", "entity_type": "protein", "pos": [145, 162]}], "task": "NER"}
{"text": "DESIGN: Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide , three times per day for 12 months.", "entity": [], "task": "NER"}
{"text": "Barrier or intrauterine contraception was used during the study in sexually active women .", "entity": [], "task": "NER"}
{"text": "Safety parameters were assessed throughout the study.", "entity": [], "task": "NER"}
{"text": "Hirsutism , graded by the modified Ferriman-Gallwey score , and hormonal parameters were evaluated basally and at 4-month intervals during treatment.", "entity": [], "task": "NER"}
{"text": "Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy .", "entity": [], "task": "NER"}
{"text": "In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle , basally and after 4 months of flutamide treatment.", "entity": [{"entity": "androgen receptors", "entity_type": "protein", "pos": [34, 52]}, {"entity": "mononuclear leukocytes", "entity_type": "cell type", "pos": [56, 78]}], "task": "NER"}
{"text": "RESULTS: Flutamide was well tolerated in all women , with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy .", "entity": [{"entity": "therapy", "entity_type": "protein", "pos": [159, 166]}, {"entity": "serum transaminase", "entity_type": "protein", "pos": [122, 140]}], "task": "NER"}
{"text": "Hirsutism markedly improved in all women during the treatment ( Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9).", "entity": [], "task": "NER"}
{"text": "A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH .", "entity": [], "task": "NER"}
{"text": "Cycles remained ovulatory.", "entity": [], "task": "NER"}
{"text": "Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase .", "entity": [{"entity": "androgen receptors", "entity_type": "protein", "pos": [32, 50]}], "task": "NER"}
{"text": "This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug .", "entity": [], "task": "NER"}
{"text": "CONCLUSIONS: Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function .", "entity": [], "task": "NER"}
{"text": "Androgen receptor blockade might be potentiated by a reduction of serum androgens .", "entity": [], "task": "NER"}
{"text": "Flutamide affects androgen receptor behavior during the menstrual cycle .", "entity": [{"entity": "androgen receptor", "entity_type": "protein", "pos": [18, 35]}], "task": "NER"}
{"text": "The meaning of this finding remains to be elucidated .", "entity": [], "task": "NER"}
{"text": "Constitutive expression of HIV-1 tat protein in human Jurkat T cells using a BK virus vector .", "entity": [{"entity": "Jurkat T cells", "entity_type": "cell line", "pos": [54, 68]}, {"entity": "human Jurkat T cells", "entity_type": "cell line", "pos": [48, 68]}, {"entity": "HIV-1 tat protein", "entity_type": "protein", "pos": [27, 44]}], "task": "NER"}
{"text": "The production and characterization of Jurkat cell lines that constitutively express functional human immune deficiency virus type 1 ( HIV-1 ) tat protein , using a BK virus plasmid expression vector and HIV-1 tat cDNA , is described.", "entity": [{"entity": "human immune deficiency virus type 1 ( HIV-1 ) tat protein", "entity_type": "protein", "pos": [96, 154]}, {"entity": "tat protein", "entity_type": "protein", "pos": [143, 154]}, {"entity": "Jurkat cell lines", "entity_type": "cell line", "pos": [39, 56]}, {"entity": "HIV-1 tat cDNA", "entity_type": "DNA", "pos": [204, 218]}], "task": "NER"}
{"text": "An increased growth rate of these Jurkat-tat cell lines as compared with control cell lines was observed.", "entity": [{"entity": "Jurkat-tat cell lines", "entity_type": "cell line", "pos": [34, 55]}, {"entity": "control cell lines", "entity_type": "cell line", "pos": [73, 91]}], "task": "NER"}
{"text": "A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity through its binding to an osteoblast-specific cis-acting element .", "entity": [{"entity": "PEBP2 alpha/AML-1-related factor", "entity_type": "protein", "pos": [2, 34]}, {"entity": "osteocalcin promoter", "entity_type": "DNA", "pos": [45, 65]}, {"entity": "osteoblast-specific cis-acting element", "entity_type": "DNA", "pos": [101, 139]}], "task": "NER"}
{"text": "To identify osteoblast-specific cis-acting elements and trans-acting factors , we initiated an analysis of the promoter of a mouse osteocalcin gene , an osteoblast-specific gene .", "entity": [{"entity": "mouse osteocalcin gene", "entity_type": "DNA", "pos": [125, 147]}, {"entity": "promoter", "entity_type": "DNA", "pos": [111, 119]}, {"entity": "osteoblast-specific cis-acting elements", "entity_type": "DNA", "pos": [12, 51]}, {"entity": "trans-acting factors", "entity_type": "protein", "pos": [56, 76]}, {"entity": "osteoblast-specific gene", "entity_type": "DNA", "pos": [153, 177]}], "task": "NER"}
{"text": "In this promoter, we identified two osteoblast-specific cis-acting elements (Ducy, P.and Karsenty, G.(1995) Mol.Cell.Biol.15, 1858-1869).", "entity": [{"entity": "osteoblast-specific cis-acting elements", "entity_type": "DNA", "pos": [36, 75]}], "task": "NER"}
{"text": "The sequence of one of these elements , OSE2 , is identical to the DNA-binding site of the PEBP2 alpha/AML-1 transcription factors , the mammalian homologues of the Drosophila Runt protein .", "entity": [{"entity": "DNA-binding site", "entity_type": "DNA", "pos": [67, 83]}, {"entity": "mammalian homologues", "entity_type": "protein", "pos": [137, 157]}, {"entity": "OSE2", "entity_type": "DNA", "pos": [40, 44]}, {"entity": "elements", "entity_type": "DNA", "pos": [29, 37]}, {"entity": "Drosophila Runt protein", "entity_type": "protein", "pos": [165, 188]}, {"entity": "PEBP2 alpha/AML-1 transcription factors", "entity_type": "protein", "pos": [91, 130]}], "task": "NER"}
{"text": "Here we show, using nuclear extracts , recombinant protein , and a specific antiserum against AML-1 proteins in DNA-binding assays , that one member of this family, AML-1B , binds specifically to OSE2 and is immunologically related to OSF2 , the factor present in osteoblast nuclear extracts that binds to OSE2 .", "entity": [{"entity": "AML-1B", "entity_type": "protein", "pos": [165, 171]}, {"entity": "OSE2", "entity_type": "DNA", "pos": [196, 200]}, {"entity": "OSE2", "entity_type": "DNA", "pos": [306, 310]}, {"entity": "OSF2", "entity_type": "protein", "pos": [235, 239]}, {"entity": "AML-1 proteins", "entity_type": "protein", "pos": [94, 108]}, {"entity": "recombinant protein", "entity_type": "protein", "pos": [39, 58]}], "task": "NER"}
{"text": "By DNA cotransfection experiments , we also demonstrate that AML-1B can increase the activity of a short osteocalcin promoter through its binding to OSE2 .", "entity": [{"entity": "osteocalcin promoter", "entity_type": "DNA", "pos": [105, 125]}, {"entity": "OSE2", "entity_type": "DNA", "pos": [149, 153]}, {"entity": "AML-1B", "entity_type": "protein", "pos": [61, 67]}], "task": "NER"}
{"text": "Lastly, the different mobilities of osteoblast nuclear extract-DNA complexes compared with T-cell nuclear extract-DNA complexes , along with the inability of OSF2 to be upregulated by retinoic acid , unlike the other PEBP2 alpha factors , suggest that OSF2 is a new member of this family of transcription factors .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [291, 312]}, {"entity": "T-cell nuclear extract-DNA complexes", "entity_type": "protein", "pos": [91, 127]}, {"entity": "OSF2", "entity_type": "protein", "pos": [158, 162]}, {"entity": "osteoblast nuclear extract-DNA complexes", "entity_type": "protein", "pos": [36, 76]}, {"entity": "PEBP2 alpha factors", "entity_type": "protein", "pos": [217, 236]}, {"entity": "OSF2", "entity_type": "protein", "pos": [252, 256]}], "task": "NER"}
{"text": "Thus, this study demonstrates that AML-1B can increase gene expression of an osteoblast-specific gene through its binding to an osteoblast-specific cis-acting element and presents evidence that OSF2 is a member of the PEBP2 alpha/AML-1 family of transcription factors .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [246, 267]}, {"entity": "osteoblast-specific gene", "entity_type": "DNA", "pos": [77, 101]}, {"entity": "PEBP2 alpha/AML-1 family", "entity_type": "protein", "pos": [218, 242]}, {"entity": "osteoblast-specific cis-acting element", "entity_type": "DNA", "pos": [128, 166]}, {"entity": "OSF2", "entity_type": "protein", "pos": [194, 198]}, {"entity": "AML-1B", "entity_type": "protein", "pos": [35, 41]}], "task": "NER"}
{"text": "Initiation binding repressor , a factor that binds to the transcription initiation site of the histone h5 gene , is a glycosylated member of a family of cell growth regulators [corrected] [published erratum appears in Mol Cell Biol 1996 Feb;16(2):735]", "entity": [{"entity": "cell growth regulators", "entity_type": "protein", "pos": [153, 175]}, {"entity": "histone h5 gene", "entity_type": "DNA", "pos": [95, 110]}, {"entity": "transcription initiation site", "entity_type": "DNA", "pos": [58, 87]}, {"entity": "Initiation binding repressor", "entity_type": "protein", "pos": [0, 28]}, {"entity": "glycosylated member", "entity_type": "protein", "pos": [118, 137]}, {"entity": "histone h5", "entity_type": "protein", "pos": [95, 105]}], "task": "NER"}
{"text": "Initiation binding repressor [corrected] ( IBR ) is a chicken erythrocyte factor (apparent molecular mass, 70 to 73 kDa) that binds to the sequences spanning the transcription initiation site of the histone h5 gene , repressing its transcription .", "entity": [{"entity": "chicken erythrocyte factor", "entity_type": "protein", "pos": [54, 80]}, {"entity": "IBR", "entity_type": "protein", "pos": [43, 46]}, {"entity": "Initiation binding repressor", "entity_type": "protein", "pos": [0, 28]}, {"entity": "histone h5 gene", "entity_type": "DNA", "pos": [199, 214]}, {"entity": "histone h5", "entity_type": "protein", "pos": [199, 209]}, {"entity": "transcription initiation site", "entity_type": "DNA", "pos": [162, 191]}], "task": "NER"}
{"text": "A variety of other cells, including transformed erythroid precursors , do not have IBR but a factor referred to as IBF (68 to 70 kDa) that recognizes the same IBR sites.", "entity": [{"entity": "IBR", "entity_type": "protein", "pos": [83, 86]}, {"entity": "transformed erythroid precursors", "entity_type": "cell type", "pos": [36, 68]}, {"entity": "IBF", "entity_type": "protein", "pos": [115, 118]}, {"entity": "IBR", "entity_type": "protein", "pos": [159, 162]}], "task": "NER"}
{"text": "We have cloned the IBR cDNA and studied the relationship of IBR and IBF .", "entity": [{"entity": "IBR", "entity_type": "protein", "pos": [19, 22]}, {"entity": "IBR", "entity_type": "protein", "pos": [60, 63]}, {"entity": "IBR cDNA", "entity_type": "DNA", "pos": [19, 27]}, {"entity": "IBF", "entity_type": "protein", "pos": [68, 71]}], "task": "NER"}
{"text": "IBR is a 503-amino-acid-long acidic protein which is 99.0% identical to the recently reported human NRF-1/alpha-Pal factor and highly related to the invertebrate transcription factors P3A2 and erected wing gene product ( EWG ).", "entity": [{"entity": "IBR", "entity_type": "protein", "pos": [0, 3]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [162, 183]}, {"entity": "erected wing gene product", "entity_type": "protein", "pos": [193, 218]}, {"entity": "human NRF-1/alpha-Pal factor", "entity_type": "protein", "pos": [94, 122]}, {"entity": "EWG", "entity_type": "protein", "pos": [221, 224]}, {"entity": "P3A2", "entity_type": "protein", "pos": [184, 188]}, {"entity": "503-amino-acid-long acidic protein", "entity_type": "protein", "pos": [9, 43]}], "task": "NER"}
{"text": "We present evidence that IBR and IBF are most likely identical proteins, differing in their degree of glycosylation .", "entity": [{"entity": "IBF", "entity_type": "protein", "pos": [33, 36]}, {"entity": "IBR", "entity_type": "protein", "pos": [25, 28]}], "task": "NER"}
{"text": "We have analyzed several molecular aspects of IBR/F and shown that the factor associates as stable homodimers and that the dimer is the relevant DNA-binding species .", "entity": [{"entity": "dimer", "entity_type": "protein", "pos": [103, 108]}, {"entity": "relevant DNA-binding species", "entity_type": "protein", "pos": [136, 164]}, {"entity": "IBR/F", "entity_type": "protein", "pos": [46, 51]}, {"entity": "homodimers", "entity_type": "protein", "pos": [99, 109]}], "task": "NER"}
{"text": "The evolutionarily conserved N-terminal half of IBR/F harbors the DNA-binding/dimerization domain (outer limits, 127 to 283), one or several casein kinase II sites (37 to 67), and a bipartite nuclear localization signal (89 to 106) which appears to be necessary for nuclear targeting .", "entity": [{"entity": "DNA-binding/dimerization domain", "entity_type": "protein", "pos": [66, 97]}, {"entity": "N-terminal half", "entity_type": "protein", "pos": [29, 44]}, {"entity": "IBR/F", "entity_type": "protein", "pos": [48, 53]}, {"entity": "casein kinase II sites", "entity_type": "protein", "pos": [141, 163]}, {"entity": "bipartite nuclear localization signal", "entity_type": "protein", "pos": [182, 219]}], "task": "NER"}
{"text": "Binding site selection revealed that the alternating RCGCRYGCGY consensus constitutes high-affinity IBR/F binding sites and that the direct-repeat palindrome TGCGCATGCGCA is the optimal site .", "entity": [{"entity": "direct-repeat palindrome", "entity_type": "DNA", "pos": [133, 157]}, {"entity": "IBR/F", "entity_type": "protein", "pos": [100, 105]}, {"entity": "IBR/F binding sites", "entity_type": "DNA", "pos": [100, 119]}, {"entity": "optimal site", "entity_type": "DNA", "pos": [178, 190]}, {"entity": "alternating RCGCRYGCGY consensus", "entity_type": "protein", "pos": [41, 73]}], "task": "NER"}
{"text": "A survey of genes potentially regulated by this family of factors primarily revealed genes involved in growth-related metabolism .", "entity": [{"entity": "genes", "entity_type": "DNA", "pos": [12, 17]}, {"entity": "genes", "entity_type": "DNA", "pos": [85, 90]}, {"entity": "factors", "entity_type": "protein", "pos": [58, 65]}], "task": "NER"}
{"text": "Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between interferon regulatory factor-1 , NF kappa B , and Sp1 transcription factors .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [197, 218]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [176, 186]}, {"entity": "Sp1", "entity_type": "protein", "pos": [193, 196]}, {"entity": "interferon regulatory factor-1", "entity_type": "protein", "pos": [143, 173]}], "task": "NER"}
{"text": "We investigated the molecular basis of the synergistic induction by interferon-gamma ( IFN-gamma )/ tumor necrosis factor-alpha ( TNF-alpha ) of human interleukin-6 (IL-6) gene in THP-1 monocytic cells , and compared it with the basis of this induction by lipopolysaccharide ( LPS ).", "entity": [{"entity": "IFN-gamma", "entity_type": "protein", "pos": [87, 96]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [130, 139]}, {"entity": "tumor necrosis factor-alpha", "entity_type": "protein", "pos": [100, 127]}, {"entity": "THP-1 monocytic cells", "entity_type": "cell type", "pos": [180, 201]}, {"entity": "human interleukin-6 (IL-6) gene", "entity_type": "DNA", "pos": [145, 176]}, {"entity": "interferon-gamma", "entity_type": "protein", "pos": [68, 84]}], "task": "NER"}
{"text": "Functional studies with IL-6 promoter demonstrated that three regions are the targets of the IFN-gamma and/or TNF-alpha action, whereas only one of these regions seemed to be implicated in LPS activation .", "entity": [{"entity": "IFN-gamma", "entity_type": "protein", "pos": [93, 102]}, {"entity": "IL-6 promoter", "entity_type": "DNA", "pos": [24, 37]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [110, 119]}], "task": "NER"}
{"text": "The three regions concerned are: 1) a region between -73 and -36, which is the minimal element inducible by LPS or TNF-alpha ; 2) an element located between -181 and -73, which appeared to regulate the response to IFN-gamma and TNF-alpha negatively; and 3) a distal element upstream of -224, which was inducible by IFN-gamma alone.", "entity": [{"entity": "TNF-alpha", "entity_type": "protein", "pos": [115, 124]}, {"entity": "distal element upstream", "entity_type": "DNA", "pos": [259, 282]}, {"entity": "minimal element", "entity_type": "DNA", "pos": [79, 94]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [228, 237]}, {"entity": "IFN-gamma", "entity_type": "protein", "pos": [214, 223]}, {"entity": "IFN-gamma", "entity_type": "protein", "pos": [315, 324]}], "task": "NER"}
{"text": "LPS signaling was found to involve NF kappa B activation by the p50/p65 heterodimers .", "entity": [{"entity": "NF kappa B", "entity_type": "protein", "pos": [35, 45]}, {"entity": "p50/p65 heterodimers", "entity_type": "protein", "pos": [64, 84]}], "task": "NER"}
{"text": "Synergistic induction of the IL-6 gene by IFN-gamma and TNF-alpha , in monocytic cells , involved cooperation between the IRF-1 and NF kappa B p65 homodimers with concomitant removal of the negative effect of the retinoblastoma control element present in the IL-6 promoter .", "entity": [{"entity": "IL-6 gene", "entity_type": "DNA", "pos": [29, 38]}, {"entity": "NF kappa B p65 homodimers", "entity_type": "protein", "pos": [132, 157]}, {"entity": "retinoblastoma control element", "entity_type": "DNA", "pos": [213, 243]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [56, 65]}, {"entity": "IRF-1", "entity_type": "protein", "pos": [122, 127]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [132, 142]}, {"entity": "IFN-gamma", "entity_type": "protein", "pos": [42, 51]}, {"entity": "IL-6", "entity_type": "protein", "pos": [29, 33]}, {"entity": "IL-6 promoter", "entity_type": "DNA", "pos": [259, 272]}, {"entity": "p65", "entity_type": "protein", "pos": [143, 146]}, {"entity": "monocytic cells", "entity_type": "cell type", "pos": [71, 86]}], "task": "NER"}
{"text": "This removal occurred by activation of the constitutive Sp1 factor , whose increased binding activity and phosphorylation were mediated by IFN-gamma .", "entity": [{"entity": "constitutive Sp1 factor", "entity_type": "protein", "pos": [43, 66]}, {"entity": "IFN-gamma", "entity_type": "protein", "pos": [139, 148]}, {"entity": "Sp1", "entity_type": "protein", "pos": [56, 59]}], "task": "NER"}
{"text": "Mutation of Jak3 in a patient with SCID : essential role of Jak3 in lymphoid development .", "entity": [{"entity": "Jak3", "entity_type": "protein", "pos": [12, 16]}, {"entity": "Jak3", "entity_type": "protein", "pos": [60, 64]}], "task": "NER"}
{"text": "Males with X-linked severe combined immunodeficiency ( XSCID ) have defects in the common cytokine receptor gamma chain ( gamma c ) gene that encodes a shared, essential component of the receptors of interleukin-2 ( IL-2 ), IL-4 , IL-7 , IL-9 , and IL-15 .", "entity": [{"entity": "IL-9", "entity_type": "protein", "pos": [238, 242]}, {"entity": "gamma c", "entity_type": "protein", "pos": [108, 115]}, {"entity": "IL-2", "entity_type": "protein", "pos": [216, 220]}, {"entity": "IL-7", "entity_type": "protein", "pos": [231, 235]}, {"entity": "IL-15", "entity_type": "protein", "pos": [249, 254]}, {"entity": "cytokine receptor gamma chain ( gamma c ) gene", "entity_type": "DNA", "pos": [90, 136]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [200, 213]}, {"entity": "cytokine receptor gamma chain", "entity_type": "protein", "pos": [90, 119]}, {"entity": "IL-4", "entity_type": "protein", "pos": [224, 228]}], "task": "NER"}
{"text": "The Janus family tyrosine kinase Jak3 is the only signaling molecule known to be associated with gamma c , so it was hypothesized that defects in Jak3 might cause an XSCID -like phenotype .", "entity": [{"entity": "Janus family tyrosine kinase", "entity_type": "protein", "pos": [4, 32]}, {"entity": "Jak3", "entity_type": "protein", "pos": [33, 37]}, {"entity": "Jak3", "entity_type": "protein", "pos": [146, 150]}, {"entity": "gamma c", "entity_type": "protein", "pos": [97, 104]}], "task": "NER"}
{"text": "A girl with immunological features indistinguishable from those of XSCID was therefore selected for analysis.", "entity": [], "task": "NER"}
{"text": "An Epstein-Barr virus ( EBV )-transformed cell line derived from her lymphocytes had normal gamma c expression but lacked Jak3 protein and had greatly diminished Jak3 messenger RNA .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [69, 80]}, {"entity": "Jak3 messenger RNA", "entity_type": "RNA", "pos": [162, 180]}, {"entity": "gamma c", "entity_type": "protein", "pos": [92, 99]}, {"entity": "Jak3", "entity_type": "protein", "pos": [122, 126]}, {"entity": "Jak3", "entity_type": "protein", "pos": [162, 166]}, {"entity": "Epstein-Barr virus ( EBV )-transformed cell line", "entity_type": "cell line", "pos": [3, 51]}, {"entity": "Jak3 protein", "entity_type": "protein", "pos": [122, 134]}], "task": "NER"}
{"text": "Sequencing revealed a different mutation on each allele: a single nucleotide insertion resulting in a frame shift and premature termination in the Jak3 JH4 domain and a nonsense mutation in the Jak3 JH2 domain .", "entity": [{"entity": "Jak3", "entity_type": "protein", "pos": [147, 151]}, {"entity": "Jak3 JH4 domain", "entity_type": "protein", "pos": [147, 162]}, {"entity": "Jak3", "entity_type": "protein", "pos": [194, 198]}], "task": "NER"}
{"text": "The lack of Jak3 expression correlated with impaired B cell signaling , as demonstrated by the inability of IL-4 to activate Stat6 in the EBV -transformed cell line from the patient. These observations indicate that the functions of gamma c are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling.", "entity": [{"entity": "Jak3", "entity_type": "protein", "pos": [12, 16]}, {"entity": "gamma c", "entity_type": "protein", "pos": [233, 240]}, {"entity": "Jak3", "entity_type": "protein", "pos": [258, 262]}, {"entity": "Stat6", "entity_type": "protein", "pos": [125, 130]}, {"entity": "EBV -transformed cell line", "entity_type": "cell line", "pos": [138, 164]}, {"entity": "Jak3", "entity_type": "protein", "pos": [272, 276]}, {"entity": "IL-4", "entity_type": "protein", "pos": [108, 112]}], "task": "NER"}
{"text": "Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T-cell lymphotropic virus type 1 Tax .", "entity": [{"entity": "L-selectin", "entity_type": "protein", "pos": [35, 45]}, {"entity": "human T-cell lymphotropic virus type 1 Tax", "entity_type": "protein", "pos": [130, 172]}, {"entity": "L-selectin gene", "entity_type": "DNA", "pos": [35, 50]}, {"entity": "leukemic cells", "entity_type": "cell type", "pos": [60, 74]}], "task": "NER"}
{"text": "L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium .", "entity": [{"entity": "L-selectin", "entity_type": "protein", "pos": [0, 10]}], "task": "NER"}
{"text": "Upon cellular activation , expression of the L-selectin gene is downregulated at both the protein and mRNA levels .", "entity": [{"entity": "L-selectin gene", "entity_type": "DNA", "pos": [45, 60]}, {"entity": "L-selectin", "entity_type": "protein", "pos": [45, 55]}], "task": "NER"}
{"text": "To understand the mechanism of leukemic cell infiltration into organs , we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia ( ATL ) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 ( HTLV-1 ) Tax , which is a viral transcriptional transactivator .", "entity": [{"entity": "L-selectin", "entity_type": "protein", "pos": [116, 126]}, {"entity": "L-selectin", "entity_type": "protein", "pos": [235, 245]}, {"entity": "leukemic cell", "entity_type": "cell type", "pos": [31, 44]}, {"entity": "leukemic cells", "entity_type": "cell type", "pos": [141, 155]}, {"entity": "human T-cell lymphotropic virus type 1 ( HTLV-1 ) Tax", "entity_type": "protein", "pos": [258, 311]}, {"entity": "viral transcriptional transactivator", "entity_type": "protein", "pos": [325, 361]}, {"entity": "L-selectin promoter", "entity_type": "DNA", "pos": [235, 254]}, {"entity": "L-selectin mRNA", "entity_type": "RNA", "pos": [116, 131]}], "task": "NER"}
{"text": "Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens .", "entity": [{"entity": "L-selectin", "entity_type": "protein", "pos": [27, 37]}, {"entity": "activation antigens", "entity_type": "protein", "pos": [88, 107]}, {"entity": "ATL cells", "entity_type": "cell line", "pos": [61, 70]}], "task": "NER"}
{"text": "Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation .", "entity": [{"entity": "ATL cells", "entity_type": "cell line", "pos": [35, 44]}, {"entity": "L-selectin", "entity_type": "protein", "pos": [64, 74]}, {"entity": "L-selectin mRNA", "entity_type": "RNA", "pos": [64, 79]}], "task": "NER"}
{"text": "Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients .", "entity": [{"entity": "L-selectin mRNA", "entity_type": "RNA", "pos": [61, 76]}, {"entity": "leukemic cells", "entity_type": "cell type", "pos": [97, 111]}, {"entity": "L-selectin", "entity_type": "protein", "pos": [61, 71]}], "task": "NER"}
{"text": "Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration .", "entity": [{"entity": "rat T-cell line", "entity_type": "cell line", "pos": [27, 42]}, {"entity": "L-selectin", "entity_type": "protein", "pos": [62, 72]}], "task": "NER"}
{"text": "The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level .", "entity": [{"entity": "Tax", "entity_type": "protein", "pos": [17, 20]}, {"entity": "mRNA", "entity_type": "RNA", "pos": [90, 94]}, {"entity": "JPX9 cells", "entity_type": "cell line", "pos": [35, 45]}], "task": "NER"}
{"text": "Chloramphenicol acetyltransferase ( CAT ) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax .", "entity": [{"entity": "L-selectin promoter", "entity_type": "DNA", "pos": [126, 145]}, {"entity": "Tax", "entity_type": "protein", "pos": [149, 152]}, {"entity": "Chloramphenicol acetyltransferase", "entity_type": "protein", "pos": [0, 33]}, {"entity": "CAT", "entity_type": "protein", "pos": [36, 39]}], "task": "NER"}
{"text": "The serum level of the shed form of L-selectin was significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111 ng/mL) compared with those of asymptomatic carriers and healthy blood donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL, respectively).", "entity": [{"entity": "L-selectin", "entity_type": "protein", "pos": [36, 46]}], "task": "NER"}
{"text": "These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax .", "entity": [{"entity": "Tax", "entity_type": "protein", "pos": [123, 126]}, {"entity": "ATL cells", "entity_type": "cell line", "pos": [29, 38]}, {"entity": "L-selectin", "entity_type": "protein", "pos": [70, 80]}, {"entity": "L-selectin gene", "entity_type": "DNA", "pos": [70, 85]}], "task": "NER"}
{"text": "The overexpression of L-selectin , as well as of inflammatory cytokines , by ATL cells may provide a basis for ATL cells to attach the vascular endothelium , leading to transmigration and organ infitration .", "entity": [{"entity": "ATL cells", "entity_type": "cell line", "pos": [77, 86]}, {"entity": "L-selectin", "entity_type": "protein", "pos": [22, 32]}, {"entity": "ATL cells", "entity_type": "cell line", "pos": [111, 120]}, {"entity": "inflammatory cytokines", "entity_type": "protein", "pos": [49, 71]}], "task": "NER"}
{"text": "Human herpesvirus 6 variant A , but not variant B , infects EBV -positive B lymphoid cells , activating the latent EBV genome through a BZLF-1 -dependent mechanism .", "entity": [{"entity": "latent EBV genome", "entity_type": "DNA", "pos": [108, 125]}, {"entity": "BZLF-1", "entity_type": "protein", "pos": [136, 142]}, {"entity": "EBV -positive B lymphoid cells", "entity_type": "cell line", "pos": [60, 90]}], "task": "NER"}
{"text": "Human herpesvirus 6 , a predominantly T lymphotropic virus , has been recently shown to infect some EBV -positive B cell lines , and to induce in them the activation of the EBV lytic cycle .", "entity": [{"entity": "EBV -positive B cell lines", "entity_type": "cell line", "pos": [100, 126]}], "task": "NER"}
{"text": "Here we have confirmed and extended such observations, showing that (1) this phenomenon is restricted to the variant A of HHV-6 : in fact two isolates belonging to the HHV-6 variant B ( BA92 and Z29 ) were neither able to infect any B cell line , independently of the EBV status , nor to induce the EBV genome expression .", "entity": [{"entity": "B cell line", "entity_type": "cell line", "pos": [233, 244]}], "task": "NER"}
{"text": "The only exception is represented by the P3HR1 cells , in which, however, the infection by the variant B does not determine induction of EBV antigens ; (2) the presence of the EBV genome contributes to the susceptibility of the B cell lines to HHV-6 infection , increasing the binding sites and the percentage of infectable cells , as detected by immunoelectron microscopy ; and (3) HHV-6 infected T cells , transfected with plasmids bearing the promoter regions of the EBV early genes BZLF1 and BMRF1 , show a strong transactivation of these promoters .", "entity": [{"entity": "promoters", "entity_type": "DNA", "pos": [543, 552]}, {"entity": "EBV antigens", "entity_type": "protein", "pos": [137, 149]}, {"entity": "P3HR1 cells", "entity_type": "cell line", "pos": [41, 52]}, {"entity": "BZLF1", "entity_type": "DNA", "pos": [486, 491]}, {"entity": "plasmids", "entity_type": "DNA", "pos": [425, 433]}, {"entity": "infectable cells", "entity_type": "cell type", "pos": [313, 329]}, {"entity": "EBV genome", "entity_type": "DNA", "pos": [176, 186]}, {"entity": "promoter regions", "entity_type": "DNA", "pos": [446, 462]}, {"entity": "B cell lines", "entity_type": "cell line", "pos": [228, 240]}, {"entity": "BMRF1", "entity_type": "DNA", "pos": [496, 501]}, {"entity": "HHV-6 infected T cells", "entity_type": "cell line", "pos": [383, 405]}], "task": "NER"}
{"text": "Evidence for normal vitamin D receptor messenger ribonucleic acid and genotype in absorptive hypercalciuria .", "entity": [{"entity": "vitamin D receptor messenger ribonucleic acid", "entity_type": "RNA", "pos": [20, 65]}, {"entity": "vitamin D receptor", "entity_type": "protein", "pos": [20, 38]}], "task": "NER"}
{"text": "Absorptive hypercalciuria (a stone-forming condition ) is characterized by gut hyperabsorption of calcium , hypercalciuria , and reduced bone density .", "entity": [], "task": "NER"}
{"text": "Inasmuch as these features implicate enhanced calcitriol action in gut and bone , we analyzed the vitamin D receptor ( VDR ) gene to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium .", "entity": [{"entity": "vitamin D receptor ( VDR ) gene", "entity_type": "DNA", "pos": [98, 129]}, {"entity": "vitamin D receptor", "entity_type": "protein", "pos": [98, 116]}, {"entity": "VDR", "entity_type": "protein", "pos": [119, 122]}], "task": "NER"}
{"text": "We have compared the frequency of a restriction fragment length polymorphism ( Bsm I ) associated with different alleles of the VDR gene in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects .", "entity": [{"entity": "VDR gene", "entity_type": "DNA", "pos": [128, 136]}, {"entity": "VDR", "entity_type": "protein", "pos": [128, 131]}, {"entity": "restriction fragment length polymorphism", "entity_type": "DNA", "pos": [36, 76]}, {"entity": "Bsm I", "entity_type": "DNA", "pos": [79, 84]}], "task": "NER"}
{"text": "There was no difference between the distribution of the VDR alleles in the patient population when compared with the normal population .", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [56, 59]}], "task": "NER"}
{"text": "The coding region of VDR messenger RNA was also normal, as determined by both DNA sequence analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients .", "entity": [{"entity": "DNA sequence", "entity_type": "DNA", "pos": [78, 90]}, {"entity": "VDR messenger RNA", "entity_type": "RNA", "pos": [21, 38]}, {"entity": "VDR", "entity_type": "protein", "pos": [21, 24]}], "task": "NER"}
{"text": "On the basis of these results, we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the VDR and are not linked to a common VDR genotype .", "entity": [{"entity": "VDR genotype", "entity_type": "DNA", "pos": [251, 263]}, {"entity": "VDR", "entity_type": "protein", "pos": [216, 219]}, {"entity": "VDR", "entity_type": "protein", "pos": [251, 254]}], "task": "NER"}
{"text": "Transcriptional regulation of the gene encoding the human C-type lectin leukocyte receptor AIM/CD69 and functional characterization of its tumor necrosis factor-alpha -responsive elements .", "entity": [{"entity": "tumor necrosis factor-alpha -responsive elements", "entity_type": "DNA", "pos": [139, 187]}, {"entity": "AIM/CD69", "entity_type": "protein", "pos": [91, 99]}, {"entity": "human C-type lectin leukocyte receptor", "entity_type": "protein", "pos": [52, 90]}, {"entity": "elements", "entity_type": "DNA", "pos": [179, 187]}, {"entity": "tumor necrosis factor-alpha", "entity_type": "protein", "pos": [139, 166]}], "task": "NER"}
{"text": "The human activation antigen CD69 is a member of the C-type animal lectin superfamily that functions as a signal-transmitting receptor .", "entity": [{"entity": "signal-transmitting receptor", "entity_type": "protein", "pos": [106, 134]}, {"entity": "human activation antigen", "entity_type": "protein", "pos": [4, 28]}, {"entity": "C-type animal lectin superfamily", "entity_type": "protein", "pos": [53, 85]}, {"entity": "CD69", "entity_type": "protein", "pos": [29, 33]}], "task": "NER"}
{"text": "Although the expression of CD69 can be induced in vitro on cells of most hematopoietic lineages with a wide variety of stimuli, in vivo it is mainly expressed by T- lymphocytes located in the inflammatory infiltrates of several human diseases .", "entity": [{"entity": "lymphocytes", "entity_type": "cell type", "pos": [165, 176]}, {"entity": "T- lymphocytes", "entity_type": "cell type", "pos": [162, 176]}, {"entity": "CD69", "entity_type": "protein", "pos": [27, 31]}], "task": "NER"}
{"text": "To elucidate the mechanisms that regulate the constitutive and inducible expression of CD69 by leukocytes , we isolated the promoter region of the CD69 gene and carried out its functional characterization .", "entity": [{"entity": "CD69", "entity_type": "protein", "pos": [87, 91]}, {"entity": "promoter region", "entity_type": "DNA", "pos": [124, 139]}, {"entity": "leukocytes", "entity_type": "cell type", "pos": [95, 105]}, {"entity": "CD69", "entity_type": "protein", "pos": [147, 151]}], "task": "NER"}
{"text": "Sequence analysis of the 5'-flanking region of the CD69 gene revealed the presence of a potential TATA element 30 base pairs upstream of the major transcription initiation site and several putative binding sequences for inducible transcription factors ( NF-kappa B , Egr-1 , AP-1 ), which might mediate the inducible expression of this gene.", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [254, 264]}, {"entity": "TATA element", "entity_type": "DNA", "pos": [98, 110]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [230, 251]}, {"entity": "CD69", "entity_type": "protein", "pos": [51, 55]}, {"entity": "AP-1", "entity_type": "protein", "pos": [275, 279]}, {"entity": "30 base pairs upstream", "entity_type": "DNA", "pos": [111, 133]}, {"entity": "CD69 gene", "entity_type": "DNA", "pos": [51, 60]}, {"entity": "5'-flanking region", "entity_type": "DNA", "pos": [25, 43]}, {"entity": "transcription initiation site", "entity_type": "DNA", "pos": [147, 176]}, {"entity": "Egr-1", "entity_type": "protein", "pos": [267, 272]}], "task": "NER"}
