{"input": "The inhibition of c-fos and c-jun expression by IL-4 in LPS-treated cells was shown to be due to a lower transcription rate of the c-fos and c-jun genes.", "output": {"entities": {"dna": [{"text": "c-fos", "start": 18, "end": 23}, {"text": "c-fos and c-jun genes", "start": 131, "end": 152}], "protein": [{"text": "IL-4", "start": 48, "end": 52}], "cell_type": [{"text": "LPS-treated cells", "start": 56, "end": 73}]}}, "schema": []} {"input": "IL-4 did not affect the stability of the c-fos and c-jun transcripts.", "output": {"entities": {"protein": [{"text": "IL-4", "start": 0, "end": 4}, {"text": "c-fos", "start": 41, "end": 46}, {"text": "c-jun transcripts", "start": 51, "end": 68}]}}, "schema": []} {"input": "Finally, using electrophoretic mobility shift assays, evidence was obtained that IL-4 inhibits LPS-induced expression of AP-1 protein.", "output": {"entities": {"protein": [{"text": "IL-4", "start": 81, "end": 85}, {"text": "AP-1", "start": 121, "end": 125}]}}, "schema": []} {"input": "These data indicate that IL-4 suppresses the induction of transcription factors in human activated monocytes.", "output": {"entities": {"protein": [{"text": "IL-4", "start": 25, "end": 29}, {"text": "transcription factors", "start": 58, "end": 79}], "cell_type": [{"text": "human activated monocytes", "start": 83, "end": 108}]}}, "schema": []} {"input": "Transient pseudohypoaldosteronism in obstructive renal disease with transient reduction of lymphocytic aldosterone receptors.", "output": {"entities": {"protein": [{"text": "lymphocytic aldosterone receptors", "start": 91, "end": 124}]}}, "schema": []} {"input": "Results in two affected infants.", "output": {"entities": {}}, "schema": []} {"input": "We report two patients with transient pseudohypoaldosteronism due to obstructive renal disease.", "output": {"entities": {}}, "schema": []} {"input": "Both patients presented with a salt-losing episode simulating adrenal insufficiency.", "output": {"entities": {}}, "schema": []} {"input": "In one patient, transient reduction of aldosterone receptors could be documented, while in the second patient the clinical and biochemical parameters were consistent with transient pseudohypoaldosteronism.", "output": {"entities": {"protein": [{"text": "aldosterone receptors", "start": 39, "end": 60}]}}, "schema": []} {"input": "Aldosterone receptors were normal in both patients", "output": {"entities": {"protein": [{"text": "Aldosterone receptors", "start": 0, "end": 21}]}}, "schema": []} {"input": "Aldosterone-specific membrane receptors and rapid non-genomic actions of mineralocorticoids.", "output": {"entities": {"protein": [{"text": "Aldosterone-specific membrane receptors", "start": 0, "end": 39}]}}, "schema": []} {"input": "Functional studies in extrarenal, non-epithelial cells such as smooth muscle cells and more recently circulating human lymphocytes have provided increasing evidence that aldosterone produces not only classical genomic effects, but also rapid, non-genomic effects on transmembrane electrolyte movements.", "output": {"entities": {"cell_type": [{"text": "extrarenal, non-epithelial cells", "start": 22, "end": 54}, {"text": "smooth muscle cells", "start": 63, "end": 82}, {"text": "circulating", "start": 101, "end": 112}, {"text": "human lymphocytes", "start": 113, "end": 130}]}}, "schema": []} {"input": "These involve activation of the sodium/proton exchanger of the cell membrane at very low, physiological concentrations of aldosterone with an acute onset within 1-2 min.", "output": {"entities": {"protein": [{"text": "sodium/proton exchanger", "start": 32, "end": 55}]}}, "schema": []} {"input": "A second messenger cascade involved is the inositol 1,4,5-trisphosphate /calcium pathway which responds over the same rapid time course.", "output": {"entities": {}}, "schema": []} {"input": "Such changes clearly cannot be explained by genomic mechanisms, which are responsible for later effects than the membrane related rapid responses.", "output": {"entities": {}}, "schema": []} {"input": "The mechanisms underlying these rapid effects of aldosterone on electrolytes have been extensively studied in human lymphocytes, which thus may represent valuable tools in the delineation of the receptor-effector mechanisms involved.", "output": {"entities": {"cell_type": [{"text": "human lymphocytes", "start": 110, "end": 127}]}}, "schema": []} {"input": "The unique characteristics of this new pathway for steroid action include its rapid time course, 10,000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones, classical mineralocorticoid antagonists, as antagonists of the response.", "output": {"entities": {}}, "schema": []} {"input": "Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.", "output": {"entities": {"protein": [{"text": "Human immunodeficiency virus type 1 Nef protein", "start": 0, "end": 47}, {"text": "NF-kappa B", "start": 57, "end": 67}], "cell_type": [{"text": "human T cells", "start": 81, "end": 94}]}}, "schema": []} {"input": "Human immunodeficiency virus type 1 (HIV-1) can establish a persistent and latent infection in CD4+ T lymphocytes (W.C.Greene, N.Engl.J. Med.324:308-317, 1991; S.M.Schnittman, M.C.Psallidopoulos, H.C. Lane, L.Thompson, M.Baseler, F.Massari, C.H.Fox, N.P.Salzman, and A.S.Fauci, Science 245:305-308, 1989).", "output": {"entities": {"cell_type": [{"text": "CD4+ T lymphocytes", "start": 95, "end": 113}]}}, "schema": []} {"input": "Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens (T.Folks, D.M.Powell, M.M.Lightfoote, S.Benn, M.A. Martin, and A.S.Fauci, Science 231:600-602, 1986; D.Zagury, J. Bernard, R.Leonard, R.Cheynier, M.Feldman, P.S.Sarin, and R.C. Gallo, Science 231:850-853, 1986).", "output": {"entities": {"protein": [{"text": "T-cell mitogens", "start": 82, "end": 97}]}}, "schema": []} {"input": "This activation is mediated by the host transcription factor NF-kappa B [G.Nabel and D.Baltimore, Nature (London) 326:711-717, 1987].", "output": {"entities": {"protein": [{"text": "host transcription factor", "start": 35, "end": 60}, {"text": "NF-kappa B", "start": 61, "end": 71}]}}, "schema": []} {"input": "We report here that the HIV-1 -encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T- cell mitogens.", "output": {"entities": {"protein": [{"text": "HIV-1 -encoded Nef protein", "start": 24, "end": 50}, {"text": "NF-kappa B", "start": 77, "end": 87}, {"text": "T- cell mitogens", "start": 112, "end": 128}]}}, "schema": []} {"input": "However, Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation, including SP-1, USF, URS, and NF-AT.", "output": {"entities": {"protein": [{"text": "Nef", "start": 9, "end": 12}, {"text": "transcription factors", "start": 63, "end": 84}, {"text": "SP-1", "start": 127, "end": 131}, {"text": "USF", "start": 133, "end": 136}, {"text": "URS", "start": 138, "end": 141}, {"text": "NF-AT", "start": 147, "end": 152}]}}, "schema": []} {"input": "Additionally, Nef inhibits the induction of HIV-1- and interleukin 2- directed gene expression, and the effect on HIV-1 transcription depends on an intact NF-kappa B -binding site.", "output": {"entities": {"protein": [{"text": "Nef", "start": 14, "end": 17}], "dna": [{"text": "NF-kappa B -binding site", "start": 155, "end": 179}]}}, "schema": []} {"input": "These results indicate that defective recruitment of NF-kappa B may underlie Nef's negative transcriptional effects on the HIV-1 and interleukin 2 promoters.