{"text": "Transient expression of CD69 promoter-based reporter gene constructs in K562 cells indicated that the proximal promoter region spanning positions -78 to +16 contained the cis-acting sequences necessary for basal and phorbol 12-myristate 13-acetate -inducible transcription of the CD69 gene .", "entity": [{"entity": "CD69", "entity_type": "protein", "pos": [24, 28]}, {"entity": "CD69 promoter-based reporter gene constructs", "entity_type": "DNA", "pos": [24, 68]}, {"entity": "cis-acting sequences", "entity_type": "DNA", "pos": [171, 191]}, {"entity": "proximal promoter region", "entity_type": "DNA", "pos": [102, 126]}, {"entity": "CD69", "entity_type": "protein", "pos": [280, 284]}, {"entity": "CD69 gene", "entity_type": "DNA", "pos": [280, 289]}, {"entity": "K562 cells", "entity_type": "cell line", "pos": [72, 82]}, {"entity": "promoter region", "entity_type": "DNA", "pos": [111, 126]}], "task": "NER"}
{"text": "Removal of the upstream sequences located between positions -78 and -38 resulted in decreased promoter strength and abolished the response to phorbol 12-myristate 13-acetate.", "entity": [], "task": "NER"}
{"text": "We also found that tumor necrosis factor-alpha ( TNF-alpha ) is capable of inducing the surface expression of the CD69 molecule as well as the promoter activity of fusion plasmids that contain 5'-flanking sequences of the CD69 gene, suggesting that this cytokine may regulate in vivo the expression of CD69 .", "entity": [{"entity": "CD69", "entity_type": "protein", "pos": [114, 118]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [49, 58]}, {"entity": "tumor necrosis factor-alpha", "entity_type": "protein", "pos": [19, 46]}, {"entity": "CD69", "entity_type": "protein", "pos": [222, 226]}, {"entity": "CD69", "entity_type": "protein", "pos": [302, 306]}], "task": "NER"}
{"text": "Characterization of 5' end of human thromboxane receptor gene .", "entity": [{"entity": "5' end of human thromboxane receptor gene", "entity_type": "DNA", "pos": [20, 61]}, {"entity": "human thromboxane receptor gene", "entity_type": "DNA", "pos": [30, 61]}], "task": "NER"}
{"text": "Organizational analysis and mapping of protein kinase C--responsive elements regulating expression in platelets .", "entity": [{"entity": "protein kinase C--responsive elements", "entity_type": "DNA", "pos": [39, 76]}, {"entity": "platelets", "entity_type": "cell type", "pos": [102, 111]}, {"entity": "elements", "entity_type": "DNA", "pos": [68, 76]}], "task": "NER"}
{"text": "Platelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction .", "entity": [{"entity": "Platelet thromboxane receptors", "entity_type": "protein", "pos": [0, 30]}, {"entity": "Platelet", "entity_type": "cell type", "pos": [0, 8]}], "task": "NER"}
{"text": "To determine if platelet thromboxane receptors are under transcriptional control , we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene .", "entity": [{"entity": "5' flanking region", "entity_type": "DNA", "pos": [153, 171]}, {"entity": "thromboxane receptors", "entity_type": "protein", "pos": [25, 46]}, {"entity": "human genomic DNA clones", "entity_type": "DNA", "pos": [113, 137]}, {"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [179, 204]}], "task": "NER"}
{"text": "The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA .", "entity": [{"entity": "thromboxane receptor", "entity_type": "protein", "pos": [51, 71]}, {"entity": "5' portion", "entity_type": "DNA", "pos": [33, 43]}, {"entity": "141 bp further upstream", "entity_type": "DNA", "pos": [256, 279]}, {"entity": "thromboxane receptor", "entity_type": "protein", "pos": [207, 227]}, {"entity": "previously identified human placental cDNA", "entity_type": "DNA", "pos": [289, 331]}, {"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [51, 76]}, {"entity": "exon-intron structure", "entity_type": "DNA", "pos": [4, 25]}, {"entity": "novel human uterine thromboxane receptor cDNA", "entity_type": "DNA", "pos": [187, 232]}, {"entity": "5' flanking genomic clone", "entity_type": "DNA", "pos": [146, 171]}, {"entity": "nucleotide sequence", "entity_type": "DNA", "pos": [119, 138]}, {"entity": "mRNA", "entity_type": "RNA", "pos": [251, 255]}], "task": "NER"}
{"text": "A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site .", "entity": [{"entity": "380 bp upstream", "entity_type": "DNA", "pos": [145, 160]}, {"entity": "translation initiation codon", "entity_type": "DNA", "pos": [112, 140]}, {"entity": "transcription initiation site", "entity_type": "DNA", "pos": [8, 37]}, {"entity": "560 bp upstream", "entity_type": "DNA", "pos": [87, 102]}, {"entity": "transcription initiation site", "entity_type": "DNA", "pos": [192, 221]}], "task": "NER"}
{"text": "The thromboxane receptor gene has neither a TATA nor a CAAT consensus site .", "entity": [{"entity": "CAAT consensus site", "entity_type": "DNA", "pos": [55, 74]}, {"entity": "TATA", "entity_type": "DNA", "pos": [44, 48]}, {"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [4, 29]}, {"entity": "thromboxane receptor", "entity_type": "protein", "pos": [4, 24]}], "task": "NER"}
{"text": "Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/ chloramphenicol acetyltransferase ( CAT ) chimera plasmids into platelet-like K562 cells .", "entity": [{"entity": "thromboxane receptor", "entity_type": "protein", "pos": [51, 71]}, {"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [51, 76]}, {"entity": "CAT", "entity_type": "protein", "pos": [182, 185]}, {"entity": "thromboxane receptor", "entity_type": "protein", "pos": [110, 130]}, {"entity": "chloramphenicol acetyltransferase", "entity_type": "protein", "pos": [146, 179]}, {"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [110, 135]}, {"entity": "5' flanking region", "entity_type": "DNA", "pos": [25, 43]}, {"entity": "thromboxane receptor gene promoter/ chloramphenicol acetyltransferase ( CAT ) chimera plasmids", "entity_type": "DNA", "pos": [110, 204]}, {"entity": "K562 cells", "entity_type": "cell line", "pos": [224, 234]}], "task": "NER"}
{"text": "Thromboxane receptor promoter activity , as assessed by CAT expression , was relatively weak but was significantly enhanced by phorbol ester treatment .", "entity": [{"entity": "CAT", "entity_type": "protein", "pos": [56, 59]}, {"entity": "receptor promoter", "entity_type": "DNA", "pos": [12, 29]}], "task": "NER"}
{"text": "Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester -responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 ( AP-2 ) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site .", "entity": [{"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [155, 180]}, {"entity": "AP-2", "entity_type": "protein", "pos": [228, 232]}, {"entity": "activator protein-2", "entity_type": "protein", "pos": [206, 225]}, {"entity": "activator protein-2 ( AP-2 ) binding consensus sites", "entity_type": "DNA", "pos": [206, 258]}, {"entity": "5' deletion constructs", "entity_type": "DNA", "pos": [23, 45]}, {"entity": "thromboxane receptor", "entity_type": "protein", "pos": [155, 175]}, {"entity": "K562 cells", "entity_type": "cell line", "pos": [61, 71]}, {"entity": "transcription initiation site", "entity_type": "DNA", "pos": [300, 329]}], "task": "NER"}
{"text": "These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2 -like nuclear factor binding to upstream promoter elements .", "entity": [{"entity": "upstream promoter elements", "entity_type": "DNA", "pos": [285, 311]}, {"entity": "AP-2 -like nuclear factor", "entity_type": "protein", "pos": [248, 273]}, {"entity": "thromboxane receptor", "entity_type": "protein", "pos": [93, 113]}, {"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [93, 118]}, {"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [140, 165]}, {"entity": "thromboxane receptor", "entity_type": "protein", "pos": [140, 160]}, {"entity": "AP-2", "entity_type": "protein", "pos": [248, 252]}, {"entity": "protein kinase C", "entity_type": "protein", "pos": [211, 227]}], "task": "NER"}
{"text": "These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells .", "entity": [{"entity": "thromboxane receptor", "entity_type": "protein", "pos": [101, 121]}, {"entity": "thromboxane receptor gene", "entity_type": "DNA", "pos": [170, 195]}, {"entity": "platelet thromboxane receptors", "entity_type": "protein", "pos": [92, 122]}, {"entity": "platelet-progenitor cells", "entity_type": "cell type", "pos": [213, 238]}], "task": "NER"}
{"text": "Estrogen receptor concentration and social factors as predictors of natural killer cell activity in early-stage breast cancer patients .", "entity": [{"entity": "Estrogen receptor", "entity_type": "protein", "pos": [0, 17]}], "task": "NER"}
{"text": "Confirmation of a model.", "entity": [], "task": "NER"}
{"text": "Previous work of ours has demonstrated that a significant amount of natural killer (NK) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the estrogen receptor ( ER ) status of the tumor and by social factors , namely, perceived social support and seeking social support as a general coping strategy .", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [216, 218]}, {"entity": "estrogen receptor", "entity_type": "protein", "pos": [196, 213]}], "task": "NER"}
{"text": "As considerable evidence has accumulated that social support in both animal and human populations may have survival value, we sought to test the reliability of this regression model , using coping and perceived support factor values obtained at 3 months after surgery to account for concurrent follow-up NK activity in this serially assessed group of patients .", "entity": [], "task": "NER"}
{"text": "It was found that the most significant variable predicting NK activity at follow-up was tumor ER concentration , with higher NK activity associated with ER -status .", "entity": [{"entity": "ER", "entity_type": "protein", "pos": [94, 96]}, {"entity": "ER", "entity_type": "protein", "pos": [153, 155]}], "task": "NER"}
{"text": "In addition, seeking social support as a coping strategy, as well as the perceived quality of support, also entered the model to account for a significant amount of NK activity variance (multivariate F = 5.25, p less than 0.001).", "entity": [], "task": "NER"}
{"text": "If, as the literature suggests, NK activity is relevant to breast cancer control , and since ER -tumors have a worse prognosis, we suggest here that perhaps such tumors are resistant to control by NK cells because they lack the ability to attract an accumulation of effector cells to the tumor site , or because blocking factors at the site of the tumor prevent local tumor control at the site of action.", "entity": [{"entity": "NK cells", "entity_type": "cell type", "pos": [197, 205]}, {"entity": "effector cells", "entity_type": "cell type", "pos": [266, 280]}, {"entity": "ER", "entity_type": "protein", "pos": [93, 95]}], "task": "NER"}
{"text": "The finding related to social support also replicates results from an independent sample of breast cancer patients .", "entity": [], "task": "NER"}
{"text": "This finding, taken together with other evidence that this social variable is associated with longer survival in breast cancer populations , underscores the potential importance of this social support variable .", "entity": [], "task": "NER"}
{"text": "Our findings also suggest one possible immunological variable involved , with potential clinical significance , for this patient population .", "entity": [], "task": "NER"}
{"text": "Solution structure of the sequence-specific HMG box of the lymphocyte transcriptional activator Sox-4 .", "entity": [{"entity": "Sox-4", "entity_type": "protein", "pos": [96, 101]}, {"entity": "lymphocyte transcriptional activator", "entity_type": "protein", "pos": [59, 95]}, {"entity": "sequence-specific HMG box", "entity_type": "DNA", "pos": [26, 51]}], "task": "NER"}
{"text": "Two groups of HMG box proteins are distinguished.", "entity": [{"entity": "HMG box proteins", "entity_type": "protein", "pos": [14, 30]}], "task": "NER"}
{"text": "Proteins in the first group contain multiple HMG boxes , are non-sequence-specific , and recognize structural features as found in cruciform DNA and cross-over DNA .", "entity": [{"entity": "cruciform DNA", "entity_type": "DNA", "pos": [131, 144]}, {"entity": "HMG boxes", "entity_type": "protein", "pos": [45, 54]}, {"entity": "cross-over DNA", "entity_type": "DNA", "pos": [149, 163]}], "task": "NER"}
{"text": "The abundant chromosomal protein HMG-1 belongs to this subgroup.", "entity": [{"entity": "HMG-1", "entity_type": "protein", "pos": [33, 38]}, {"entity": "chromosomal protein", "entity_type": "protein", "pos": [13, 32]}], "task": "NER"}
{"text": "Proteins in the second group carry a single HMG box with affinity for the minor groove of the heptamer motif AACAAAG or variations thereof.", "entity": [{"entity": "heptamer motif", "entity_type": "DNA", "pos": [94, 108]}, {"entity": "minor groove", "entity_type": "DNA", "pos": [74, 86]}, {"entity": "single HMG box", "entity_type": "protein", "pos": [37, 51]}], "task": "NER"}
{"text": "A solution structure for the non-sequence-specific C-terminal HMG box of HMG-1 has recently been proposed.", "entity": [{"entity": "HMG-1", "entity_type": "protein", "pos": [73, 78]}, {"entity": "C-terminal HMG box", "entity_type": "protein", "pos": [51, 69]}], "task": "NER"}
{"text": "Now, we report the solution structure of the sequence-specific HMG-box of the SRY-related protein Sox-4 .", "entity": [{"entity": "sequence-specific HMG-box", "entity_type": "protein", "pos": [45, 70]}, {"entity": "SRY-related protein", "entity_type": "protein", "pos": [78, 97]}, {"entity": "Sox-4", "entity_type": "protein", "pos": [98, 103]}], "task": "NER"}
{"text": "NMR analysis demonstrated the presence of three alpha-helices ( Val10-Gln22 , Glu30-Leu41 and Phe50-Tyr65 ) connected by loop regions ( Ser23-Ala49 and Leu42-Pro49 ).", "entity": [{"entity": "Leu42-Pro49", "entity_type": "protein", "pos": [152, 163]}, {"entity": "Val10-Gln22", "entity_type": "protein", "pos": [64, 75]}, {"entity": "loop regions", "entity_type": "protein", "pos": [121, 133]}, {"entity": "Phe50-Tyr65", "entity_type": "protein", "pos": [94, 105]}, {"entity": "Ser23-Ala49", "entity_type": "protein", "pos": [136, 147]}, {"entity": "Glu30-Leu41", "entity_type": "protein", "pos": [78, 89]}, {"entity": "alpha-helices", "entity_type": "protein", "pos": [48, 61]}], "task": "NER"}
{"text": "Helices I and II are positioned in an antiparallel mode and form one arm of the HMG box .", "entity": [{"entity": "antiparallel mode", "entity_type": "protein", "pos": [38, 55]}, {"entity": "HMG box", "entity_type": "protein", "pos": [80, 87]}], "task": "NER"}
{"text": "Helix III is less rigid, makes an average angle of about 90 degrees with helices I and II , and constitutes the other arm of the molecule.", "entity": [{"entity": "Helix III", "entity_type": "protein", "pos": [0, 9]}], "task": "NER"}
{"text": "As in HMG1B , the overall structure of the Sox-4 HMG box is L-shaped and is maintained by a cluster of conserved, mainly aromatic residues .", "entity": [{"entity": "HMG1B", "entity_type": "protein", "pos": [6, 11]}, {"entity": "Sox-4", "entity_type": "protein", "pos": [43, 48]}, {"entity": "HMG box", "entity_type": "protein", "pos": [49, 56]}], "task": "NER"}
{"text": "Nuclear factor-IL6 activates the human IL-4 promoter in T cells .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [56, 63]}, {"entity": "Nuclear factor-IL6", "entity_type": "protein", "pos": [0, 18]}, {"entity": "human IL-4 promoter", "entity_type": "DNA", "pos": [33, 52]}], "task": "NER"}
{"text": "Positive regulatory element I ( PRE-I ) is a strong enhancer element essential for expression of the human IL-4 gene .", "entity": [{"entity": "PRE-I", "entity_type": "DNA", "pos": [32, 37]}, {"entity": "Positive regulatory element I", "entity_type": "DNA", "pos": [0, 29]}, {"entity": "human IL-4 gene", "entity_type": "DNA", "pos": [101, 116]}, {"entity": "enhancer element", "entity_type": "DNA", "pos": [52, 68]}], "task": "NER"}
{"text": "To identify transcription factors binding to PRE-I , we screened a cDNA expression library from Jurkat T cells and isolated a cDNA encoding nuclear factor (NF)-IL6 (also known as C/EBP beta ).", "entity": [{"entity": "cDNA", "entity_type": "DNA", "pos": [67, 71]}, {"entity": "C/EBP beta", "entity_type": "protein", "pos": [179, 189]}, {"entity": "(NF)-IL6", "entity_type": "protein", "pos": [155, 163]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [12, 33]}, {"entity": "Jurkat T cells", "entity_type": "cell line", "pos": [96, 110]}, {"entity": "cDNA expression library", "entity_type": "DNA", "pos": [67, 90]}, {"entity": "T cells", "entity_type": "cell type", "pos": [103, 110]}, {"entity": "PRE-I", "entity_type": "DNA", "pos": [45, 50]}, {"entity": "nuclear factor", "entity_type": "protein", "pos": [140, 154]}], "task": "NER"}
{"text": "NF-IL6 mRNA was found in human Jurkat T cells and in the mouse Th2 clone D10 , but not in Th1 clone 29 .", "entity": [{"entity": "human Jurkat T cells", "entity_type": "cell line", "pos": [25, 45]}, {"entity": "NF-IL6 mRNA", "entity_type": "RNA", "pos": [0, 11]}, {"entity": "D10", "entity_type": "cell line", "pos": [73, 76]}, {"entity": "mouse Th2 clone", "entity_type": "cell line", "pos": [57, 72]}, {"entity": "Th1 clone 29", "entity_type": "cell line", "pos": [90, 102]}, {"entity": "T cells", "entity_type": "cell type", "pos": [38, 45]}], "task": "NER"}
{"text": "rNF-IL6 expressed in bacteria was shown to specifically bind to PRE-I .", "entity": [{"entity": "rNF-IL6", "entity_type": "protein", "pos": [0, 7]}, {"entity": "PRE-I", "entity_type": "DNA", "pos": [64, 69]}], "task": "NER"}
{"text": "PRE-I forms multiple DNA-protein complexes with nuclear extracts from Jurkat cells .", "entity": [{"entity": "PRE-I", "entity_type": "DNA", "pos": [0, 5]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [70, 82]}, {"entity": "multiple DNA-protein complexes", "entity_type": "protein", "pos": [12, 42]}], "task": "NER"}
{"text": "Some of these complexes were demonstrated to contain NF-IL6 by using anti- C/EBP beta Abs .", "entity": [{"entity": "NF-IL6", "entity_type": "protein", "pos": [53, 59]}, {"entity": "anti- C/EBP beta Abs", "entity_type": "protein", "pos": [69, 89]}, {"entity": "C/EBP beta", "entity_type": "protein", "pos": [75, 85]}], "task": "NER"}
{"text": "Overexpression of NF-IL6 enhanced expression of the chloramphenicol acetyl transferase reporter gene linked to the PRE-I -thymidine kinase or the human IL-4 promoter more than 10-fold in Jurkat cells .", "entity": [{"entity": "PRE-I -thymidine kinase", "entity_type": "protein", "pos": [115, 138]}, {"entity": "chloramphenicol acetyl transferase reporter gene", "entity_type": "DNA", "pos": [52, 100]}, {"entity": "human IL-4", "entity_type": "protein", "pos": [146, 156]}, {"entity": "human IL-4 promoter", "entity_type": "DNA", "pos": [146, 165]}, {"entity": "NF-IL6", "entity_type": "protein", "pos": [18, 24]}, {"entity": "chloramphenicol acetyl transferase", "entity_type": "protein", "pos": [52, 86]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [187, 199]}, {"entity": "PRE-I", "entity_type": "DNA", "pos": [115, 120]}], "task": "NER"}
{"text": "Promoter deletion studies revealed two additional NF-IL6 binding sites located at positions -44 to -36 ( C/EBP proximal ) and -87 to -79 ( C/EBP medial ), respectively.", "entity": [{"entity": "C/EBP medial", "entity_type": "protein", "pos": [139, 151]}, {"entity": "NF-IL6", "entity_type": "protein", "pos": [50, 56]}, {"entity": "NF-IL6 binding sites", "entity_type": "DNA", "pos": [50, 70]}, {"entity": "C/EBP proximal", "entity_type": "protein", "pos": [105, 119]}], "task": "NER"}
{"text": "Our results demonstrate that NF-IL6 is involved in transcriptional activation of the human IL-4 promoter in T cells .", "entity": [{"entity": "human IL-4", "entity_type": "protein", "pos": [85, 95]}, {"entity": "human IL-4 promoter", "entity_type": "DNA", "pos": [85, 104]}, {"entity": "NF-IL6", "entity_type": "protein", "pos": [29, 35]}, {"entity": "T cells", "entity_type": "cell type", "pos": [108, 115]}], "task": "NER"}
{"text": "Identification of an I kappa B alpha-associated protein kinase in a human monocytic cell line and determination of its phosphorylation sites on I kappa B alpha .", "entity": [{"entity": "human monocytic cell line", "entity_type": "cell line", "pos": [68, 93]}, {"entity": "phosphorylation sites", "entity_type": "protein", "pos": [119, 140]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [21, 36]}, {"entity": "I kappa B alpha-associated protein kinase", "entity_type": "protein", "pos": [21, 62]}], "task": "NER"}
{"text": "Nuclear factor kappa B ( NF-kappa B ) is stored in the cytoplasm as an inactive form through interaction with I kappa B .", "entity": [{"entity": "I kappa B", "entity_type": "protein", "pos": [110, 119]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [25, 35]}, {"entity": "Nuclear factor kappa B", "entity_type": "protein", "pos": [0, 22]}], "task": "NER"}
{"text": "Stimulation of cells leads to a rapid phosphorylation of I kappa B alpha , which is presumed to be important for the subsequent degradation .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [57, 72]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [57, 66]}], "task": "NER"}
{"text": "We have recently reported the establishment of a lipopolysaccharide ( LPS )-dependent cell-free activation system of NF-kappa B in association with the induction of I kappa B alpha phosphorylation .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [117, 127]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [165, 174]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [165, 180]}], "task": "NER"}
{"text": "In this study, we have identified a kinase in cell extracts from the LPS -stimulated human monocytic cell line , THP-1 , that specifically binds and phosphorylates I kappa B alpha .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [164, 179]}, {"entity": "THP-1", "entity_type": "cell line", "pos": [113, 118]}, {"entity": "kinase", "entity_type": "protein", "pos": [36, 42]}, {"entity": "LPS -stimulated human monocytic cell line", "entity_type": "cell line", "pos": [69, 110]}], "task": "NER"}
{"text": "LPS stimulation transiently enhanced the I kappa B alpha -bound kinase activity in THP-1 cells .", "entity": [{"entity": "-bound kinase", "entity_type": "protein", "pos": [57, 70]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [41, 56]}, {"entity": "THP-1 cells", "entity_type": "cell line", "pos": [83, 94]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [41, 50]}], "task": "NER"}
{"text": "Mutational analyses of I kappa B alpha and competition experiments with the synthetic peptides identified major phosphorylation sites by the bound kinase as Ser and Thr residues in the C-terminal acidic domain of I kappa B alpha .", "entity": [{"entity": "phosphorylation sites", "entity_type": "protein", "pos": [112, 133]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [23, 32]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [213, 222]}, {"entity": "C-terminal acidic domain", "entity_type": "protein", "pos": [185, 209]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [23, 38]}, {"entity": "kinase", "entity_type": "protein", "pos": [147, 153]}], "task": "NER"}
{"text": "Moreover, we show that the peptide , corresponding to the C-terminal acidic domain of I kappa B alpha , blocked the LPS -induced NF-kappa B activation as well as inducible phosphorylation of endogenous I kappa B alpha in a cell-free system using THP-1 cells .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [86, 101]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [202, 217]}, {"entity": "THP-1 cells", "entity_type": "cell line", "pos": [246, 257]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [129, 139]}, {"entity": "C-terminal acidic domain", "entity_type": "protein", "pos": [58, 82]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [86, 95]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [202, 211]}], "task": "NER"}
{"text": "These results suggested that the bound kinase is involved in the signaling pathway of LPS by inducing the phosphorylation of the C-terminal region of I kappa B alpha and subsequent dissociation of the NF-kappa B . I kappa B alpha complex .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [150, 165]}, {"entity": "bound kinase", "entity_type": "protein", "pos": [33, 45]}, {"entity": "I kappa B alpha", "entity_type": "protein", "pos": [214, 229]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [201, 211]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [150, 159]}, {"entity": "I kappa B alpha complex", "entity_type": "protein", "pos": [214, 237]}, {"entity": "C-terminal region", "entity_type": "protein", "pos": [129, 146]}], "task": "NER"}
{"text": "Bik , a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins .", "entity": [{"entity": "cellular survival-promoting proteins", "entity_type": "protein", "pos": [126, 162]}, {"entity": "Bik", "entity_type": "protein", "pos": [0, 3]}, {"entity": "Bcl-2 family proteins", "entity_type": "protein", "pos": [75, 96]}, {"entity": "death-inducing protein", "entity_type": "protein", "pos": [14, 36]}], "task": "NER"}
{"text": "The survival-promoting activity of the Bcl-2 family of proteins appears to be modulated by interactions between various cellular proteins .", "entity": [{"entity": "Bcl-2 family", "entity_type": "protein", "pos": [39, 51]}, {"entity": "cellular proteins", "entity_type": "protein", "pos": [120, 137]}], "task": "NER"}
{"text": "We have identified a novel cellular protein , Bik , that interacts with the cellular survival-promoting proteins , Bcl-2 and Bcl-xL , as well as the viral survival-promoting proteins , Epstein Barr virus -BHRF1 and adenovirus E1B-19 kDa .", "entity": [{"entity": "Bik", "entity_type": "protein", "pos": [46, 49]}, {"entity": "Bcl-xL", "entity_type": "protein", "pos": [125, 131]}, {"entity": "cellular protein", "entity_type": "protein", "pos": [27, 43]}, {"entity": "Bcl-2", "entity_type": "protein", "pos": [115, 120]}, {"entity": "Epstein Barr virus -BHRF1", "entity_type": "protein", "pos": [185, 210]}, {"entity": "cellular survival-promoting proteins", "entity_type": "protein", "pos": [76, 112]}, {"entity": "adenovirus E1B-19 kDa", "entity_type": "protein", "pos": [215, 236]}, {"entity": "viral survival-promoting proteins", "entity_type": "protein", "pos": [149, 182]}], "task": "NER"}
{"text": "In transient transfection assays , Bik promotes cell death in a manner similar to the death-promoting members of the Bcl-2 family , Bax and Bak .", "entity": [{"entity": "Bak", "entity_type": "protein", "pos": [140, 143]}, {"entity": "death-promoting members", "entity_type": "protein", "pos": [86, 109]}, {"entity": "Bcl-2", "entity_type": "protein", "pos": [117, 122]}, {"entity": "Bik", "entity_type": "protein", "pos": [35, 38]}, {"entity": "Bcl-2 family", "entity_type": "protein", "pos": [117, 129]}, {"entity": "Bax", "entity_type": "protein", "pos": [132, 135]}], "task": "NER"}
{"text": "This death-promoting activity of Bik can be suppressed by coexpression of Bcl-2 , Bcl-XL , EBV-BHRF1 and E1B-19 kDa proteins suggesting that Bik may be a common target for both cellular and viral anti-apoptotic proteins .", "entity": [{"entity": "Bcl-XL", "entity_type": "protein", "pos": [82, 88]}, {"entity": "Bik", "entity_type": "protein", "pos": [33, 36]}, {"entity": "EBV-BHRF1", "entity_type": "protein", "pos": [91, 100]}, {"entity": "Bik", "entity_type": "protein", "pos": [141, 144]}, {"entity": "E1B-19 kDa", "entity_type": "protein", "pos": [105, 115]}, {"entity": "Bcl-2", "entity_type": "protein", "pos": [74, 79]}], "task": "NER"}
{"text": "While Bik does not show overt homology to the BH1 and BH2 conserved domains characteristic of the Bcl-2 family , it does share a 9 amino acid domain ( BH3 ) with Bax and Bak which may be a critical determinant for the death-promoting activity of these proteins.", "entity": [{"entity": "amino acid domain", "entity_type": "protein", "pos": [131, 148]}, {"entity": "BH1", "entity_type": "protein", "pos": [46, 49]}, {"entity": "BH3", "entity_type": "protein", "pos": [151, 154]}, {"entity": "Bak", "entity_type": "protein", "pos": [170, 173]}, {"entity": "BH2", "entity_type": "protein", "pos": [54, 57]}, {"entity": "Bax", "entity_type": "protein", "pos": [162, 165]}, {"entity": "Bik", "entity_type": "protein", "pos": [6, 9]}, {"entity": "Bcl-2 family", "entity_type": "protein", "pos": [98, 110]}], "task": "NER"}
{"text": "The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes .", "entity": [{"entity": "human TCF-1 gene", "entity_type": "DNA", "pos": [4, 20]}, {"entity": "nuclear DNA-binding protein", "entity_type": "protein", "pos": [31, 58]}], "task": "NER"}
{"text": "The TCF-1 gene encodes a putative transcription factor with affinity for a sequence motif occurring in a number of T-cell enhancers .", "entity": [{"entity": "TCF-1", "entity_type": "protein", "pos": [4, 9]}, {"entity": "sequence motif", "entity_type": "DNA", "pos": [75, 89]}, {"entity": "putative transcription factor", "entity_type": "protein", "pos": [25, 54]}, {"entity": "T-cell enhancers", "entity_type": "DNA", "pos": [115, 131]}, {"entity": "TCF-1 gene", "entity_type": "DNA", "pos": [4, 14]}], "task": "NER"}
{"text": "TCF-1 mRNA was originally found to be expressed in a T cell-specific fashion within a set of human and mouse cell lines .", "entity": [{"entity": "human and mouse cell lines", "entity_type": "cell line", "pos": [93, 119]}, {"entity": "human", "entity_type": "cell line", "pos": [93, 98]}, {"entity": "TCF-1 mRNA", "entity_type": "RNA", "pos": [0, 10]}, {"entity": "mouse cell lines", "entity_type": "cell line", "pos": [103, 119]}, {"entity": "TCF-1", "entity_type": "protein", "pos": [0, 5]}], "task": "NER"}
{"text": "In contrast, expression reportedly occurs in multiple nonlymphoid tissues during murine embryogenesis .", "entity": [], "task": "NER"}
{"text": "We have now raised a monoclonal antibody to document expression and biochemistry of the human TCF-1 protein .", "entity": [{"entity": "human TCF-1 protein", "entity_type": "protein", "pos": [88, 107]}, {"entity": "TCF-1", "entity_type": "protein", "pos": [94, 99]}, {"entity": "monoclonal antibody", "entity_type": "protein", "pos": [21, 40]}], "task": "NER"}
{"text": "As expected, the TCF-1 protein was detectable only in cell lines of T lineage .", "entity": [{"entity": "TCF-1 protein", "entity_type": "protein", "pos": [17, 30]}, {"entity": "cell lines of T lineage", "entity_type": "cell line", "pos": [54, 77]}], "task": "NER"}
{"text": "Its expression was always restricted to the nucleus .", "entity": [], "task": "NER"}
{"text": "Immunohistochemistry on a panel of human tissues revealed that the TCF-1 protein was found exclusively in thymocytes and in CD3+ T cells in peripheral lymphoid tissues .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [129, 136]}, {"entity": "TCF-1 protein", "entity_type": "protein", "pos": [67, 80]}, {"entity": "CD3+ T cells", "entity_type": "cell line", "pos": [124, 136]}, {"entity": "TCF-1", "entity_type": "protein", "pos": [67, 72]}], "task": "NER"}
{"text": "Western blotting yielded a set of bands ranging from 25 kD to 55 kD, resulting from extensive alternative splicing .", "entity": [], "task": "NER"}
{"text": "The TCF-1 protein was detectable in all samples of a set of 22 T-cell malignancies of various stages of maturation, but was absent from a large number of other hematologic neoplasms .", "entity": [{"entity": "TCF-1", "entity_type": "protein", "pos": [4, 9]}, {"entity": "T-cell malignancies", "entity_type": "cell type", "pos": [63, 82]}, {"entity": "hematologic neoplasms", "entity_type": "cell type", "pos": [160, 181]}], "task": "NER"}
{"text": "These observations imply a T cell-specific function for TCF-1 , a notion corroborated by recent observations on Tcf-1 knock-out mice .", "entity": [{"entity": "TCF-1", "entity_type": "protein", "pos": [56, 61]}], "task": "NER"}
{"text": "In addition, these results indicate that nuclear TCF-1 expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies .", "entity": [{"entity": "TCF-1", "entity_type": "protein", "pos": [49, 54]}], "task": "NER"}
{"text": "Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat -driven transcription in human monocytes .", "entity": [{"entity": "HIV-1 long terminal repeat", "entity_type": "DNA", "pos": [46, 72]}, {"entity": "Fc gamma receptors", "entity_type": "protein", "pos": [17, 35]}, {"entity": "human monocytes", "entity_type": "cell type", "pos": [98, 113]}], "task": "NER"}
{"text": "Elevation of the levels of circulating immune complexes frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS .", "entity": [{"entity": "circulating immune complexes", "entity_type": "protein", "pos": [27, 55]}], "task": "NER"}
{"text": "Here we report that cross-linking of Fc gamma RI or Fc gamma RII by adherent human IgG or by specific anti-Fc gamma R mAb activates HIV-1 gene expression in the human monocytic cell line BF24 and increased HIV RNA expression in monocytes from HIV infected patients as assayed by reverse transcription-PCR .", "entity": [{"entity": "monocytes", "entity_type": "cell type", "pos": [228, 237]}, {"entity": "BF24", "entity_type": "cell line", "pos": [187, 191]}, {"entity": "anti-Fc gamma R mAb", "entity_type": "protein", "pos": [102, 121]}, {"entity": "Fc gamma RII", "entity_type": "protein", "pos": [52, 64]}, {"entity": "human monocytic cell line", "entity_type": "cell line", "pos": [161, 186]}, {"entity": "adherent human IgG", "entity_type": "protein", "pos": [68, 86]}, {"entity": "HIV RNA", "entity_type": "RNA", "pos": [206, 213]}, {"entity": "Fc gamma RI", "entity_type": "protein", "pos": [37, 48]}], "task": "NER"}
{"text": "In THP-1 cells , Fc gamma R cross-linking induced NF-kappa B , which is known to bind to the regulatory region of the long terminal repeat ( LTR ) of HIV-1 and to activate HIV-1 transcription . Anti-TNF-alpha antibody but not anti-IL-1 beta antibody strongly inhibited both the induction of HIV-1 - LTR -driven transcription and the induction of NF-kappa B by Fc gamma R cross-linking .", "entity": [{"entity": "LTR", "entity_type": "DNA", "pos": [141, 144]}, {"entity": "THP-1 cells", "entity_type": "cell line", "pos": [3, 14]}, {"entity": "regulatory region", "entity_type": "DNA", "pos": [93, 110]}, {"entity": "Fc gamma R", "entity_type": "protein", "pos": [17, 27]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [50, 60]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [346, 356]}, {"entity": "Fc gamma R", "entity_type": "protein", "pos": [360, 370]}, {"entity": "long terminal repeat", "entity_type": "DNA", "pos": [118, 138]}, {"entity": "anti-IL-1 beta antibody", "entity_type": "protein", "pos": [226, 249]}, {"entity": "THP-1", "entity_type": "cell line", "pos": [3, 8]}, {"entity": "LTR", "entity_type": "DNA", "pos": [299, 302]}, {"entity": "Anti-TNF-alpha antibody", "entity_type": "protein", "pos": [194, 217]}], "task": "NER"}
{"text": "These results indicate that Fc gamma R can mediate a TNF-alpha -dependent induction of HIV-1 gene transcription and suggest that immune complexes may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in monocytes .", "entity": [{"entity": "monocytes", "entity_type": "cell type", "pos": [238, 247]}, {"entity": "HIV-1 gene", "entity_type": "DNA", "pos": [87, 97]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [53, 62]}, {"entity": "Fc gamma R", "entity_type": "protein", "pos": [28, 38]}, {"entity": "immune complexes", "entity_type": "protein", "pos": [129, 145]}], "task": "NER"}
{"text": "Signalling via CD28 of human naive neonatal T lymphocytes .", "entity": [{"entity": "human naive neonatal T lymphocytes", "entity_type": "cell line", "pos": [23, 57]}, {"entity": "CD28", "entity_type": "protein", "pos": [15, 19]}], "task": "NER"}
{"text": "Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge.", "entity": [], "task": "NER"}