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 53, "end": 63}, {"text": "Nef", "start": 77, "end": 80}]}}, "schema": []} {"input": "Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex.", "output": {"entities": {"protein": [{"text": "Nef", "start": 31, "end": 34}, {"text": "NF-kappa B", "start": 44, "end": 54}, {"text": "T-cell receptor complex", "start": 111, "end": 134}]}}, "schema": []} {"input": "Expression of c-fos, c-jun and jun B in peripheral blood lymphocytes from young and elderly adults.", "output": {"entities": {"dna": [{"text": "c-fos", "start": 14, "end": 19}, {"text": "c-jun", "start": 21, "end": 26}, {"text": "jun B", "start": 31, "end": 36}]}}, "schema": []} {"input": "The expression of c-fos, c-jun and jun B proto-oncogenes was studied in phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) from young and aged humans.", "output": {"entities": {"protein": [{"text": "phytohemagglutinin", "start": 72, "end": 90}], "cell_line": [{"text": "(PHA) activated peripheral blood lymphocytes", "start": 91, "end": 135}], "cell_type": [{"text": "PBL", "start": 137, "end": 140}]}}, "schema": []} {"input": "Specific mRNAs for c-fos and c-jun were detectable within 30 min after cell activation and reached maximal levels within 2 h.", "output": {"entities": {"rna": [{"text": "mRNAs", "start": 9, "end": 14}], "dna": [{"text": "c-fos", "start": 19, "end": 24}, {"text": "c-jun", "start": 29, "end": 34}]}}, "schema": []} {"input": "Both c-fos and jun B mRNAs decreased to pre-activation levels within 6 h, while c-jun mRNA remained elevated.", "output": {"entities": {"rna": [{"text": "c-fos and", "start": 5, "end": 14}, {"text": "jun B mRNAs", "start": 15, "end": 26}, {"text": "c-jun mRNA", "start": 80, "end": 90}]}}, "schema": []} {"input": "In PHA -activated PBL, no age-related differences were observed in c-fos or jun B mRNA expression.", "output": {"entities": {"protein": [{"text": "PHA", "start": 3, "end": 6}], "cell_line": [{"text": "-activated PBL", "start": 7, "end": 21}]}}, "schema": []} {"input": "However, c-jun mRNA levels decreased significantly (1.73 +/- 0.08 vs. 1.16 +/- 0.09 arbitrary units, P < 0.01, young vs. old) in PBL from elderly individuals activated with PHA.", "output": {"entities": {"rna": [{"text": "c-jun mRNA", "start": 9, "end": 19}], "cell_type": [{"text": "PBL", "start": 129, "end": 132}], "protein": [{"text": "PHA", "start": 173, "end": 176}]}}, "schema": []} {"input": "Because previous work has demonstrated that T cells from elderly individuals may display normal proliferative responses when activated via the anti-CD2 pathway, c-jun and jun B mRNA expression was also studied in anti-CD2-activated purified T cells.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 44, "end": 51}], "protein": [{"text": "anti-CD2", "start": 143, "end": 151}], "cell_line": [{"text": "anti-CD2-activated purified T cells", "start": 213, "end": 248}]}}, "schema": []} {"input": "No age-related differences were found in the expression of either of these two proto-oncogenes by anti-CD2 activated T cells.", "output": {"entities": {"dna": [{"text": "proto-oncogenes", "start": 79, "end": 94}]}}, "schema": []} {"input": "These results suggest that the decreased IL-2 production and proliferative response displayed by PHA -activated PBL from elderly adults may be related to age-related changes in c-jun mRNA expression and in the ratio of c-fos to c-jun mRNA.", "output": {"entities": {"protein": [{"text": "IL-2", "start": 41, "end": 45}, {"text": "PHA", "start": 97, "end": 100}], "cell_line": [{"text": "-activated PBL", "start": 101, "end": 115}], "dna": [{"text": "c-jun", "start": 177, "end": 182}], "rna": [{"text": "mRNA", "start": 183, "end": 187}, {"text": "c-fos", "start": 219, "end": 224}, {"text": "c-jun mRNA", "start": 228, "end": 238}]}}, "schema": []} {"input": "Oct2 transactivation from a remote enhancer position requires a B-cell-restricted activity.", "output": {"entities": {"protein": [{"text": "Oct2", "start": 0, "end": 4}], "dna": [{"text": "remote enhancer position", "start": 28, "end": 52}]}}, "schema": []} {"input": "Previous cotransfection experiments had demonstrated that ectopic expression of the lymphocyte-specific transcription factor Oct2 could efficiently activate a promoter containing an octamer motif.", "output": {"entities": {"protein": [{"text": "lymphocyte-specific transcription factor", "start": 84, "end": 124}, {"text": "Oct2", "start": 125, "end": 129}], "dna": [{"text": "promoter", "start": 159, "end": 167}, {"text": "octamer motif", "start": 182, "end": 195}]}}, "schema": []} {"input": "Oct2 expression was unable to stimulate a multimerized octamer enhancer element in HeLa cells, however.", "output": {"entities": {"protein": [{"text": "Oct2", "start": 0, "end": 4}], "dna": [{"text": "multimerized octamer enhancer element", "start": 42, "end": 79}], "cell_line": [{"text": "HeLa cells", "start": 83, "end": 93}]}}, "schema": []} {"input": "We have tested a variety of Oct2 isoforms generated by alternative splicing for the capability to activate an octamer enhancer in nonlymphoid cells and a B-cell line.", "output": {"entities": {"protein": [{"text": "Oct2 isoforms", "start": 28, "end": 41}], "dna": [{"text": "octamer enhancer", "start": 110, "end": 126}], "cell_type": [{"text": "nonlymphoid cells", "start": 130, "end": 147}], "cell_line": [{"text": "B-cell line", "start": 154, "end": 165}]}}, "schema": []} {"input": "Our analyses show that several Oct2 isoforms can stimulate from a remote position but that this stimulation is restricted to B cells.", "output": {"entities": {"protein": [{"text": "Oct2 isoforms", "start": 31, "end": 44}], "cell_type": [{"text": "B cells", "start": 125, "end": 132}]}}, "schema": []} {"input": "This result indicates the involvement of either a B-cell-specific cofactor or a specific modification of a cofactor or the Oct2 protein in Oct2 -mediated enhancer activation.", "output": {"entities": {"protein": [{"text": "B-cell-specific cofactor", "start": 50, "end": 74}, {"text": "cofactor", "start": 107, "end": 115}, {"text": "Oct2 protein", "start": 123, "end": 135}, {"text": "Oct2", "start": 139, "end": 143}]}}, "schema": []} {"input": "Mutational analyses indicate that the carboxy-terminal domain of Oct2 is critical for enhancer activation.", "output": {"entities": {"protein": [{"text": "carboxy-terminal domain", "start": 38, "end": 61}, {"text": "Oct2", "start": 65, "end": 69}]}}, "schema": []} {"input": "Moreover, this domain conferred enhancing activity when fused to the Oct1 protein, which by itself was unable to stimulate from a remote position.", "output": {"entities": {"protein": [{"text": "Oct1 protein", "start": 69, "end": 81}]}}, "schema": []} {"input": "The glutamine-rich activation domain present in the amino-terminal portion of Oct2 and the POU domain contribute only marginally to the transactivation function from a distal position.", "output": {"entities": {"protein": [{"text": "glutamine-rich activation domain", "start": 4, "end": 36}, {"text": "amino-terminal portion of Oct2", "start": 52, "end": 82}, {"text": "POU domain", "start": 91, "end": 101}]}}, "schema": []} {"input": "The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP.", "output": {"entities": {"dna": [{"text": "promoter", "start": 4, "end": 12}, {"text": "CD19 gene", "start": 20, "end": 29}], "protein": [{"text": "B-cell-specific transcription factor", "start": 50, "end": 86}, {"text": "BSAP", "start": 87, "end": 91}]}}, "schema": []} {"input": "The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation.", "output": {"entities": {"protein": [{"text": "CD19 protein", "start": 4, "end": 16}], "cell_type": [{"text": "B-lymphoid