{"text": "We have examined the role of CD28 in modulating the ' naive' neonatal T cell response to anti-CD2 -mediated activation .", "entity": [{"entity": "anti-CD2", "entity_type": "protein", "pos": [89, 97]}, {"entity": "CD28", "entity_type": "protein", "pos": [29, 33]}], "task": "NER"}
{"text": "To compare the role of CD28 , neonatal and adult T cells were stimulated with a pair of mitogenic anti-CD2 antibodies in the presence or absence of anti- CD28 MoAb .", "entity": [{"entity": "CD28", "entity_type": "protein", "pos": [23, 27]}, {"entity": "CD28", "entity_type": "protein", "pos": [154, 158]}, {"entity": "T cells", "entity_type": "cell type", "pos": [49, 56]}, {"entity": "adult T cells", "entity_type": "cell type", "pos": [43, 56]}, {"entity": "neonatal", "entity_type": "cell type", "pos": [30, 38]}, {"entity": "anti- CD28 MoAb", "entity_type": "protein", "pos": [148, 163]}, {"entity": "mitogenic anti-CD2 antibodies", "entity_type": "protein", "pos": [88, 117]}], "task": "NER"}
{"text": "With anti-CD2 alone, neonatal T cells proliferated slightly but produced no detectable IL-2 , whereas adult T cells proliferated vigorously, with significant IL-2 production .", "entity": [{"entity": "anti-CD2", "entity_type": "protein", "pos": [5, 13]}, {"entity": "IL-2", "entity_type": "protein", "pos": [87, 91]}, {"entity": "T cells", "entity_type": "cell type", "pos": [30, 37]}, {"entity": "neonatal T cells", "entity_type": "cell type", "pos": [21, 37]}, {"entity": "IL-2", "entity_type": "protein", "pos": [158, 162]}], "task": "NER"}
{"text": "Costimulation with anti- CD28 MoAb greatly enhanced the proliferative response of neonatal T cells to levels equivalent to those of adult T cells , whereas adult T cells showed only slight increases.", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [91, 98]}, {"entity": "adult T cells", "entity_type": "cell type", "pos": [132, 145]}, {"entity": "CD28", "entity_type": "protein", "pos": [25, 29]}, {"entity": "T cells", "entity_type": "cell type", "pos": [138, 145]}, {"entity": "anti- CD28 MoAb", "entity_type": "protein", "pos": [19, 34]}, {"entity": "neonatal T cells", "entity_type": "cell type", "pos": [82, 98]}, {"entity": "T cells", "entity_type": "cell type", "pos": [162, 169]}, {"entity": "adult T cells", "entity_type": "cell type", "pos": [156, 169]}], "task": "NER"}
{"text": "Although IL-2 secretion was increased in the presence of anti- CD28 MoAb , neonatal T cell IL-2 production remained lower than in adults .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [9, 13]}, {"entity": "anti- CD28 MoAb", "entity_type": "protein", "pos": [57, 72]}, {"entity": "neonatal T cell", "entity_type": "cell type", "pos": [75, 90]}, {"entity": "IL-2", "entity_type": "protein", "pos": [91, 95]}, {"entity": "CD28", "entity_type": "protein", "pos": [63, 67]}], "task": "NER"}
{"text": "In contrast, enhancement of IL-2 mRNA expression in neonates was similar to adult levels .", "entity": [{"entity": "IL-2 mRNA", "entity_type": "RNA", "pos": [28, 37]}, {"entity": "IL-2", "entity_type": "protein", "pos": [28, 32]}], "task": "NER"}
{"text": "Anti- CD28 MoAb costimulation increased NF kappa B levels in neonates , albeit to levels lower than that of adults .", "entity": [{"entity": "CD28", "entity_type": "protein", "pos": [6, 10]}, {"entity": "NF kappa B", "entity_type": "protein", "pos": [40, 50]}, {"entity": "CD28 MoAb", "entity_type": "protein", "pos": [6, 15]}], "task": "NER"}
{"text": "The cellular mechanism governing the diminished proliferative response of neonatal T lymphocytes to anti-CD2 may therefore be due to decreased NF kappa B induction , reduced IL-2 mRNA expression and deficient IL-2 production .", "entity": [{"entity": "NF kappa B", "entity_type": "protein", "pos": [143, 153]}, {"entity": "IL-2", "entity_type": "protein", "pos": [174, 178]}, {"entity": "IL-2 mRNA", "entity_type": "RNA", "pos": [174, 183]}, {"entity": "IL-2", "entity_type": "protein", "pos": [209, 213]}, {"entity": "anti-CD2", "entity_type": "protein", "pos": [100, 108]}, {"entity": "neonatal T lymphocytes", "entity_type": "cell type", "pos": [74, 96]}], "task": "NER"}
{"text": "Although anti- CD28 MoAb costimulation enhances all of the above signals, NF kappa B and IL-2 levels remain lower than in adults , suggesting the need for further activation requirements in the neonate .", "entity": [{"entity": "CD28", "entity_type": "protein", "pos": [15, 19]}, {"entity": "anti- CD28 MoAb", "entity_type": "protein", "pos": [9, 24]}], "task": "NER"}
{"text": "TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [40, 47]}, {"entity": "preleukemic T cells", "entity_type": "cell type", "pos": [28, 47]}], "task": "NER"}
{"text": "The TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [ t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1) ] and inversions [ inv14(q11;q32.1) ] with TCR alpha/beta loci in T-cell leukemias , such as T-prolymphocytic ( T-PLL ).", "entity": [{"entity": "14q32.1", "entity_type": "DNA", "pos": [38, 45]}, {"entity": "TCR alpha/beta loci", "entity_type": "DNA", "pos": [175, 194]}, {"entity": "t(14;14)(q11;q32.1)", "entity_type": "DNA", "pos": [89, 108]}, {"entity": "TCL1 oncogene", "entity_type": "DNA", "pos": [4, 17]}, {"entity": "human chromosome", "entity_type": "DNA", "pos": [21, 37]}, {"entity": "t(7;14)(q35;q32.1)", "entity_type": "DNA", "pos": [113, 131]}, {"entity": "inv14(q11;q32.1)", "entity_type": "DNA", "pos": [151, 167]}], "task": "NER"}
{"text": "It is also involved in T- acute and- chronic leukemias arising in cases of ataxia-telangiectasia ( AT ), an immunodeficiency syndrome .", "entity": [], "task": "NER"}
{"text": "Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [71, 78]}], "task": "NER"}
{"text": "We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes ( PBLs ) from four AT cases and from healthy controls .", "entity": [{"entity": "PBLs", "entity_type": "cell type", "pos": [91, 95]}, {"entity": "peripheral blood lymphocytes", "entity_type": "cell type", "pos": [60, 88]}, {"entity": "TCL1 mRNA", "entity_type": "RNA", "pos": [35, 44]}, {"entity": "protein", "entity_type": "protein", "pos": [49, 56]}], "task": "NER"}
{"text": "We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases.", "entity": [{"entity": "PBLs", "entity_type": "cell type", "pos": [53, 57]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [166, 177]}, {"entity": "large clonal T-cell population", "entity_type": "cell line", "pos": [82, 112]}, {"entity": "TCL1 gene", "entity_type": "DNA", "pos": [18, 27]}], "task": "NER"}
{"text": "Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14 .", "entity": [{"entity": "inverted duplication", "entity_type": "DNA", "pos": [248, 268]}, {"entity": "distal part", "entity_type": "DNA", "pos": [276, 287]}, {"entity": "chromosome 14", "entity_type": "DNA", "pos": [291, 304]}, {"entity": "TCL1 locus", "entity_type": "DNA", "pos": [212, 222]}, {"entity": "TCL1 genomic locus", "entity_type": "DNA", "pos": [42, 60]}], "task": "NER"}
{"text": "These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11 .", "entity": [{"entity": "TCR locus", "entity_type": "DNA", "pos": [145, 154]}, {"entity": "TCL1", "entity_type": "DNA", "pos": [25, 29]}, {"entity": "preleukemic clonal cells", "entity_type": "cell line", "pos": [46, 70]}, {"entity": "14q11", "entity_type": "DNA", "pos": [158, 163]}], "task": "NER"}
{"text": "Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation .", "entity": [{"entity": "TCL1", "entity_type": "DNA", "pos": [16, 20]}], "task": "NER"}
{"text": "C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/ monocytes .", "entity": [{"entity": "monocytes", "entity_type": "cell type", "pos": [120, 129]}, {"entity": "C/EBP proteins", "entity_type": "protein", "pos": [0, 14]}, {"entity": "human immunodeficiency virus type 1 long terminal repeat", "entity_type": "DNA", "pos": [47, 103]}], "task": "NER"}
{"text": "Three binding sites for C/EBP proteins are found in the human immunodeficiency virus type 1 ( HIV-1 ) long terminal repeat ( LTR ) (V.M. Tesmer, A.Rajadhyaksha, J.Babin, and M.Bina, Proc.Natl.Acad.Sci. USA 90:7298-7302, 1993).", "entity": [{"entity": "C/EBP proteins", "entity_type": "protein", "pos": [24, 38]}, {"entity": "human immunodeficiency virus type 1 ( HIV-1 ) long terminal repeat", "entity_type": "DNA", "pos": [56, 122]}, {"entity": "LTR", "entity_type": "DNA", "pos": [125, 128]}], "task": "NER"}
{"text": "We have determined the functional role of C/EBP proteins and C/EBP sites in regulating transcription from the HIV- 1 LTR in monocytes /macrophages .", "entity": [{"entity": "LTR", "entity_type": "DNA", "pos": [117, 120]}, {"entity": "monocytes /macrophages", "entity_type": "cell type", "pos": [124, 146]}, {"entity": "C/EBP sites", "entity_type": "DNA", "pos": [61, 72]}, {"entity": "C/EBP proteins", "entity_type": "protein", "pos": [42, 56]}, {"entity": "HIV- 1 LTR", "entity_type": "DNA", "pos": [110, 120]}, {"entity": "monocytes", "entity_type": "cell type", "pos": [124, 133]}], "task": "NER"}
{"text": "Inhibition of endogenous C/EBP proteins , using either an excess of C/EBP binding sites or a trans- dominant negative inhibitor , demonstrated that C/EBP proteins are required for basal and activated levels of HIV-1 LTR transcription in the promonocytic cell line U937 .", "entity": [{"entity": "promonocytic cell line U937", "entity_type": "cell line", "pos": [241, 268]}, {"entity": "C/EBP proteins", "entity_type": "protein", "pos": [25, 39]}, {"entity": "C/EBP binding sites", "entity_type": "DNA", "pos": [68, 87]}, {"entity": "trans- dominant negative inhibitor", "entity_type": "DNA", "pos": [93, 127]}, {"entity": "endogenous C/EBP proteins", "entity_type": "protein", "pos": [14, 39]}, {"entity": "HIV-1 LTR", "entity_type": "DNA", "pos": [210, 219]}, {"entity": "LTR", "entity_type": "DNA", "pos": [216, 219]}, {"entity": "C/EBP proteins", "entity_type": "protein", "pos": [148, 162]}], "task": "NER"}
{"text": "Northern (RNA) blots and binding assays showed that NF-IL6 is the only known C/EBP family member which is increased when U937 cells are activated.", "entity": [{"entity": "NF-IL6", "entity_type": "protein", "pos": [52, 58]}, {"entity": "U937 cells", "entity_type": "cell line", "pos": [121, 131]}, {"entity": "C/EBP family member", "entity_type": "protein", "pos": [77, 96]}], "task": "NER"}
{"text": "Mutational analyses of the HIV-1 LTR showed that one C/EBP site is required for normal LTR transcription both before and after cellular activation and that the two 3' C/EBP sites are functionally equivalent.", "entity": [{"entity": "LTR", "entity_type": "DNA", "pos": [33, 36]}, {"entity": "HIV-1 LTR", "entity_type": "DNA", "pos": [27, 36]}, {"entity": "C/EBP sites", "entity_type": "DNA", "pos": [167, 178]}, {"entity": "LTR", "entity_type": "DNA", "pos": [87, 90]}, {"entity": "C/EBP site", "entity_type": "DNA", "pos": [53, 63]}], "task": "NER"}
{"text": "However, transcription from crippled HIV-1 LTRs lacking C/EBP sites can still be induced following activation of U937 cells .", "entity": [{"entity": "LTRs", "entity_type": "DNA", "pos": [43, 47]}, {"entity": "C/EBP sites", "entity_type": "DNA", "pos": [56, 67]}, {"entity": "U937 cells", "entity_type": "cell line", "pos": [113, 123]}, {"entity": "crippled HIV-1 LTRs", "entity_type": "DNA", "pos": [28, 47]}], "task": "NER"}
{"text": "Several models are suggested for how elevated NF-IL6 may participate in an autostimulatory loop involving HIV infection , macrophage activation , cytokine expression , and HIV replication .", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [146, 154]}, {"entity": "NF-IL6", "entity_type": "protein", "pos": [46, 52]}], "task": "NER"}
{"text": "Human immunodeficiency virus type-2 gene expression : two enhancers and their activation by T-cell activators .", "entity": [{"entity": "enhancers", "entity_type": "DNA", "pos": [58, 67]}, {"entity": "T-cell", "entity_type": "cell type", "pos": [92, 98]}], "task": "NER"}
{"text": "The human immunodeficiency viruses ( HIVs ) may include a spectrum of retroviruses with varying potential to infect their host, undergo long periods of latent infection , and induce pathology .", "entity": [], "task": "NER"}
{"text": "Since expression of the viruses is in large part regulated by the sequence elements in their long terminal repeats ( LTRs ), this study was directed to an analysis of the regulatory elements in the HIV-2 LTR .", "entity": [{"entity": "LTRs", "entity_type": "DNA", "pos": [117, 121]}, {"entity": "regulatory elements", "entity_type": "DNA", "pos": [171, 190]}, {"entity": "HIV-2 LTR", "entity_type": "DNA", "pos": [198, 207]}, {"entity": "long terminal repeats", "entity_type": "DNA", "pos": [93, 114]}, {"entity": "sequence elements", "entity_type": "DNA", "pos": [66, 83]}], "task": "NER"}
{"text": "The HIV-2 LTR was found to contain two enhancers .", "entity": [{"entity": "HIV-2 LTR", "entity_type": "DNA", "pos": [4, 13]}, {"entity": "enhancers", "entity_type": "DNA", "pos": [39, 48]}], "task": "NER"}
{"text": "One of these enhancers is, in part, identical to the HIV-1 enhancer .", "entity": [{"entity": "HIV-1 enhancer", "entity_type": "DNA", "pos": [53, 67]}, {"entity": "enhancers", "entity_type": "DNA", "pos": [13, 22]}], "task": "NER"}
{"text": "This enhancer in HIV-1 is the T-cell activation response element ; in HIV-2 , however, it is the second enhancer that is mainly responsible for activation in response to T-cell activators .", "entity": [{"entity": "second enhancer", "entity_type": "DNA", "pos": [97, 112]}, {"entity": "T-cell activation response element", "entity_type": "DNA", "pos": [30, 64]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [5, 13]}], "task": "NER"}
{"text": "The second enhancer interacts with two nuclear binding proteins (85 kD and 27 kD mobility) that appear to be required for optimal enhancer function and activation.", "entity": [{"entity": "enhancer", "entity_type": "DNA", "pos": [11, 19]}, {"entity": "nuclear binding proteins", "entity_type": "protein", "pos": [39, 63]}], "task": "NER"}
{"text": "Observations such as these encourage the speculation that there may be subtle differences in the regulation of HIV-1 and HIV-2 expression that may be relevant to the possible longer latency and reduced pathogenicity of HIV-2 .", "entity": [], "task": "NER"}
{"text": "NF-M ( chicken C/EBP beta ) induces eosinophilic differentiation and apoptosis in a hematopoietic progenitor cell line .", "entity": [{"entity": "hematopoietic progenitor cell line", "entity_type": "cell line", "pos": [84, 118]}, {"entity": "NF-M", "entity_type": "protein", "pos": [0, 4]}, {"entity": "chicken C/EBP beta", "entity_type": "protein", "pos": [7, 25]}], "task": "NER"}
{"text": "CAAT/enhancer binding proteins ( C/EBPs ) are transcriptional activators implicated in the differentiation processes of various cell lineages.", "entity": [{"entity": "CAAT/enhancer binding proteins", "entity_type": "protein", "pos": [0, 30]}, {"entity": "C/EBPs", "entity_type": "protein", "pos": [33, 39]}, {"entity": "CAAT/enhancer", "entity_type": "DNA", "pos": [0, 13]}], "task": "NER"}
{"text": "We have shown earlier that NF-M , the chicken homolog of C/EBP beta , is specifically expressed in myelomonocytic and eosinophilic cells of the hematopoietic system.", "entity": [{"entity": "chicken homolog", "entity_type": "protein", "pos": [38, 53]}, {"entity": "C/EBP beta", "entity_type": "protein", "pos": [57, 67]}, {"entity": "NF-M", "entity_type": "protein", "pos": [27, 31]}], "task": "NER"}
{"text": "To investigate the role of NF-M in hematopoietic cell lineage commitment, we constructed a conditional form of the protein by fusing it to the hormone binding domain of the human estrogen receptor .", "entity": [{"entity": "hematopoietic cell lineage", "entity_type": "cell line", "pos": [35, 61]}, {"entity": "human estrogen receptor", "entity_type": "protein", "pos": [173, 196]}, {"entity": "NF-M", "entity_type": "protein", "pos": [27, 31]}, {"entity": "hormone binding domain", "entity_type": "protein", "pos": [143, 165]}], "task": "NER"}
{"text": "This construct was stably expressed in a multipotent progenitor cell line transformed by the Myb-Ets oncoprotein .", "entity": [{"entity": "multipotent progenitor cell line", "entity_type": "cell line", "pos": [41, 73]}, {"entity": "Myb-Ets oncoprotein", "entity_type": "protein", "pos": [93, 112]}], "task": "NER"}
{"text": "We report here that both NF-M -dependent promoter constructs and resident genes could be activated by addition of beta-estradiol to the NF-M -estrogen receptor expressing progenitors .", "entity": [{"entity": "NF-M -estrogen receptor expressing progenitors", "entity_type": "cell line", "pos": [136, 182]}, {"entity": "NF-M", "entity_type": "protein", "pos": [25, 29]}, {"entity": "NF-M", "entity_type": "protein", "pos": [136, 140]}, {"entity": "NF-M -estrogen receptor", "entity_type": "protein", "pos": [136, 159]}, {"entity": "NF-M -dependent promoter constructs", "entity_type": "DNA", "pos": [25, 60]}], "task": "NER"}
{"text": "At the same time, we observed a down-regulation of progenitor-specific surface markers and the up-regulation of differentiation markers restricted to the eosinophil and myeloid lineages .", "entity": [{"entity": "eosinophil", "entity_type": "cell type", "pos": [154, 164]}, {"entity": "myeloid lineages", "entity_type": "cell type", "pos": [169, 185]}, {"entity": "differentiation markers", "entity_type": "protein", "pos": [112, 135]}, {"entity": "progenitor-specific surface markers", "entity_type": "protein", "pos": [51, 86]}], "task": "NER"}
{"text": "In addition to the onset of differentiation , cell death was induced with typical apoptotic features.", "entity": [], "task": "NER"}
{"text": "Our results suggest that NF-M plays an important role in commitment along the eosinophil lineage and in the induction of apoptosis .", "entity": [{"entity": "NF-M", "entity_type": "protein", "pos": [25, 29]}, {"entity": "eosinophil lineage", "entity_type": "cell type", "pos": [78, 96]}], "task": "NER"}
{"text": "Prolactin and interleukin-2 receptors in T lymphocytes signal through a MGF-STAT5-like transcription factor .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [41, 54]}, {"entity": "MGF-STAT5-like transcription factor", "entity_type": "protein", "pos": [72, 107]}, {"entity": "Prolactin", "entity_type": "protein", "pos": [0, 9]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [14, 27]}, {"entity": "interleukin-2 receptors", "entity_type": "protein", "pos": [14, 37]}], "task": "NER"}
{"text": "The cell surface receptors for PRL and interleukin-2 ( IL-2 ) are structurally distinct, but share regulatory tasks in T lymphocytes .", "entity": [{"entity": "PRL", "entity_type": "protein", "pos": [31, 34]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [39, 52]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [119, 132]}, {"entity": "IL-2", "entity_type": "protein", "pos": [55, 59]}], "task": "NER"}
{"text": "They can stimulate proliferation and activate transcription of over-lapping sets of genes of T cells .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [93, 100]}], "task": "NER"}
{"text": "PRL and IL-2 receptor activation are both linked to the Jak/Stat ( signal transducer and activator of transcription ) pathway .", "entity": [{"entity": "PRL", "entity_type": "protein", "pos": [0, 3]}, {"entity": "Jak/Stat", "entity_type": "protein", "pos": [56, 64]}, {"entity": "IL-2", "entity_type": "protein", "pos": [8, 12]}, {"entity": "signal transducer and activator of transcription", "entity_type": "protein", "pos": [67, 115]}], "task": "NER"}
{"text": "We investigated the ability of PRL and IL-2 to activate Stat proteins in different T cell lines .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [39, 43]}, {"entity": "T cell lines", "entity_type": "cell line", "pos": [83, 95]}, {"entity": "PRL", "entity_type": "protein", "pos": [31, 34]}, {"entity": "Stat proteins", "entity_type": "protein", "pos": [56, 69]}], "task": "NER"}
{"text": "The DNA binding specificities, the reactivities toward Stat-specific antisera , and the mol wt of IL-2 -and PRL -induced DNA-binding proteins in Nb2 and C196 T cell lines were investigated.", "entity": [{"entity": "PRL", "entity_type": "protein", "pos": [108, 111]}, {"entity": "PRL -induced DNA-binding proteins", "entity_type": "protein", "pos": [108, 141]}, {"entity": "IL-2", "entity_type": "protein", "pos": [98, 102]}], "task": "NER"}
{"text": "A comparison with the Stat proteins induced by interferon-gamma , PRL , and IL-6 in T47D mammary tumor cells was made.", "entity": [{"entity": "IL-6", "entity_type": "protein", "pos": [76, 80]}, {"entity": "PRL", "entity_type": "protein", "pos": [66, 69]}, {"entity": "Stat proteins", "entity_type": "protein", "pos": [22, 35]}, {"entity": "interferon-gamma", "entity_type": "protein", "pos": [47, 63]}, {"entity": "T47D mammary tumor cells", "entity_type": "cell line", "pos": [84, 108]}], "task": "NER"}
{"text": "We found that these parameters were indistinguishable for one of the PRL- and IL-2- induced factors .", "entity": [], "task": "NER"}
{"text": "A transcription factor closely related to mammary gland factor-Stat5 is rapidly activated upon interaction of IL-2 and PRL with their respective receptors.", "entity": [{"entity": "PRL", "entity_type": "protein", "pos": [119, 122]}, {"entity": "mammary gland factor-Stat5", "entity_type": "protein", "pos": [42, 68]}, {"entity": "IL-2", "entity_type": "protein", "pos": [110, 114]}], "task": "NER"}
{"text": "Activation of a second protein related to Stat1 was also observed.", "entity": [{"entity": "Stat1", "entity_type": "protein", "pos": [42, 47]}], "task": "NER"}
{"text": "Our results emphasize the role of PRL as a regulator of the immune response and indicate that the Stat factors mammary gland factor-Stat5 and Stat1 play a role in the regulation of gene expression during T cell development .", "entity": [{"entity": "Stat factors", "entity_type": "protein", "pos": [98, 110]}, {"entity": "PRL", "entity_type": "protein", "pos": [34, 37]}, {"entity": "mammary gland factor-Stat5", "entity_type": "protein", "pos": [111, 137]}, {"entity": "Stat1", "entity_type": "protein", "pos": [142, 147]}], "task": "NER"}
{"text": "ETS1 transactivates the human GM-CSF promoter in Jurkat T cells stimulated with PMA and ionomycin .", "entity": [{"entity": "Jurkat T cells", "entity_type": "cell line", "pos": [49, 63]}, {"entity": "ETS1", "entity_type": "protein", "pos": [0, 4]}, {"entity": "human GM-CSF promoter", "entity_type": "DNA", "pos": [24, 45]}], "task": "NER"}
{"text": "Activation of T helper cells results in coordinate expression of a number of cytokines involved in differentiation , proliferation and activation of the haematopoietic system .", "entity": [{"entity": "T helper cells", "entity_type": "cell type", "pos": [14, 28]}, {"entity": "cytokines", "entity_type": "protein", "pos": [77, 86]}], "task": "NER"}
{"text": "Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is one such cytokine whose increased expression results partly from increases in transcription .", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [72, 80]}, {"entity": "Granulocyte-macrophage colony-stimulating factor", "entity_type": "protein", "pos": [0, 48]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [51, 57]}], "task": "NER"}
{"text": "Cis-acting elements with NF kappa B , AP-1 and ETS-like motifs have been identified in the promoter region of the GM-CSF gene , which are important for transcriptional activity following PMA and ionomycin stimulation.", "entity": [{"entity": "NF kappa B", "entity_type": "protein", "pos": [25, 35]}, {"entity": "GM-CSF gene", "entity_type": "DNA", "pos": [114, 125]}, {"entity": "AP-1", "entity_type": "protein", "pos": [38, 42]}, {"entity": "Cis-acting elements", "entity_type": "DNA", "pos": [0, 19]}, {"entity": "ETS-like motifs", "entity_type": "DNA", "pos": [47, 62]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [114, 120]}], "task": "NER"}
{"text": "A number of the ETS family of transcription factors are expressed in T cells , including ETS1 and ELF1 .", "entity": [{"entity": "ETS family", "entity_type": "protein", "pos": [16, 26]}, {"entity": "ETS1", "entity_type": "protein", "pos": [89, 93]}, {"entity": "ELF1", "entity_type": "protein", "pos": [98, 102]}, {"entity": "T cells", "entity_type": "cell type", "pos": [69, 76]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [30, 51]}], "task": "NER"}
{"text": "Here we describe the ability of these factors to interact with a site ( GM5 ), located within the CLE0 element , -47 to -40 upstream of the GM-CSF transcription initiation site .", "entity": [{"entity": "GM5", "entity_type": "DNA", "pos": [72, 75]}, {"entity": "-47 to -40 upstream", "entity_type": "DNA", "pos": [113, 132]}, {"entity": "GM-CSF transcription initiation site", "entity_type": "DNA", "pos": [140, 176]}, {"entity": "CLE0 element", "entity_type": "DNA", "pos": [98, 110]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [140, 146]}], "task": "NER"}
{"text": "Exogenous ETS1 , but not ELF1 , can transactivate GM-CSF , through the GM5 site, in a PMA / ionomycin dependent manner .", "entity": [{"entity": "GM5", "entity_type": "DNA", "pos": [71, 74]}, {"entity": "ELF1", "entity_type": "protein", "pos": [25, 29]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [50, 56]}, {"entity": "ETS1", "entity_type": "protein", "pos": [10, 14]}], "task": "NER"}
{"text": "Other unidentified ETS-like factors present in Jurkat cells are also capable of binding GM5 .", "entity": [{"entity": "Jurkat cells", "entity_type": "cell line", "pos": [47, 59]}, {"entity": "GM5", "entity_type": "DNA", "pos": [88, 91]}, {"entity": "ETS-like factors", "entity_type": "protein", "pos": [19, 35]}], "task": "NER"}
{"text": "Mutation of the core ETS binding site from -GGAA- to -GGAT- prevents the binding of ETS-like factors with the exception of ETS1 .", "entity": [{"entity": "ETS-like factors", "entity_type": "protein", "pos": [84, 100]}, {"entity": "-GGAA- to -GGAT-", "entity_type": "DNA", "pos": [43, 59]}, {"entity": "ETS1", "entity_type": "protein", "pos": [123, 127]}, {"entity": "ETS binding site", "entity_type": "DNA", "pos": [21, 37]}], "task": "NER"}
{"text": "The GM-CSF promoter , modified in this way to be ETS1 specific , is fully responsive to PMA / ionomycin induction, in addition to ETS1 transactivation in the presence of PMA and ionomycin .", "entity": [{"entity": "ETS1", "entity_type": "protein", "pos": [49, 53]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [4, 10]}, {"entity": "GM-CSF promoter", "entity_type": "DNA", "pos": [4, 19]}, {"entity": "ETS1", "entity_type": "protein", "pos": [130, 134]}], "task": "NER"}
{"text": "Together these data suggest that ETS1 may be involved in mediating the increased GM-CSF production associated with T cell activation .", "entity": [{"entity": "T cell", "entity_type": "cell type", "pos": [115, 121]}, {"entity": "ETS1", "entity_type": "protein", "pos": [33, 37]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [81, 87]}], "task": "NER"}
{"text": "Quantitation of beta 1 triiodothyronine receptor mRNA in human tissues by competitive reverse transcription polymerase chain reaction .", "entity": [{"entity": "beta 1 triiodothyronine receptor", "entity_type": "protein", "pos": [16, 48]}, {"entity": "beta 1 triiodothyronine receptor mRNA", "entity_type": "RNA", "pos": [16, 53]}], "task": "NER"}
{"text": "Thyroid hormones act by binding to nuclear receptor proteins , the thyroid hormone receptors ( TR ) alpha and beta .", "entity": [{"entity": "nuclear receptor proteins", "entity_type": "protein", "pos": [35, 60]}, {"entity": "thyroid hormone receptors", "entity_type": "protein", "pos": [67, 92]}, {"entity": "TR", "entity_type": "protein", "pos": [95, 97]}], "task": "NER"}
{"text": "Data from cell culture and animal studies indicate that TR expression may be regulated to modulate target organ responsiveness to thyroid hormone .", "entity": [{"entity": "TR", "entity_type": "protein", "pos": [56, 58]}], "task": "NER"}
{"text": "To investigate whether such adaptive changes in TR expression occur in humans, we determined the mRNA levels of the hTR beta 1 in various thyroid states .", "entity": [{"entity": "hTR beta 1", "entity_type": "protein", "pos": [116, 126]}, {"entity": "TR", "entity_type": "protein", "pos": [48, 50]}], "task": "NER"}
{"text": "Patients with overt hypo -or hyper thyroidism were enrolled in the study.", "entity": [], "task": "NER"}
{"text": "Total RNA was isolated from peripheral blood mononuclear cells and hTR beta 1 mRNA levels determined by quantitative competitive reverse transcription PCR .", "entity": [{"entity": "hTR beta 1", "entity_type": "protein", "pos": [67, 77]}, {"entity": "Total RNA", "entity_type": "RNA", "pos": [0, 9]}, {"entity": "peripheral blood mononuclear cells", "entity_type": "cell type", "pos": [28, 62]}, {"entity": "hTR beta 1 mRNA", "entity_type": "RNA", "pos": [67, 82]}], "task": "NER"}
{"text": "For comparison, hTR beta 1 mRNA levels were determined in lymphocytes and normal thyroid tissue of euthyroid patients .", "entity": [{"entity": "hTR beta 1", "entity_type": "protein", "pos": [16, 26]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [58, 69]}, {"entity": "hTR beta 1 mRNA", "entity_type": "RNA", "pos": [16, 31]}], "task": "NER"}
{"text": "Human TR beta 1 mRNA levels in lymphocytes were 1.8 +/- 0.4, 1.9 +/- 0.5, 1.1 +/- 0.4 10(-18) mol/microgram RNA in hypo -, eu -and hyper thyroid patients , respectively, corresponding to an estimated 0.5 -2 molecules per cell.", "entity": [{"entity": "Human TR beta 1 mRNA", "entity_type": "RNA", "pos": [0, 20]}, {"entity": "Human TR beta 1", "entity_type": "protein", "pos": [0, 15]}, {"entity": "lymphocytes", "entity_type": "cell type", "pos": [31, 42]}], "task": "NER"}
{"text": "Although the mean hTR beta 1 mRNA levels were 40% lower in hyperthyroid than in euthyroid subjects, this difference did not reach statistical significance .", "entity": [{"entity": "hTR beta 1", "entity_type": "protein", "pos": [18, 28]}, {"entity": "hTR beta 1 mRNA", "entity_type": "RNA", "pos": [18, 33]}], "task": "NER"}
{"text": "Similar levels of hTR beta 1 mRNA levels were detected in thyroid gland from euthyroid patients .", "entity": [{"entity": "hTR beta 1 mRNA", "entity_type": "RNA", "pos": [18, 33]}, {"entity": "hTR beta 1", "entity_type": "protein", "pos": [18, 28]}], "task": "NER"}
{"text": "In summary, we developed an assay for the quantitative determination of hTR beta 1 mRNA levels in small human tissue samples , containing as little as 50 ng of total RNA.", "entity": [{"entity": "hTR beta 1", "entity_type": "protein", "pos": [72, 82]}, {"entity": "hTR beta 1 mRNA", "entity_type": "RNA", "pos": [72, 87]}], "task": "NER"}
{"text": "Absolute hTR beta 1 mRNA levels are very low with an estimated one molecule of mRNA being present in a mononuclear blood cell or thyrocyte .", "entity": [{"entity": "hTR beta 1", "entity_type": "protein", "pos": [9, 19]}, {"entity": "mononuclear blood cell", "entity_type": "cell type", "pos": [103, 125]}, {"entity": "mRNA", "entity_type": "RNA", "pos": [20, 24]}, {"entity": "hTR beta 1 mRNA", "entity_type": "RNA", "pos": [9, 24]}, {"entity": "thyrocyte", "entity_type": "cell type", "pos": [129, 138]}], "task": "NER"}
{"text": "No up-regulation of hTR beta 1 was seen in hypothyroid relative to euthyroid patients .", "entity": [{"entity": "hTR beta 1", "entity_type": "protein", "pos": [20, 30]}], "task": "NER"}
{"text": "However, there is a non-significant trend towards a down-regulation of hTR beta 1 mRNA levels in hyperthyroid patients .", "entity": [{"entity": "hTR beta 1 mRNA", "entity_type": "RNA", "pos": [71, 86]}, {"entity": "hTR beta 1", "entity_type": "protein", "pos": [71, 81]}], "task": "NER"}
{"text": "Multiple proteins interact with the nuclear inhibitory protein repressor element in the human interleukin-3 promoter .", "entity": [{"entity": "nuclear inhibitory protein repressor element", "entity_type": "DNA", "pos": [36, 80]}, {"entity": "human interleukin-3 promoter", "entity_type": "DNA", "pos": [88, 116]}, {"entity": "proteins", "entity_type": "protein", "pos": [9, 17]}], "task": "NER"}
{"text": "T cell expression of interleukin 3 ( IL-3 ) is directed by positive and negative cis-acting DNA elements clustered within 300 base pairs of the transcriptional start site .", "entity": [{"entity": "interleukin 3", "entity_type": "protein", "pos": [21, 34]}, {"entity": "transcriptional start site", "entity_type": "DNA", "pos": [144, 170]}, {"entity": "IL-3", "entity_type": "protein", "pos": [37, 41]}], "task": "NER"}
{"text": "A strong repressor element , termed nuclear inhibitory protein ( NIP ), was previously mapped to a segment of the IL-3 promoter between nucleotides -271 and -250 .", "entity": [{"entity": "nucleotides -271 and -250", "entity_type": "DNA", "pos": [136, 161]}, {"entity": "NIP", "entity_type": "protein", "pos": [65, 68]}, {"entity": "IL-3 promoter", "entity_type": "DNA", "pos": [114, 127]}, {"entity": "repressor element", "entity_type": "protein", "pos": [9, 26]}, {"entity": "nuclear inhibitory protein", "entity_type": "protein", "pos": [36, 62]}], "task": "NER"}
{"text": "Functional characterization of this element demonstrates that it can mediate repression when linked in cis to a heterologous promoter .", "entity": [{"entity": "heterologous promoter", "entity_type": "DNA", "pos": [112, 133]}], "task": "NER"}
{"text": "DNA binding experiments were carried out to characterize the repressor activity .", "entity": [], "task": "NER"}
{"text": "Using varying conditions, three distinct complexes were shown to interact specifically with the NIP region , although only one correlates with repressor activity .", "entity": [{"entity": "NIP region", "entity_type": "DNA", "pos": [96, 106]}, {"entity": "NIP", "entity_type": "protein", "pos": [96, 99]}], "task": "NER"}
{"text": "Complex 1 results from binding of a ubiquitous polypeptide that recognizes the 3' portion of this sequence and is not required for repression .", "entity": [{"entity": "Complex 1", "entity_type": "protein", "pos": [0, 9]}, {"entity": "3' portion", "entity_type": "DNA", "pos": [79, 89]}], "task": "NER"}
{"text": "Complex 2 corresponds to binding of transcription factor ( upstream stimulatory factor ) to an E-box motif in the 5' portion of the NIP region .", "entity": [{"entity": "E-box motif", "entity_type": "DNA", "pos": [95, 106]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [36, 56]}, {"entity": "Complex 2", "entity_type": "protein", "pos": [0, 9]}, {"entity": "upstream stimulatory factor", "entity_type": "protein", "pos": [59, 86]}, {"entity": "NIP", "entity_type": "protein", "pos": [132, 135]}, {"entity": "NIP region", "entity_type": "DNA", "pos": [132, 142]}, {"entity": "5' portion", "entity_type": "DNA", "pos": [114, 124]}], "task": "NER"}
{"text": "DNA binding specificity of complex 3 overlaps with that of upstream stimulatory factor but is clearly distinct.", "entity": [{"entity": "upstream stimulatory factor", "entity_type": "protein", "pos": [59, 86]}], "task": "NER"}
{"text": "To determine which of the latter two complexes represents NIP activity , we incorporated small alterations into the NIP site of an IL-3 promoter -linked reporter construct and examined their effects on NIP -mediated repression .", "entity": [{"entity": "NIP", "entity_type": "protein", "pos": [58, 61]}, {"entity": "NIP", "entity_type": "protein", "pos": [116, 119]}, {"entity": "NIP site", "entity_type": "DNA", "pos": [116, 124]}, {"entity": "NIP", "entity_type": "protein", "pos": [202, 205]}, {"entity": "IL-3 promoter -linked reporter construct", "entity_type": "DNA", "pos": [131, 171]}, {"entity": "IL-3 promoter", "entity_type": "DNA", "pos": [131, 144]}], "task": "NER"}