cells", "start": 52, "end": 68}, {"text": "terminally differentiated plasma cells", "start": 91, "end": 129}]}}, "schema": []} {"input": "Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines.", "output": {"entities": {"dna": [{"text": "CD19 gene", "start": 79, "end": 88}], "protein": [{"text": "B-cell-specific transcription factor", "start": 97, "end": 133}, {"text": "BSAP", "start": 134, "end": 138}], "cell_line": [{"text": "B-lymphoid cell lines", "start": 159, "end": 180}]}}, "schema": []} {"input": "The human CD19 gene has been cloned, and several BSAP -binding sites have been mapped by in vitro protein-DNA binding studies.", "output": {"entities": {"dna": [{"text": "human", "start": 4, "end": 9}, {"text": "CD19 gene", "start": 10, "end": 19}, {"text": "-binding sites", "start": 54, "end": 68}], "protein": [{"text": "BSAP", "start": 49, "end": 53}]}}, "schema": []} {"input": "In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites.", "output": {"entities": {"dna": [{"text": "high-affinity BSAP-binding site", "start": 17, "end": 48}, {"text": "TATA sequence", "start": 62, "end": 75}, {"text": "-30 promoter region", "start": 94, "end": 113}, {"text": "heterogeneous transcription start sites", "start": 139, "end": 178}]}}, "schema": []} {"input": "Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 35, "end": 39}], "cell_line": [{"text": "CD19-expressing", "start": 53, "end": 68}, {"text": "B-cell line", "start": 69, "end": 80}, {"text": "HeLa cells", "start": 102, "end": 112}], "cell_type": [{"text": "plasma", "start": 92, "end": 98}]}}, "schema": []} {"input": "This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments.", "output": {"entities": {"dna": [{"text": "high-affinity site", "start": 5, "end": 23}, {"text": "promoters", "start": 50, "end": 59}]}}, "schema": []} {"input": "In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 13, "end": 17}], "dna": [{"text": "CD19 promoter", "start": 124, "end": 137}]}}, "schema": []} {"input": "Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 44, "end": 48}], "dna": [{"text": "CD19 gene", "start": 74, "end": 83}]}}, "schema": []} {"input": "Eicosanoids in breast cancer patients before and after mastectomy.", "output": {"entities": {}}, "schema": []} {"input": "In 19 patients with a malignant breast tumor, tumor tissue and blood were taken to determine the eicosanoid profile and platelet aggregation.", "output": {"entities": {"cell_type": [{"text": "platelet", "start": 120, "end": 128}]}}, "schema": []} {"input": "Values were compared with those of patients with benign tumors (n = 4), or undergoing a mammary reduction (n = 7).", "output": {"entities": {}}, "schema": []} {"input": "Postoperatively, blood was taken as well in order to compare pre- and postoperative values.", "output": {"entities": {}}, "schema": []} {"input": "Eicosanoids were measured in peripheral blood monocytes and mammary tissue by means of HPLC; furthermore, TXA2, 6-keto-PGF1 alpha, and PGE2 were determined by RIA.", "output": {"entities": {"cell_type": [{"text": "peripheral blood monocytes", "start": 29, "end": 55}]}}, "schema": []} {"input": "Differences in pre- and postoperative values of cancer patients were seen in plasma RIA values: PGE2 and 6-k-PGF1 alpha were significantly higher preoperatively when compared with postoperatively, however, such differences were seen in the control groups as well.", "output": {"entities": {}}, "schema": []} {"input": "Compared to benign tumor or mammary reduction test material the eicosanoid profile of tissue obtained from malignant mammary tumors showed important differences.", "output": {"entities": {}}, "schema": []} {"input": "Except for PGF2 alpha, HHT and 15-HETE no detectable quantities of eicosanoids were found in the non-tumor material, whereas in the malignant tumor material substantial quantities of a number of eicosanoid metabolites were present.", "output": {"entities": {}}, "schema": []} {"input": "Statistically significant correlations could be established between patient/histopathology data and the results of the platelet aggregation assays, e.g. between menopausal status and ADP aggregation; oestrogen receptor (+/-) and collagen and arachidonic acid aggregation, inflammatory cell infiltration score and arachidonic acid aggregation and fibrosis score and ADP aggregation.", "output": {"entities": {"cell_type": [{"text": "platelet", "start": 119, "end": 127}], "protein": [{"text": "oestrogen receptor", "start": 200, "end": 218}, {"text": "collagen", "start": 229, "end": 237}]}}, "schema": []} {"input": "The results show that eicosanoid synthesis in material from mammary cancer patients is different from that in benign mammary tissue.", "output": {"entities": {}}, "schema": []} {"input": "The implications, in particular, in relation to future prognosis of the patient, remain obscure.", "output": {"entities": {}}, "schema": []} {"input": "Mineralocorticoids and mineralocorticoid receptors in mononuclear leukocytes in patients with pregnancy-induced hypertension.", "output": {"entities": {"protein": [{"text": "mineralocorticoid receptors", "start": 23, "end": 50}], "cell_type": [{"text": "mononuclear leukocytes", "start": 54, "end": 76}]}}, "schema": []} {"input": "To examine the role of mineralocorticoids in the pathophysiology of pregnancy-induced hypertension (PIH ), we studied plasma aldosterone and 18-hydroxycorticosterone levels in 25 women with PIH and 25 normal pregnant women, as controls.", "output": {"entities": {}}, "schema": []} {"input": "Furthermore, we evaluated the mineralocorticoid receptor (MR) status in mononuclear leukocytes in the 2 groups.", "output": {"entities": {"protein": [{"text": "mineralocorticoid receptor", "start": 30, "end": 56}, {"text": "MR", "start": 58, "end": 60}], "cell_type": [{"text": "mononuclear leukocytes", "start": 72, "end": 94}]}}, "schema": []} {"input": "MR count was significantly (P less than 0.0005) decreased in the PIH group (148 +/- 9 binding sites/cell) compared with the control group (300 +/- 17 binding sites/cell; mean +/- SEM).", "output": {"entities": {"protein": [{"text": "MR", "start": 0, "end": 2}]}}, "schema": []} {"input": "Plasma aldosterone in women with PIH was 281 +/- 61 pmol/L; in normal pregnant women it was 697 +/- 172 pmol/L (P less than 0.025).", "output": {"entities": {}}, "schema": []} {"input": "Plasma 18-hydroxycorticosterone was also significantly (P less than 0.025) lower (PIH, 1071 +/- 149 pmol/L; controls, 1907 +/- 318 pmol/L).", "output": {"entities": {}}, "schema": []} {"input": "These values were determined at the onset of clinical symptoms of PIH.", "output": {"entities": {}}, "schema": []} {"input": "These results cannot be explained by receptor down-regulation due to higher levels of mineralocorticoids in PIH; a hitherto unknown mineralocorticoid may, thus, be responsible for the hypertension and altered MR status.", "output": {"entities": {"protein": [{"text": "MR", "start": 209, "end": 211}]}}, "schema": []} {"input": "Structure function analysis of vitamin D analogs with C-ring modifications.", "output": {"entities": {}}, "schema": []} {"input": "Analogs of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) with substitutions on C-11 were synthesized.", "output": {"entities": {}}, "schema": []} {"input": "Small apolar substitutions (11 alpha-methyl, 11 alpha-fluoromethyl) did not markedly decrease the affinity for the vitamin D receptor, but larger (11 alpha-chloromethyl or 11 alpha- or 11 beta-phenyl) or more polar substitutions (11 alpha-hydroxymethyl, 11 alpha-(2-hydroxyethyl] decreased the affinity to less than 5% of that of 1 alpha,25-OH)2D3.", "output": {"entities": {"protein": [{"text": "vitamin D receptor", "start": 115, "end": 133}]}}, "schema": []} {"input": "Their affinity for the vitamin D -binding protein, however, increased up to 4-fold.", "output": {"entities": {"protein": [{"text": "vitamin D -binding protein", "start": 23, "end": 49}]}}, "schema": []} {"input": "The biological activity of 11 alpha-methyl-1 alpha,25-(OH)2D3 closely resembled that of the natural hormone on normal and leukemic cell proliferation and bone resorption, whereas its in vivo effect on calcium metabolism of the rachitic chick was about 50% of that of 1 alpha,25-(OH)2D3.", "output": {"entities": {"cell_type": [{"text": "leukemic cell", "start": 122, "end": 135}]}}, "schema": []} {"input": "The 11 beta-methyl analog had a greater than 10-fold lower activity.", "output": {"entities": {}}, "schema": []} {"input": "The differentiating effects of the other C-11 analogs on human promyeloid leukemia cells (HL-60) agreed well with their bone-resorbing activity and receptor affinity, but they demonstrated lower calcemic effects in vivo.", "output": {"entities": {"cell_line": [{"text": "human promyeloid leukemia cells", "start": 57, "end": 88}, {"text": "HL-60", "start": 90, "end": 95}]}}, "schema": []} {"input": "Large or polar substitutions on C-11 of 1 alpha,25-(OH)2D3 thus impair the binding of the vitamin D receptor but increase the affinity to vitamin D-binding protein.", "output": {"entities": {"protein": [{"text": "vitamin D receptor", "start": 90, "end": 108}, {"text": "vitamin D-binding protein", "start": 138, "end": 163}]}}, "schema": []} {"input": "The effects of many C-11-substituted 1 alpha,25-(OH)2D3 analogs on HL-60 cell differentiation exceeded their activity on calcium metabolism.", "output": {"entities": {"cell_line": [{"text": "HL-60", "start": 67, "end": 72}]}}, "schema": []} {"input": "Glucocorticoid receptor binding in three different cell types in major depressive disorder: lack of evidence of receptor binding defect.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptor", "start": 0, "end": 23}]}}, "schema": []} {"input": "1.", "output": {"entities": {}}, "schema": []} {"input": "In order to further understand the apparent glucocorticoid resistance in major depressive disorder, circadian variation in cortisol concentration, dexamethasone suppression and glucocorticoid receptor binding in mononuclear leukocytes, polymorphonuclear leukocytes and cultured skin fibroblasts were measured in rigidly defined major depressive disorder patients and non-depressed psychiatric controls.", "output": {"entities": {"cell_type": [{"text": "mononuclear leukocytes", "start": 212, "end": 234}, {"text": "polymorphonuclear leukocytes", "start": 236, "end": 264}], "cell_line": [{"text": "cultured skin fibroblasts", "start": 269, "end": 294}]}}, "schema": []} {"input": "2.", "output": {"entities": {}}, "schema": []} {"input": "Mononuclear leukocytes binding to glucocorticoid correlated significantly with polymorphonuclear leukocytes binding to glucocorticoid, but both determinations failed to differentiate major depressive disorder and control subjects.", "output": {"entities": {"cell_type": [{"text": "Mononuclear leukocytes", "start": 0, "end": 22}, {"text": "polymorphonuclear leukocytes", "start": 79, "end": 107}]}}, "schema": []} {"input": "3.", "output": {"entities": {}}, "schema": []} {"input": "Initial and post- dexamethasone in vitro fibroblast binding to glucocorticoid was not different between major depressive disorder and non-depressed control subjects.", "output": {"entities": {}}, "schema": []} {"input": "4.", "output": {"entities": {}}, "schema": []} {"input": "The phenomenon of glucocorticoid resistance in major depressive disorder remains unexplained.", "output": {"entities": {}}, "schema": []} {"input": "High affinity aldosterone binding to plasma membrane rich fractions from mononuclear leukocytes: is there a membrane receptor for mineralocorticoids?", "output": {"entities": {"cell_type": [{"text": "mononuclear leukocytes", "start": 73, "end": 95}], "protein": [{"text": "membrane receptor", "start": 108, "end": 125}]}}, "schema": []} {"input": "In vitro effects of aldosterone on the intracellular concentrations of sodium, potassium and calcium, cell volume and the sodium -proton-antiport have been described in intact human mononuclear leukocytes (HML ).", "output": {"entities": {"protein": [{"text": "sodium -proton-antiport", "start": 122, "end": 145}], "cell_type": [{"text": "human mononuclear leukocytes", "start": 176, "end": 204}, {"text": "HML", "start": 206, "end": 209}]}}, "schema": []} {"input": "In the present paper, the binding of a [125I]-labeled aldosterone derivative to plasma membrane rich fractions of HML was studied.", "output": {"entities": {"cell_type": [{"text": "HML", "start": 114, "end": 117}]}}, "schema": []} {"input": "High affinity binding of the radioligand with an apparent Kd of approximately 0.1 nM was found.", "output": {"entities": {}}, "schema": []} {"input": "Aldosterone displaced the tracer at a similar Kd.", "output": {"entities": {}}, "schema": []} {"input": "Both canrenone and cortisol were inactive as ligands up to concentrations of 0.1 microM.", "output": {"entities": {}}, "schema": []} {"input": "The findings are the first to demonstrate membrane binding sites with a high affinity for aldosterone, but not for cortisol.", "output": {"entities": {}}, "schema": []} {"input": "These data are perfectly compatible with major properties of steroidal effects on the sodium-proton-antiport in HML and thus very likely represent membrane receptors for aldosterone.", "output": {"entities": {"protein": [{"text": "sodium-proton-antiport", "start": 86, "end": 108}, {"text": "membrane receptors", "start": 147, "end": 165}], "cell_type": [{"text": "HML", "start": 112, "end": 115}]}}, "schema": []} {"input": "Natural variants of the HIV-1 long terminal repeat: analysis of promoters with duplicated DNA regulatory motifs.", "output": {"entities": {"dna": [{"text": "HIV-1 long terminal repeat", "start": 24, "end": 50}, {"text": "promoters", "start": 64, "end": 73}, {"text": "DNA regulatory motifs", "start": 90, "end": 111}]}}, "schema": []} {"input": "Sequence variation in the long terminal repeat (LTR) region of HIV-1 was analyzed in viral isolates of 17 infected individuals.", "output": {"entities": {"dna": [{"text": "long terminal repeat (LTR) region", "start": 26, "end": 59}]}}, "schema": []} {"input": "Two classes of LTR size variants were found.", "output": {"entities": {}}, "schema": []} {"input": "One HIV-1 variant was detected containing an additional binding site for the transcription factor Sp1.", "output": {"entities": {"protein": [{"text": "Sp1", "start": 98, "end": 101}]}}, "schema": []} {"input": "Another LTR size variation was observed in four patients in a region just upstream of the NF-kappa B enhancer.", "output": {"entities": {"dna": [{"text": "LTR size variation", "start": 8, "end": 26}, {"text": "NF-kappa B enhancer", "start": 90, "end": 109}]}}, "schema": []} {"input": "This variation was the result of a duplication of a short DNA sequence (CTG-motif ).", "output": {"entities": {"dna": [{"text": "short DNA sequence", "start": 52, "end": 70}, {"text": "CTG-motif", "start": 72, "end": 81}]}}, "schema": []} {"input": "Cell culture experiments demonstrated that the natural variant with four Sp1 sites had a slightly higher promoter activity and viral replication rate