{"text": "Functional specificity for repression matches the DNA binding specificity of complex 3 ; both repressor activity and complex 3 binding require the consensus sequence CTCACNTNC .", "entity": [{"entity": "complex 3", "entity_type": "protein", "pos": [77, 86]}, {"entity": "complex 3", "entity_type": "protein", "pos": [117, 126]}, {"entity": "consensus sequence", "entity_type": "DNA", "pos": [147, 165]}], "task": "NER"}
{"text": "The hematopoietic transcription factor PU.1 is downregulated in human multiple myeloma cell lines .", "entity": [{"entity": "hematopoietic transcription factor", "entity_type": "protein", "pos": [4, 38]}, {"entity": "PU.1", "entity_type": "protein", "pos": [39, 43]}, {"entity": "human multiple myeloma cell lines", "entity_type": "cell line", "pos": [64, 97]}], "task": "NER"}
{"text": "PU.1 is a hematopoietic transcription factor belonging to the Ets-family .", "entity": [{"entity": "PU.1", "entity_type": "protein", "pos": [0, 4]}, {"entity": "hematopoietic transcription factor", "entity_type": "protein", "pos": [10, 44]}, {"entity": "Ets-family", "entity_type": "protein", "pos": [62, 72]}], "task": "NER"}
{"text": "It is identical to the Spi-1 oncogene , which is implicated in spleen focus-forming virus-induced murine erythroleukemias .", "entity": [{"entity": "Spi-1 oncogene", "entity_type": "DNA", "pos": [23, 37]}], "task": "NER"}
{"text": "PU.1 seems to be required for early development of multiple hematopoietic lineages , but its expression in mature cells is preferentially observed in cells of the B-cell-and monocyte/macrophage- differentiation lineage .", "entity": [{"entity": "PU.1", "entity_type": "protein", "pos": [0, 4]}, {"entity": "B-cell-and monocyte/macrophage- differentiation lineage", "entity_type": "cell type", "pos": [163, 218]}, {"entity": "multiple hematopoietic lineages", "entity_type": "cell type", "pos": [51, 82]}, {"entity": "mature cells", "entity_type": "cell type", "pos": [107, 119]}], "task": "NER"}
{"text": "It binds the so-called Pu box , an important tissue-specific regulatory DNA element present in a number of genes expressed in these cell lineages .", "entity": [{"entity": "tissue-specific regulatory DNA element", "entity_type": "DNA", "pos": [45, 83]}, {"entity": "cell lineages", "entity_type": "cell type", "pos": [132, 145]}, {"entity": "Pu box", "entity_type": "DNA", "pos": [23, 29]}], "task": "NER"}
{"text": "We have analyzed the expression and activity of PU.1 during human B-cell development using a panel of B-cell lines representing different stages of maturation, from early precursors to differentiated plasma cells .", "entity": [{"entity": "PU.1", "entity_type": "protein", "pos": [48, 52]}, {"entity": "B-cell lines", "entity_type": "cell line", "pos": [102, 114]}, {"entity": "early precursors", "entity_type": "cell line", "pos": [165, 181]}, {"entity": "differentiated plasma cells", "entity_type": "cell line", "pos": [185, 212]}], "task": "NER"}
{"text": "PU.1 mRNA expression and PU.1 DNA binding activity , as measured by Northern blot analysis and electrophoretic mobility shift assay , respectively, were evident in cell lines representing pro-B , pre-B , and mature B cells .", "entity": [{"entity": "cell lines", "entity_type": "cell line", "pos": [164, 174]}, {"entity": "PU.1", "entity_type": "protein", "pos": [0, 4]}, {"entity": "PU.1", "entity_type": "protein", "pos": [25, 29]}, {"entity": "PU.1 mRNA", "entity_type": "RNA", "pos": [0, 9]}], "task": "NER"}
{"text": "We could also show Pu box -dependent transactivation of a reporter gene in transient transfections in these cell lines .", "entity": [{"entity": "cell lines", "entity_type": "cell line", "pos": [108, 118]}, {"entity": "Pu box", "entity_type": "DNA", "pos": [19, 25]}], "task": "NER"}
{"text": "In contrast, in a number of multiple myeloma cell lines , representing differentiated, plasma cell-like B cells , PU.1 DNA binding activity , mRNA expression , and Pu box -dependent transactivation were absent or detectable at a very low level.", "entity": [{"entity": "multiple myeloma cell lines", "entity_type": "cell line", "pos": [28, 55]}, {"entity": "PU.1", "entity_type": "protein", "pos": [114, 118]}, {"entity": "Pu box", "entity_type": "DNA", "pos": [164, 170]}, {"entity": "differentiated, plasma cell-like B cells", "entity_type": "cell type", "pos": [71, 111]}], "task": "NER"}
{"text": "In lymphoblastoid cell lines , which exemplify an intermediate stage of B-cell differentiation , a reduced expression and activity were observed.", "entity": [{"entity": "lymphoblastoid cell lines", "entity_type": "cell line", "pos": [3, 28]}], "task": "NER"}
{"text": "The findings in the human multiple myeloma cell lines represent the first examples of B cells with downregulated PU.1 expression and apparently contradict observations in the murine system in which PU.1 is expressed and active in plasmacytoma cell lines .", "entity": [{"entity": "PU.1", "entity_type": "protein", "pos": [113, 117]}, {"entity": "PU.1", "entity_type": "protein", "pos": [198, 202]}, {"entity": "multiple myeloma cell lines", "entity_type": "cell line", "pos": [26, 53]}, {"entity": "human multiple myeloma cell lines", "entity_type": "cell line", "pos": [20, 53]}, {"entity": "plasmacytoma cell lines", "entity_type": "cell line", "pos": [230, 253]}, {"entity": "B cells", "entity_type": "cell type", "pos": [86, 93]}], "task": "NER"}
{"text": "At present, it is unclear whether the lack of PU.1 expression and activity in human multiple myeloma cell lines represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in terminally differentiated B cells .", "entity": [{"entity": "terminally differentiated B cells", "entity_type": "cell type", "pos": [221, 254]}, {"entity": "multiple myeloma cell lines", "entity_type": "cell line", "pos": [84, 111]}, {"entity": "human multiple myeloma cell lines", "entity_type": "cell line", "pos": [78, 111]}, {"entity": "PU.1", "entity_type": "protein", "pos": [46, 50]}, {"entity": "B cells", "entity_type": "cell type", "pos": [247, 254]}], "task": "NER"}
{"text": "Regulation of granulocyte-macrophage colony-stimulating factor and E-selectin expression in endothelial cells by cyclosporin A and the T-cell transcription factor NFAT .", "entity": [{"entity": "NFAT", "entity_type": "protein", "pos": [163, 167]}, {"entity": "E-selectin", "entity_type": "protein", "pos": [67, 77]}, {"entity": "endothelial cells", "entity_type": "cell type", "pos": [92, 109]}, {"entity": "T-cell transcription factor", "entity_type": "protein", "pos": [135, 162]}, {"entity": "granulocyte-macrophage colony-stimulating factor", "entity_type": "protein", "pos": [14, 62]}], "task": "NER"}
{"text": "Nuclear factor of activated T cells ( NFAT ) was originally described as a T-cell-specific transcription factor athat supported the activation of cytokine gene expression and mediated the immunoregulatory effects of cyclosporin A ( CsA ).", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [146, 154]}, {"entity": "T-cell-specific transcription factor", "entity_type": "protein", "pos": [75, 111]}, {"entity": "immunoregulatory", "entity_type": "protein", "pos": [188, 204]}, {"entity": "Nuclear factor of activated T cells", "entity_type": "protein", "pos": [0, 35]}, {"entity": "NFAT", "entity_type": "protein", "pos": [38, 42]}], "task": "NER"}
{"text": "As we observed that activated endothelial cells also expressed NFAT , we tested the antiinflammatory properties of CsA in endothelial cells .", "entity": [{"entity": "endothelial cells", "entity_type": "cell type", "pos": [30, 47]}, {"entity": "NFAT", "entity_type": "protein", "pos": [63, 67]}, {"entity": "activated endothelial cells", "entity_type": "cell type", "pos": [20, 47]}], "task": "NER"}
{"text": "Significantly, CsA completely suppressed the induction of NFAT in endothelial cells and inhibited the activity of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene regulatory elements that use NFAT by 60%.", "entity": [{"entity": "granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene regulatory elements", "entity_type": "DNA", "pos": [114, 198]}, {"entity": "NFAT", "entity_type": "protein", "pos": [58, 62]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [165, 171]}, {"entity": "NFAT", "entity_type": "protein", "pos": [208, 212]}, {"entity": "endothelial cells", "entity_type": "cell type", "pos": [66, 83]}, {"entity": "granulocyte-macrophage colony-stimulating factor", "entity_type": "protein", "pos": [114, 162]}], "task": "NER"}
{"text": "CsA similarly mediated a reduction of up to 65% in GM-CSF mRNA and protein expression in activated endothelial cells .", "entity": [{"entity": "activated endothelial cells", "entity_type": "cell type", "pos": [89, 116]}, {"entity": "GM-CSF mRNA", "entity_type": "RNA", "pos": [51, 62]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [51, 57]}], "task": "NER"}
{"text": "CsA also suppressed E-selectin , but not vascular cell adhesion molecule-1 ( VCAM-1 ) expression in endothelial cells, even though the E-selectin promoter is activated by NF-kappa B rather than NFAT .", "entity": [{"entity": "E-selectin promoter", "entity_type": "DNA", "pos": [135, 154]}, {"entity": "E-selectin", "entity_type": "protein", "pos": [20, 30]}, {"entity": "VCAM-1", "entity_type": "protein", "pos": [77, 83]}, {"entity": "E-selectin", "entity_type": "protein", "pos": [135, 145]}, {"entity": "NFAT", "entity_type": "protein", "pos": [194, 198]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [171, 181]}, {"entity": "vascular cell adhesion molecule-1", "entity_type": "protein", "pos": [41, 74]}], "task": "NER"}
{"text": "Hence, induction of cell surface expression of this leukocyte adhesion molecule by tumor necrosis factor (TNF)-alpha was reduced by 40% in the presence of CsA , and this was reflected by a 29% decrease in neutrophil adhesion .", "entity": [{"entity": "neutrophil", "entity_type": "cell type", "pos": [205, 215]}, {"entity": "tumor necrosis factor (TNF)-alpha", "entity_type": "protein", "pos": [83, 116]}, {"entity": "leukocyte adhesion molecule", "entity_type": "protein", "pos": [52, 79]}], "task": "NER"}
{"text": "The effects of CsA on endothelial cells were also detected at the chromatin structure level , as DNasel hypersensitive sites within both the GM-CSF enhancer and the E-selectin promoter were suppressed by CsA .", "entity": [{"entity": "DNasel hypersensitive sites", "entity_type": "DNA", "pos": [97, 124]}, {"entity": "E-selectin promoter", "entity_type": "DNA", "pos": [165, 184]}, {"entity": "chromatin", "entity_type": "DNA", "pos": [66, 75]}, {"entity": "E-selectin", "entity_type": "protein", "pos": [165, 175]}, {"entity": "endothelial cells", "entity_type": "cell type", "pos": [22, 39]}, {"entity": "DNasel", "entity_type": "protein", "pos": [97, 103]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [141, 147]}], "task": "NER"}
{"text": "This represents the first report of NFAT in endothelial cells and suggests mechanisms by which CsA could function as an antiinflammatory agent .", "entity": [{"entity": "endothelial cells", "entity_type": "cell type", "pos": [44, 61]}, {"entity": "NFAT", "entity_type": "protein", "pos": [36, 40]}], "task": "NER"}
{"text": "Costimulation requirement for AP-1 and NF-kappa B transcription factor activation in T cells .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [39, 49]}, {"entity": "T cells", "entity_type": "cell type", "pos": [85, 92]}, {"entity": "AP-1", "entity_type": "protein", "pos": [30, 34]}], "task": "NER"}
{"text": "The transcriptional activity of the IL-2 promoter requires T-cell costimulation delivered by the TCR and the auxiliary receptor CD28 .", "entity": [{"entity": "auxiliary receptor CD28", "entity_type": "protein", "pos": [109, 132]}, {"entity": "IL-2", "entity_type": "protein", "pos": [36, 40]}, {"entity": "IL-2 promoter", "entity_type": "DNA", "pos": [36, 49]}, {"entity": "TCR", "entity_type": "protein", "pos": [97, 100]}, {"entity": "T-cell", "entity_type": "cell type", "pos": [59, 65]}], "task": "NER"}
{"text": "Several transcription factors participate in IL-2 promoter activation , among which are AP-1 -like factors and NF-kappa B .", "entity": [{"entity": "AP-1 -like factors", "entity_type": "protein", "pos": [88, 106]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [8, 29]}, {"entity": "IL-2", "entity_type": "protein", "pos": [45, 49]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [111, 121]}, {"entity": "AP-1", "entity_type": "protein", "pos": [88, 92]}], "task": "NER"}
{"text": "Protein phosphorylation has an important role in the regulation of these two factors: (1) it induces the transactivating capacity of the AP-1 protein c-Jun ; and (2) it is involved in the release of the cytoplasmic inhibitor , I kappa B , from NF-kappa B , allowing translocation of the latter into the nucleus .", "entity": [{"entity": "AP-1 protein", "entity_type": "protein", "pos": [137, 149]}, {"entity": "c-Jun", "entity_type": "protein", "pos": [150, 155]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [227, 236]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [244, 254]}, {"entity": "cytoplasmic inhibitor", "entity_type": "protein", "pos": [203, 224]}], "task": "NER"}
{"text": "We have recently shown that both phosphorylation processes require T-cell costimulation .", "entity": [], "task": "NER"}
{"text": "Furthermore, in activated T cells , the kinetics of the two phosphorylation events are essentially similar.", "entity": [{"entity": "activated T cells", "entity_type": "cell type", "pos": [16, 33]}], "task": "NER"}
{"text": "According to our results, however, the kinases responsible for the two processes are distinct entities.", "entity": [], "task": "NER"}
{"text": "Whereas TPCK inhibits phosphorylation of I kappa B and, consequently, activation of NF-kappa B , it markedly enhances the activity of JNK , the MAP kinase-related kinase that phosphorylates the transactivation domain of c-Jun .", "entity": [{"entity": "c-Jun", "entity_type": "protein", "pos": [220, 225]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [41, 50]}, {"entity": "MAP kinase-related kinase", "entity_type": "protein", "pos": [144, 169]}, {"entity": "JNK", "entity_type": "protein", "pos": [134, 137]}, {"entity": "TPCK", "entity_type": "protein", "pos": [8, 12]}, {"entity": "transactivation domain", "entity_type": "protein", "pos": [194, 216]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [84, 94]}], "task": "NER"}
{"text": "We, therefore, propose the activation scheme presented in FIGURE 3 for T-cell costimulation .", "entity": [], "task": "NER"}
{"text": "Costimulation results in the activation of a signaling pathway that leads to the simultaneous induction of the two transcription factors , AP-1 and NF-kappa B .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [148, 158]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [115, 136]}, {"entity": "AP-1", "entity_type": "protein", "pos": [139, 143]}], "task": "NER"}
{"text": "Integration of the signals generated by TCR and CD28 engagement occurs along this pathway, which then bifurcates to induce I kappa B phosphorylation and NF-kappa B activation on the one hand, and JNK activation and c-Jun phosphorylation on the other.", "entity": [{"entity": "c-Jun", "entity_type": "protein", "pos": [215, 220]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [153, 163]}, {"entity": "JNK", "entity_type": "protein", "pos": [196, 199]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [123, 132]}, {"entity": "CD28", "entity_type": "protein", "pos": [48, 52]}, {"entity": "TCR", "entity_type": "protein", "pos": [40, 43]}], "task": "NER"}
{"text": "We are currently engaged in defining where the two signals integrate along the AP-1 / NF-kappa B pathway .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [86, 96]}, {"entity": "AP-1", "entity_type": "protein", "pos": [79, 83]}], "task": "NER"}
{"text": "Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B /Rel transcription factors .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [115, 136]}, {"entity": "myeloid cells", "entity_type": "cell type", "pos": [82, 95]}, {"entity": "NF-kappa B /Rel", "entity_type": "protein", "pos": [99, 114]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [99, 109]}], "task": "NER"}
{"text": "CD4+ macrophages in tissues such as lung , skin , and lymph nodes , promyelocytic cells in bone marrow , and peripheral blood monocytes serve as important targets and reservoirs for human immunodeficiency virus type 1 ( HIV-1 ) replication .", "entity": [{"entity": "peripheral blood monocytes", "entity_type": "cell type", "pos": [109, 135]}, {"entity": "promyelocytic cells", "entity_type": "cell type", "pos": [68, 87]}, {"entity": "CD4+ macrophages", "entity_type": "cell line", "pos": [0, 16]}], "task": "NER"}
{"text": "HIV-1 -infected myeloid cells are often diminished in their ability to participate in chemotaxis , phagocytosis , and intracellular killing .", "entity": [{"entity": "myeloid cells", "entity_type": "cell type", "pos": [16, 29]}], "task": "NER"}
{"text": "HIV-1 infection of myeloid cells can lead to the expression of surface receptors associated with cellular activation and/or differentiation that increase the responsiveness of these cells to cytokines secreted by neighboring cells as well as to bacteria or other pathogens.", "entity": [{"entity": "myeloid cells", "entity_type": "cell type", "pos": [19, 32]}, {"entity": "cytokines", "entity_type": "protein", "pos": [191, 200]}, {"entity": "surface receptors", "entity_type": "protein", "pos": [63, 80]}], "task": "NER"}
{"text": "Enhancement of HIV-1 replication is related in part to increased DNA-binding activity of cellular transcription factors such as NF-kappa B .", "entity": [{"entity": "cellular transcription factors", "entity_type": "protein", "pos": [89, 119]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [98, 119]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [128, 138]}], "task": "NER"}
{"text": "NF-kappa B binds to the HIV-1 enhancer region of the long terminal repeat and contributes to the inducibility of HIV-1 gene expression in response to multiple activating agents.", "entity": [{"entity": "long terminal repeat", "entity_type": "DNA", "pos": [53, 73]}, {"entity": "HIV-1 enhancer", "entity_type": "DNA", "pos": [24, 38]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [0, 10]}], "task": "NER"}
{"text": "Phosphorylation and degradation of the cytoplasmic inhibitor I kappa B alpha are crucial regulatory events in the activation of NF-kappa B DNA-binding activity .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [128, 138]}, {"entity": "cytoplasmic inhibitor", "entity_type": "protein", "pos": [39, 60]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [61, 70]}], "task": "NER"}
{"text": "Both N- and C- terminal residues of I kappa B alpha are required for inducer-mediated degradation .", "entity": [{"entity": "I kappa B", "entity_type": "protein", "pos": [36, 45]}], "task": "NER"}
{"text": "Chronic HIV-1 infection of myeloid cells leads to constitutive NF-kappa B DNA-binding activity and provides an intranuclear environment capable of perpetuating HIV-1 replication .", "entity": [{"entity": "myeloid cells", "entity_type": "cell type", "pos": [27, 40]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [63, 73]}], "task": "NER"}
{"text": "Increased intracellular stores of latent NF-kappa B may also result in rapid inducibility of NF-kappa B -dependent cytokine gene expression .", "entity": [{"entity": "latent NF-kappa B", "entity_type": "protein", "pos": [34, 51]}, {"entity": "cytokine", "entity_type": "protein", "pos": [115, 123]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [41, 51]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [93, 103]}], "task": "NER"}
{"text": "In response to secondary pathogenic infections or antigenic challenge, cytokine gene expression is rapidly induced, enhanced, and sustained over prolonged periods in HIV-1 -infected myeloid cells compared with uninfected cells .", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [71, 79]}, {"entity": "HIV-1 -infected myeloid cells", "entity_type": "cell line", "pos": [166, 195]}, {"entity": "uninfected cells", "entity_type": "cell type", "pos": [210, 226]}, {"entity": "myeloid cells", "entity_type": "cell type", "pos": [182, 195]}], "task": "NER"}
{"text": "Elevated levels of several inflammatory cytokines have been detected in the sera of HIV-1 -infected individuals .", "entity": [{"entity": "inflammatory cytokines", "entity_type": "protein", "pos": [27, 49]}], "task": "NER"}
{"text": "Secretion of myeloid cell-derived cytokines may both increase virus production and contribute to AIDS-associated disorders .", "entity": [{"entity": "myeloid cell-derived cytokines", "entity_type": "protein", "pos": [13, 43]}, {"entity": "cytokines", "entity_type": "protein", "pos": [34, 43]}], "task": "NER"}
{"text": "Steroid mediated lysis of lymphoblasts requires the DNA binding region of the steroid hormone receptor.", "entity": [{"entity": "lymphoblasts", "entity_type": "cell type", "pos": [26, 38]}], "task": "NER"}
{"text": "Glucocorticoids kill certain types of lymphoblasts , but the mechanisms are unknown.", "entity": [{"entity": "lymphoblasts", "entity_type": "cell type", "pos": [38, 50]}], "task": "NER"}
{"text": "It is clear that sufficient numbers of functional glucocorticoid receptors are required to mediate lysis, but whether they do so through the classical model of steroid hormone activation and modulation of gene expression has not been established.", "entity": [{"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [50, 74]}], "task": "NER"}
{"text": "In this report we have asked which region(s) of the steroid receptor are important for mediating lysis in leukemic T lymphoblasts .", "entity": [{"entity": "steroid receptor", "entity_type": "protein", "pos": [52, 68]}, {"entity": "lymphoblasts", "entity_type": "cell type", "pos": [117, 129]}, {"entity": "leukemic T lymphoblasts", "entity_type": "cell type", "pos": [106, 129]}], "task": "NER"}
{"text": "CEM-ICR 27 leukemic lymphoblasts , a clone of CEM cells which lack functional glucocorticoid receptors and therefore are neither lysed by dexamethasone nor capable of showing glutamine synthetase induction , were provided with steroid receptors by DNA transfections of various receptor gene constructs.", "entity": [{"entity": "glutamine synthetase", "entity_type": "protein", "pos": [175, 195]}, {"entity": "CEM-ICR 27 leukemic lymphoblasts", "entity_type": "cell line", "pos": [0, 32]}, {"entity": "steroid receptors", "entity_type": "protein", "pos": [227, 244]}, {"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [78, 102]}, {"entity": "lymphoblasts", "entity_type": "cell type", "pos": [20, 32]}, {"entity": "CEM cells", "entity_type": "cell line", "pos": [46, 55]}], "task": "NER"}
{"text": "We measured steroid mediated lysis , receptor number and induction of glutamine synthetase in the transfected cells .", "entity": [{"entity": "transfected cells", "entity_type": "cell line", "pos": [98, 115]}, {"entity": "glutamine synthetase", "entity_type": "protein", "pos": [70, 90]}], "task": "NER"}
{"text": "Our results provide evidence that the lysis mechanism in the ICR27 lymphoblasts is restored when functional receptor number is restored.", "entity": [{"entity": "ICR27 lymphoblasts", "entity_type": "cell line", "pos": [61, 79]}, {"entity": "lymphoblasts", "entity_type": "cell type", "pos": [67, 79]}], "task": "NER"}
{"text": "The DNA binding region specifying high affinity for GRE sites is required.", "entity": [{"entity": "GRE sites", "entity_type": "DNA", "pos": [52, 61]}, {"entity": "DNA binding region", "entity_type": "protein", "pos": [4, 22]}], "task": "NER"}
{"text": "Lysis is mediated by any steroid that allows for activation of the receptor containing such a region.", "entity": [], "task": "NER"}
{"text": "Our data support the view that steroid -mediated cell death occurs by a process requiring direct interaction of steroid -receptor complexes with the genome.", "entity": [{"entity": "steroid -receptor complexes", "entity_type": "protein", "pos": [112, 139]}], "task": "NER"}
{"text": "Functional characterization of the murine homolog of the B cell-specific coactivator BOB.1/OBF.1 .", "entity": [{"entity": "BOB.1/OBF.1", "entity_type": "protein", "pos": [85, 96]}, {"entity": "B cell-specific coactivator", "entity_type": "protein", "pos": [57, 84]}, {"entity": "murine homolog", "entity_type": "protein", "pos": [35, 49]}], "task": "NER"}
{"text": "B cell-specific transcriptional promoter activity mediated by the octamer motif requires the Oct1 or Oct2 protein and additional B cell-restricted cofactors .", "entity": [{"entity": "Oct2 protein", "entity_type": "protein", "pos": [101, 113]}, {"entity": "Oct1", "entity_type": "protein", "pos": [93, 97]}, {"entity": "octamer motif", "entity_type": "DNA", "pos": [66, 79]}, {"entity": "B cell-restricted cofactors", "entity_type": "protein", "pos": [129, 156]}], "task": "NER"}
{"text": "One such cofactor , BOB.1/OBF.1 , was recently isolated from human B cells .", "entity": [{"entity": "human B cells", "entity_type": "cell type", "pos": [61, 74]}, {"entity": "BOB.1/OBF.1", "entity_type": "protein", "pos": [20, 31]}, {"entity": "cofactor", "entity_type": "protein", "pos": [9, 17]}], "task": "NER"}
{"text": "Here, we describe the isolation and detailed characterization of the murine homolog .", "entity": [{"entity": "murine homolog", "entity_type": "protein", "pos": [69, 83]}], "task": "NER"}
{"text": "Full-length cDNAs and genomic clones were isolated, and the gene structure was determined. Comparison of the deduced amino acids shows 88% sequence identity between mouse and human BOB.1/OBF.1 .", "entity": [{"entity": "genomic clones", "entity_type": "DNA", "pos": [22, 36]}, {"entity": "cDNAs", "entity_type": "DNA", "pos": [12, 17]}], "task": "NER"}
{"text": "The NH2-terminal 126 amino acids of BOB.1/OBF.1 are both essential and sufficient for interaction with the POU domains of either Oct1 or Oct2 .", "entity": [{"entity": "Oct2", "entity_type": "protein", "pos": [137, 141]}, {"entity": "NH2-terminal 126 amino acids", "entity_type": "protein", "pos": [4, 32]}, {"entity": "POU domains", "entity_type": "protein", "pos": [107, 118]}, {"entity": "BOB.1/OBF.1", "entity_type": "protein", "pos": [36, 47]}, {"entity": "Oct1", "entity_type": "protein", "pos": [129, 133]}], "task": "NER"}
{"text": "This protein-protein interaction does not require the simultaneous binding of Oct proteins to DNA, and high resolution footprinting of the Oct -DNA interaction reveals that binding of BOB.1/OBF.1 to Oct1 or Oct2 does not alter the interaction with DNA.", "entity": [{"entity": "Oct1", "entity_type": "protein", "pos": [199, 203]}, {"entity": "Oct proteins", "entity_type": "protein", "pos": [78, 90]}, {"entity": "Oct", "entity_type": "DNA", "pos": [78, 81]}, {"entity": "BOB.1/OBF.1", "entity_type": "protein", "pos": [184, 195]}, {"entity": "Oct2", "entity_type": "protein", "pos": [207, 211]}], "task": "NER"}
{"text": "BOB.1/OBF.1 can efficiently activate octamer-dependent promoters in fibroblasts ; however, it fails to stimulate octamer-dependent enhancer activity .", "entity": [{"entity": "octamer-dependent enhancer", "entity_type": "DNA", "pos": [113, 139]}, {"entity": "fibroblasts", "entity_type": "cell type", "pos": [68, 79]}, {"entity": "BOB.1/OBF.1", "entity_type": "protein", "pos": [0, 11]}], "task": "NER"}
{"text": "Fusion of subdomains of BOB.1/OBF.1 with the GAL4 DNA binding domain reveals that both NH2- and COOH- terminal domains of BOB.1/OBF.1 contribute to full transactivation function, the COOH-terminal domain is more efficient in this transactivation assay .", "entity": [{"entity": "BOB.1/OBF.1", "entity_type": "protein", "pos": [24, 35]}, {"entity": "BOB.1/OBF.1", "entity_type": "protein", "pos": [122, 133]}, {"entity": "GAL4 DNA binding domain", "entity_type": "protein", "pos": [45, 68]}, {"entity": "COOH-terminal domain", "entity_type": "protein", "pos": [183, 203]}], "task": "NER"}
{"text": "Consistent with the failure of full-length BOB.1/OBF.1 to stimulate octamer-dependent enhancer elements in non B cells , the GAL4 fusions likewise only stimulate from a promoter-proximal position .", "entity": [{"entity": "full-length BOB.1/OBF.1", "entity_type": "protein", "pos": [31, 54]}, {"entity": "non B cells", "entity_type": "cell type", "pos": [107, 118]}, {"entity": "octamer-dependent enhancer elements", "entity_type": "DNA", "pos": [68, 103]}, {"entity": "GAL4 fusions", "entity_type": "protein", "pos": [125, 137]}, {"entity": "BOB.1/OBF.1", "entity_type": "protein", "pos": [43, 54]}], "task": "NER"}
{"text": "Anti-immunoglobulin M activates nuclear calcium/calmodulin-dependent protein kinase II in human B lymphocytes .", "entity": [{"entity": "nuclear calcium/calmodulin-dependent protein kinase II", "entity_type": "protein", "pos": [32, 86]}, {"entity": "human B lymphocytes", "entity_type": "cell type", "pos": [90, 109]}, {"entity": "Anti-immunoglobulin M", "entity_type": "protein", "pos": [0, 21]}], "task": "NER"}
{"text": "We and others have previously shown that the nuclear protein , Ets-1 , is phosphorylated in a calcium-dependent manner after ligation of immunoglobulin (Ig) M on B lymphocytes .", "entity": [{"entity": "immunoglobulin (Ig) M", "entity_type": "protein", "pos": [137, 158]}, {"entity": "Ets-1", "entity_type": "protein", "pos": [63, 68]}, {"entity": "B lymphocytes", "entity_type": "cell type", "pos": [162, 175]}, {"entity": "nuclear protein", "entity_type": "protein", "pos": [45, 60]}], "task": "NER"}
{"text": "As this phosphorylation was independent of protein kinase C activity , we tested whether a calcium/calmodulin-dependent protein kinase ( CaM kinase ) might phosphorylate the Ets-1 protein after elevation of intracellular free calcium concentrations .", "entity": [{"entity": "CaM kinase", "entity_type": "protein", "pos": [137, 147]}, {"entity": "protein kinase C", "entity_type": "protein", "pos": [43, 59]}, {"entity": "calcium/calmodulin-dependent protein kinase", "entity_type": "protein", "pos": [91, 134]}, {"entity": "Ets-1", "entity_type": "protein", "pos": [174, 179]}, {"entity": "Ets-1 protein", "entity_type": "protein", "pos": [174, 187]}], "task": "NER"}
{"text": "The dephosphorylated form of Ets-1 has been shown to bind to chromatin , suggesting that the operative kinase should be detectable in the nucleus .", "entity": [{"entity": "operative kinase", "entity_type": "protein", "pos": [93, 109]}, {"entity": "chromatin", "entity_type": "DNA", "pos": [61, 70]}, {"entity": "Ets-1", "entity_type": "protein", "pos": [29, 34]}], "task": "NER"}
{"text": "We prepared nuclear extracts from two human B cell lines in which increased intracellular free calcium levels correlated with increased phosphorylation of the Ets-1 protein.", "entity": [{"entity": "Ets-1", "entity_type": "protein", "pos": [159, 164]}, {"entity": "human B cell lines", "entity_type": "cell line", "pos": [38, 56]}], "task": "NER"}
{"text": "Activity of the CaM kinases was determined using a synthetic peptide substrate both in the absence and presence of an inhibitor specific for the CaM kinase family , KN-62 .", "entity": [{"entity": "CaM kinase family", "entity_type": "protein", "pos": [145, 162]}, {"entity": "CaM kinases", "entity_type": "protein", "pos": [16, 27]}, {"entity": "CaM kinase", "entity_type": "protein", "pos": [16, 26]}], "task": "NER"}
{"text": "Stimulation of cells with anti-IgM led to increased activity of a nuclear kinase that could phosphorylate the peptide, and this activity was reduced by 10 microM KN-62 .", "entity": [{"entity": "nuclear kinase", "entity_type": "protein", "pos": [66, 80]}, {"entity": "anti-IgM", "entity_type": "protein", "pos": [26, 34]}], "task": "NER"}
{"text": "Kinase activity was reduced in lysates preadsorbed using an antibody specific for CaM kinase II .", "entity": [{"entity": "antibody", "entity_type": "protein", "pos": [60, 68]}, {"entity": "CaM kinase II", "entity_type": "protein", "pos": [82, 95]}], "task": "NER"}
{"text": "Two-dimensional phosphopeptide maps of the Ets-1 protein from cells incubated with ionomycin or anti-IgM contained two unique phosphopeptides that were absent in untreated cells.", "entity": [{"entity": "Ets-1", "entity_type": "protein", "pos": [43, 48]}, {"entity": "anti-IgM", "entity_type": "protein", "pos": [96, 104]}], "task": "NER"}
{"text": "Incubation of isolated Ets-1 protein with purified CaM kinase II produced phosphorylation of peptides that migrated identically to those found in cells incubated with either anti-IgM or ionomycin .", "entity": [{"entity": "anti-IgM", "entity_type": "protein", "pos": [174, 182]}, {"entity": "CaM kinase II", "entity_type": "protein", "pos": [51, 64]}, {"entity": "isolated Ets-1 protein", "entity_type": "protein", "pos": [14, 36]}], "task": "NER"}
{"text": "These data suggest a model of signal transduction by the antigen receptor on B lymphocytes in which increased intracellular free calcium can rapidly activate nuclear CaM kinase II , potentially resulting in phosphorylation and regulation of DNA-binding proteins .", "entity": [{"entity": "DNA-binding proteins", "entity_type": "protein", "pos": [241, 261]}, {"entity": "B lymphocytes", "entity_type": "cell type", "pos": [77, 90]}, {"entity": "nuclear CaM kinase II", "entity_type": "protein", "pos": [158, 179]}, {"entity": "antigen receptor", "entity_type": "protein", "pos": [57, 73]}], "task": "NER"}
{"text": "Transcriptional activation and repression , two properties of the lymphoid-specific transcription factor Oct-2a .", "entity": [{"entity": "Oct-2a", "entity_type": "protein", "pos": [105, 111]}, {"entity": "lymphoid-specific transcription factor", "entity_type": "protein", "pos": [66, 104]}], "task": "NER"}
{"text": "The lymphoid-specific transcription factor Oct-2a contains two transcriptional activation domains which are located within the N-terminal and C-terminal regions .", "entity": [{"entity": "C-terminal regions", "entity_type": "protein", "pos": [142, 160]}, {"entity": "transcriptional activation domains", "entity_type": "protein", "pos": [63, 97]}, {"entity": "lymphoid-specific transcription factor", "entity_type": "protein", "pos": [4, 42]}, {"entity": "N-terminal", "entity_type": "protein", "pos": [127, 137]}, {"entity": "Oct-2a", "entity_type": "protein", "pos": [43, 49]}], "task": "NER"}
{"text": "To study their differential activation properties , we linked the isolated effector domains to the GAL4 DNA-binding domain .", "entity": [{"entity": "GAL4 DNA-binding domain", "entity_type": "protein", "pos": [99, 122]}, {"entity": "differential activation properties", "entity_type": "protein", "pos": [15, 49]}, {"entity": "effector domains", "entity_type": "protein", "pos": [75, 91]}], "task": "NER"}
{"text": "We have shown that both activating regions of Oct-2a , isolated from their natural context, can activate transcription as promoter factors .", "entity": [{"entity": "Oct-2a", "entity_type": "protein", "pos": [46, 52]}, {"entity": "promoter factors", "entity_type": "protein", "pos": [122, 138]}], "task": "NER"}
{"text": "In contrast to the C-terminus , activation by the N-terminal domain is dependent on a yet unidentified factor(s) binding to the simian virus 40 enhancer .", "entity": [{"entity": "N-terminal domain", "entity_type": "protein", "pos": [50, 67]}, {"entity": "C-terminus", "entity_type": "protein", "pos": [19, 29]}, {"entity": "simian virus 40 enhancer", "entity_type": "DNA", "pos": [128, 152]}], "task": "NER"}
{"text": "The results obtained by duplication of activation domains or their mixed combination suggest that the domains are functionally independent.", "entity": [{"entity": "activation domains", "entity_type": "protein", "pos": [39, 57]}], "task": "NER"}
{"text": "However, activation from a remote position could only be achieved with the C-terminus of Oct-2a in B cells .", "entity": [{"entity": "Oct-2a", "entity_type": "protein", "pos": [89, 95]}, {"entity": "B cells", "entity_type": "cell type", "pos": [99, 106]}, {"entity": "C-terminus", "entity_type": "protein", "pos": [75, 85]}], "task": "NER"}
{"text": "In lymphoid cells , higher activation levels were observed, suggesting that distinct B-cell-specific cofactors in concert with the effector domains of Oct-2a might be involved in mediating transcription from proximal and remote positions .", "entity": [{"entity": "Oct-2a", "entity_type": "protein", "pos": [151, 157]}, {"entity": "effector domains", "entity_type": "protein", "pos": [131, 147]}, {"entity": "B-cell-specific cofactors", "entity_type": "protein", "pos": [85, 110]}, {"entity": "lymphoid cells", "entity_type": "cell type", "pos": [3, 17]}], "task": "NER"}
{"text": "Furthermore, we identified a repression domain at the N-terminus of Oct-2a .", "entity": [{"entity": "Oct-2a", "entity_type": "protein", "pos": [68, 74]}], "task": "NER"}
{"text": "When transferred to a potent activator , transcriptional stimulation was inhibited efficiently.", "entity": [], "task": "NER"}
{"text": "These results underscore the modular structure of Oct-2a with separable domains for activation and repression and suggest that Oct-2a might have complex regulatory functions in vivo.", "entity": [{"entity": "Oct-2a", "entity_type": "protein", "pos": [50, 56]}, {"entity": "Oct-2a", "entity_type": "protein", "pos": [127, 133]}], "task": "NER"}
{"text": "Nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages and polymorphonuclear leukocytes requires the presence of the bacterial flagellum .", "entity": [{"entity": "macrophages", "entity_type": "cell type", "pos": [53, 64]}, {"entity": "polymorphonuclear leukocytes", "entity_type": "cell type", "pos": [69, 97]}], "task": "NER"}
{"text": "Whereas the mechanism of nonopsonic phagocytosis of Pseudomonas aeruginosa has been described, the bacterial ligands required are poorly understood.", "entity": [], "task": "NER"}
{"text": "To identify the requisite bacterial ligands , studies with isogenic mutants of P. aeruginosa PAK lacking pili , flagella , and the RpoN sigma factor were undertaken.", "entity": [{"entity": "RpoN sigma factor", "entity_type": "protein", "pos": [131, 148]}], "task": "NER"}
{"text": "The RpoN mutant , lacking pili , flagella , and nonpilus adhesins , bound poorly and was resistant to ingestion by both macrophages and neutrophils .", "entity": [{"entity": "nonpilus adhesins", "entity_type": "protein", "pos": [48, 65]}, {"entity": "macrophages", "entity_type": "cell type", "pos": [120, 131]}, {"entity": "neutrophils", "entity_type": "cell type", "pos": [136, 147]}], "task": "NER"}
{"text": "Pili were not absolutely required for binding or phagocytosis of P. aeruginosa .", "entity": [], "task": "NER"}
{"text": "The presence of a flagellum was not required for binding of P. aeruginosa to macrophages but was critical for the subsequent internalization of the bacterium , suggesting that this factor or a surface ligand associated with its assembly was responsible for stimulation of nonopsonic phagocytosis .", "entity": [{"entity": "macrophages", "entity_type": "cell type", "pos": [77, 88]}], "task": "NER"}
{"text": "Identification of essential GATA and Ets binding motifs within the promoter of the platelet glycoprotein Ib alpha gene .", "entity": [{"entity": "platelet glycoprotein Ib alpha gene", "entity_type": "DNA", "pos": [83, 118]}, {"entity": "GATA", "entity_type": "DNA", "pos": [28, 32]}, {"entity": "Ets binding motifs", "entity_type": "DNA", "pos": [37, 55]}], "task": "NER"}
{"text": "Platelet glycoprotein ( GP ) Ib-IX-V is a multisubunit adhesion receptor that supports platelet attachment to thrombogenic surfaces at sites of vascular injury .", "entity": [{"entity": "multisubunit adhesion receptor", "entity_type": "protein", "pos": [42, 72]}, {"entity": "Ib-IX-V", "entity_type": "protein", "pos": [29, 36]}, {"entity": "Platelet glycoprotein", "entity_type": "protein", "pos": [0, 21]}, {"entity": "GP", "entity_type": "protein", "pos": [24, 26]}], "task": "NER"}
{"text": "The congenital absence of the receptor results in a bleeding disorder associated with \"giant\" platelets , a condition linking the expression of the complex to platelet morphogenesis .", "entity": [{"entity": "\"giant\" platelets", "entity_type": "cell type", "pos": [86, 103]}], "task": "NER"}
{"text": "To understand better the expression of the GP Ib-IX-V complex , studies were undertaken to define the essential genetic elements supporting the expression of the alpha-subunit of the complex ( GP Ib alpha ).", "entity": [{"entity": "alpha-subunit", "entity_type": "protein", "pos": [162, 175]}, {"entity": "GP Ib-IX-V complex", "entity_type": "protein", "pos": [43, 61]}, {"entity": "GP Ib alpha", "entity_type": "protein", "pos": [193, 204]}, {"entity": "genetic elements", "entity_type": "DNA", "pos": [112, 128]}, {"entity": "Ib-IX-V", "entity_type": "protein", "pos": [46, 53]}, {"entity": "GP", "entity_type": "protein", "pos": [43, 45]}, {"entity": "GP", "entity_type": "protein", "pos": [193, 195]}], "task": "NER"}
{"text": "GP Ib alpha promoter activity was evaluated by transfection of human erythroleukemia cells with reporter plasmids coding for the enzyme , luciferase .", "entity": [{"entity": "enzyme", "entity_type": "protein", "pos": [129, 135]}, {"entity": "luciferase", "entity_type": "protein", "pos": [138, 148]}, {"entity": "human erythroleukemia cells", "entity_type": "cell type", "pos": [63, 90]}, {"entity": "GP", "entity_type": "protein", "pos": [0, 2]}, {"entity": "GP Ib alpha promoter", "entity_type": "DNA", "pos": [0, 20]}], "task": "NER"}
{"text": "Studies were initiated with a fragment extending 2,738 nucleotides 5' to the transcription start site and lead to the identification of 253 nucleotides retaining full promoter activity in human erythroleukemia cells .", "entity": [{"entity": "transcription start site", "entity_type": "DNA", "pos": [77, 101]}, {"entity": "human erythroleukemia cells", "entity_type": "cell type", "pos": [188, 215]}], "task": "NER"}
{"text": "In cells of nonhematopoietic lineage , human endothelial and HeLa cells , the GP Ib alpha promoter activity was no greater than background levels obtained with promoterless constructs .", "entity": [{"entity": "GP", "entity_type": "protein", "pos": [78, 80]}, {"entity": "promoterless constructs", "entity_type": "DNA", "pos": [160, 183]}, {"entity": "GP Ib alpha promoter", "entity_type": "DNA", "pos": [78, 98]}, {"entity": "nonhematopoietic lineage", "entity_type": "cell type", "pos": [12, 36]}, {"entity": "GP Ib alpha", "entity_type": "protein", "pos": [78, 89]}, {"entity": "HeLa cells", "entity_type": "cell type", "pos": [61, 71]}, {"entity": "human endothelial", "entity_type": "cell type", "pos": [39, 56]}], "task": "NER"}
{"text": "Gel shift assays and site-directed mutagenesis studies defined essential GATA and Ets binding motifs 93 and 150 nucleotides upstream of the transcription start site , a finding which further substantiates these elements as important determinants of megakaryocytic gene expression .", "entity": [{"entity": "GATA", "entity_type": "DNA", "pos": [73, 77]}, {"entity": "Ets binding motifs", "entity_type": "DNA", "pos": [82, 100]}, {"entity": "transcription start site", "entity_type": "DNA", "pos": [140, 164]}, {"entity": "93 and 150 nucleotides upstream", "entity_type": "DNA", "pos": [101, 132]}], "task": "NER"}
{"text": "The results define essential cis-acting elements responsible for the expression of GP Ib alpha and provide insights into molecular events coinciding with the release of normal platelets into the bloodstream .", "entity": [{"entity": "GP", "entity_type": "protein", "pos": [83, 85]}, {"entity": "normal platelets", "entity_type": "cell type", "pos": [169, 185]}, {"entity": "cis-acting elements", "entity_type": "DNA", "pos": [29, 48]}, {"entity": "GP Ib alpha", "entity_type": "protein", "pos": [83, 94]}], "task": "NER"}
{"text": "CD30 ligation induces nuclear factor-kappa B activation in human T cell lines .", "entity": [{"entity": "nuclear factor-kappa B", "entity_type": "protein", "pos": [22, 44]}, {"entity": "CD30", "entity_type": "protein", "pos": [0, 4]}, {"entity": "human T cell lines", "entity_type": "cell line", "pos": [59, 77]}], "task": "NER"}
{"text": "CD30 is a recently described member of the tumor necrosis factor /nerve growth factor receptor superfamily .", "entity": [{"entity": "CD30", "entity_type": "protein", "pos": [0, 4]}, {"entity": "tumor necrosis factor /nerve growth factor receptor superfamily", "entity_type": "protein", "pos": [43, 106]}, {"entity": "/nerve growth factor", "entity_type": "protein", "pos": [65, 85]}, {"entity": "tumor necrosis factor", "entity_type": "protein", "pos": [43, 64]}], "task": "NER"}
{"text": "In this report, we show that following incubation of L540 cells ( Hodgkin's disease -derived, T cell-like, CD30 + cells ) with the agonistic anti- CD30 monoclonal antibodies ( mAb ) M44 and M67 , two nuclear factor (NF)-kappa B DNA binding activities were induced in nuclear extracts , as determined in gel retardation assays .", "entity": [{"entity": "Hodgkin's disease -derived, T cell-like, CD30 + cells", "entity_type": "cell line", "pos": [66, 119]}, {"entity": "nuclear factor (NF)-kappa B", "entity_type": "protein", "pos": [200, 227]}, {"entity": "M44", "entity_type": "protein", "pos": [182, 185]}, {"entity": "L540 cells", "entity_type": "cell line", "pos": [53, 63]}, {"entity": "M67", "entity_type": "protein", "pos": [190, 193]}, {"entity": "mAb", "entity_type": "protein", "pos": [176, 179]}, {"entity": "agonistic anti- CD30 monoclonal antibodies", "entity_type": "protein", "pos": [131, 173]}, {"entity": "CD30", "entity_type": "protein", "pos": [107, 111]}, {"entity": "CD30", "entity_type": "protein", "pos": [147, 151]}], "task": "NER"}
{"text": "The effect of the mAb towards NF-kappa B activation was rapid, as it occurred within 20 min, and was sustained for up to 6 h.", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [30, 40]}, {"entity": "mAb", "entity_type": "protein", "pos": [18, 21]}], "task": "NER"}
{"text": "By comparison, an isotype-matched antibody had no effect on NF-kappa B activation .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [60, 70]}, {"entity": "isotype-matched antibody", "entity_type": "protein", "pos": [18, 42]}], "task": "NER"}
{"text": "Moreover, in human T helper (Th) clones functionally characterized as being of the type 0, type 1 and type 2 (28%, < 1% und 93% CD30+, respectively), the extent of CD30 -mediated NF-kappa B activation correlated with the proportion of CD30+ cells .", "entity": [{"entity": "human T helper (Th) clones", "entity_type": "cell line", "pos": [13, 39]}, {"entity": "CD30+ cells", "entity_type": "cell line", "pos": [235, 246]}, {"entity": "CD30", "entity_type": "protein", "pos": [128, 132]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [179, 189]}], "task": "NER"}
{"text": "In all cell lines investigated, the NF-kappa B complexes induced following CD30 engagement were shown to contain p50 NF-kappa B1 , p65 RelA , and possibly other transcription factors .", "entity": [{"entity": "CD30", "entity_type": "protein", "pos": [75, 79]}, {"entity": "NF-kappa B complexes", "entity_type": "protein", "pos": [36, 56]}, {"entity": "p65 RelA", "entity_type": "protein", "pos": [131, 139]}, {"entity": "p50 NF-kappa B1", "entity_type": "protein", "pos": [113, 128]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [36, 46]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [161, 182]}], "task": "NER"}
{"text": "Collectively, our results demonstrate that nuclear translocation and activation of NF-kappa B rank among the short-term cellular responses elicited following CD30 ligation .", "entity": [{"entity": "CD30", "entity_type": "protein", "pos": [158, 162]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [83, 93]}], "task": "NER"}
{"text": "Pathogenesis of atherosclerosis .", "entity": [], "task": "NER"}
{"text": "The earliest lesion in the development of an atherosclerotic plaque is the fatty streak .", "entity": [], "task": "NER"}
{"text": "This chronic inflammatory reaction results from a sequence of events that begins with the trapping of low density lipoprotein ( LDL ) in the subendothelial space of the artery wall .", "entity": [], "task": "NER"}
{"text": "The trapped LDL is seeded with oxidative species released by the overlying endothelium , and lipid oxidation is initiated within the LDL particle. Some of the lipids that result lead to the activation of NFkB-like transcription factors that cause the expression of genes whose protein products mediate monocyte binding , monocyte chemotaxis into the subendothelial space , and conversion into macrophages .", "entity": [{"entity": "NFkB-like transcription factors", "entity_type": "protein", "pos": [204, 235]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [214, 235]}, {"entity": "monocyte", "entity_type": "cell type", "pos": [302, 310]}, {"entity": "protein products", "entity_type": "protein", "pos": [277, 293]}, {"entity": "macrophages", "entity_type": "cell type", "pos": [393, 404]}], "task": "NER"}
{"text": "At least 1 major gene modulates the oxidation of LDL lipids and/or the biologic response to these lipids.", "entity": [{"entity": "major gene", "entity_type": "DNA", "pos": [11, 21]}], "task": "NER"}
{"text": "The inverse relation between high density lipoprotein ( HDL ) and atherosclerotic events may in part be due to enzymes associated with HDL that destroy the biologically active lipids generated in LDL .", "entity": [{"entity": "enzymes", "entity_type": "protein", "pos": [111, 118]}], "task": "NER"}
{"text": "Estrogen and progesterone receptors in vernal keratoconjunctivitis .", "entity": [{"entity": "Estrogen", "entity_type": "protein", "pos": [0, 8]}, {"entity": "progesterone receptors", "entity_type": "protein", "pos": [13, 35]}], "task": "NER"}
{"text": "PURPOSE: Sex-related influences have been implicated in the pathogenesis of vernal keratoconjunctivitis ( VKC ), an allergic eosinophilic disease.", "entity": [], "task": "NER"}
{"text": "METHODS: The authors evaluated tarsal and bulbar conjunctival biopsies from seven patients with severe and symptomatic VKC for the presence of estrogen and progesterone receptors by using monoclonal antibodies with a peroxidase-antiperoxidase technique .", "entity": [{"entity": "estrogen", "entity_type": "protein", "pos": [143, 151]}, {"entity": "monoclonal antibodies", "entity_type": "protein", "pos": [188, 209]}, {"entity": "progesterone receptors", "entity_type": "protein", "pos": [156, 178]}], "task": "NER"}
{"text": "RESULTS: Both the epithelium and subepithelium of the tarsal and bulbar conjunctiva of patients with VKC , but not those of four nonatopic control subjects , showed intense positive staining for estrogen and progesterone receptors .", "entity": [{"entity": "progesterone receptors", "entity_type": "protein", "pos": [208, 230]}], "task": "NER"}
{"text": "Immunofluorescence colocalization of both estrogen and progesterone receptors with eosinophil cationic protein showed that approximately 70% of positive cells were eosinophils .", "entity": [{"entity": "estrogen", "entity_type": "protein", "pos": [42, 50]}, {"entity": "eosinophil cationic protein", "entity_type": "protein", "pos": [83, 110]}, {"entity": "positive cells", "entity_type": "cell type", "pos": [144, 158]}, {"entity": "progesterone receptors", "entity_type": "protein", "pos": [55, 77]}, {"entity": "eosinophils", "entity_type": "cell type", "pos": [164, 175]}], "task": "NER"}
{"text": "CONCLUSIONS: Sexual hormones , through their receptors , may influence the activity of eosinophils in patients with VKC .", "entity": [{"entity": "receptors", "entity_type": "protein", "pos": [45, 54]}, {"entity": "eosinophils", "entity_type": "cell type", "pos": [87, 98]}], "task": "NER"}
{"text": "CIITA activates the expression of MHC class II genes in mouse T cells.", "entity": [{"entity": "CIITA", "entity_type": "protein", "pos": [0, 5]}, {"entity": "MHC class II genes", "entity_type": "DNA", "pos": [34, 52]}], "task": "NER"}
{"text": "It has long been a puzzle that MHC class II molecules are expressed in human T cells after activation but not in mouse T cells ; this expression is believed to play a role in the cell mediated immune response .", "entity": [{"entity": "MHC class II molecules", "entity_type": "protein", "pos": [31, 53]}, {"entity": "human T cells", "entity_type": "cell type", "pos": [71, 84]}, {"entity": "mouse T cells", "entity_type": "cell type", "pos": [113, 126]}], "task": "NER"}
{"text": "Recently the MHC class II transactivator ( CIITA ) has been reported to be a major regulatory factor for both the constitutive and IFN inducible expression of MHC class II genes .", "entity": [{"entity": "CIITA", "entity_type": "protein", "pos": [43, 48]}, {"entity": "MHC class II transactivator", "entity_type": "protein", "pos": [13, 40]}, {"entity": "major regulatory factor", "entity_type": "protein", "pos": [77, 100]}, {"entity": "MHC class II genes", "entity_type": "DNA", "pos": [159, 177]}], "task": "NER"}
{"text": "Here we show that human T cells expressing MHC class II have CIITA transcripts while MHC class II-negative human T cells and mouse T cells do not.", "entity": [{"entity": "human T cells", "entity_type": "cell type", "pos": [18, 31]}, {"entity": "human T cells", "entity_type": "cell type", "pos": [107, 120]}, {"entity": "CIITA", "entity_type": "protein", "pos": [61, 66]}, {"entity": "mouse T cells", "entity_type": "cell type", "pos": [125, 138]}], "task": "NER"}
{"text": "The expression of MHC class II genes in mouse T cells can be reconstituted upon transfection with the human CIITA cDNA .", "entity": [{"entity": "MHC class II genes", "entity_type": "DNA", "pos": [18, 36]}, {"entity": "mouse T cells", "entity_type": "cell type", "pos": [40, 53]}, {"entity": "CIITA", "entity_type": "protein", "pos": [108, 113]}, {"entity": "human CIITA cDNA", "entity_type": "DNA", "pos": [102, 118]}], "task": "NER"}
{"text": "These data indicate that the expression of CIITA explains the expression or lack of expression of MHC class II in human and mouse T cells respectively.", "entity": [{"entity": "MHC class II", "entity_type": "protein", "pos": [98, 110]}, {"entity": "CIITA", "entity_type": "protein", "pos": [43, 48]}, {"entity": "human", "entity_type": "cell type", "pos": [114, 119]}, {"entity": "mouse T cells", "entity_type": "cell type", "pos": [124, 137]}], "task": "NER"}
{"text": "Anti-Ro(SSA) autoantibodies are associated with T cell receptor beta genes in systemic lupus erythematosus patients .", "entity": [{"entity": "T cell receptor beta genes", "entity_type": "DNA", "pos": [48, 74]}, {"entity": "Anti-Ro(SSA) autoantibodies", "entity_type": "protein", "pos": [0, 27]}], "task": "NER"}
{"text": "Several of the heterogeneous clinical manifestations of systemic lupus erythematosus have been associated with specific autoantibodies .", "entity": [{"entity": "autoantibodies", "entity_type": "protein", "pos": [120, 134]}], "task": "NER"}
{"text": "Associations between HLA class II antigens and autoantibodies to the ribonucleoproteins Ro(SSA) and La(SSB) have been reported in these patients.", "entity": [{"entity": "ribonucleoproteins", "entity_type": "protein", "pos": [69, 87]}, {"entity": "Ro(SSA)", "entity_type": "protein", "pos": [88, 95]}, {"entity": "autoantibodies", "entity_type": "protein", "pos": [47, 61]}, {"entity": "HLA class II antigens", "entity_type": "protein", "pos": [21, 42]}, {"entity": "La(SSB)", "entity_type": "protein", "pos": [100, 107]}], "task": "NER"}
{"text": "Because HLA class II molecules present antigen to T cell receptors ( TCRs ), we have searched for a TCR gene associated with the production of anti- Ro(SSA) antibodies .", "entity": [{"entity": "Ro(SSA)", "entity_type": "protein", "pos": [149, 156]}, {"entity": "TCR gene", "entity_type": "DNA", "pos": [100, 108]}, {"entity": "anti- Ro(SSA) antibodies", "entity_type": "protein", "pos": [143, 167]}, {"entity": "TCRs", "entity_type": "protein", "pos": [69, 73]}, {"entity": "HLA class II molecules", "entity_type": "protein", "pos": [8, 30]}, {"entity": "T cell receptors", "entity_type": "protein", "pos": [50, 66]}], "task": "NER"}
{"text": "A pair of restriction fragment length polymorphisms ( RFLPs ), one of which hybridizes to the TCR constant region C beta 1 and the other to the C beta 2 gene , has been identified, suggesting these may be genotypic markers for an extended region of the TCR beta locus .", "entity": [{"entity": "TCR constant region C beta 1", "entity_type": "DNA", "pos": [94, 122]}, {"entity": "C beta 2 gene", "entity_type": "DNA", "pos": [144, 157]}, {"entity": "restriction fragment length polymorphisms", "entity_type": "DNA", "pos": [10, 51]}, {"entity": "RFLPs", "entity_type": "DNA", "pos": [54, 59]}, {"entity": "TCR beta locus", "entity_type": "DNA", "pos": [253, 267]}], "task": "NER"}
{"text": "This RFLP pair occurs in 76% of patients with Ro(SSA) precipitins, 84% of anti- Ro(SSA) -positive patients lacking La(SSB) precipitins , but only 41% of the patients lacking both precipitins (P = 0.0004).", "entity": [{"entity": "precipitins", "entity_type": "protein", "pos": [54, 65]}, {"entity": "Ro(SSA)", "entity_type": "protein", "pos": [46, 53]}, {"entity": "precipitins", "entity_type": "protein", "pos": [123, 134]}, {"entity": "La(SSB)", "entity_type": "protein", "pos": [115, 122]}, {"entity": "Ro(SSA)", "entity_type": "protein", "pos": [80, 87]}, {"entity": "RFLP pair", "entity_type": "DNA", "pos": [5, 14]}], "task": "NER"}
{"text": "This disproportionate occurrence in a subset of lupus patients indicates that these RFLPs are not disease susceptibility markers, but rather are important markers for TCR genes whose products are involved in the production of anti- Ro(SSA) antibodies .", "entity": [{"entity": "TCR genes", "entity_type": "DNA", "pos": [167, 176]}, {"entity": "RFLPs", "entity_type": "DNA", "pos": [84, 89]}, {"entity": "anti- Ro(SSA) antibodies", "entity_type": "protein", "pos": [226, 250]}, {"entity": "Ro(SSA)", "entity_type": "protein", "pos": [232, 239]}], "task": "NER"}
{"text": "The majority of patients who have these RFLPs and HLA class II antigens previously associated with the anti- Ro(SSA) response make this antibody, suggesting that interactions between products of these loci occur in response to Ro(SSA) .", "entity": [{"entity": "RFLPs", "entity_type": "DNA", "pos": [40, 45]}, {"entity": "Ro(SSA)", "entity_type": "protein", "pos": [109, 116]}, {"entity": "Ro(SSA)", "entity_type": "protein", "pos": [227, 234]}, {"entity": "HLA class II antigens", "entity_type": "protein", "pos": [50, 71]}, {"entity": "loci occur", "entity_type": "DNA", "pos": [201, 211]}], "task": "NER"}
{"text": "Inhibition of NF-AT -dependent transcription by NF-kappa B : implications for differential gene expression in T helper cell subsets .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [48, 58]}, {"entity": "T helper cell subsets", "entity_type": "cell type", "pos": [110, 131]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [14, 19]}], "task": "NER"}
{"text": "Activation of individual CD4+ T cells results in differential lymphokine expression : interleukin 2 ( IL-2 ) is preferentially produced by T helper type 1 (TH1) cells , which are involved in cell-mediated immune responses, whereas IL-4 is synthesized by TH2 cells , which are essential for humoral immunity .", "entity": [{"entity": "IL-4", "entity_type": "protein", "pos": [231, 235]}, {"entity": "interleukin 2", "entity_type": "protein", "pos": [86, 99]}, {"entity": "T helper type 1 (TH1) cells", "entity_type": "cell line", "pos": [139, 166]}, {"entity": "TH2 cells", "entity_type": "cell line", "pos": [254, 263]}, {"entity": "lymphokine", "entity_type": "protein", "pos": [62, 72]}, {"entity": "IL-2", "entity_type": "protein", "pos": [102, 106]}, {"entity": "CD4+ T cells", "entity_type": "cell line", "pos": [25, 37]}], "task": "NER"}
{"text": "The Ca(2+) -dependent factor NF-ATp plays a key role in the inducible transcription of both these lymphokine genes .", "entity": [{"entity": "lymphokine genes", "entity_type": "DNA", "pos": [98, 114]}, {"entity": "Ca(2+) -dependent factor", "entity_type": "protein", "pos": [4, 28]}, {"entity": "NF-ATp", "entity_type": "protein", "pos": [29, 35]}], "task": "NER"}
{"text": "However, while IL2 expression requires the contribution of Ca(2+)- and protein kinase C -dependent signals , we report that activation of human IL4 transcription through the Ca(2+)-dependent pathway is diminished by protein kinase C stimulation in Jurkat T cells .", "entity": [{"entity": "human IL4", "entity_type": "protein", "pos": [138, 147]}, {"entity": "IL2", "entity_type": "protein", "pos": [15, 18]}, {"entity": "protein kinase C", "entity_type": "protein", "pos": [71, 87]}, {"entity": "protein kinase C", "entity_type": "protein", "pos": [216, 232]}, {"entity": "Jurkat T cells", "entity_type": "cell line", "pos": [248, 262]}], "task": "NER"}
{"text": "This phenomenon is due to mutually exclusive binding of NF-ATp and NF-kappa B to the P sequence , an element located 69 bp upstream of the IL4 transcription initiation site .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [67, 77]}, {"entity": "NF-ATp", "entity_type": "protein", "pos": [56, 62]}, {"entity": "P sequence", "entity_type": "DNA", "pos": [85, 95]}, {"entity": "69 bp upstream", "entity_type": "DNA", "pos": [117, 131]}, {"entity": "IL4 transcription initiation site", "entity_type": "DNA", "pos": [139, 172]}], "task": "NER"}
{"text": "Human IL4 promoter -mediated transcription is downregulated in Jurkat cells stimulated with the NF-kappa B -activating cytokine tumor necrosis factor alpha and suppressed in RelA -overexpressing cells .", "entity": [{"entity": "Jurkat cells", "entity_type": "cell line", "pos": [63, 75]}, {"entity": "NF-kappa B -activating cytokine", "entity_type": "protein", "pos": [96, 127]}, {"entity": "Human IL4 promoter", "entity_type": "DNA", "pos": [0, 18]}, {"entity": "tumor necrosis factor alpha", "entity_type": "protein", "pos": [128, 155]}, {"entity": "RelA -overexpressing cells", "entity_type": "cell line", "pos": [174, 200]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [96, 106]}, {"entity": "RelA", "entity_type": "protein", "pos": [174, 178]}], "task": "NER"}
{"text": "In contrast, protein kinase C stimulation or RelA overexpression does not affect the activity of a human IL4 promoter containing a mouse P sequence , which is a higher-affinity site for NF-ATp and a lower-affinity site for RelA .", "entity": [{"entity": "NF-ATp", "entity_type": "protein", "pos": [186, 192]}, {"entity": "protein kinase C", "entity_type": "protein", "pos": [13, 29]}, {"entity": "RelA", "entity_type": "protein", "pos": [45, 49]}, {"entity": "mouse P sequence", "entity_type": "DNA", "pos": [131, 147]}, {"entity": "lower-affinity site", "entity_type": "DNA", "pos": [199, 218]}, {"entity": "higher-affinity site", "entity_type": "DNA", "pos": [161, 181]}, {"entity": "human IL4", "entity_type": "protein", "pos": [99, 108]}, {"entity": "human IL4 promoter", "entity_type": "DNA", "pos": [99, 117]}, {"entity": "P sequence", "entity_type": "DNA", "pos": [137, 147]}, {"entity": "RelA", "entity_type": "protein", "pos": [223, 227]}], "task": "NER"}
{"text": "Thus, competition between two general transcriptional activators , RelA and NF-ATp , mediates the inhibitory effect of protein kinase C stimulation on IL4 expression and may contribute to differential gene expression in TH cells .", "entity": [{"entity": "protein kinase C", "entity_type": "protein", "pos": [119, 135]}, {"entity": "IL4", "entity_type": "protein", "pos": [151, 154]}, {"entity": "RelA", "entity_type": "protein", "pos": [67, 71]}, {"entity": "transcriptional activators", "entity_type": "protein", "pos": [38, 64]}, {"entity": "NF-ATp", "entity_type": "protein", "pos": [76, 82]}, {"entity": "TH cells", "entity_type": "cell line", "pos": [220, 228]}], "task": "NER"}
{"text": "Regulation of the balance of cytokine production and the signal transducer and activator of transcription ( STAT ) transcription factor activity by cytokines and inflammatory synovial fluids.", "entity": [{"entity": "STAT", "entity_type": "protein", "pos": [108, 112]}, {"entity": "cytokine", "entity_type": "protein", "pos": [29, 37]}, {"entity": "cytokines", "entity_type": "protein", "pos": [148, 157]}], "task": "NER"}
{"text": "The balance between type 1 and 2 T helper cell cytokine production plays an important role in several animal models of autoimmunity, and skewed patterns of cytokine expression have been described in human inflammatory diseases .", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [47, 55]}], "task": "NER"}
{"text": "Many cytokines activate signal transducer and activation of transcription ( STAT ) transcription factors , which, in turn, activate transcription of inflammatory effector genes.", "entity": [{"entity": "signal transducer and activation of transcription ( STAT ) transcription factors", "entity_type": "protein", "pos": [24, 104]}, {"entity": "cytokines", "entity_type": "protein", "pos": [5, 14]}, {"entity": "STAT", "entity_type": "protein", "pos": [76, 80]}], "task": "NER"}
{"text": "We used mononuclear cell priming cultures and inflammatory synovial fluids ( SFs ) derived from arthritis patients to examine the regulation of cytokine production and STAT activity by an inflammatory synovial microenvironment .", "entity": [{"entity": "cytokine", "entity_type": "protein", "pos": [144, 152]}, {"entity": "STAT", "entity_type": "protein", "pos": [168, 172]}, {"entity": "mononuclear cell priming cultures", "entity_type": "cell line", "pos": [8, 41]}, {"entity": "inflammatory synovial fluids", "entity_type": "cell type", "pos": [46, 74]}, {"entity": "SFs", "entity_type": "cell type", "pos": [77, 80]}], "task": "NER"}
{"text": "Exposure to SFs during priming resulted in an 81% inhibition of interferon (IFN)-gamma , but not interleukin (IL) 4 , production by effector cells generated in priming cultures.", "entity": [{"entity": "SFs", "entity_type": "cell type", "pos": [12, 15]}, {"entity": "interleukin (IL) 4", "entity_type": "protein", "pos": [97, 115]}, {"entity": "effector cells", "entity_type": "cell type", "pos": [132, 146]}, {"entity": "interferon (IFN)-gamma", "entity_type": "protein", "pos": [64, 86]}], "task": "NER"}
{"text": "SF suppression was mediated by IL-4 and IL-10 and inhibition of IL-12 expression , and it was reversed in a dominant fashion by exogenous IL-12.", "entity": [{"entity": "IL-4", "entity_type": "protein", "pos": [31, 35]}, {"entity": "IL-10", "entity_type": "protein", "pos": [40, 45]}, {"entity": "IL-12", "entity_type": "protein", "pos": [64, 69]}], "task": "NER"}
{"text": "SFs blocked the sustained activity of transcription factor Stat1 , but not Stat3 , during the priming period, and Stat1 activity was differentially regulated by cytokines in parallel with their positive or negative regulation of IFN-gamma production .", "entity": [{"entity": "Stat1", "entity_type": "protein", "pos": [59, 64]}, {"entity": "Stat3", "entity_type": "protein", "pos": [75, 80]}, {"entity": "cytokines", "entity_type": "protein", "pos": [161, 170]}, {"entity": "IFN-gamma", "entity_type": "protein", "pos": [229, 238]}, {"entity": "transcription factor Stat1", "entity_type": "protein", "pos": [38, 64]}, {"entity": "SFs", "entity_type": "cell type", "pos": [0, 3]}], "task": "NER"}
{"text": "Active Stat3 , but not Stat1 , was detected in cells from inflamed joints .", "entity": [{"entity": "Stat3", "entity_type": "protein", "pos": [7, 12]}, {"entity": "Stat1", "entity_type": "protein", "pos": [23, 28]}], "task": "NER"}
{"text": "These results suggest a role for altered balance of Stat1 and Stat3 transcriptional activity in the regulation of T cell differentiation and in the pathogenesis of inflammatory synovitis .", "entity": [{"entity": "T cell", "entity_type": "cell type", "pos": [114, 120]}], "task": "NER"}
{"text": "Triggering of complement receptors CR1 ( CD35 ) and CR3 ( CD11b/CD18 ) induces nuclear translocation of NF-kappa B ( p50/p65 ) in human monocytes and enhances viral replication in HIV-infected monocytic cells .", "entity": [{"entity": "CD11b/CD18", "entity_type": "protein", "pos": [58, 68]}, {"entity": "CD35", "entity_type": "protein", "pos": [41, 45]}, {"entity": "p50/p65", "entity_type": "protein", "pos": [117, 124]}, {"entity": "CR1", "entity_type": "protein", "pos": [35, 38]}, {"entity": "HIV-infected monocytic cells", "entity_type": "cell type", "pos": [180, 208]}, {"entity": "complement receptors", "entity_type": "protein", "pos": [14, 34]}, {"entity": "human monocytes", "entity_type": "cell type", "pos": [130, 145]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [104, 114]}, {"entity": "CR3", "entity_type": "protein", "pos": [52, 55]}], "task": "NER"}
{"text": "Monocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time.", "entity": [{"entity": "Monocyte/macrophages", "entity_type": "cell type", "pos": [0, 20]}], "task": "NER"}
{"text": "Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro.", "entity": [{"entity": "TNF-alpha", "entity_type": "protein", "pos": [99, 108]}, {"entity": "cytokines", "entity_type": "protein", "pos": [81, 90]}], "task": "NER"}
{"text": "The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B ( p50/p65 ), which binds to a specific sequence in the HIV-long terminal repeat .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [124, 134]}, {"entity": "DNA-binding heterodimer", "entity_type": "protein", "pos": [100, 123]}, {"entity": "HIV-long terminal repeat", "entity_type": "DNA", "pos": [190, 214]}, {"entity": "p50/p65", "entity_type": "protein", "pos": [137, 144]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [22, 31]}], "task": "NER"}
{"text": "The present study demonstrates that triggering of complement receptors CR1 ( CD35 ) and CR3 ( CD11b/CD18 ) enhances viral replication in HIV-infected human monocytic cells .", "entity": [{"entity": "CD11b/CD18", "entity_type": "protein", "pos": [94, 104]}, {"entity": "complement receptors", "entity_type": "protein", "pos": [50, 70]}, {"entity": "CR3", "entity_type": "protein", "pos": [88, 91]}, {"entity": "CD35", "entity_type": "protein", "pos": [77, 81]}, {"entity": "CR1", "entity_type": "protein", "pos": [71, 74]}, {"entity": "HIV-infected human monocytic cells", "entity_type": "cell line", "pos": [137, 171]}], "task": "NER"}
{"text": "Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti- CR1 or anti- CR3 Abs or with C3 fragments .", "entity": [{"entity": "CR3", "entity_type": "protein", "pos": [187, 190]}, {"entity": "C3 fragments", "entity_type": "protein", "pos": [203, 215]}, {"entity": "CR1", "entity_type": "protein", "pos": [174, 177]}, {"entity": "F(ab')2 fragments", "entity_type": "protein", "pos": [136, 153]}, {"entity": "monoclonal anti- CR1", "entity_type": "protein", "pos": [157, 177]}, {"entity": "Monocytic cell lines", "entity_type": "cell line", "pos": [0, 20]}, {"entity": "anti- CR3 Abs", "entity_type": "protein", "pos": [181, 194]}], "task": "NER"}