than the isogenic control LTR with three Sp1 sites.", "output": {"entities": {"dna": [{"text": "Sp1 sites", "start": 73, "end": 82}, {"text": "isogenic control LTR", "start": 159, "end": 179}, {"text": "sites", "start": 195, "end": 200}], "protein": [{"text": "Sp1", "start": 191, "end": 194}]}}, "schema": []} {"input": "No positive effect of the duplicated CTG-motif could be detected.", "output": {"entities": {"dna": [{"text": "CTG-motif", "start": 37, "end": 46}]}}, "schema": []} {"input": "In order to measure small differences in virus production more accurately, equal amounts of a size variant and the wild-type plasmid were cotransfected into T-cells.", "output": {"entities": {"dna": [{"text": "wild-type plasmid", "start": 115, "end": 132}], "cell_type": [{"text": "T-cells", "start": 157, "end": 164}]}}, "schema": []} {"input": "The virus with four Sp1 sites did outgrow the three Sp1 virus in 35 days of culture and CTG-monomer virus outcompeted the CTG-dimer virus in 42 days.", "output": {"entities": {"protein": [{"text": "Sp1", "start": 52, "end": 55}]}}, "schema": []} {"input": "Based on these results we estimate a 5-10% difference in virus production of the LTR variants when compared to that of wild-type.", "output": {"entities": {"dna": [{"text": "LTR variants", "start": 81, "end": 93}]}}, "schema": []} {"input": "A novel B cell-derived coactivator potentiates the activation of immunoglobulin promoters by octamer-binding transcription factors.", "output": {"entities": {"protein": [{"text": "novel B cell-derived coactivator", "start": 2, "end": 34}, {"text": "octamer-binding transcription factors", "start": 93, "end": 130}], "dna": [{"text": "immunoglobulin promoters", "start": 65, "end": 89}]}}, "schema": []} {"input": "A novel B cell-restricted activity, required for high levels of octamer / Oct -dependent transcription from an immunoglobulin heavy chain (IgH) promoter, was detected in an in vitro system consisting of HeLa cell -derived extracts complemented with fractionated B cell nuclear proteins.", "output": {"entities": {"dna": [{"text": "octamer", "start": 64, "end": 71}, {"text": "Oct", "start": 74, "end": 77}, {"text": "immunoglobulin heavy chain (IgH) promoter", "start": 111, "end": 152}], "cell_line": [{"text": "HeLa cell", "start": 203, "end": 212}], "protein": [{"text": "fractionated B cell nuclear proteins", "start": 249, "end": 285}]}}, "schema": []} {"input": "The factor responsible for this activity was designated Oct coactivator from B cells (OCA-B ).", "output": {"entities": {"protein": [{"text": "Oct coactivator", "start": 56, "end": 71}, {"text": "OCA-B", "start": 86, "end": 91}], "cell_type": [{"text": "B cells", "start": 77, "end": 84}]}}, "schema": []} {"input": "OCA-B stimulates the transcription from an IgH promoter in conjunction with either Oct-1 or Oct-2 but shows no significant effect on the octamer / Oct -dependent transcription of the ubiquitously expressed histone H2B promoter and the transcription of USF- and Sp1- regulated promoters.", "output": {"entities": {"protein": [{"text": "OCA-B", "start": 0, "end": 5}, {"text": "Oct-1", "start": 83, "end": 88}, {"text": "Oct-2", "start": 92, "end": 97}], "dna": [{"text": "IgH promoter", "start": 43, "end": 55}, {"text": "octamer", "start": 137, "end": 144}, {"text": "Oct", "start": 147, "end": 150}, {"text": "ubiquitously expressed histone H2B promoter", "start": 183, "end": 226}]}}, "schema": []} {"input": "Taken together, our results suggest that OCA-B is a tissue-, promoter-, and factor- specific coactivator and that OCA-B may be a major determinant for B cell-specific activation of immunoglobulin promoters.", "output": {"entities": {"protein": [{"text": "OCA-B", "start": 41, "end": 46}, {"text": "OCA-B", "start": 114, "end": 119}], "dna": [{"text": "immunoglobulin promoters", "start": 181, "end": 205}]}}, "schema": []} {"input": "In light of the evidence showing physical and functional interactions between Oct factors and OCA-B, we propose a mechanism of action for OCA-B and discuss the implications of OCA-B for the transcriptional regulation of other tissue-specific promoters.", "output": {"entities": {"protein": [{"text": "Oct factors", "start": 78, "end": 89}, {"text": "OCA-B", "start": 94, "end": 99}, {"text": "OCA-B", "start": 138, "end": 143}, {"text": "OCA-B", "start": 176, "end": 181}], "dna": [{"text": "tissue-specific promoters", "start": 226, "end": 251}]}}, "schema": []} {"input": "SCL and related hemopoietic helix-loop-helix transcription factors.", "output": {"entities": {"protein": [{"text": "SCL", "start": 0, "end": 3}, {"text": "hemopoietic helix-loop-helix transcription factors", "start": 16, "end": 66}]}}, "schema": []} {"input": "The helix-loop-helix (HLH) proteins are a family of transcription factors that include proteins critical to differentiation and development in species ranging from plants to mammals.", "output": {"entities": {"protein": [{"text": "helix-loop-helix (HLH) proteins", "start": 4, "end": 35}, {"text": "transcription factors", "start": 52, "end": 73}]}}, "schema": []} {"input": "Five members of this family (MYC, SCL, TAL-2, LYL-1 and E2A) are implicated in oncogenic events in human lymphoid tumors because of their consistent involvement in chromosomal translocations.", "output": {"entities": {"protein": [{"text": "MYC", "start": 29, "end": 32}, {"text": "SCL", "start": 34, "end": 37}, {"text": "TAL-2", "start": 39, "end": 44}, {"text": "LYL-1", "start": 46, "end": 51}, {"text": "E2A", "start": 56, "end": 59}]}}, "schema": []} {"input": "Although activated in T cell leukemias, expression of SCL and LYL-1 is low or undetectable in normal T cell populations.", "output": {"entities": {"protein": [{"text": "SCL", "start": 54, "end": 57}, {"text": "LYL-1", "start": 62, "end": 67}], "cell_type": [{"text": "normal T cell populations", "start": 94, "end": 119}]}}, "schema": []} {"input": "SCL is expressed in erythroid, megakaryocyte and mast cell populations (the same cell lineages as GATA-1, a zinc-finger transcription factor ).", "output": {"entities": {"protein": [{"text": "SCL", "start": 0, "end": 3}, {"text": "GATA-1", "start": 98, "end": 104}, {"text": "zinc-finger transcription factor", "start": 108, "end": 140}]}}, "schema": []} {"input": "In addition, both SCL and GATA-1 undergo coordinate modulation during chemically induced erythroid differentiation of mouse erythroleukemia cells and are down-modulated during myeloid differentiation of human K562 cells, thus implying a role for SCL in erythroid differentiation events.", "output": {"entities": {"protein": [{"text": "SCL", "start": 18, "end": 21}, {"text": "GATA-1", "start": 26, "end": 32}, {"text": "SCL", "start": 246, "end": 249}], "cell_type": [{"text": "mouse erythroleukemia cells", "start": 118, "end": 145}], "cell_line": [{"text": "human K562 cells", "start": 203, "end": 219}]}}, "schema": []} {"input": "However, in contrast to GATA-1, SCL is expressed in the developing brain.", "output": {"entities": {"protein": [{"text": "GATA-1", "start": 24, "end": 30}, {"text": "SCL", "start": 32, "end": 35}]}}, "schema": []} {"input": "Studies of the function of SCL suggest it is also important in proliferation and self-renewal events in erythroid cells.", "output": {"entities": {"protein": [{"text": "SCL", "start": 27, "end": 30}], "cell_type": [{"text": "erythroid cells", "start": 104, "end": 119}]}}, "schema": []} {"input": "Induction of the POU domain transcription factor Oct-2 during T-cell activation by cognate antigen.", "output": {"entities": {"protein": [{"text": "POU