{"text": "Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS .", "entity": [{"entity": "p24 Ag", "entity_type": "protein", "pos": [108, 114]}, {"entity": "CR1", "entity_type": "protein", "pos": [15, 18]}, {"entity": "control cultures", "entity_type": "cell line", "pos": [172, 188]}, {"entity": "cell cultures", "entity_type": "cell line", "pos": [118, 131]}, {"entity": "CR3", "entity_type": "protein", "pos": [22, 25]}], "task": "NER"}
{"text": "We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50/p65 in infected cells .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [88, 98]}, {"entity": "CR3", "entity_type": "protein", "pos": [47, 50]}, {"entity": "infected cells", "entity_type": "cell type", "pos": [110, 124]}, {"entity": "p50/p65", "entity_type": "protein", "pos": [99, 106]}, {"entity": "CR1", "entity_type": "protein", "pos": [40, 43]}], "task": "NER"}
{"text": "Translocation of NF-kappa B p50/p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors .", "entity": [{"entity": "CR1", "entity_type": "protein", "pos": [79, 82]}, {"entity": "p50/p65", "entity_type": "protein", "pos": [28, 35]}, {"entity": "CR3", "entity_type": "protein", "pos": [86, 89]}, {"entity": "uninfected peripheral blood monocytes", "entity_type": "cell type", "pos": [93, 130]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [17, 27]}], "task": "NER"}
{"text": "The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha .", "entity": [{"entity": "rhTNF-alpha", "entity_type": "protein", "pos": [96, 107]}], "task": "NER"}
{"text": "TNF-alpha did not mediate the translocation of NF-kappa B p50/p65 induced by triggering of complement receptors .", "entity": [{"entity": "complement receptors", "entity_type": "protein", "pos": [91, 111]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [0, 9]}, {"entity": "p50/p65", "entity_type": "protein", "pos": [58, 65]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [47, 57]}], "task": "NER"}
{"text": "Taken together, these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor -mediated nuclear translocation of the NF-kappa B complex .", "entity": [{"entity": "complement-opsonized particles", "entity_type": "protein", "pos": [145, 175]}, {"entity": "C3 receptor", "entity_type": "protein", "pos": [231, 242]}, {"entity": "infected monocytes", "entity_type": "cell type", "pos": [88, 106]}, {"entity": "NF-kappa B complex", "entity_type": "protein", "pos": [282, 300]}], "task": "NER"}
{"text": "Attenuation of gamma interferon -induced tyrosine phosphorylation in mononuclear phagocytes infected with Leishmania donovani : selective inhibition of signaling through Janus kinases and Stat1 .", "entity": [{"entity": "mononuclear phagocytes", "entity_type": "cell type", "pos": [69, 91]}, {"entity": "Janus kinases", "entity_type": "protein", "pos": [170, 183]}, {"entity": "gamma interferon", "entity_type": "protein", "pos": [15, 31]}, {"entity": "Stat1", "entity_type": "protein", "pos": [188, 193]}], "task": "NER"}
{"text": "The induction of gene transcription in response to gamma interferon is impaired in mononuclear phagocytes infected with Leishmania donovani , and the mechanisms involved are not fully understood.", "entity": [{"entity": "gamma interferon", "entity_type": "protein", "pos": [51, 67]}, {"entity": "mononuclear phagocytes", "entity_type": "cell type", "pos": [83, 105]}], "task": "NER"}
{"text": "The changes in gene expression brought about by gamma interferon are thought to involve transient increases in the activities of cellular protein tyrosine kinases , including the Janus kinases Jak1 and Jak2 , leading to tyrosine phosphorylation of the transcription factor Stat1 .", "entity": [{"entity": "gamma interferon", "entity_type": "protein", "pos": [48, 64]}, {"entity": "Jak2", "entity_type": "protein", "pos": [202, 206]}, {"entity": "Janus kinases", "entity_type": "protein", "pos": [179, 192]}, {"entity": "transcription factor Stat1", "entity_type": "protein", "pos": [252, 278]}, {"entity": "Jak1", "entity_type": "protein", "pos": [193, 197]}, {"entity": "Stat1", "entity_type": "protein", "pos": [273, 278]}, {"entity": "cellular protein tyrosine kinases", "entity_type": "protein", "pos": [129, 162]}], "task": "NER"}
{"text": "To investigate the mechanisms accounting for the impaired responses to gamma interferon , a model system for examining overall changes in protein tyrosine phosphorylation , activation of Jak1 and Jak2 and phosphorylation of Stat1 was developed in phorbol 12-myristate 13-acetate -differentiated U-937 cells .", "entity": [{"entity": "gamma interferon", "entity_type": "protein", "pos": [71, 87]}, {"entity": "Jak1", "entity_type": "protein", "pos": [187, 191]}, {"entity": "Stat1", "entity_type": "protein", "pos": [224, 229]}, {"entity": "phorbol 12-myristate 13-acetate -differentiated U-937 cells", "entity_type": "cell line", "pos": [247, 306]}, {"entity": "Jak2", "entity_type": "protein", "pos": [196, 200]}], "task": "NER"}
{"text": "Analysis of whole-cell lysates by antiphosphotyrosine immunoblotting showed that incubation with gamma interferon brought about specific increases in phosphotyrosine labeling of several proteins.", "entity": [{"entity": "gamma interferon", "entity_type": "protein", "pos": [97, 113]}], "task": "NER"}
{"text": "Increased labeling of these proteins occurred to similar extents in control cells and in cells that had been infected with L. donovani for 16 h.", "entity": [{"entity": "control cells", "entity_type": "cell type", "pos": [68, 81]}], "task": "NER"}
{"text": "Jak1 , Jak2 , and Stat1 were immunoprecipitated from control and interferon-treated cells , and tyrosine phosphorylation of these proteins, detected by antiphosphotyrosine immunoblotting was used to measured their activation.", "entity": [{"entity": "Jak1", "entity_type": "protein", "pos": [0, 4]}, {"entity": "Jak2", "entity_type": "protein", "pos": [7, 11]}, {"entity": "Stat1", "entity_type": "protein", "pos": [18, 23]}, {"entity": "interferon-treated cells", "entity_type": "cell line", "pos": [65, 89]}], "task": "NER"}
{"text": "Tyrosine phosphorylation of Jak1 , Jak2 , and Stat1 increased markedly, in a dose-dependent manner, in U-937 cells incubated with gamma interferon .", "entity": [{"entity": "gamma interferon", "entity_type": "protein", "pos": [130, 146]}, {"entity": "U-937 cells", "entity_type": "cell line", "pos": [103, 114]}, {"entity": "Stat1", "entity_type": "protein", "pos": [46, 51]}, {"entity": "Jak1", "entity_type": "protein", "pos": [28, 32]}, {"entity": "Jak2", "entity_type": "protein", "pos": [35, 39]}], "task": "NER"}
{"text": "In contrast, in cells infected with L. donovani , tyrosine phosphorylation of Jak1 , Jak2 , and Stat1 was markedly impaired.", "entity": [{"entity": "Stat1", "entity_type": "protein", "pos": [96, 101]}, {"entity": "Jak1", "entity_type": "protein", "pos": [78, 82]}, {"entity": "Jak2", "entity_type": "protein", "pos": [85, 89]}], "task": "NER"}
{"text": "This effect was dependent upon the duration of exposure to L. donovani and was maximal and complete at 16 h.", "entity": [], "task": "NER"}
{"text": "Results similar to those observed with U-937 cells were also obtained with human peripheral blood monocytes .", "entity": [{"entity": "U-937 cells", "entity_type": "cell line", "pos": [39, 50]}, {"entity": "human peripheral blood monocytes", "entity_type": "cell type", "pos": [75, 107]}], "task": "NER"}
{"text": "These findings indicate that infection of human mononuclear phagocytes with L. donovani leads to impaired gamma interferon -mediated tyrosine phosphorylation and selective effects on the Jak- Stat1 pathway .", "entity": [{"entity": "human mononuclear phagocytes", "entity_type": "cell type", "pos": [42, 70]}, {"entity": "Stat1", "entity_type": "protein", "pos": [192, 197]}, {"entity": "gamma interferon", "entity_type": "protein", "pos": [106, 122]}], "task": "NER"}
{"text": "Unresponsiveness to gamma interferon for activation of this pathway may explain impaired transcriptional responses in leishmania-infected cells .", "entity": [{"entity": "gamma interferon", "entity_type": "protein", "pos": [20, 36]}, {"entity": "leishmania-infected cells", "entity_type": "cell type", "pos": [118, 143]}], "task": "NER"}
{"text": "Mutually exclusive interaction of a novel matrix attachment region binding protein and the NF-muNR enhancer repressor .", "entity": [{"entity": "matrix attachment region binding protein", "entity_type": "protein", "pos": [42, 82]}, {"entity": "NF-muNR enhancer repressor", "entity_type": "protein", "pos": [91, 117]}], "task": "NER"}
{"text": "Implications for regulation of immunoglobulin heavy chain expression .", "entity": [{"entity": "immunoglobulin heavy chain", "entity_type": "protein", "pos": [31, 57]}], "task": "NER"}
{"text": "The immunoglobulin heavy chain ( IgH ) intronic enhancer stimulates transcription from functional promoters in B lymphocytes but not other cell types.", "entity": [{"entity": "immunoglobulin heavy chain", "entity_type": "protein", "pos": [4, 30]}, {"entity": "IgH", "entity_type": "protein", "pos": [33, 36]}], "task": "NER"}
{"text": "The observation that binding sites for the nuclear factor-mu negative regulator ( NF-muNR ) enhancer repressor overlap nuclear matrix attachment regions ( MARs ) in this enhancer has lead to the hypothesis that the cell type specificity of the enhancer might be controlled by regulating nuclear matrix attachment (Scheuermann, R. H., and Chen, U. (1989) Genes & Dev. 3, 1255-1266).", "entity": [{"entity": "NF-muNR", "entity_type": "protein", "pos": [82, 89]}, {"entity": "MARs", "entity_type": "protein", "pos": [155, 159]}, {"entity": "nuclear factor-mu negative regulator", "entity_type": "protein", "pos": [43, 79]}, {"entity": "nuclear matrix attachment regions", "entity_type": "protein", "pos": [119, 152]}, {"entity": "nuclear factor-mu negative regulator ( NF-muNR ) enhancer repressor overlap nuclear matrix attachment regions", "entity_type": "protein", "pos": [43, 152]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [92, 100]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [170, 178]}], "task": "NER"}
{"text": "To understand the role of MARs in IgH enhancer regulation , we have identified a novel MAR-binding protein , MAR-BP1 , from soluble nuclear matrix preparations based on its ability to bind to the MARs associated with the IgH enhancer .", "entity": [{"entity": "IgH", "entity_type": "protein", "pos": [34, 37]}, {"entity": "IgH enhancer", "entity_type": "DNA", "pos": [34, 46]}, {"entity": "MARs", "entity_type": "protein", "pos": [26, 30]}, {"entity": "MARs", "entity_type": "protein", "pos": [196, 200]}, {"entity": "MAR-binding protein", "entity_type": "protein", "pos": [87, 106]}, {"entity": "IgH enhancer", "entity_type": "DNA", "pos": [221, 233]}, {"entity": "MAR-BP1", "entity_type": "protein", "pos": [109, 116]}, {"entity": "IgH", "entity_type": "protein", "pos": [221, 224]}], "task": "NER"}
{"text": "Purified MAR-BP1 migrates as a 33-kDa protein , and it can be found in nuclear matrix preparations from a number of different types of lymphoid cell lines .", "entity": [{"entity": "lymphoid cell lines", "entity_type": "cell line", "pos": [135, 154]}, {"entity": "33-kDa protein", "entity_type": "protein", "pos": [31, 45]}, {"entity": "MAR-BP1", "entity_type": "protein", "pos": [9, 16]}], "task": "NER"}
{"text": "Although specific binding sites have been difficult to localize by chemical or enzymatic footprinting procedures , NF-muNR binding sites are critical for efficient MAR-BP1 binding .", "entity": [{"entity": "NF-muNR", "entity_type": "protein", "pos": [115, 122]}, {"entity": "MAR-BP1", "entity_type": "protein", "pos": [164, 171]}], "task": "NER"}
{"text": "Indeed, binding of the IgH enhancer to either intact nuclear matrix preparations or to MAR-BP1 is mutually exclusive to NF-muNR binding .", "entity": [{"entity": "IgH", "entity_type": "protein", "pos": [23, 26]}, {"entity": "MAR-BP1", "entity_type": "protein", "pos": [87, 94]}, {"entity": "NF-muNR", "entity_type": "protein", "pos": [120, 127]}, {"entity": "IgH enhancer", "entity_type": "DNA", "pos": [23, 35]}], "task": "NER"}
{"text": "These results are consistent with a model for cell-type specific regulation in which binding of the NF-muNR repressor to the IgH enhancer prevents nuclear matrix attachment in inappropriate cells by interfering with MAR-BP1 /enhancer interaction .", "entity": [{"entity": "/enhancer", "entity_type": "DNA", "pos": [224, 233]}, {"entity": "IgH", "entity_type": "protein", "pos": [125, 128]}, {"entity": "NF-muNR repressor", "entity_type": "protein", "pos": [100, 117]}, {"entity": "MAR-BP1", "entity_type": "protein", "pos": [216, 223]}, {"entity": "IgH enhancer", "entity_type": "DNA", "pos": [125, 137]}, {"entity": "NF-muNR", "entity_type": "protein", "pos": [100, 107]}], "task": "NER"}
{"text": "PU.1 ( Spi-1 ) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene .", "entity": [{"entity": "granulocyte-macrophage colony-stimulating factor receptor alpha gene", "entity_type": "DNA", "pos": [58, 126]}, {"entity": "C/EBP alpha", "entity_type": "protein", "pos": [19, 30]}, {"entity": "granulocyte-macrophage colony-stimulating factor receptor", "entity_type": "protein", "pos": [58, 115]}, {"entity": "PU.1", "entity_type": "protein", "pos": [0, 4]}, {"entity": "Spi-1", "entity_type": "protein", "pos": [7, 12]}], "task": "NER"}
{"text": "Growth factor receptors play an important role in hematopoiesis .", "entity": [{"entity": "Growth factor receptors", "entity_type": "protein", "pos": [0, 23]}], "task": "NER"}
{"text": "In order to further understand the mechanisms directing the expression of these key regulators of hematopoiesis , we initiated a study investigating the transcription factors activating the expression of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) receptor alpha gene .", "entity": [{"entity": "transcription factors", "entity_type": "protein", "pos": [153, 174]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [259, 265]}, {"entity": "granulocyte-macrophage colony-stimulating factor", "entity_type": "protein", "pos": [208, 256]}, {"entity": "granulocyte-macrophage colony-stimulating factor ( GM-CSF ) receptor alpha gene", "entity_type": "DNA", "pos": [208, 287]}], "task": "NER"}
{"text": "Here, we demonstrate that the human GM-CSF receptor alpha promoter directs reporter gene activity in a tissue-specific fashion in myelomonocytic cells , which correlates with its expression pattern as analyzed by reverse transcription PCR .", "entity": [{"entity": "GM-CSF receptor alpha", "entity_type": "protein", "pos": [36, 57]}, {"entity": "myelomonocytic cells", "entity_type": "cell type", "pos": [130, 150]}, {"entity": "human GM-CSF receptor alpha promoter", "entity_type": "DNA", "pos": [30, 66]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [36, 42]}, {"entity": "reporter gene", "entity_type": "DNA", "pos": [75, 88]}], "task": "NER"}
{"text": "The GM-CSF receptor alpha promoter contains an important functional site between positions -53 and -41 as identified by deletion analysis of reporter constructs .", "entity": [{"entity": "GM-CSF receptor alpha", "entity_type": "protein", "pos": [4, 25]}, {"entity": "reporter constructs", "entity_type": "DNA", "pos": [141, 160]}, {"entity": "GM-CSF receptor alpha promoter", "entity_type": "DNA", "pos": [4, 34]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [4, 10]}], "task": "NER"}
{"text": "We show that the myeloid and B cell transcription factor PU.1 binds specifically to this site.", "entity": [{"entity": "B cell transcription factor", "entity_type": "protein", "pos": [29, 56]}, {"entity": "PU.1", "entity_type": "protein", "pos": [57, 61]}], "task": "NER"}
{"text": "Furthermore, we demonstrate that a CCAAT site located upstream of the PU.1 site between positions -70 and -54 is involved in positive-negative regulation of the GM-CSF receptor alpha promoter activity .", "entity": [{"entity": "CCAAT site", "entity_type": "DNA", "pos": [35, 45]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [161, 167]}, {"entity": "PU.1", "entity_type": "protein", "pos": [70, 74]}, {"entity": "PU.1 site", "entity_type": "DNA", "pos": [70, 79]}, {"entity": "GM-CSF receptor alpha promoter", "entity_type": "DNA", "pos": [161, 191]}, {"entity": "GM-CSF receptor alpha", "entity_type": "protein", "pos": [161, 182]}], "task": "NER"}
{"text": "C/EBP alpha is the major CCAAT/enhancer -binding protein ( C/EBP ) form binding to this site in nuclear extracts of U937 cells .", "entity": [{"entity": "CCAAT/enhancer", "entity_type": "DNA", "pos": [25, 39]}, {"entity": "C/EBP alpha", "entity_type": "protein", "pos": [0, 11]}, {"entity": "CCAAT/enhancer -binding protein", "entity_type": "protein", "pos": [25, 56]}, {"entity": "U937 cells", "entity_type": "cell line", "pos": [116, 126]}, {"entity": "C/EBP", "entity_type": "protein", "pos": [0, 5]}], "task": "NER"}
{"text": "Point mutations of either the PU.1 site or the C/EBP site that abolish the binding of the respective factors result in a significant decrease of GM-CSF receptor alpha promoter activity in myelomonocytic cells only.", "entity": [{"entity": "PU.1 site", "entity_type": "DNA", "pos": [30, 39]}, {"entity": "GM-CSF receptor alpha", "entity_type": "protein", "pos": [145, 166]}, {"entity": "GM-CSF receptor alpha promoter", "entity_type": "DNA", "pos": [145, 175]}, {"entity": "myelomonocytic cells", "entity_type": "cell type", "pos": [188, 208]}, {"entity": "C/EBP", "entity_type": "protein", "pos": [47, 52]}, {"entity": "PU.1", "entity_type": "protein", "pos": [30, 34]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [145, 151]}, {"entity": "C/EBP site", "entity_type": "DNA", "pos": [47, 57]}], "task": "NER"}
{"text": "Furthermore, we demonstrate that in myeloid and B cell extracts , PU.1 forms a novel, specific, more slowly migrating complex ( PU-SF ) when binding the GM-CSF receptor alpha promoter PU.1 site .", "entity": [{"entity": "GM-CSF receptor alpha", "entity_type": "protein", "pos": [153, 174]}, {"entity": "PU.1 site", "entity_type": "DNA", "pos": [184, 193]}, {"entity": "PU.1", "entity_type": "protein", "pos": [66, 70]}, {"entity": "PU-SF", "entity_type": "protein", "pos": [128, 133]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [153, 159]}, {"entity": "GM-CSF receptor alpha promoter", "entity_type": "DNA", "pos": [153, 183]}, {"entity": "PU.1", "entity_type": "protein", "pos": [184, 188]}], "task": "NER"}
{"text": "This is the first demonstration of a specific interaction with PU.1 on a myeloid PU.1 binding site .", "entity": [{"entity": "PU.1", "entity_type": "protein", "pos": [63, 67]}, {"entity": "myeloid PU.1 binding site", "entity_type": "DNA", "pos": [73, 98]}, {"entity": "PU.1", "entity_type": "protein", "pos": [81, 85]}], "task": "NER"}
{"text": "The novel complex is distinct from that described previously as binding to B cell enhancer sites and can be formed by addition of PU.1 to extracts from certain nonmyeloid cell types which do not express PU.1 , including T cells and epithelial cells , but not from erythroid cells .", "entity": [{"entity": "PU.1", "entity_type": "protein", "pos": [130, 134]}, {"entity": "B cell enhancer sites", "entity_type": "DNA", "pos": [75, 96]}, {"entity": "erythroid cells", "entity_type": "cell type", "pos": [264, 279]}, {"entity": "PU.1", "entity_type": "protein", "pos": [203, 207]}, {"entity": "T cells", "entity_type": "cell type", "pos": [220, 227]}, {"entity": "epithelial cells", "entity_type": "cell type", "pos": [232, 248]}, {"entity": "nonmyeloid cell types", "entity_type": "cell type", "pos": [160, 181]}], "task": "NER"}
{"text": "Furthermore, we demonstrate that the PU-SF complex binds to PU.1 sites found on a number of myeloid promoters , and its formation requires an intact PU.1 site adjacent to a single-stranded region.", "entity": [{"entity": "PU.1", "entity_type": "protein", "pos": [60, 64]}, {"entity": "PU-SF complex", "entity_type": "protein", "pos": [37, 50]}, {"entity": "myeloid promoters", "entity_type": "DNA", "pos": [92, 109]}, {"entity": "PU.1", "entity_type": "protein", "pos": [149, 153]}, {"entity": "PU.1 site", "entity_type": "DNA", "pos": [60, 69]}, {"entity": "PU-SF", "entity_type": "protein", "pos": [37, 42]}], "task": "NER"}
{"text": "Expression of PU.1 in nonmyeloid cells can activate the GM-CSF receptor alpha promoter .", "entity": [{"entity": "nonmyeloid cells", "entity_type": "cell type", "pos": [22, 38]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [56, 62]}, {"entity": "PU.1", "entity_type": "protein", "pos": [14, 18]}, {"entity": "GM-CSF receptor alpha promoter", "entity_type": "DNA", "pos": [56, 86]}], "task": "NER"}
{"text": "Deletion of the amino-terminal region of PU.1 results in a failure to form the PU-SF complex and in a concomitant loss of transactivation, suggesting that formation of the PU-SF complex is of functional importance for the activity of the GM-CSF receptor alpha promoter .", "entity": [{"entity": "GM-CSF", "entity_type": "protein", "pos": [238, 244]}, {"entity": "GM-CSF receptor alpha promoter", "entity_type": "DNA", "pos": [238, 268]}, {"entity": "PU.1", "entity_type": "protein", "pos": [41, 45]}, {"entity": "PU-SF", "entity_type": "protein", "pos": [79, 84]}, {"entity": "amino-terminal region", "entity_type": "protein", "pos": [16, 37]}, {"entity": "PU-SF", "entity_type": "protein", "pos": [172, 177]}, {"entity": "PU-SF complex", "entity_type": "protein", "pos": [79, 92]}], "task": "NER"}
{"text": "Finally, we demonstrate that C/EBP alpha can also active the GM-CSF receptor alpha promoter in nonmyeloid cells .", "entity": [{"entity": "GM-CSF receptor alpha promoter", "entity_type": "DNA", "pos": [61, 91]}, {"entity": "C/EBP alpha", "entity_type": "protein", "pos": [29, 40]}, {"entity": "GM-CSF receptor alpha", "entity_type": "protein", "pos": [61, 82]}, {"entity": "C/EBP", "entity_type": "protein", "pos": [29, 34]}, {"entity": "nonmyeloid cells", "entity_type": "cell type", "pos": [95, 111]}, {"entity": "GM-CSF", "entity_type": "protein", "pos": [61, 67]}], "task": "NER"}
{"text": "(ABSTRACT TRUNCATED AT 400 WORDS)", "entity": [], "task": "NER"}
{"text": "HMG-I binds to GATA motifs : implications for an HPFH syndrome .", "entity": [{"entity": "HMG-I", "entity_type": "protein", "pos": [0, 5]}, {"entity": "GATA motifs", "entity_type": "DNA", "pos": [15, 26]}], "task": "NER"}
{"text": "We have examined binding of the nuclear protein HMG-I to the human gamma-globin promoter .", "entity": [{"entity": "HMG-I", "entity_type": "protein", "pos": [48, 53]}, {"entity": "nuclear protein", "entity_type": "protein", "pos": [32, 47]}, {"entity": "human gamma-globin promoter", "entity_type": "DNA", "pos": [61, 88]}], "task": "NER"}
{"text": "We find that HMG-I binds preferentially to the more 3' of a pair of GATA motifs in the gamma-globin promoter ; this paired motif is bound by the erythroid factor GATA-1 .", "entity": [{"entity": "GATA-1", "entity_type": "protein", "pos": [162, 168]}, {"entity": "erythroid factor GATA-1", "entity_type": "protein", "pos": [145, 168]}, {"entity": "HMG-I", "entity_type": "protein", "pos": [13, 18]}, {"entity": "GATA motifs", "entity_type": "DNA", "pos": [68, 79]}, {"entity": "gamma-globin promoter", "entity_type": "DNA", "pos": [87, 108]}], "task": "NER"}
{"text": "A naturally occurring mutation (-175 T-C) in the area bound by HMG-I results in overexpression of gamma-globin in adult red blood cells ( HPFH ) and up-regulation of the gamma-globin promoter in in vitro expression assays ; HMG-I does not bind to this mutant sequence .", "entity": [{"entity": "HMG-I", "entity_type": "protein", "pos": [63, 68]}, {"entity": "gamma-globin", "entity_type": "protein", "pos": [98, 110]}, {"entity": "HMG-I", "entity_type": "protein", "pos": [224, 229]}, {"entity": "adult red blood cells", "entity_type": "cell type", "pos": [114, 135]}, {"entity": "gamma-globin", "entity_type": "protein", "pos": [170, 182]}, {"entity": "mutant sequence", "entity_type": "DNA", "pos": [252, 267]}, {"entity": "gamma-globin promoter", "entity_type": "DNA", "pos": [170, 191]}, {"entity": "HPFH", "entity_type": "cell type", "pos": [138, 142]}], "task": "NER"}
{"text": "A survey of GATA motifs from other globin cis-elements demonstrates HMG-I binding to most of them.", "entity": [{"entity": "HMG-I", "entity_type": "protein", "pos": [68, 73]}, {"entity": "GATA motifs", "entity_type": "DNA", "pos": [12, 23]}, {"entity": "globin cis-elements", "entity_type": "DNA", "pos": [35, 54]}], "task": "NER"}
{"text": "These findings implicate HMG-I in the HPFH phenotype ; we speculate that it may participate in the formation of multiprotein complexes that regulate globin gene expression .", "entity": [{"entity": "HMG-I", "entity_type": "protein", "pos": [25, 30]}, {"entity": "HPFH", "entity_type": "cell type", "pos": [38, 42]}, {"entity": "multiprotein complexes", "entity_type": "protein", "pos": [112, 134]}], "task": "NER"}
{"text": "Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 ( HTLV-1 ) tax protein or virus-transformed cells .", "entity": [{"entity": "human T cell leukemia virus type 1 ( HTLV-1 ) tax protein", "entity_type": "protein", "pos": [61, 118]}, {"entity": "Jak tyrosine kinases", "entity_type": "protein", "pos": [37, 57]}, {"entity": "virus-transformed cells", "entity_type": "cell line", "pos": [122, 145]}], "task": "NER"}
{"text": "HTLV-1 infection causes an adult T cell leukemia in humans .", "entity": [], "task": "NER"}
{"text": "The viral encoded protein tax , is thought to play an important role in oncogenesis .", "entity": [{"entity": "viral encoded protein", "entity_type": "protein", "pos": [4, 25]}, {"entity": "tax", "entity_type": "protein", "pos": [26, 29]}], "task": "NER"}
{"text": "Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes , despite comparable levels of tax expression in both tissues.", "entity": [{"entity": "tax", "entity_type": "protein", "pos": [34, 37]}, {"entity": "tax", "entity_type": "protein", "pos": [75, 78]}, {"entity": "mouse fibroblasts", "entity_type": "cell type", "pos": [90, 107]}, {"entity": "thymocytes", "entity_type": "cell type", "pos": [116, 126]}, {"entity": "tax", "entity_type": "protein", "pos": [158, 161]}], "task": "NER"}
{"text": "Constitutive tyrosine phosphorylation of a 130-kD protein (s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines , but not in thymocytes from Thy-tax transgenic mice .", "entity": [{"entity": "thymocytes", "entity_type": "cell type", "pos": [176, 186]}, {"entity": "HTLV-1 transformed human lymphoid lines", "entity_type": "cell line", "pos": [123, 162]}, {"entity": "tax", "entity_type": "protein", "pos": [82, 85]}, {"entity": "transformed fibroblast B line", "entity_type": "cell line", "pos": [86, 115]}, {"entity": "130-kD protein", "entity_type": "protein", "pos": [43, 57]}], "task": "NER"}
{"text": "Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies , identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines .", "entity": [{"entity": "Jak kinase", "entity_type": "protein", "pos": [84, 94]}, {"entity": "Jak kinase specific antibodies", "entity_type": "protein", "pos": [84, 114]}, {"entity": "Jak3", "entity_type": "protein", "pos": [197, 201]}, {"entity": "mouse fibroblastic cell line", "entity_type": "cell line", "pos": [164, 192]}, {"entity": "HTLV-1 transformed human T cell lines", "entity_type": "cell line", "pos": [205, 242]}, {"entity": "Jak2", "entity_type": "protein", "pos": [136, 140]}, {"entity": "tax", "entity_type": "protein", "pos": [148, 151]}], "task": "NER"}
{"text": "Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6 .", "entity": [{"entity": "tax transformed cells", "entity_type": "cell line", "pos": [27, 48]}, {"entity": "tax", "entity_type": "protein", "pos": [27, 30]}, {"entity": "IL-6", "entity_type": "protein", "pos": [82, 86]}, {"entity": "Jak2", "entity_type": "protein", "pos": [19, 23]}], "task": "NER"}
{"text": "Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line , which was associated with induction of cell proliferation .", "entity": [{"entity": "B line", "entity_type": "cell line", "pos": [111, 117]}, {"entity": "Balb/c3T3 cells", "entity_type": "cell line", "pos": [66, 81]}], "task": "NER"}
{"text": "Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies .", "entity": [{"entity": "IL-6 neutralizing antibodies", "entity_type": "protein", "pos": [57, 85]}, {"entity": "IL-6", "entity_type": "protein", "pos": [57, 61]}], "task": "NER"}
{"text": "Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model .", "entity": [{"entity": "HTLV-1 infected human T cells", "entity_type": "cell type", "pos": [80, 109]}, {"entity": "T cells", "entity_type": "cell type", "pos": [102, 109]}, {"entity": "Jak kinases", "entity_type": "protein", "pos": [32, 43]}], "task": "NER"}
{"text": "Regulation of c-jun mRNA expression by hydroxyurea in human K562 cells during erythroid differentiation [published erratum appears in Biochim Biophys Acta 1995 Dec 27;1264(3):409]", "entity": [{"entity": "human K562 cells", "entity_type": "cell line", "pos": [54, 70]}, {"entity": "c-jun mRNA", "entity_type": "RNA", "pos": [14, 24]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [14, 19]}], "task": "NER"}
{"text": "Hydroxyurea ( HU ) is an antitumor agent which also induces hemoglobinization during erythroid differentiation .", "entity": [], "task": "NER"}
{"text": "In addition, HU stimulates the synthesis of fetal hemoglobin in sickle cell anemia patients .", "entity": [{"entity": "fetal hemoglobin", "entity_type": "protein", "pos": [44, 60]}], "task": "NER"}
{"text": "To further understand its mechanism of action, we investigated the effects of HU on regulation of c-jun expression prior to the onset of erythroid differentiation of K562 cells .", "entity": [{"entity": "K562 cells", "entity_type": "cell line", "pos": [166, 176]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [98, 103]}], "task": "NER"}
{"text": "HU induced a dose-dependent stimulation of c-jun synthesis.", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [43, 48]}], "task": "NER"}
{"text": "The levels of c-jun mRNA was elevated 4 to 7.5-fold by HU within 2 h.", "entity": [{"entity": "c-jun mRNA", "entity_type": "RNA", "pos": [14, 24]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [14, 19]}], "task": "NER"}
{"text": "This was followed by a gradual decline to the basal level by 24 h.", "entity": [], "task": "NER"}
{"text": "Both nuclear run-on and actinomycin D pulse experiments strongly indicate that HU regulates c-jun mRNA expression by increasing the rate of synthesis as well as stabilizing the c-jun mRNA .", "entity": [{"entity": "c-jun mRNA", "entity_type": "RNA", "pos": [92, 102]}, {"entity": "c-jun mRNA", "entity_type": "RNA", "pos": [177, 187]}, {"entity": "c-jun", "entity_type": "DNA", "pos": [92, 97]}], "task": "NER"}
{"text": "In addition, the level of jun protein was elevated by 2 to 5-fold within 4 h in HU treated cells .", "entity": [{"entity": "HU treated cells", "entity_type": "cell line", "pos": [80, 96]}, {"entity": "jun protein", "entity_type": "protein", "pos": [26, 37]}], "task": "NER"}
{"text": "Furthermore, concentrations of HU below 250 microM slightly increased the 5X AP-1 /CAT activity .", "entity": [{"entity": "AP-1", "entity_type": "protein", "pos": [77, 81]}, {"entity": "/CAT", "entity_type": "protein", "pos": [82, 86]}], "task": "NER"}
{"text": "These results strongly suggest that HU induces both transcriptional and post-transcription regulation of c-jun during erythroid differentiation .", "entity": [{"entity": "c-jun", "entity_type": "DNA", "pos": [105, 110]}], "task": "NER"}
{"text": "In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in man : relationship to glucocorticoid receptors .", "entity": [{"entity": "glucocorticoid receptors", "entity_type": "protein", "pos": [101, 125]}], "task": "NER"}
{"text": "Interrelations between the hypothalamic-pituitary-adrenal system ( HPA ) and the immune system represent a well-documented biological phenomenon .", "entity": [], "task": "NER"}
{"text": "While in vitro administration of glucocorticoids may inhibit concanavalin A (Con A)- and phytohemagglutinin (PHA)- induced T-cell proliferation , pokeweed mitogen ( PWM )-driven B-cell mitogenesis is relatively resistant to glucocorticoids .", "entity": [{"entity": "pokeweed mitogen", "entity_type": "protein", "pos": [146, 162]}, {"entity": "PWM", "entity_type": "protein", "pos": [165, 168]}], "task": "NER"}
{"text": "To further explore the link between the HPA and the immune system in relation to glucocorticoid receptor function , dose-response curves were obtained for Con A -and PHA -induced T-cell mitogenesis , PWM -generated B-cell mitogenesis and spontaneous lymphocyte proliferation in 13 healthy controls .", "entity": [{"entity": "PHA", "entity_type": "protein", "pos": [166, 169]}, {"entity": "PWM", "entity_type": "protein", "pos": [200, 203]}, {"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [81, 104]}], "task": "NER"}
{"text": "Glucocorticoid effects were assessed in vivo by depletion of endogenous glucocorticoids after oral administration of 1.5 g metyrapone ( MET ) and subsequent glucocorticoid replacement , and in vitro by incubation of the cells with different doses of dexamethasone ( DEX ).", "entity": [], "task": "NER"}
{"text": "There was a significant decrease in PWM -induced B-cell mitogenesis and a more pronounced effect of DEX administered in vitro on spontaneous lymphocyte proliferation after MET treatment when compared with the DEX plus MET pretreated condition in vivo.", "entity": [{"entity": "PWM", "entity_type": "protein", "pos": [36, 39]}], "task": "NER"}
{"text": "These data suggest that the inhibition of spontaneous lymphocyte proliferation by glucocorticoids in vitro is related to glucocorticoid receptor function .", "entity": [{"entity": "glucocorticoid receptor", "entity_type": "protein", "pos": [121, 144]}], "task": "NER"}
{"text": "The decrease in PWM -generated B-cell proliferation following cortisol depletion by MET may be seen in connection with impaired glucocorticoid -mediated induction of interleukin-1 receptor synthesis .", "entity": [{"entity": "PWM", "entity_type": "protein", "pos": [16, 19]}, {"entity": "interleukin-1 receptor", "entity_type": "protein", "pos": [166, 188]}], "task": "NER"}
{"text": "Transcription specific differences visualized by fluorescence in situ hybridization pattern on interphase nuclei of different cell types.", "entity": [], "task": "NER"}
{"text": "Application of a \"formamide free\" and thus \"material preserving\" in situ hybridization technique using the cDNA of the myf3 gene revealed the following results: Human rhabdomyosarcoma cells , characterized by a high expression of myf3 show intensive hybridization signals in their interphase .", "entity": [{"entity": "cDNA", "entity_type": "DNA", "pos": [107, 111]}, {"entity": "myf3", "entity_type": "DNA", "pos": [119, 123]}, {"entity": "Human rhabdomyosarcoma cells", "entity_type": "cell type", "pos": [161, 189]}, {"entity": "myf3 gene", "entity_type": "DNA", "pos": [119, 128]}], "task": "NER"}
{"text": "RNase treatment prior to hybridization considerably reduces the size of this signals.", "entity": [{"entity": "RNase", "entity_type": "protein", "pos": [0, 5]}], "task": "NER"}
{"text": "In comparison, isolated nuclei of human lymphocytes in which no need for the expression of this gene exists, show barely hybridization signals .", "entity": [{"entity": "human lymphocytes", "entity_type": "cell type", "pos": [34, 51]}], "task": "NER"}
{"text": "Correspondingly, RNase treatment had no effect on hybridization pattern at all.", "entity": [{"entity": "RNase", "entity_type": "protein", "pos": [17, 22]}], "task": "NER"}
{"text": "In conclusion an increased transcription efficiency of a cell type specific gene is accompanied by a higher hybridization accessibility in the corresponding cell nuclei .", "entity": [], "task": "NER"}