domain transcription factor", "start": 17, "end": 48}, {"text": "Oct-2", "start": 49, "end": 54}], "cell_type": [{"text": "T-cell", "start": 62, "end": 68}]}}, "schema": []} {"input": "Oct-2 is a transcription factor that binds specifically to octamer DNA motifs in the promoters of immunoglobulin and interleukin-2 genes.", "output": {"entities": {"protein": [{"text": "Oct-2", "start": 0, "end": 5}, {"text": "transcription factor", "start": 11, "end": 31}], "dna": [{"text": "octamer DNA motifs", "start": 59, "end": 77}, {"text": "promoters", "start": 85, "end": 94}]}}, "schema": []} {"input": "All tumor cell lines from the B-cell lineage and a few from the T-cell lineage express Oct-2.", "output": {"entities": {"cell_line": [{"text": "tumor cell lines", "start": 4, "end": 20}], "cell_type": [{"text": "B-cell lineage", "start": 30, "end": 44}, {"text": "T-cell lineage", "start": 64, "end": 78}], "protein": [{"text": "Oct-2", "start": 87, "end": 92}]}}, "schema": []} {"input": "To address the role of Oct-2 in the T-cell lineage, we studied the expression of Oct-2 mRNA and protein in nontransformed human and mouse T cells.", "output": {"entities": {"protein": [{"text": "Oct-2", "start": 23, "end": 28}], "cell_type": [{"text": "T-cell lineage", "start": 36, "end": 50}], "rna": [{"text": "Oct-2 mRNA", "start": 81, "end": 91}]}}, "schema": []} {"input": "Oct-2 was found in CD4+ and CD8+ T cells prepared from human peripheral blood and in mouse lymph node T cells.", "output": {"entities": {"protein": [{"text": "Oct-2", "start": 0, "end": 5}], "cell_type": [{"text": "mouse lymph node T cells", "start": 85, "end": 109}]}}, "schema": []} {"input": "In a T-cell clone specific for pigeon cytochrome c in the context of I-Ek, Oct-2 was induced by antigen stimulation, with the increase in Oct-2 protein seen first at 3 h after activation and continuing for at least 24 h.", "output": {"entities": {"cell_line": [{"text": "T-cell clone", "start": 5, "end": 17}], "protein": [{"text": "pigeon cytochrome c", "start": 31, "end": 50}, {"text": "I-Ek", "start": 69, "end": 73}, {"text": "Oct-2", "start": 75, "end": 80}, {"text": "Oct-2 protein", "start": 138, "end": 151}]}}, "schema": []} {"input": "Oct-2 mRNA induction during antigen-driven T-cell activation was blocked by cyclosporin A, as well as by protein synthesis inhibitors.", "output": {"entities": {"rna": [{"text": "Oct-2 mRNA", "start": 0, "end": 10}], "cell_type": [{"text": "T-cell", "start": 43, "end": 49}]}}, "schema": []} {"input": "These results suggest that Oct-2 participates in transcriptional regulation during T-cell activation. The relatively delayed kinetics of Oct-2 induction suggests that Oct-2 mediates the changes in gene expression which occur many hours or days following antigen stimulation of T lymphocytes.", "output": {"entities": {"protein": [{"text": "Oct-2", "start": 27, "end": 32}, {"text": "Oct-2", "start": 137, "end": 142}, {"text": "Oct-2", "start": 167, "end": 172}], "cell_type": [{"text": "T-cell", "start": 83, "end": 89}, {"text": "T lymphocytes", "start": 277, "end": 290}]}}, "schema": []} {"input": "Glucocorticoid receptor in patients with lupus nephritis: relationship between receptor levels in mononuclear leukocytes and effect of glucocorticoid therapy.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptor", "start": 0, "end": 23}], "cell_type": [{"text": "mononuclear leukocytes", "start": 98, "end": 120}]}}, "schema": []} {"input": "We investigated the clinical significance of glucocorticoid receptor determination in 20 patients with systemic lupus erythematosus (SLE) who afterwards developed nephrotic syndrome.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 45, "end": 68}]}}, "schema": []} {"input": "Glucocorticoid receptor concentrations in mononuclear leukocytes (MNL) in these patients were comparable with those in both other patients with SLE and healthy persons.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptor", "start": 0, "end": 23}], "cell_type": [{"text": "mononuclear leukocytes", "start": 42, "end": 64}, {"text": "MNL", "start": 66, "end": 69}]}}, "schema": []} {"input": "Improvement in urinary protein excretion and in disease activity, which was scored according to the SLE Disease Activity Index system of the University of Toronto, closely related to the glucocorticoid receptor concentrations in MNL isolated from the corresponding patients.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 187, "end": 210}], "cell_type": [{"text": "MNL", "start": 229, "end": 232}]}}, "schema": []} {"input": "In summary, glucocorticoid receptor determination in patients with lupus nephritis may be a predictive clue for assessing responsiveness to glucocorticoid therapy.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 12, "end": 35}]}}, "schema": []} {"input": "[Changes in plasma interleukin-1 and their possible relationship with the changes in glucocorticoid receptor in aged long-distance runner]", "output": {"entities": {"protein": [{"text": "plasma interleukin-1", "start": 12, "end": 32}, {"text": "glucocorticoid receptor", "start": 85, "end": 108}]}}, "schema": []} {"input": "For the study of the changes in plasma interleukin-1 (IL-1) and their possible relationship with the changes in glucocorticoid receptor (GR ), plasma IL-1 and GR in peripheral blood leukocytes in aged long-distance runner were measured simultaneously.", "output": {"entities": {"protein": [{"text": "plasma interleukin-1", "start": 32, "end": 52}, {"text": "IL-1", "start": 54, "end": 58}, {"text": "glucocorticoid receptor", "start": 112, "end": 135}, {"text": "GR", "start": 137, "end": 139}, {"text": "plasma", "start": 143, "end": 149}, {"text": "IL-1", "start": 150, "end": 154}, {"text": "GR", "start": 159, "end": 161}], "cell_type": [{"text": "peripheral blood leukocytes", "start": 165, "end": 192}]}}, "schema": []} {"input": "The activity of IL-1 was expressed as its ability to stimulate 3H-TdR incorporation in the thymocytes of C57 mice.", "output": {"entities": {"protein": [{"text": "IL-1", "start": 16, "end": 20}, {"text": "3H-TdR", "start": 63, "end": 69}], "cell_type": [{"text": "thymocytes", "start": 91, "end": 101}]}}, "schema": []} {"input": "GR was determined by whole cell assay with 3H-Dex.", "output": {"entities": {"protein": [{"text": "GR", "start": 0, "end": 2}]}}, "schema": []} {"input": "The results showed that the activity of plasma IL-1 in aged long-distance runner was 209%, 223% and 145% of the control at 14.7-18.7, 3.8-7.0 and 1.5-2.6 KD fractions.", "output": {"entities": {"protein": [{"text": "IL-1", "start": 47, "end": 51}]}}, "schema": []} {"input": "The GR in peripheral blood leukocytes in aged runner was 65% of the control.", "output": {"entities": {"protein": [{"text": "GR", "start": 4, "end": 6}], "cell_type": [{"text": "peripheral blood leukocytes", "start": 10, "end": 37}]}}, "schema": []} {"input": "Possible relationship between the changes in IL-1 and GR in aged long-distance runner and its physiological significance are discussed.", "output": {"entities": {"protein": [{"text": "IL-1", "start": 45, "end": 49}, {"text": "GR", "start": 54, "end": 56}]}}, "schema": []} {"input": "Mineralocorticoid effector mechanism in preeclampsia.", "output": {"entities": {}}, "schema": []} {"input": "Mineralocorticoid effector mechanisms were evaluated in 29 patients with preeclampsia and in 25 uncomplicated pregnancies by measurement of plasma aldosterone, levels of mineralocorticoid receptor (MR) in mononuclear leucocytes, and subtraction potential difference (SPD; rectal minus oral values ).", "output": {"entities": {"protein": [{"text": "mineralocorticoid receptor", "start": 170, "end": 196}, {"text": "MR", "start": 198, "end": 200}], "cell_type": [{"text": "mononuclear leucocytes", "start": 205, "end": 227}]}}, "schema": []} {"input": "Mean values for plasma aldosterone were not different between the two groups, but significant differences were observed for MR (preeclampsia, 81 +/- 44 receptors/cell; controls, 306 +/- 168) and SPD (preeclampsia, 65 +/- 7 mV; controls, 12 +/- 5 mV).", "output": {"entities": {"protein": [{"text": "MR", "start": 124, "end": 126}]}}, "schema": []} {"input": "In six cases we determined MR, plasma aldosterone, and SPD in patients with preeclampsia before and 3 months after delivery.", "output": {"entities": {"protein": [{"text": "MR", "start": 27, "end": 29}]}}, "schema": []} {"input": "MR were reduced before delivery (96 +/- 27 receptors/cell), and SPD increased (64 +/- 8 mV), with both parameters normalizing after delivery (MR, 242 +/- 79; SPD, 14.0 +/- 4 mV).", "output": {"entities": {"protein": [{"text": "MR", "start": 0, "end": 2}, {"text": "MR", "start": 142, "end": 144}]}}, "schema": []} {"input": "Aldosterone levels returned to normal nonpregnant values after delivery.", "output": {"entities": {}}, "schema": []} {"input": "These data suggest an important role for abnormalities in mineralocorticoid effector mechanisms in the etiology of preeclampsia and could be an useful marker for diagnosis.", "output": {"entities": {}}, "schema": []} {"input": "Kinetics of nuclear translocation and turnover of the vitamin D receptor in human HL60 leukemia cells and peripheral blood lymphocytes --coincident rise of DNA-relaxing activity in nuclear extracts.", "output": {"entities": {"protein": [{"text": "vitamin D receptor", "start": 54, "end": 72}], "cell_line": [{"text": "human HL60 leukemia cells", "start": 76, "end": 101}], "cell_type": [{"text": "peripheral blood lymphocytes", "start": 106, "end": 134}]}}, "schema": []} {"input": "High affinity receptors (VDR) for 1,25-dihydroxycholecalciferol (calcitriol) are expressed in HL60 human leukemia cells and in low numbers in peripheral blood lymphocytes (PBL ).", "output": {"entities": {"protein": [{"text": "High affinity receptors", "start": 0, "end": 23}, {"text": "VDR", "start": 25, "end": 28}], "cell_type": [{"text": "peripheral blood lymphocytes", "start": 142, "end": 170}, {"text": "PBL", "start": 172, "end": 175}]}}, "schema": []} {"input": "HL60 cells, expressing some characteristics of promyelocytes, can be induced to monocytoid differentiation by calcitriol.", "output": {"entities": {"cell_line": [{"text": "HL60 cells", "start": 0, "end": 10}, {"text": "promyelocytes", "start": 47, "end": 60}]}}, "schema": []} {"input": "Specific nuclear translocation of [3H]calcitriol/VDR was examined after exposure of whole cells to 10(-9) M/l calcitriol in the presence and absence of a 500-fold excess of unlabeled ligand and subsequent isolation of nuclei.", "output": {"entities": {"protein": [{"text": "[3H]calcitriol/VDR", "start": 34, "end": 52}], "cell_type": [{"text": "whole cells", "start": 84, "end": 95}]}}, "schema": []} {"input": "Specific nuclear translocation of [3H]calcitriol/VDR was found to be time dependent reaching a maximum of approximately 2100 binding sites/nucleus after 3 h of incubation in HL60 cells, whereas a maximum of approximately 310 binding sites/nucleus was found after 3 h in PBL.", "output": {"entities": {"protein": [{"text": "[3H]calcitriol/VDR", "start": 34, "end": 52}], "cell_line": [{"text": "HL60 cells", "start": 174, "end": 184}], "cell_type": [{"text": "PBL", "start": 270, "end": 273}]}}, "schema": []} {"input": "Pulse exposure of HL60 to radiolabeled hormone for 3 h followed by culture in medium without serum and calcitriol lead to nuclear retention of approximately 1600 radiolabeled VDR by 8 h and approximately 1000 VDR by 24 h.", "output": {"entities": {"cell_line": [{"text": "HL60", "start": 18, "end": 22}], "protein": [{"text": "1600 radiolabeled VDR", "start": 157, "end": 178}, {"text": "VDR", "start": 209, "end": 212}]}}, "schema": []} {"input": "Radiolabeled VDR disappeared from the nuclear compartment with a halflife of approximately 30 min if cells were cultured with identical concentrations of unlabeled hormone after the pulse (pulse/chase-experiments).", "output": {"entities": {"protein": [{"text": "Radiolabeled", "start": 0, "end": 12}, {"text": "VDR", "start": 13, "end": 16}]}}, "schema": []} {"input": "No difference of VDR retention in pulse and pulse/chase-experiments was seen in PBL, where VDR halflife was approximately 30 min.", "output": {"entities": {"protein": [{"text": "VDR", "start": 17, "end": 20}, {"text": "VDR", "start": 91, "end": 94}], "cell_type": [{"text": "PBL", "start": 80, "end": 83}]}}, "schema": []} {"input": "No specific translocation into the nuclear compartment was seen when isolated nuclei were incubated in [3H]calcitriol.", "output": {"entities": {}}, "schema": []} {"input": "Radiolabeled hormone/receptor complexes of nuclei isolated from cells exposed for 3 h to radiolabeled hormone --in contrast to identical experiments with intact cells--did not disappear from the nuclear compartment upon incubation of nuclei with identical concentrations of the unlabeled compound.", "output": {"entities": {"protein": [{"text": "Radiolabeled hormone/receptor complexes", "start": 0, "end": 39}]}}, "schema": []} {"input": "The activity of DNA relaxing enzymes (e.g. topoisomerases I and II) in nuclear extracts was measured using a PBR 322-relaxation-assay.", "output": {"entities": {"protein": [{"text": "DNA relaxing enzymes", "start": 16, "end": 36}]}}, "schema": []} {"input": "Enhanced overall enzyme activity was found in nuclear extracts by 1 h after incubation with calcitriol (final ethanol concentration 0.0001% v/v) in HL60 and PBL.", "output": {"entities": {"cell_line": [{"text": "HL60", "start": 148, "end": 152}], "cell_type": [{"text": "PBL", "start": 157, "end": 160}]}}, "schema": []} {"input": "The enhanced activity disappeared after 2 h in PBL, whereas it was still enhanced by 4 h in HL60.", "output": {"entities": {"cell_type": [{"text": "PBL", "start": 47, "end": 50}], "cell_line": [{"text": "HL60", "start": 92, "end": 96}]}}, "schema": []} {"input": "No effect was seen in ethanol treated controls.", "output": {"entities": {"cell_line": [{"text": "ethanol treated controls", "start": 22, "end": 46}]}}, "schema": []} {"input": "We conclude that a specific nuclear translocation mechanism exists for calcitriol in both cell types examined, most likely due to translocation of receptor proteins after hormone binding.", "output": {"entities": {"protein": [{"text": "receptor proteins", "start": 147, "end": 164}]}}, "schema": []} {"input": "Translocated hormone/receptor complexes compete for a limited number of specific nuclear binding sites.", "output": {"entities": {"protein": [{"text": "Translocated hormone/receptor complexes", "start": 0, "end": 39}]}}, "schema": []} {"input": "Enhanced activity of topoisomerases in nuclear extracts upon translocation of VDR might reflect interaction of both within the nuclear compartment, thus initiating DNA-unwinding, a prerequisite of transcription initiation.", "output": {"entities": {"protein": [{"text": "topoisomerases", "start": 21, "end": 35}, {"text": "VDR", "start": 78, "end": 81}]}}, "schema": []} {"input": "Influence of estradiol and tamoxifen on susceptibility of human breast cancer cell lines to lysis by lymphokine-activated