{"text": "Oncogenicity of human papillomavirus- or adenovirus- transformed cells correlates with resistance to lysis by natural killer cells .", "entity": [{"entity": "natural killer cells", "entity_type": "cell type", "pos": [110, 130]}], "task": "NER"}
{"text": "The reasons for the dissimilar oncogenicities of human adenoviruses and human papillomaviruses ( HPV ) in humans are unknown but may relate to differences in the capacities of the E1A and E7 proteins to target cells for rejection by the host natural killer (NK) cell response .", "entity": [{"entity": "host natural killer (NK) cell", "entity_type": "cell type", "pos": [237, 266]}, {"entity": "E7 proteins", "entity_type": "protein", "pos": [188, 199]}, {"entity": "target cells", "entity_type": "cell type", "pos": [203, 215]}, {"entity": "E1A", "entity_type": "protein", "pos": [180, 183]}], "task": "NER"}
{"text": "As one test of this hypothesis, we compared the abilities of E1A -and E7 -expressing human fibroblastic or keratinocyte-derived human cells to be selectively killed by either unstimulated or interferon (IFN)-activated NK cells .", "entity": [{"entity": "E1A", "entity_type": "protein", "pos": [61, 64]}, {"entity": "interferon (IFN)-activated NK cells", "entity_type": "cell line", "pos": [191, 226]}, {"entity": "E7", "entity_type": "protein", "pos": [70, 72]}, {"entity": "unstimulated", "entity_type": "cell type", "pos": [175, 187]}], "task": "NER"}
{"text": "Cells expressing the E1A oncoprotein were selectively killed by unstimulated NK cells , while the same parental cells but expressing the HPV type 16 ( HPV-16 ) or HPV-18 E7 oncoprotein were resistant to NK cell lysis .", "entity": [{"entity": "unstimulated NK cells", "entity_type": "cell line", "pos": [64, 85]}, {"entity": "E7", "entity_type": "protein", "pos": [170, 172]}, {"entity": "E1A", "entity_type": "protein", "pos": [21, 24]}, {"entity": "parental cells", "entity_type": "cell type", "pos": [103, 117]}, {"entity": "E7 oncoprotein", "entity_type": "protein", "pos": [170, 184]}, {"entity": "E1A oncoprotein", "entity_type": "protein", "pos": [21, 36]}], "task": "NER"}
{"text": "The ability of IFN-activated NK cells to selectively kill virally transformed cells depends on IFN 's ability to induce resistance to NK cell lysis in normal (i.e., non-viral oncogene-expressing ) but not virally transformed cells .", "entity": [{"entity": "non-viral oncogene-expressing", "entity_type": "cell line", "pos": [165, 194]}, {"entity": "virally transformed cells", "entity_type": "cell line", "pos": [58, 83]}, {"entity": "IFN-activated NK cells", "entity_type": "cell line", "pos": [15, 37]}, {"entity": "IFN", "entity_type": "protein", "pos": [15, 18]}], "task": "NER"}
{"text": "E1A blocked IFN 's induction of cytolytic resistance , resulting in the selective lysis of adenovirus-transformed cells by IFN -activated NK cells .", "entity": [{"entity": "E1A", "entity_type": "protein", "pos": [0, 3]}, {"entity": "IFN", "entity_type": "protein", "pos": [12, 15]}, {"entity": "adenovirus-transformed cells", "entity_type": "cell line", "pos": [91, 119]}, {"entity": "IFN -activated NK cells", "entity_type": "cell line", "pos": [123, 146]}, {"entity": "IFN", "entity_type": "protein", "pos": [123, 126]}], "task": "NER"}
{"text": "The extent of IFN -induced NK cell killing of E1A -expressing cells was proportional to the level of E1A expression and correlated with the ability of E1A to block IFN -stimulated gene expression in target cells .", "entity": [{"entity": "IFN", "entity_type": "protein", "pos": [14, 17]}, {"entity": "E1A", "entity_type": "protein", "pos": [46, 49]}, {"entity": "IFN", "entity_type": "protein", "pos": [164, 167]}, {"entity": "E1A -expressing cells", "entity_type": "cell line", "pos": [46, 67]}, {"entity": "target cells", "entity_type": "cell type", "pos": [199, 211]}, {"entity": "E1A", "entity_type": "protein", "pos": [101, 104]}, {"entity": "E1A", "entity_type": "protein", "pos": [151, 154]}], "task": "NER"}
{"text": "In contrast, E7 blocked neither IFN -stimulated gene expression nor IFN 's induction of cytolytic resistance , thereby precluding the selective lysis of HPV -transformed cells by IFN -activated NK cells .", "entity": [{"entity": "IFN -activated NK cells", "entity_type": "cell line", "pos": [179, 202]}, {"entity": "IFN", "entity_type": "protein", "pos": [32, 35]}, {"entity": "E7", "entity_type": "protein", "pos": [13, 15]}, {"entity": "IFN", "entity_type": "protein", "pos": [68, 71]}, {"entity": "HPV -transformed cells", "entity_type": "cell line", "pos": [153, 175]}, {"entity": "IFN", "entity_type": "protein", "pos": [179, 182]}], "task": "NER"}
{"text": "In conclusion, E1A expression marks cells for destruction by the host NK cell response , whereas the E7 oncoprotein lacks this activity.", "entity": [{"entity": "E7", "entity_type": "protein", "pos": [101, 103]}, {"entity": "E1A", "entity_type": "protein", "pos": [15, 18]}, {"entity": "E7 oncoprotein", "entity_type": "protein", "pos": [101, 115]}, {"entity": "NK cell", "entity_type": "cell type", "pos": [70, 77]}], "task": "NER"}
{"text": "Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)- dependent signal transduction pathways .", "entity": [{"entity": "IkB alpha", "entity_type": "protein", "pos": [14, 23]}], "task": "NER"}
{"text": "The Ca(2+) -dependent phosphatase calcineurin , a target of FK506 and CsA , synergizes with PKC -induced activation of nuclear factor (NF)-kappa B in T cell lines .", "entity": [{"entity": "nuclear factor (NF)-kappa B", "entity_type": "protein", "pos": [119, 146]}, {"entity": "T cell lines", "entity_type": "cell line", "pos": [150, 162]}, {"entity": "Ca(2+) -dependent phosphatase", "entity_type": "protein", "pos": [4, 33]}, {"entity": "PKC", "entity_type": "protein", "pos": [92, 95]}, {"entity": "calcineurin", "entity_type": "protein", "pos": [34, 45]}], "task": "NER"}
{"text": "We have investigated whether this synergy is present in other cell types and the mechanism(s) by which these two pathways lead to NF-kappa B activation .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [130, 140]}], "task": "NER"}
{"text": "While this synergy is present in other cell types, in the monocytic cell line U937 calcineurin is also sufficient to activate NF-kappa B .", "entity": [{"entity": "calcineurin", "entity_type": "protein", "pos": [83, 94]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [126, 136]}, {"entity": "monocytic cell line U937", "entity_type": "cell line", "pos": [58, 82]}], "task": "NER"}
{"text": "Having previously shown that Ca(2+)- and PKC- dependent pathways synergize by accelerating the degradation of IkB alpha , we focused on the regulation of IkB alpha phosphorylation .", "entity": [{"entity": "IkB alpha", "entity_type": "protein", "pos": [110, 119]}, {"entity": "IkB alpha", "entity_type": "protein", "pos": [154, 163]}], "task": "NER"}
{"text": "While PKC -dependent pathways sequentially result in the phosphorylation and in an incomplete degradation of IkB alpha in T cell lines , co-activation of Ca(2+) -dependent pathways accelerates the rate of IkB alpha phosphorylation and results in its complete degradation.", "entity": [{"entity": "PKC", "entity_type": "protein", "pos": [6, 9]}, {"entity": "T cell lines", "entity_type": "cell line", "pos": [122, 134]}, {"entity": "IkB alpha", "entity_type": "protein", "pos": [109, 118]}, {"entity": "IkB alpha", "entity_type": "protein", "pos": [205, 214]}], "task": "NER"}
{"text": "Activation of Ca(2+) -dependent pathways alone do not result in the phosphorylation and/or degradation of IkB alpha in Jurkat T or in U937 cells .", "entity": [{"entity": "U937 cells", "entity_type": "cell line", "pos": [134, 144]}, {"entity": "IkB alpha", "entity_type": "protein", "pos": [106, 115]}, {"entity": "Jurkat T", "entity_type": "cell line", "pos": [119, 127]}], "task": "NER"}
{"text": "Treatment of T cells with the selective PKC inhibitor GF109203X abrogates the PMA -induced IkB alpha phosphorylation /degradation irrespective of activation of Ca(2+) -dependent pathways , but not the phosphorylation and degradation of IkB alpha induced by TNF-alpha , a PKC -independent stimulus .", "entity": [{"entity": "IkB alpha", "entity_type": "protein", "pos": [91, 100]}, {"entity": "PKC", "entity_type": "protein", "pos": [40, 43]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [257, 266]}, {"entity": "IkB alpha", "entity_type": "protein", "pos": [236, 245]}, {"entity": "T cells", "entity_type": "cell type", "pos": [13, 20]}, {"entity": "PKC", "entity_type": "protein", "pos": [271, 274]}], "task": "NER"}
{"text": "Contrary to the interaction with PKC , Ca(2+) -dependent pathways synergize with TNF-alpha not at the level of IkB alpha phosphorylation , but at the level of its degradation.", "entity": [{"entity": "IkB alpha", "entity_type": "protein", "pos": [111, 120]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [81, 90]}, {"entity": "PKC", "entity_type": "protein", "pos": [33, 36]}], "task": "NER"}
{"text": "These results indicate that Ca(2+) -dependent pathways , including the phosphatase calcineurin , participate in the regulation of NF-kappa B in a cell specific fashion and synergize with PKC -dependent and -independent pathways at the level of IkB alpha phosphorylation and degradation .", "entity": [{"entity": "phosphatase", "entity_type": "protein", "pos": [71, 82]}, {"entity": "calcineurin", "entity_type": "protein", "pos": [83, 94]}, {"entity": "PKC", "entity_type": "protein", "pos": [187, 190]}, {"entity": "IkB alpha", "entity_type": "protein", "pos": [244, 253]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [130, 140]}], "task": "NER"}
{"text": "Vitamin E therapy of acute CCl4 -induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding .", "entity": [{"entity": "nuclear factor kappa B", "entity_type": "protein", "pos": [97, 119]}], "task": "NER"}
{"text": "Oxidative stress , with reactive oxygen intermediate formation , may represent a common mechanism by which liver injury is induced by diverse etiologies.", "entity": [], "task": "NER"}
{"text": "Oxidative stress enhances nuclear factor kappa B ( NF-kappa B ) activity , and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines .", "entity": [{"entity": "cytotoxic cytokines", "entity_type": "protein", "pos": [143, 162]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [51, 61]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [79, 89]}, {"entity": "nuclear factor kappa B", "entity_type": "protein", "pos": [26, 48]}], "task": "NER"}
{"text": "Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice .", "entity": [], "task": "NER"}
{"text": "This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol .", "entity": [], "task": "NER"}
{"text": "Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [71, 81]}], "task": "NER"}
{"text": "In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha ( TNF-alpha ) messenger RNA levels .", "entity": [{"entity": "tumor necrosis factor-alpha ( TNF-alpha ) messenger RNA", "entity_type": "RNA", "pos": [118, 173]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [80, 90]}, {"entity": "tumor necrosis factor-alpha", "entity_type": "protein", "pos": [118, 145]}, {"entity": "TNF-alpha", "entity_type": "protein", "pos": [148, 157]}], "task": "NER"}
{"text": "Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [90, 100]}], "task": "NER"}
{"text": "These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol , a free radical scavenger , also eliminated increased NF-kappa B binding .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [137, 147]}], "task": "NER"}
{"text": "It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury , perhaps through an effect on cytotoxic cytokine synthesis .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [42, 52]}, {"entity": "cytotoxic cytokine", "entity_type": "protein", "pos": [172, 190]}], "task": "NER"}
{"text": "Immunosuppression by glucocorticoids : inhibition of NF-kappa B activity through induction of I kappa B synthesis [see comments]", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [53, 63]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [94, 103]}], "task": "NER"}
{"text": "Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents .", "entity": [], "task": "NER"}
{"text": "They inhibit synthesis of almost all known cytokines and of several cell surface molecules required for immune function , but the mechanism underlying this activity has been unclear. Here it is shown that glucocorticoids are potent inhibitors of nuclear factor kappa B ( NF-kappa B ) activation in mice and cultured cells .", "entity": [{"entity": "cytokines", "entity_type": "protein", "pos": [43, 52]}, {"entity": "cell surface molecules", "entity_type": "protein", "pos": [68, 90]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [271, 281]}, {"entity": "nuclear factor kappa B", "entity_type": "protein", "pos": [246, 268]}, {"entity": "cultured cells", "entity_type": "cell line", "pos": [307, 321]}], "task": "NER"}
{"text": "This inhibition is mediated by induction of the I kappa B alpha inhibitory protein, which traps activated NF-kappa B in inactive cytoplasmic complexes .", "entity": [{"entity": "NF-kappa B", "entity_type": "protein", "pos": [106, 116]}, {"entity": "I kappa B", "entity_type": "protein", "pos": [48, 57]}, {"entity": "inactive cytoplasmic complexes", "entity_type": "protein", "pos": [120, 150]}], "task": "NER"}
{"text": "Because NF-kappa B activates many immunoregulatory genes in response to pro-inflammatory stimuli, the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids .", "entity": [{"entity": "immunoregulatory genes", "entity_type": "DNA", "pos": [34, 56]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [8, 18]}], "task": "NER"}
{"text": "Transcriptional repression of the interleukin-2 gene by vitamin D3 : direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor .", "entity": [{"entity": "interleukin-2 gene", "entity_type": "DNA", "pos": [34, 52]}, {"entity": "NFATp/AP-1 complex", "entity_type": "protein", "pos": [90, 108]}, {"entity": "nuclear hormone receptor", "entity_type": "protein", "pos": [124, 148]}], "task": "NER"}
{"text": "T- lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3 [ 1,25(OH)2D3 ], the active metabolite of vitamin D3 , and is associated with a decrease in interleukin 2 (IL-2) , gamma interferon , and granulocyte-macrophage colony-stimulating factor mRNA levels .", "entity": [], "task": "NER"}
{"text": "We report here that 1,25(OH)2D3 -mediated repression in Jurkat cells is cycloheximide resistant , suggesting that it is a direct transcriptional repressive effect on IL-2 expression by the vitamin D3 receptor ( VDR ).", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [166, 170]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [56, 68]}, {"entity": "vitamin D3 receptor", "entity_type": "protein", "pos": [189, 208]}, {"entity": "VDR", "entity_type": "protein", "pos": [211, 214]}], "task": "NER"}
{"text": "We therefore examined vitamin D3 -mediated repression of activated IL-2 expression by cotransfecting Jurkat cells with IL-2 promoter/reporter constructs and a VDR overexpression vector and by DNA binding .", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [159, 162]}, {"entity": "IL-2 promoter/reporter constructs", "entity_type": "DNA", "pos": [119, 152]}, {"entity": "Jurkat cells", "entity_type": "cell line", "pos": [101, 113]}, {"entity": "VDR overexpression vector", "entity_type": "DNA", "pos": [159, 184]}, {"entity": "IL-2", "entity_type": "protein", "pos": [67, 71]}, {"entity": "IL-2", "entity_type": "protein", "pos": [119, 123]}], "task": "NER"}
{"text": "We delineated an element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3 -mediated repression in vivo to a short 40-bp region encompassing an important positive regulatory element , NF-AT-1 , which is bound by a T-cell-specific transcription factor , NFATp , as well as by AP-1 .", "entity": [{"entity": "40-bp region", "entity_type": "DNA", "pos": [134, 146]}, {"entity": "AP-1", "entity_type": "protein", "pos": [294, 298]}, {"entity": "T-cell-specific transcription factor", "entity_type": "protein", "pos": [233, 269]}, {"entity": "positive regulatory element", "entity_type": "DNA", "pos": [173, 200]}, {"entity": "NFATp", "entity_type": "protein", "pos": [272, 277]}, {"entity": "NF-AT-1", "entity_type": "DNA", "pos": [203, 210]}], "task": "NER"}
{"text": "VDR DNA-binding mutants were unable to either bind to this element in vitro or repress in vivo; the VDR DNA-binding domain alone, however, bound the element but also could not repress IL-2 expression .", "entity": [{"entity": "VDR DNA-binding mutants", "entity_type": "protein", "pos": [0, 23]}, {"entity": "VDR", "entity_type": "protein", "pos": [0, 3]}, {"entity": "IL-2", "entity_type": "protein", "pos": [184, 188]}, {"entity": "VDR", "entity_type": "protein", "pos": [100, 103]}, {"entity": "VDR DNA-binding domain", "entity_type": "protein", "pos": [100, 122]}], "task": "NER"}
{"text": "These results indicate that DNA binding by VDR is necessary but not sufficient to mediate IL-2 repression .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [90, 94]}, {"entity": "VDR", "entity_type": "protein", "pos": [43, 46]}], "task": "NER"}
{"text": "By combining partially purified proteins in vitro, we observed the loss of the bound NFATp /AP-1-DNA complex upon inclusion of VDR or VDR -retinoid X receptor .", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [127, 130]}, {"entity": "partially purified proteins", "entity_type": "protein", "pos": [13, 40]}, {"entity": "NFATp", "entity_type": "protein", "pos": [85, 90]}, {"entity": "NFATp /AP-1-DNA complex", "entity_type": "protein", "pos": [85, 108]}, {"entity": "VDR", "entity_type": "protein", "pos": [134, 137]}, {"entity": "VDR -retinoid X receptor", "entity_type": "protein", "pos": [134, 158]}], "task": "NER"}
{"text": "Order of addition and off-rate experiments indicate that the VDR -retinoid X receptor heterodimer blocks NFATp / AP-1 complex formation and then stably associates with the NF-AT-1 element .", "entity": [{"entity": "VDR", "entity_type": "protein", "pos": [61, 64]}, {"entity": "NF-AT-1", "entity_type": "DNA", "pos": [172, 179]}, {"entity": "VDR -retinoid X receptor heterodimer", "entity_type": "protein", "pos": [61, 97]}, {"entity": "AP-1", "entity_type": "protein", "pos": [113, 117]}, {"entity": "NFATp", "entity_type": "protein", "pos": [105, 110]}, {"entity": "NF-AT-1 element", "entity_type": "DNA", "pos": [172, 187]}, {"entity": "NFATp / AP-1 complex", "entity_type": "protein", "pos": [105, 125]}], "task": "NER"}
{"text": "This direct inhibition by a nuclear hormone receptor of transcriptional activators of the IL-2 gene may provide a mechanistic explanation of how vitamin derivatives can act as potent immunosuppressive agents .", "entity": [{"entity": "transcriptional activators", "entity_type": "protein", "pos": [56, 82]}, {"entity": "IL-2", "entity_type": "protein", "pos": [90, 94]}, {"entity": "IL-2 gene", "entity_type": "DNA", "pos": [90, 99]}], "task": "NER"}
{"text": "Tissue-specific regulation of the rabbit 15-lipoxygenase gene in erythroid cells by a transcriptional silencer .", "entity": [{"entity": "rabbit 15-lipoxygenase gene", "entity_type": "DNA", "pos": [34, 61]}, {"entity": "erythroid cells", "entity_type": "cell type", "pos": [65, 80]}, {"entity": "15-lipoxygenase", "entity_type": "protein", "pos": [41, 56]}, {"entity": "transcriptional silencer", "entity_type": "DNA", "pos": [86, 110]}], "task": "NER"}
{"text": "The 15-lipoxygenase (lox) gene is expressed in a tissue-specific manner , predominantly in erythroid cells but also in airway epithelial cells and eosinophils .", "entity": [{"entity": "erythroid cells", "entity_type": "cell type", "pos": [91, 106]}, {"entity": "15-lipoxygenase (lox) gene", "entity_type": "DNA", "pos": [4, 30]}, {"entity": "airway epithelial cells", "entity_type": "cell type", "pos": [119, 142]}, {"entity": "eosinophils", "entity_type": "cell type", "pos": [147, 158]}], "task": "NER"}
{"text": "We demonstrate in this report that the 5' flanking DNA of the 15-lox gene contains sequences which down-regulate its activity in a variety of non-erythroid cell lines but not in two erythroid cell lines .", "entity": [{"entity": "15-lox gene", "entity_type": "DNA", "pos": [62, 73]}, {"entity": "5' flanking DNA", "entity_type": "DNA", "pos": [39, 54]}, {"entity": "erythroid cell lines", "entity_type": "cell line", "pos": [146, 166]}, {"entity": "non-erythroid cell lines", "entity_type": "cell line", "pos": [142, 166]}], "task": "NER"}
{"text": "The element has characteristics of a transcriptional 'silencer' since it functions in both orientations.", "entity": [{"entity": "transcriptional 'silencer'", "entity_type": "DNA", "pos": [37, 63]}], "task": "NER"}
{"text": "The main activity of the silencer has been mapped to the first 900 bp of 5' flanking DNA , which contains nine binding sites for a nuclear factor present in non- erythroid cells but not in erythroid cells .", "entity": [{"entity": "5' flanking DNA", "entity_type": "DNA", "pos": [73, 88]}, {"entity": "erythroid cells", "entity_type": "cell type", "pos": [162, 177]}, {"entity": "nuclear factor", "entity_type": "protein", "pos": [131, 145]}, {"entity": "erythroid cells", "entity_type": "cell type", "pos": [189, 204]}, {"entity": "silencer", "entity_type": "DNA", "pos": [25, 33]}], "task": "NER"}
{"text": "These binding sites have similar sequences and multiple copies of the binding sites confer tissue-specific down-regulation when attached to a minimal lox promoter fragment .", "entity": [{"entity": "binding sites", "entity_type": "DNA", "pos": [6, 19]}, {"entity": "minimal lox promoter fragment", "entity_type": "DNA", "pos": [142, 171]}, {"entity": "lox promoter", "entity_type": "DNA", "pos": [150, 162]}], "task": "NER"}
{"text": "The 5' flanking DNA also contains a cluster of three binding sites for the GATA family of transcription factors .", "entity": [{"entity": "5' flanking DNA", "entity_type": "DNA", "pos": [4, 19]}, {"entity": "binding sites", "entity_type": "DNA", "pos": [53, 66]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [90, 111]}, {"entity": "GATA family", "entity_type": "protein", "pos": [75, 86]}], "task": "NER"}
{"text": "Phosphorylation of the transcription factor NFATp inhibits its DNA binding activity in cyclosporin A-treated human B and T cells .", "entity": [{"entity": "NFATp", "entity_type": "protein", "pos": [44, 49]}, {"entity": "T cells", "entity_type": "cell type", "pos": [121, 128]}, {"entity": "cyclosporin A-treated human B", "entity_type": "cell line", "pos": [87, 116]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [23, 43]}], "task": "NER"}
{"text": "Cyclosporin A ( CsA ) exerts its immunosuppressive effect by inhibiting the activity of nuclear factor of activated T cells ( NFAT ), thus preventing transcriptional induction of several cytokine genes.", "entity": [{"entity": "nuclear factor", "entity_type": "protein", "pos": [88, 102]}, {"entity": "T cells", "entity_type": "cell type", "pos": [116, 123]}, {"entity": "NFAT", "entity_type": "protein", "pos": [126, 130]}], "task": "NER"}
{"text": "This effect is thought to be largely mediated through inactivation of the phosphatase calcineurin , which in turn inhibits translocation of an NFAT component to the nucleus.", "entity": [{"entity": "NFAT", "entity_type": "protein", "pos": [143, 147]}, {"entity": "calcineurin", "entity_type": "protein", "pos": [86, 97]}], "task": "NER"}
{"text": "Here we report that CsA treatment of Raji B and Jurkat T cell lines yields a phosphorylated form of NFATp that is inhibited in DNA-binding and in its ability to form an NFAT complex with Fos and Jun .", "entity": [{"entity": "T cell lines", "entity_type": "cell line", "pos": [55, 67]}, {"entity": "Jun", "entity_type": "protein", "pos": [195, 198]}, {"entity": "Jurkat T cell lines", "entity_type": "cell line", "pos": [48, 67]}, {"entity": "Fos", "entity_type": "protein", "pos": [187, 190]}, {"entity": "Raji B", "entity_type": "cell line", "pos": [37, 43]}, {"entity": "NFAT complex", "entity_type": "protein", "pos": [169, 181]}, {"entity": "NFATp", "entity_type": "protein", "pos": [100, 105]}], "task": "NER"}
{"text": "Immunoblot analyses and metabolic labeling with [32P]orthophosphate show that CsA alters NFATp migration on SDS-polyacrylamide gel electrophoresis by increasing its phosphorylation level without affecting subcellular distribution.", "entity": [{"entity": "NFATp", "entity_type": "protein", "pos": [89, 94]}], "task": "NER"}
{"text": "Dephosphorylation by in vitro treatment with calcineurin or alkaline phosphatase restores NFATp DNA binding activity and its ability to reconstitute an NFAT complex with Fos and Jun proteins.", "entity": [{"entity": "Jun", "entity_type": "protein", "pos": [178, 181]}, {"entity": "calcineurin", "entity_type": "protein", "pos": [45, 56]}, {"entity": "NFAT complex", "entity_type": "protein", "pos": [152, 164]}, {"entity": "NFATp", "entity_type": "protein", "pos": [90, 95]}, {"entity": "Fos", "entity_type": "protein", "pos": [170, 173]}, {"entity": "alkaline phosphatase", "entity_type": "protein", "pos": [60, 80]}], "task": "NER"}
{"text": "These data point to a new mechanism for CsA -sensitive regulation of NFATp in which dephosphorylation is critical for DNA binding.", "entity": [{"entity": "NFATp", "entity_type": "protein", "pos": [69, 74]}], "task": "NER"}
{"text": "Transcription factors as targets for oxidative signalling during lymphocyte activation .", "entity": [{"entity": "Transcription factors", "entity_type": "protein", "pos": [0, 21]}], "task": "NER"}
{"text": "We previously have demonstrated a requirement for oxidative events during cell cycle entry in T lymphocytes and have hypothesised that reactive oxygen species may act as intracellular signalling agents during lymphocyte activation .", "entity": [{"entity": "T lymphocytes", "entity_type": "cell type", "pos": [94, 107]}], "task": "NER"}
{"text": "In the current study, cysteamine , an aminothiol compound with antioxidant activity , has been used to further investigate the role of oxidative signalling during lymphocyte activation .", "entity": [], "task": "NER"}
{"text": "Treatment of normal human peripheral blood lymphocytes with cysteamine in vitro was found to inhibit proliferation in a dose-dependent manner , with essentially complete inhibition occurring at a dose of 400 microM.", "entity": [{"entity": "human peripheral blood lymphocytes", "entity_type": "cell type", "pos": [20, 54]}], "task": "NER"}
{"text": "This inhibitory effect was limited to the first 2 h after mitogenic activation , localizing the time-frame of action of cysteamine to within the commitment period .", "entity": [], "task": "NER"}
{"text": "It therefore was of interest to establish which, if any, commitment events were affected by oxidative signalling during cell cycle entry .", "entity": [], "task": "NER"}
{"text": "Taking the IL-2 gene as a candidate, we examined the effect of cysteamine treatment on early gene expression during lymphocyte activation , and on the activity of transcription factors AP-1 , NF-kappa B , NF-AT and Oct1 , whose functions are required for expression of the IL-2 mRNA.", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [11, 15]}, {"entity": "early gene", "entity_type": "DNA", "pos": [87, 97]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [192, 202]}, {"entity": "Oct1", "entity_type": "protein", "pos": [215, 219]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [163, 184]}, {"entity": "NF-AT", "entity_type": "protein", "pos": [205, 210]}, {"entity": "IL-2", "entity_type": "protein", "pos": [273, 277]}, {"entity": "AP-1", "entity_type": "protein", "pos": [185, 189]}, {"entity": "IL-2 gene", "entity_type": "DNA", "pos": [11, 20]}], "task": "NER"}
{"text": "Cysteamine treatment inhibited both expression of the IL-2 mRNA and secretion of IL-2 into the culture medium .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [54, 58]}, {"entity": "IL-2", "entity_type": "protein", "pos": [81, 85]}, {"entity": "IL-2 mRNA", "entity_type": "RNA", "pos": [54, 63]}], "task": "NER"}
{"text": "The inhibitory effect of cysteamine may be mediated at least in part by an effect on transcription factor function , as the DNA binding activities of AP-1 and NF-kappa B extracted from mitogen-stimulated cells were significantly inhibited by cysteamine treatment .", "entity": [{"entity": "AP-1", "entity_type": "protein", "pos": [150, 154]}, {"entity": "NF-kappa B", "entity_type": "protein", "pos": [159, 169]}, {"entity": "transcription factor", "entity_type": "protein", "pos": [85, 105]}, {"entity": "mitogen-stimulated cells", "entity_type": "cell type", "pos": [185, 209]}], "task": "NER"}
{"text": "Interestingly, Oct1 and NF-AT DNA binding activity were not affected by cysteamine treatment, suggesting that oxidative signalling processes operate in a selective manner.", "entity": [], "task": "NER"}
{"text": "The identification of regulatory proteins , such as transcription factors , as molecular targets for oxidative signalling provides further evidence to implicate oxidative signalling as being intimately involved in the G0 to G1 phase transition in T lymphocytes .", "entity": [{"entity": "regulatory proteins", "entity_type": "protein", "pos": [22, 41]}, {"entity": "T lymphocytes", "entity_type": "cell type", "pos": [247, 260]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [52, 73]}], "task": "NER"}
{"text": "Sex and age distribution of 1,25(OH)2D3 receptors in peripheral blood mononuclear cells from normal human subjects .", "entity": [{"entity": "1,25(OH)2D3 receptors", "entity_type": "protein", "pos": [28, 49]}, {"entity": "peripheral blood mononuclear cells", "entity_type": "cell type", "pos": [53, 87]}], "task": "NER"}
{"text": "Specific receptors for 1,25 Dihydroxyvitamin D3 have been described in human peripheral blood mononuclear cells ( PBMC ).", "entity": [{"entity": "peripheral blood mononuclear cells", "entity_type": "cell type", "pos": [77, 111]}, {"entity": "PBMC", "entity_type": "cell type", "pos": [114, 118]}], "task": "NER"}
{"text": "We have tried to find out whether these receptors could show any difference in sex or age distribution.", "entity": [], "task": "NER"}
{"text": "Twenty two healthy men aged 21-66 yr (mean +/- SD 41.0 +/- 13.6) and nineteen healthy women aged 22-60 yr (38.9 +/- 13.9) have been studied.", "entity": [], "task": "NER"}
{"text": "The mean dissociation constant ( Kd ) was similar in both sexes (1.35 +/- 0.70 x 10(-10) M in males, 1.13 +/- 0.66 x 10(-10) M in females), but the concentration of binding sites (Nmax) was significantly lower in females (2.32 +/- 0.92 fmol/10(7) PBMC vs 4.43 +/- 1.38 fmol/10(7) PBMC in males ; p = 0.0001).", "entity": [{"entity": "PBMC", "entity_type": "cell type", "pos": [247, 251]}, {"entity": "PBMC", "entity_type": "cell type", "pos": [280, 284]}], "task": "NER"}
{"text": "Neither Kd nor Nmax were significantly correlated with age.", "entity": [], "task": "NER"}
{"text": "No difference was found between pre and post menopausal women .", "entity": [], "task": "NER"}
{"text": "Further studies are needed to elucidate if this sex difference in PBMC receptors for 1.25 Dihydroxyvitamin D3 is of any pathophysiological relevance .", "entity": [{"entity": "PBMC", "entity_type": "cell type", "pos": [66, 70]}, {"entity": "PBMC receptors", "entity_type": "protein", "pos": [66, 80]}], "task": "NER"}
{"text": "Expression of Id2 and Id3 mRNA in human lymphocytes .", "entity": [{"entity": "human lymphocytes", "entity_type": "cell type", "pos": [34, 51]}], "task": "NER"}
{"text": "Helix-loop-helix ( HLH ) transcription factors are involved in cellular growth and differentiation .", "entity": [{"entity": "HLH", "entity_type": "protein", "pos": [19, 22]}, {"entity": "Helix-loop-helix ( HLH ) transcription factors", "entity_type": "protein", "pos": [0, 46]}, {"entity": "Helix-loop-helix", "entity_type": "protein", "pos": [0, 16]}], "task": "NER"}
{"text": "The Id ( inhibitor of DNA binding and differentiation ) HLH proteins , in a dominantly negative fashion, regulate transcriptional activities of basic HLH proteins .", "entity": [{"entity": "HLH proteins", "entity_type": "protein", "pos": [56, 68]}, {"entity": "basic HLH proteins", "entity_type": "protein", "pos": [144, 162]}, {"entity": "Id", "entity_type": "protein", "pos": [4, 6]}], "task": "NER"}
{"text": "We examined by northern hybridization the expression of Id2 and Id3 mRNA in human leukemia/lymphoma lines and patient samples , as well as resting and activated normal human lymphocytes from peripheral blood ( PBL ).", "entity": [{"entity": "PBL", "entity_type": "cell type", "pos": [210, 213]}, {"entity": "activated normal human lymphocytes", "entity_type": "cell line", "pos": [151, 185]}, {"entity": "human leukemia/lymphoma lines", "entity_type": "cell line", "pos": [76, 105]}], "task": "NER"}
{"text": "The Id2 mRNA was abundantly expressed in 5/12 T-cell and 3/4 B-cell lines , and Id3 mRNA was detected in 4/12 T-cell and 3/4 B-cell lines .", "entity": [{"entity": "Id2 mRNA", "entity_type": "RNA", "pos": [4, 12]}, {"entity": "5/12 T-cell", "entity_type": "cell line", "pos": [41, 52]}, {"entity": "Id3 mRNA", "entity_type": "RNA", "pos": [80, 88]}, {"entity": "3/4 B-cell lines", "entity_type": "cell line", "pos": [57, 73]}, {"entity": "4/12 T-cell", "entity_type": "cell line", "pos": [105, 116]}, {"entity": "Id2", "entity_type": "protein", "pos": [4, 7]}, {"entity": "Id3", "entity_type": "protein", "pos": [80, 83]}, {"entity": "3/4 B-cell lines", "entity_type": "cell line", "pos": [121, 137]}], "task": "NER"}
{"text": "Interestingly, Id2 , but not Id3 , mRNA was strongly expressed in 4/5 T-cell lines infected with human T-cell leukemia virus type I ( HTLV-I ) ( ATL-1k , MT-2 , S-LB1 ) and type II ( Mo ) .", "entity": [{"entity": "Id3", "entity_type": "protein", "pos": [29, 32]}, {"entity": "Mo", "entity_type": "cell line", "pos": [183, 185]}, {"entity": "Id2", "entity_type": "protein", "pos": [15, 18]}, {"entity": "4/5 T-cell lines", "entity_type": "cell line", "pos": [66, 82]}, {"entity": "S-LB1", "entity_type": "cell line", "pos": [161, 166]}, {"entity": "MT-2", "entity_type": "cell line", "pos": [154, 158]}, {"entity": "ATL-1k", "entity_type": "cell line", "pos": [145, 151]}], "task": "NER"}
{"text": "Another unexpected finding was that T-cell leukemias and T-cell lines often expressed either Id2 or Id3 mRNA .", "entity": [{"entity": "Id3 mRNA", "entity_type": "RNA", "pos": [100, 108]}, {"entity": "T-cell lines", "entity_type": "cell line", "pos": [57, 69]}, {"entity": "Id3", "entity_type": "protein", "pos": [100, 103]}, {"entity": "Id2", "entity_type": "protein", "pos": [93, 96]}], "task": "NER"}
{"text": "In addition, resting PBL constitutively expressed prominent levels of Id2 mRNA , but not Id3 mRNA .", "entity": [{"entity": "Id3", "entity_type": "protein", "pos": [89, 92]}, {"entity": "resting PBL", "entity_type": "cell type", "pos": [13, 24]}, {"entity": "Id3 mRNA", "entity_type": "RNA", "pos": [89, 97]}, {"entity": "PBL", "entity_type": "cell type", "pos": [21, 24]}, {"entity": "Id2", "entity_type": "protein", "pos": [70, 73]}, {"entity": "Id2 mRNA", "entity_type": "RNA", "pos": [70, 78]}], "task": "NER"}
{"text": "Upon PHA -stimulation , Id2 expression decreased and Id3 levels increased with biphasic kinetics.", "entity": [{"entity": "PHA", "entity_type": "protein", "pos": [5, 8]}, {"entity": "Id2", "entity_type": "protein", "pos": [24, 27]}, {"entity": "Id3", "entity_type": "protein", "pos": [53, 56]}], "task": "NER"}
{"text": "Taken together, our studies revealed three unexpected findings which require further analysis: (1) expression of Id2 mRNA is often associated with lymphocytic transformation by HTLV-I or -II; (2) T-cells usually express either Id2 or Id3 mRNA , but B-cells often express both simultaneously; (3) non-dividing, normal PBL express high levels of Id2 and no Id3 mRNA ; and with the onset of cellular proliferation, levels of Id2 mRNA decrease while levels of Id3 mRNA increase, suggesting that regulation of expression of these closely related genes is disparate.", "entity": [{"entity": "Id2", "entity_type": "protein", "pos": [113, 116]}, {"entity": "Id3", "entity_type": "protein", "pos": [234, 237]}, {"entity": "PBL", "entity_type": "cell type", "pos": [317, 320]}, {"entity": "Id2", "entity_type": "protein", "pos": [227, 230]}, {"entity": "Id3 mRNA", "entity_type": "RNA", "pos": [234, 242]}, {"entity": "Id2 mRNA", "entity_type": "RNA", "pos": [113, 121]}, {"entity": "Id2 mRNA", "entity_type": "RNA", "pos": [422, 430]}, {"entity": "Id3 mRNA", "entity_type": "RNA", "pos": [355, 363]}, {"entity": "genes", "entity_type": "DNA", "pos": [541, 546]}, {"entity": "Id3", "entity_type": "protein", "pos": [355, 358]}, {"entity": "Id3 mRNA", "entity_type": "RNA", "pos": [456, 464]}, {"entity": "Id2", "entity_type": "protein", "pos": [344, 347]}, {"entity": "Id2", "entity_type": "protein", "pos": [422, 425]}, {"entity": "Id3", "entity_type": "protein", "pos": [456, 459]}], "task": "NER"}
{"text": "Salicylates inhibit lipopolysaccharide -induced transcriptional activation of the tissue factor gene in human monocytic cells .", "entity": [{"entity": "human monocytic cells", "entity_type": "cell type", "pos": [104, 125]}], "task": "NER"}
{"text": "Binding of plasma Factor VII/VIIa to the tissue factor (TF) receptor initiates the coagulation protease cascades .", "entity": [{"entity": "coagulation protease", "entity_type": "protein", "pos": [83, 103]}, {"entity": "tissue factor (TF) receptor", "entity_type": "protein", "pos": [41, 68]}, {"entity": "plasma Factor VII/VIIa", "entity_type": "protein", "pos": [11, 33]}], "task": "NER"}
{"text": "TF expression by circulating monocytes is associated with thrombotic and inflammatory complications in a variety of diseases.", "entity": [{"entity": "circulating monocytes", "entity_type": "cell type", "pos": [17, 38]}], "task": "NER"}
{"text": "Transcriptional activation of the human TF gene in monocytic cells exposed to bacterial lipopolysaccharide ( LPS ) is mediated by binding of c-Rel/p65 heterodimers to a kappa B site in the TF promoter .", "entity": [{"entity": "TF promoter", "entity_type": "DNA", "pos": [189, 200]}, {"entity": "kappa B site", "entity_type": "DNA", "pos": [169, 181]}, {"entity": "monocytic cells", "entity_type": "cell type", "pos": [51, 66]}, {"entity": "human TF gene", "entity_type": "DNA", "pos": [34, 47]}, {"entity": "c-Rel/p65 heterodimers", "entity_type": "protein", "pos": [141, 163]}], "task": "NER"}
{"text": "Here, we report that a family of anti-inflammatory agents , known as the salicylates, inhibited LPS induction of TF activity and TF gene transcription in human monocytes and monocytic THP-1 cells at clinically relevant doses.", "entity": [{"entity": "TF gene", "entity_type": "DNA", "pos": [129, 136]}, {"entity": "monocytic THP-1 cells", "entity_type": "cell line", "pos": [174, 195]}, {"entity": "human monocytes", "entity_type": "cell type", "pos": [154, 169]}], "task": "NER"}
{"text": "Furthermore, sodium salicylate blocked the LPS -induced proteolytic degradation of I kappa B alpha , which prevented the nuclear translocation of c-Rel/p65 heterodimers .", "entity": [{"entity": "I kappa B alpha", "entity_type": "protein", "pos": [83, 98]}, {"entity": "c-Rel/p65 heterodimers", "entity_type": "protein", "pos": [146, 168]}], "task": "NER"}
{"text": "In contrast, two other nonsteroidal anti-inflammatory drugs , ibuprofen and indomethacin , did not inhibit LPS induction of the TF gene .", "entity": [{"entity": "TF gene", "entity_type": "DNA", "pos": [128, 135]}], "task": "NER"}
{"text": "These results indicated that salicylates inhibited LPS induction of TF gene transcription in monocytic cells by preventing nuclear translocation of c-Rel/p65 heterodimers .", "entity": [{"entity": "TF gene", "entity_type": "DNA", "pos": [68, 75]}, {"entity": "monocytic cells", "entity_type": "cell type", "pos": [93, 108]}, {"entity": "c-Rel/p65 heterodimers", "entity_type": "protein", "pos": [148, 170]}], "task": "NER"}
{"text": "The clinical benefits of salicylates in the treatment of several diseases, including atherosclerosis and rheumatoid arthritis , may be related to their ability to reduce monocyte gene expression .", "entity": [], "task": "NER"}
{"text": "Activation of the signal transducer and transcription ( STAT ) signaling pathway in a primary T cell response .", "entity": [{"entity": "STAT", "entity_type": "protein", "pos": [56, 60]}], "task": "NER"}
{"text": "Critical role for IL-6 .", "entity": [{"entity": "IL-6", "entity_type": "protein", "pos": [18, 22]}], "task": "NER"}
{"text": "The T cell activation is initiated by interaction of specific Ags with TCR , followed by activation of intracellular biochemical events leading to activation of several genes.", "entity": [{"entity": "TCR", "entity_type": "protein", "pos": [71, 74]}, {"entity": "Ags", "entity_type": "protein", "pos": [62, 65]}], "task": "NER"}
{"text": "The activation of signal transducer and activator of transcription (STAT) proteins in a primary TCR -mediated activation of T cells have been explored.", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [124, 131]}, {"entity": "transcription (STAT) proteins", "entity_type": "protein", "pos": [53, 82]}, {"entity": "TCR", "entity_type": "protein", "pos": [96, 99]}], "task": "NER"}
{"text": "In purified human peripheral blood T cells , nuclear STAT proteins were activated approximately 3 h after activation by cross-linked anti-CD3 Abs .", "entity": [{"entity": "purified human peripheral blood T cells", "entity_type": "cell type", "pos": [3, 42]}, {"entity": "anti-CD3 Abs", "entity_type": "protein", "pos": [133, 145]}, {"entity": "nuclear STAT proteins", "entity_type": "protein", "pos": [45, 66]}, {"entity": "T cells", "entity_type": "cell type", "pos": [35, 42]}], "task": "NER"}
{"text": "These STAT proteins were detected by using the IFN-gamma-activated sequence ( GAS ) and related oligonucleotides as probes in electrophoretic mobility shift assay .", "entity": [{"entity": "GAS", "entity_type": "DNA", "pos": [78, 81]}, {"entity": "IFN-gamma-activated sequence", "entity_type": "DNA", "pos": [47, 75]}, {"entity": "STAT proteins", "entity_type": "protein", "pos": [6, 19]}], "task": "NER"}
{"text": "Analysis of the nuclear extracts with anti-STAT Abs indicated that they contained STAT-3 and additional proteins crossreactive with the STAT family .", "entity": [{"entity": "anti-STAT Abs", "entity_type": "protein", "pos": [38, 51]}, {"entity": "STAT-3", "entity_type": "protein", "pos": [82, 88]}, {"entity": "STAT family", "entity_type": "protein", "pos": [136, 147]}], "task": "NER"}
{"text": "The induction of STAT activity was inhibited completely by pretreatment with either cycloheximide or cyclosporin A , thus indicating that the induction was due to a secondary factor produced by the activated T cells .", "entity": [{"entity": "T cells", "entity_type": "cell type", "pos": [208, 215]}, {"entity": "STAT", "entity_type": "protein", "pos": [17, 21]}, {"entity": "secondary factor", "entity_type": "protein", "pos": [165, 181]}], "task": "NER"}
{"text": "As neutralizing anti- IL-6 Abs effectively down-regulated the early induction of STAT proteins and as exogenously added IL-6 rapidly activated DNA binding similar to TCR -mediated bindings , it can be concluded that IL-6 is the factor responsible for the activation of STAT proteins in a primary T cell response .", "entity": [{"entity": "IL-6", "entity_type": "protein", "pos": [22, 26]}, {"entity": "STAT proteins", "entity_type": "protein", "pos": [81, 94]}, {"entity": "neutralizing anti- IL-6 Abs", "entity_type": "protein", "pos": [3, 30]}, {"entity": "IL-6", "entity_type": "protein", "pos": [120, 124]}, {"entity": "STAT proteins", "entity_type": "protein", "pos": [269, 282]}, {"entity": "IL-6", "entity_type": "protein", "pos": [216, 220]}, {"entity": "TCR", "entity_type": "protein", "pos": [166, 169]}], "task": "NER"}
{"text": "The normal cell cycle activation program is exploited during the infection of quiescent B lymphocytes by Epstein-Barr virus .", "entity": [{"entity": "quiescent B lymphocytes", "entity_type": "cell type", "pos": [78, 101]}], "task": "NER"}
{"text": "B lymphocytes in the peripheral circulation are maintained in a non-proliferative state .", "entity": [{"entity": "B lymphocytes", "entity_type": "cell type", "pos": [0, 13]}], "task": "NER"}
{"text": "Antigen recognition stimulates limited proliferation, whereas infection with Epstein-Barr virus ( EBV ) results in continual proliferation and the outgrowth of immortal cell lines .", "entity": [{"entity": "immortal cell lines", "entity_type": "cell line", "pos": [160, 179]}], "task": "NER"}
{"text": "Because it is not clear at which point in cell cycle the peripheral B lymphocytes are arrested, we characterized the expression of several cell cycle-associated genes in quiescent and stimulated cells .", "entity": [{"entity": "peripheral B lymphocytes", "entity_type": "cell type", "pos": [57, 81]}, {"entity": "B lymphocytes", "entity_type": "cell type", "pos": [68, 81]}, {"entity": "cell cycle-associated genes", "entity_type": "DNA", "pos": [139, 166]}], "task": "NER"}
{"text": "We show that the expression of four cell genes , cdc-2 , cyclin E , CD23 , and cyclin D2 , are up-regulated approximately 100-fold as a result of EBV -mediated immortalization .", "entity": [{"entity": "cell genes", "entity_type": "DNA", "pos": [36, 46]}, {"entity": "cyclin E", "entity_type": "DNA", "pos": [57, 65]}, {"entity": "cyclin D2", "entity_type": "DNA", "pos": [79, 88]}, {"entity": "CD23", "entity_type": "DNA", "pos": [68, 72]}, {"entity": "cdc-2", "entity_type": "DNA", "pos": [49, 54]}], "task": "NER"}
{"text": "Because these genes play a positive role in cell proliferation, we suggest that this regulatory switch contributes to controlling entry into the cell cycle .", "entity": [], "task": "NER"}
{"text": "Transient stimulation of quiescent B lymphocytes with either a cocktail of anti-CD40 , anti-IgM , and IL4 , or EBV results in the rapid expression of the same four genes, suggesting that, after infection, EBV exploits the normal program of B-lymphocyte cell cycle activation .", "entity": [{"entity": "B-lymphocyte", "entity_type": "cell type", "pos": [240, 252]}, {"entity": "quiescent B lymphocytes", "entity_type": "cell type", "pos": [25, 48]}, {"entity": "B lymphocytes", "entity_type": "cell type", "pos": [35, 48]}, {"entity": "IL4", "entity_type": "protein", "pos": [102, 105]}, {"entity": "anti-CD40", "entity_type": "protein", "pos": [75, 84]}, {"entity": "anti-IgM", "entity_type": "protein", "pos": [87, 95]}], "task": "NER"}
{"text": "Expression of the chemokine receptor BLR2/EBI1 is specifically transactivated by Epstein-Barr virus nuclear antigen 2 .", "entity": [{"entity": "BLR2/EBI1", "entity_type": "protein", "pos": [37, 46]}, {"entity": "Epstein-Barr virus nuclear antigen 2", "entity_type": "protein", "pos": [81, 117]}, {"entity": "chemokine receptor", "entity_type": "protein", "pos": [18, 36]}], "task": "NER"}
{"text": "In our attempt to identify chemokine receptors that are related to Burkitt's lymphoma receptor 1 ( BLR1 ) and are expressed in activated lymphocytes we used RT-PCR resulting in the isolation of a cDNA encoding a seven transmembrane receptor termed BLR2 .", "entity": [{"entity": "BLR1", "entity_type": "protein", "pos": [99, 103]}, {"entity": "BLR2", "entity_type": "protein", "pos": [248, 252]}, {"entity": "seven transmembrane receptor", "entity_type": "protein", "pos": [212, 240]}, {"entity": "activated lymphocytes", "entity_type": "cell type", "pos": [127, 148]}, {"entity": "chemokine receptors", "entity_type": "protein", "pos": [27, 46]}, {"entity": "Burkitt's lymphoma receptor 1", "entity_type": "protein", "pos": [67, 96]}], "task": "NER"}
{"text": "The protein shows significant sequence similarities to the family of G-protein coupled chemokine receptors and turned out to be identical to the recently described receptor EBI1 .", "entity": [{"entity": "G-protein coupled chemokine receptors", "entity_type": "protein", "pos": [69, 106]}, {"entity": "chemokine receptors", "entity_type": "protein", "pos": [87, 106]}, {"entity": "G-protein", "entity_type": "protein", "pos": [69, 78]}, {"entity": "receptor EBI1", "entity_type": "protein", "pos": [164, 177]}], "task": "NER"}
{"text": "Northern blot analysis revealed that BLR2 mRNA could be highly stimulated in mitogen- and anti-CD3- treated peripheral blood lymphocytes .", "entity": [{"entity": "BLR2 mRNA", "entity_type": "RNA", "pos": [37, 46]}, {"entity": "BLR2", "entity_type": "protein", "pos": [37, 41]}], "task": "NER"}
{"text": "BLR2 -specific mRNA could be detected in all Epstein-Barr virus positive B cell lines .", "entity": [{"entity": "Epstein-Barr virus positive B cell lines", "entity_type": "cell line", "pos": [45, 85]}, {"entity": "BLR2 -specific mRNA", "entity_type": "RNA", "pos": [0, 19]}, {"entity": "BLR2", "entity_type": "protein", "pos": [0, 4]}], "task": "NER"}
{"text": "We show that transcription of the BLR2 gene could be specifically induced in Epstein-Barr virus negative BL 41 cells via estrogen-mediated activation of Epstein-Barr virus nuclear antigen 2 , a key regulator of viral and cellular genes in immortalized B cells .", "entity": [{"entity": "immortalized B cells", "entity_type": "cell line", "pos": [239, 259]}, {"entity": "Epstein-Barr virus nuclear antigen 2", "entity_type": "protein", "pos": [153, 189]}, {"entity": "BLR2", "entity_type": "protein", "pos": [34, 38]}, {"entity": "cellular genes", "entity_type": "DNA", "pos": [221, 235]}, {"entity": "viral", "entity_type": "DNA", "pos": [211, 216]}, {"entity": "BLR2 gene", "entity_type": "DNA", "pos": [34, 43]}, {"entity": "viral and cellular genes", "entity_type": "DNA", "pos": [211, 235]}, {"entity": "Epstein-Barr virus negative BL 41 cells", "entity_type": "cell line", "pos": [77, 116]}], "task": "NER"}
{"text": "Our data suggest an involvement of BLR2 in the regulation of migration in activated lymphocytes and in viral pathogenesis .", "entity": [{"entity": "BLR2", "entity_type": "protein", "pos": [35, 39]}, {"entity": "activated lymphocytes", "entity_type": "cell type", "pos": [74, 95]}], "task": "NER"}
{"text": "A central role for a single c-Myb binding site in a thymic locus control region .", "entity": [{"entity": "thymic locus control region", "entity_type": "DNA", "pos": [52, 79]}, {"entity": "single c-Myb binding site", "entity_type": "DNA", "pos": [21, 46]}], "task": "NER"}
{"text": "Locus control regions ( LCRs ) are powerful assemblies of cis elements that organize the actions of cell-type-specific trans-acting factors .", "entity": [{"entity": "LCRs", "entity_type": "DNA", "pos": [24, 28]}, {"entity": "Locus control regions", "entity_type": "DNA", "pos": [0, 21]}, {"entity": "cell-type-specific trans-acting factors", "entity_type": "protein", "pos": [100, 139]}, {"entity": "cis elements", "entity_type": "DNA", "pos": [58, 70]}], "task": "NER"}
{"text": "A 2.3-kb LCR in the human adenosine deaminase (ADA) gene first intron , which controls expression in thymocytes , is composed of a 200-bp enhancer domain and extended flanking sequences that facilitate activation from within chromatin .", "entity": [{"entity": "chromatin", "entity_type": "DNA", "pos": [225, 234]}, {"entity": "2.3-kb LCR", "entity_type": "protein", "pos": [2, 12]}, {"entity": "200-bp enhancer domain", "entity_type": "DNA", "pos": [131, 153]}, {"entity": "thymocytes", "entity_type": "cell type", "pos": [101, 111]}, {"entity": "human adenosine deaminase (ADA) gene first intron", "entity_type": "DNA", "pos": [20, 69]}, {"entity": "human adenosine deaminase (ADA) gene", "entity_type": "DNA", "pos": [20, 56]}], "task": "NER"}
{"text": "Prior analyses have demonstrated that the enhancer contains a 28-bp core region and local adjacent augmentative cis elements .", "entity": [{"entity": "enhancer", "entity_type": "DNA", "pos": [42, 50]}, {"entity": "cis elements", "entity_type": "DNA", "pos": [112, 124]}, {"entity": "28-bp core region", "entity_type": "DNA", "pos": [62, 79]}], "task": "NER"}
{"text": "We now show that the core contains a single critical c-Myb binding site .", "entity": [{"entity": "c-Myb binding site", "entity_type": "DNA", "pos": [53, 71]}], "task": "NER"}
{"text": "In both transiently cotransfected human cells and stable chromatin-integrated yeast cells , c-Myb strongly transactivated reporter constructs that contained polymerized core sequences .", "entity": [{"entity": "polymerized core sequences", "entity_type": "DNA", "pos": [157, 183]}, {"entity": "transiently cotransfected human cells", "entity_type": "cell line", "pos": [8, 45]}, {"entity": "chromatin-integrated yeast cells", "entity_type": "cell line", "pos": [57, 89]}, {"entity": "transactivated reporter constructs", "entity_type": "DNA", "pos": [107, 141]}, {"entity": "c-Myb", "entity_type": "protein", "pos": [92, 97]}], "task": "NER"}
{"text": "c-Myb protein was strongly evident in T lymphoblasts in which the enhancer was active and was localized within discrete nuclear structures .", "entity": [{"entity": "T lymphoblasts", "entity_type": "cell type", "pos": [38, 52]}, {"entity": "c-Myb", "entity_type": "protein", "pos": [0, 5]}, {"entity": "c-Myb protein", "entity_type": "protein", "pos": [0, 13]}, {"entity": "enhancer", "entity_type": "DNA", "pos": [66, 74]}], "task": "NER"}
{"text": "Fetal murine thymus exhibited a striking concordance of endogenous c-myb expression with that of mouse ADA and human ADA LCR -directed transgene expression .", "entity": [{"entity": "mouse ADA", "entity_type": "DNA", "pos": [97, 106]}, {"entity": "human ADA LCR", "entity_type": "DNA", "pos": [111, 124]}, {"entity": "c-myb", "entity_type": "DNA", "pos": [67, 72]}], "task": "NER"}
{"text": "Point mutation of the c-Myb site within the intact 2.3-kb LCR severely attenuated enhancer activity in transfections and LCR activity in transgenic thymocytes .", "entity": [{"entity": "thymocytes", "entity_type": "cell type", "pos": [148, 158]}, {"entity": "transgenic thymocytes", "entity_type": "cell line", "pos": [137, 158]}, {"entity": "2.3-kb LCR", "entity_type": "protein", "pos": [51, 61]}, {"entity": "c-Myb site", "entity_type": "DNA", "pos": [22, 32]}, {"entity": "LCR", "entity_type": "DNA", "pos": [58, 61]}, {"entity": "c-Myb", "entity_type": "protein", "pos": [22, 27]}], "task": "NER"}
{"text": "Within the context of a complex enhancer and LCR , c-Myb can act as an organizer of thymocyte-specific gene expression via a single binding site.", "entity": [{"entity": "LCR", "entity_type": "DNA", "pos": [45, 48]}, {"entity": "thymocyte-specific gene", "entity_type": "DNA", "pos": [84, 107]}, {"entity": "complex enhancer", "entity_type": "DNA", "pos": [24, 40]}, {"entity": "c-Myb", "entity_type": "protein", "pos": [51, 56]}], "task": "NER"}
{"text": "A regulatory element in the human interleukin 2 gene promoter is a binding site for the zinc finger proteins Sp1 and EGR-1 .", "entity": [{"entity": "human interleukin 2 gene promoter", "entity_type": "DNA", "pos": [28, 61]}, {"entity": "EGR-1", "entity_type": "protein", "pos": [117, 122]}, {"entity": "Sp1", "entity_type": "protein", "pos": [109, 112]}, {"entity": "regulatory element", "entity_type": "DNA", "pos": [2, 20]}, {"entity": "binding site", "entity_type": "DNA", "pos": [67, 79]}, {"entity": "zinc finger proteins", "entity_type": "protein", "pos": [88, 108]}], "task": "NER"}
{"text": "Activation of the interleukin 2 ( IL-2 ) gene after antigen recognition is a critical event for T cell proliferation and effector function.", "entity": [{"entity": "interleukin 2", "entity_type": "protein", "pos": [18, 31]}, {"entity": "IL-2", "entity_type": "protein", "pos": [34, 38]}, {"entity": "interleukin 2 ( IL-2 ) gene", "entity_type": "DNA", "pos": [18, 45]}], "task": "NER"}
{"text": "Prior studies have identified several transcription factors that contribute to the activity of the IL-2 promoter in stimulated T lymphocytes .", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [99, 103]}, {"entity": "IL-2 promoter", "entity_type": "DNA", "pos": [99, 112]}, {"entity": "transcription factors", "entity_type": "protein", "pos": [38, 59]}, {"entity": "stimulated T lymphocytes", "entity_type": "cell type", "pos": [116, 140]}], "task": "NER"}
{"text": "Here we describe a novel regulatory element within the IL-2 promoter located immediately upstream of the nuclear factor of activated T cell ( NFAT ) domain .", "entity": [{"entity": "regulatory element", "entity_type": "DNA", "pos": [25, 43]}, {"entity": "nuclear factor of activated T cell ( NFAT ) domain", "entity_type": "DNA", "pos": [105, 155]}, {"entity": "NFAT", "entity_type": "protein", "pos": [142, 146]}, {"entity": "nuclear factor of activated T cell", "entity_type": "protein", "pos": [105, 139]}, {"entity": "IL-2 promoter", "entity_type": "DNA", "pos": [55, 68]}], "task": "NER"}
{"text": "This region (termed the zinc finger protein binding region ( ZIP )) serves as binding site for two differently regulated zinc finger proteins : the constitutively expressed transcription factor Sp1 and the inducible early growth response protein EGR-1 .", "entity": [{"entity": "zinc finger protein binding region", "entity_type": "DNA", "pos": [24, 58]}, {"entity": "constitutively expressed transcription factor", "entity_type": "protein", "pos": [148, 193]}, {"entity": "Sp1", "entity_type": "protein", "pos": [194, 197]}, {"entity": "inducible early growth response protein", "entity_type": "protein", "pos": [206, 245]}, {"entity": "EGR-1", "entity_type": "protein", "pos": [246, 251]}, {"entity": "ZIP", "entity_type": "DNA", "pos": [61, 64]}, {"entity": "zinc finger proteins", "entity_type": "protein", "pos": [121, 141]}], "task": "NER"}
{"text": "In unstimulated cells which do not secrete IL-2 , only Sp1 binds to this region, while in stimulated IL-2 secreting cells the inducible EGR-1 protein recognizes this element.", "entity": [{"entity": "IL-2", "entity_type": "protein", "pos": [43, 47]}, {"entity": "unstimulated cells", "entity_type": "cell type", "pos": [3, 21]}, {"entity": "inducible EGR-1 protein", "entity_type": "protein", "pos": [126, 149]}, {"entity": "stimulated IL-2 secreting cells", "entity_type": "cell line", "pos": [90, 121]}, {"entity": "EGR-1", "entity_type": "protein", "pos": [136, 141]}, {"entity": "IL-2", "entity_type": "protein", "pos": [101, 105]}, {"entity": "Sp1", "entity_type": "protein", "pos": [55, 58]}], "task": "NER"}
{"text": "In Jurkat T cells , the ZIP site serves as an activator for IL-2 gene expression , and a combination of ZIP and NFAT binding sites is required for maximal IL-2 promoter activity .", "entity": [{"entity": "NFAT", "entity_type": "protein", "pos": [112, 116]}, {"entity": "IL-2 promoter", "entity_type": "DNA", "pos": [155, 168]}, {"entity": "Jurkat T cells", "entity_type": "cell line", "pos": [3, 17]}, {"entity": "IL-2", "entity_type": "protein", "pos": [60, 64]}, {"entity": "ZIP site", "entity_type": "DNA", "pos": [24, 32]}, {"entity": "ZIP", "entity_type": "DNA", "pos": [24, 27]}, {"entity": "NFAT binding sites", "entity_type": "DNA", "pos": [112, 130]}, {"entity": "ZIP", "entity_type": "DNA", "pos": [104, 107]}, {"entity": "IL-2", "entity_type": "protein", "pos": [155, 159]}], "task": "NER"}
{"text": "These results suggest a critical role of the ZIP site for IL-2 promoter activity .", "entity": [{"entity": "ZIP site", "entity_type": "DNA", "pos": [45, 53]}, {"entity": "IL-2", "entity_type": "protein", "pos": [58, 62]}, {"entity": "IL-2 promoter", "entity_type": "DNA", "pos": [58, 71]}], "task": "NER"}
{"text": "Activation of the HIV-1 enhancer by the LEF-1 HMG protein on nucleosome-assembled DNA in vitro.", "entity": [{"entity": "nucleosome-assembled DNA", "entity_type": "DNA", "pos": [61, 85]}, {"entity": "LEF-1 HMG protein", "entity_type": "protein", "pos": [40, 57]}, {"entity": "HIV-1 enhancer", "entity_type": "DNA", "pos": [18, 32]}], "task": "NER"}
{"text": "Lymphoid enhancer-binding factor 1 ( LEF-1 ) is a regulatory high mobility group (HMG) protein that activates the T cell receptor alpha ( TCR alpha ) enhancer in a context-restricted manner in T cells .", "entity": [{"entity": "LEF-1", "entity_type": "protein", "pos": [37, 42]}, {"entity": "T cell receptor alpha", "entity_type": "protein", "pos": [114, 135]}, {"entity": "T cell receptor alpha ( TCR alpha ) enhancer", "entity_type": "DNA", "pos": [114, 158]}, {"entity": "Lymphoid enhancer-binding factor 1", "entity_type": "protein", "pos": [0, 34]}, {"entity": "T cells", "entity_type": "cell type", "pos": [193, 200]}, {"entity": "TCR alpha", "entity_type": "protein", "pos": [138, 147]}, {"entity": "regulatory high mobility group (HMG) protein", "entity_type": "protein", "pos": [50, 94]}], "task": "NER"}
{"text": "In this paper we demonstrate that the distal region of the human immunodeficiency virus-1 ( HIV-1 ) enhancer , which contains DNA-binding sites for LEF-1 and Ets-1, also provides a functional context for activation by LEF-1 .", "entity": [{"entity": "LEF-1", "entity_type": "protein", "pos": [148, 153]}, {"entity": "human immunodeficiency virus-1 ( HIV-1 ) enhancer", "entity_type": "DNA", "pos": [59, 108]}, {"entity": "LEF-1", "entity_type": "protein", "pos": [218, 223]}, {"entity": "DNA-binding sites", "entity_type": "DNA", "pos": [126, 143]}], "task": "NER"}
{"text": "First, we show that mutations in the LEF-1 -binding site inhibit the activity of multimerized copies of the HIV-1 enhancer in Jurkat T cells , and that LEF-1 /GAL4 can activate a GAL4-substituted HIV-1 enhancer 80- to 100-fold in vivo.", "entity": [{"entity": "LEF-1 -binding site", "entity_type": "DNA", "pos": [37, 56]}, {"entity": "HIV-1 enhancer", "entity_type": "DNA", "pos": [108, 122]}, {"entity": "LEF-1", "entity_type": "protein", "pos": [37, 42]}, {"entity": "GAL4-substituted HIV-1 enhancer", "entity_type": "DNA", "pos": [179, 210]}, {"entity": "Jurkat T cells", "entity_type": "cell line", "pos": [126, 140]}, {"entity": "multimerized copies", "entity_type": "DNA", "pos": [81, 100]}, {"entity": "HIV-1 enhancer", "entity_type": "DNA", "pos": [196, 210]}, {"entity": "LEF-1 /GAL4", "entity_type": "protein", "pos": [152, 163]}, {"entity": "LEF-1", "entity_type": "protein", "pos": [152, 157]}], "task": "NER"}
{"text": "Second, recombinant LEF-1 is shown to activate HIV-1 transcription on chromatin-assembled DNA in vitro.", "entity": [{"entity": "LEF-1", "entity_type": "protein", "pos": [20, 25]}, {"entity": "recombinant LEF-1", "entity_type": "protein", "pos": [8, 25]}, {"entity": "chromatin-assembled DNA", "entity_type": "DNA", "pos": [70, 93]}], "task": "NER"}
{"text": "By using a nucleosome -assembly system derived from Drosophila embryos , we find that the packaging of DNA into chromatin in vitro strongly represses HIV-1 transcription and that repression can be counteracted efficiently by preincubation of the DNA with LEF-1 (or LEF-1 and Ets-1 ) supplemented with fractions containing the promoter-binding protein , Sp1 .", "entity": [{"entity": "nucleosome", "entity_type": "protein", "pos": [11, 21]}, {"entity": "chromatin", "entity_type": "DNA", "pos": [112, 121]}, {"entity": "promoter-binding protein", "entity_type": "protein", "pos": [326, 350]}, {"entity": "LEF-1", "entity_type": "protein", "pos": [255, 260]}, {"entity": "Sp1", "entity_type": "protein", "pos": [353, 356]}, {"entity": "LEF-1", "entity_type": "protein", "pos": [265, 270]}, {"entity": "Ets-1", "entity_type": "protein", "pos": [275, 280]}], "task": "NER"}
{"text": "Addition of TFE-3 , which binds to an E-box motif upstream of the LEF-1 and Ets-1 sites , further augments transcription in this system.", "entity": [{"entity": "TFE-3", "entity_type": "protein", "pos": [12, 17]}, {"entity": "E-box motif", "entity_type": "DNA", "pos": [38, 49]}], "task": "NER"}
{"text": "Individually or collectively, none of the three enhancer-binding proteins ( LEF-1 , Ets-1 , and TFE-3 ) could activate transcription in the absence of Sp1 .", "entity": [{"entity": "Ets-1", "entity_type": "protein", "pos": [84, 89]}, {"entity": "TFE-3", "entity_type": "protein", "pos": [96, 101]}, {"entity": "LEF-1", "entity_type": "protein", "pos": [76, 81]}, {"entity": "enhancer-binding proteins", "entity_type": "protein", "pos": [48, 73]}, {"entity": "Sp1", "entity_type": "protein", "pos": [151, 154]}], "task": "NER"}
{"text": "A truncation mutant of LEF-1 ( HMG-88 ), which contains the HMG box but lacks the trans-activation domain , did not activate transcription from nucleosomal DNA , indicating that bending of DNA by the HMG domain is not sufficient to activate transcription in vitro.", "entity": [{"entity": "HMG box", "entity_type": "protein", "pos": [60, 67]}, {"entity": "HMG domain", "entity_type": "protein", "pos": [200, 210]}, {"entity": "trans-activation domain", "entity_type": "protein", "pos": [82, 105]}, {"entity": "truncation mutant", "entity_type": "protein", "pos": [2, 19]}, {"entity": "LEF-1", "entity_type": "protein", "pos": [23, 28]}, {"entity": "nucleosomal DNA", "entity_type": "DNA", "pos": [144, 159]}, {"entity": "HMG-88", "entity_type": "protein", "pos": [31, 37]}], "task": "NER"}
{"text": "We conclude that transcription activation by LEF-1 in vitro is a chromatin -dependent process that requires a functional trans-activation domain in addition to the HMG domain .", "entity": [{"entity": "HMG domain", "entity_type": "protein", "pos": [164, 174]}, {"entity": "chromatin", "entity_type": "DNA", "pos": [65, 74]}, {"entity": "trans-activation domain", "entity_type": "protein", "pos": [121, 144]}, {"entity": "LEF-1", "entity_type": "protein", "pos": [45, 50]}], "task": "NER"}
{"text": "HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells [published erratum appears in J Biol Chem 1995 Dec 1;270(48):29038]", "entity": [{"entity": "protein-1", "entity_type": "protein", "pos": [60, 69]}, {"entity": "T cells", "entity_type": "cell type", "pos": [78, 85]}, {"entity": "CD4+ T cells", "entity_type": "cell type", "pos": [73, 85]}, {"entity": "HIV-1 envelope glycoproteins", "entity_type": "protein", "pos": [0, 28]}], "task": "NER"}
{"text": "Activation of CD4 positive T cells is a primary requirement for human immunodeficiency virus ( HIV ) entry , efficient HIV replication , and progression to AIDS , Utilizing CD4 positive T cell lines and purified T cells from normal individuals , we have demonstrated that native envelope glycoproteins of HIV , gp 160 , can induce activation of transcription factor, activated protein-1 ( AP-1 ).", "entity": [{"entity": "gp 160", "entity_type": "protein", "pos": [311, 317]}, {"entity": "transcription factor, activated protein-1", "entity_type": "protein", "pos": [345, 386]}, {"entity": "T cells", "entity_type": "cell type", "pos": [27, 34]}, {"entity": "CD4 positive T cells", "entity_type": "cell type", "pos": [14, 34]}, {"entity": "purified T cells", "entity_type": "cell type", "pos": [203, 219]}, {"entity": "T cells", "entity_type": "cell type", "pos": [212, 219]}, {"entity": "native envelope glycoproteins", "entity_type": "protein", "pos": [272, 301]}, {"entity": "AP-1", "entity_type": "protein", "pos": [389, 393]}, {"entity": "CD4 positive T cell lines", "entity_type": "cell line", "pos": [173, 198]}], "task": "NER"}
{"text": "The stimulatory effects of gp160 are mediated through the CD4 molecule , since treatment of gp160 with soluble CD4-IgG abrogates its activity, and CD4 negative T cell lines fail to be stimulated with gp160 .", "entity": [{"entity": "CD4-IgG", "entity_type": "protein", "pos": [111, 118]}, {"entity": "gp160", "entity_type": "protein", "pos": [27, 32]}, {"entity": "gp160", "entity_type": "protein", "pos": [92, 97]}, {"entity": "CD4 negative T cell lines", "entity_type": "cell line", "pos": [147, 172]}, {"entity": "CD4 molecule", "entity_type": "protein", "pos": [58, 70]}, {"entity": "gp160", "entity_type": "protein", "pos": [200, 205]}], "task": "NER"}
{"text": "Immunoprecipitation of the gp 160 -induced nuclear extracts with polyclonal antibodies to Fos and Jun proteins indicates that AP-1 complex is comprised of members of these family of proteins.", "entity": [{"entity": "AP-1", "entity_type": "protein", "pos": [126, 130]}, {"entity": "Fos", "entity_type": "protein", "pos": [90, 93]}, {"entity": "polyclonal antibodies", "entity_type": "protein", "pos": [65, 86]}, {"entity": "Jun proteins", "entity_type": "protein", "pos": [98, 110]}, {"entity": "gp 160", "entity_type": "protein", "pos": [27, 33]}, {"entity": "AP-1 complex", "entity_type": "protein", "pos": [126, 138]}], "task": "NER"}
{"text": "The gp160 -induced AP-1 complex is dependent upon protein tyrosine phosphorylation and is protein synthesis-independent .", "entity": [{"entity": "gp160", "entity_type": "protein", "pos": [4, 9]}, {"entity": "gp160 -induced AP-1 complex", "entity_type": "protein", "pos": [4, 31]}, {"entity": "AP-1", "entity_type": "protein", "pos": [19, 23]}], "task": "NER"}
{"text": "This stimulation can also be abolished by inhibitors of protein kinase C , but it is unaffected by calcium channel blocker or cyclosporine A .", "entity": [{"entity": "protein kinase C", "entity_type": "protein", "pos": [56, 72]}], "task": "NER"}
{"text": "This gp160 treatment adversely affects the functional capabilities of T cells : pre-treatment of CD4+ T cells with gp160 for 4 h at 37 degrees C inhibited anti-CD3 -induced interleukin-2 secretion .", "entity": [{"entity": "anti-CD3", "entity_type": "protein", "pos": [155, 163]}, {"entity": "gp160", "entity_type": "protein", "pos": [5, 10]}, {"entity": "gp160", "entity_type": "protein", "pos": [115, 120]}, {"entity": "CD4+ T cells", "entity_type": "cell type", "pos": [97, 109]}, {"entity": "T cells", "entity_type": "cell type", "pos": [70, 77]}, {"entity": "T cells", "entity_type": "cell type", "pos": [102, 109]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [173, 186]}], "task": "NER"}
{"text": "Effects similar to gp160 were seen with anti-CD4 mAb .", "entity": [{"entity": "anti-CD4 mAb", "entity_type": "protein", "pos": [40, 52]}, {"entity": "gp160", "entity_type": "protein", "pos": [19, 24]}], "task": "NER"}
{"text": "The aberrant activation of AP-1 by gp160 in CD4 positive T cells could result in up-regulation of cytokines containing AP-1 sites , e.g. interleukin-3 and granulocyte macrophage colony-stimulating factor , and concurrently lead to T cell unresponsiveness by inhibiting interleukin-2 secretion .", "entity": [{"entity": "granulocyte macrophage colony-stimulating factor", "entity_type": "protein", "pos": [155, 203]}, {"entity": "gp160", "entity_type": "protein", "pos": [35, 40]}, {"entity": "T cell", "entity_type": "cell type", "pos": [57, 63]}, {"entity": "CD4 positive T cells", "entity_type": "cell type", "pos": [44, 64]}, {"entity": "cytokines", "entity_type": "protein", "pos": [98, 107]}, {"entity": "interleukin-2", "entity_type": "protein", "pos": [269, 282]}, {"entity": "AP-1", "entity_type": "protein", "pos": [27, 31]}, {"entity": "interleukin-3", "entity_type": "protein", "pos": [137, 150]}, {"entity": "AP-1 sites", "entity_type": "DNA", "pos": [119, 129]}, {"entity": "AP-1", "entity_type": "protein", "pos": [119, 123]}, {"entity": "T cells", "entity_type": "cell type", "pos": [57, 64]}], "task": "NER"}