killer cells.", "output": {"entities": {"cell_line": [{"text": "human breast cancer cell lines", "start": 58, "end": 88}], "cell_type": [{"text": "lymphokine-activated killer cells", "start": 101, "end": 134}]}}, "schema": []} {"input": "The design of combination hormonal and immunotherapeutic protocols for breast cancer patients may be facilitated by analysis of preclinical in vitro model systems.", "output": {"entities": {}}, "schema": []} {"input": "Estrogen receptor positive (ER+: MCF-7) and negative (ER-: MDA-MB-231) human breast cancer cell lines were utilized to evaluate the effects of tamoxifen (TAM) and estradiol (E2) on modulation of breast cancer target susceptibility to lysis by lymphokine-activated killer (LAK) cells.", "output": {"entities": {"cell_line": [{"text": "Estrogen receptor positive (ER+: MCF-7) and negative (ER-: MDA-MB-231) human breast cancer cell lines", "start": 0, "end": 101}], "cell_type": [{"text": "lymphokine-activated killer (LAK) cells", "start": 243, "end": 282}]}}, "schema": []} {"input": "E2 -stimulated ER+ cells were more susceptible to lysis by LAK cells than corresponding TAM -treated or control cells, while treatment of ER- cells with either E2 or TAM alone did not alter from control their susceptibility to this immune-mediated lysis.", "output": {"entities": {"cell_line": [{"text": "E2 -stimulated ER+ cells", "start": 0, "end": 24}, {"text": "TAM -treated", "start": 88, "end": 100}, {"text": "ER- cells", "start": 138, "end": 147}], "cell_type": [{"text": "LAK cells", "start": 59, "end": 68}, {"text": "control cells", "start": 104, "end": 117}]}}, "schema": []} {"input": "All ER+ and ER- cells tested remained sensitive after treatment with TAM to lysis by LAK cells.", "output": {"entities": {"cell_type": [{"text": "LAK cells", "start": 85, "end": 94}]}}, "schema": []} {"input": "In addition, an adenocarcinoma reactive human-mouse chimeric monoclonal antibody (ING-1) was able to significantly boost in vivo generated LAK cell-mediated lysis of control, E2-treated, and TAM-treated ER+ and ER- cells.", "output": {"entities": {"protein": [{"text": "adenocarcinoma reactive human-mouse chimeric monoclonal antibody", "start": 16, "end": 80}, {"text": "ING-1", "start": 82, "end": 87}]}}, "schema": []} {"input": "These in vitro results provide a preclinical rationale for in vivo testing of TAM, interleukin-2 (IL-2 ), and breast cancer reactive antibody-dependent cellular cytotoxicity facilitating antibody in patients with refractory or high risk breast cancer.", "output": {"entities": {"protein": [{"text": "interleukin-2", "start": 83, "end": 96}, {"text": "IL-2", "start": 98, "end": 102}]}}, "schema": []} {"input": "The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells.", "output": {"entities": {"dna": [{"text": "cellular oncogene", "start": 4, "end": 21}, {"text": "c-myb", "start": 22, "end": 27}], "protein": [{"text": "Epstein-Barr virus BZLF1 transactivator", "start": 66, "end": 105}], "cell_type": [{"text": "lymphoid cells", "start": 109, "end": 123}]}}, "schema": []} {"input": "Regulation of replicative functions in the Epstein-Barr virus (EBV) genome is mediated through activation of a virally encoded transcription factor, Z (BZLF1 ).", "output": {"entities": {"dna": [{"text": "Epstein-Barr virus (EBV) genome", "start": 43, "end": 74}], "protein": [{"text": "virally encoded transcription factor", "start": 111, "end": 147}, {"text": "Z", "start": 149, "end": 150}, {"text": "BZLF1", "start": 152, "end": 157}]}}, "schema": []} {"input": "We have shown that the Z gene product, which binds to AP-1 sites as a homodimer and has sequence similarity to c-Fos, can efficiently activate the EBV early promoter, BMRF1, in certain cell types (i.e., HeLa cells) but not others (i.e., Jurkat cells ).", "output": {"entities": {"protein": [{"text": "Z gene product", "start": 23, "end": 37}, {"text": "homodimer", "start": 70, "end": 79}], "dna": [{"text": "AP-1 sites", "start": 54, "end": 64}, {"text": "c-Fos", "start": 111, "end": 116}, {"text": "EBV early promoter", "start": 147, "end": 165}, {"text": "BMRF1", "start": 167, "end": 172}], "cell_line": [{"text": "HeLa cells", "start": 203, "end": 213}, {"text": "Jurkat cells", "start": 237, "end": 249}]}}, "schema": []} {"input": "Here we demonstrate that the c-myb proto-oncogene product, which is itself a DNA-binding protein and transcriptional transactivator, can interact synergistically with Z in activating the BMRF1 promoter in Jurkat cells (a T-cell line) or Raji cells (an EBV -positive B-cell ), whereas the c-myb gene product by itself has little effect.", "output": {"entities": {"dna": [{"text": "c-myb", "start": 29, "end": 34}, {"text": "BMRF1 promoter", "start": 187, "end": 201}], "protein": [{"text": "proto-oncogene product", "start": 35, "end": 57}, {"text": "DNA-binding protein", "start": 77, "end": 96}, {"text": "transcriptional transactivator", "start": 101, "end": 131}, {"text": "Z", "start": 167, "end": 168}, {"text": "c-myb gene product", "start": 288, "end": 306}], "cell_line": [{"text": "Jurkat cells", "start": 205, "end": 217}, {"text": "T-cell line", "start": 221, "end": 232}, {"text": "Raji cells", "start": 237, "end": 247}, {"text": "EBV -positive B-cell", "start": 252, "end": 272}]}}, "schema": []} {"input": "The simian virus 40 early promoter is also synergistically activated by the Z/c-myb combination.", "output": {"entities": {"dna": [{"text": "simian virus 40 early promoter", "start": 4, "end": 34}], "protein": [{"text": "Z/c-myb combination", "start": 76, "end": 95}]}}, "schema": []} {"input": "Synergistic transactivation of the BMRF1 promoter by the Z/c-myb combination appears to involve direct binding by the Z protein but not the c-myb protein.", "output": {"entities": {"dna": [{"text": "BMRF1 promoter", "start": 35, "end": 49}], "protein": [{"text": "Z/c-myb combination", "start": 57, "end": 76}, {"text": "Z protein", "start": 118, "end": 127}, {"text": "c-myb protein", "start": 140, "end": 153}]}}, "schema": []} {"input": "A 30-bp sequence in the BMRF1 promoter which contains a Z binding site (a consensus AP-1 site) is sufficient to transfer high-level lymphoid-specific responsiveness to the Z/c-myb combination to a heterologous promoter.", "output": {"entities": {"dna": [{"text": "30-bp sequence", "start": 2, "end": 16}, {"text": "BMRF1 promoter", "start": 24, "end": 38}, {"text": "Z binding site", "start": 56, "end": 70}, {"text": "consensus AP-1 site", "start": 74, "end": 93}, {"text": "heterologous promoter", "start": 197, "end": 218}], "protein": [{"text": "Z/c-myb combination", "start": 172, "end": 191}]}}, "schema": []} {"input": "That the c-myb oncogene product can interact synergistically with an EBV -encoded member of the leucine zipper protein family suggests c-myb is likely to engage in similar interactions with cellularly encoded transcription factors.", "output": {"entities": {"protein": [{"text": "c-myb oncogene product", "start": 9, "end": 31}, {"text": "EBV -encoded member", "start": 69, "end": 88}, {"text": "leucine zipper protein family", "start": 96, "end": 125}, {"text": "cellularly encoded transcription factors", "start": 190, "end": 230}], "dna": [{"text": "c-myb", "start": 135, "end": 140}]}}, "schema": []} {"input": "Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 43, "end": 53}], "cell_type": [{"text": "human T cells", "start": 68, "end": 81}]}}, "schema": []} {"input": "Acquired immunodeficiency syndrome (AIDS) results from infection with a human immunodeficiency virus (HIV ).", "output": {"entities": {}}, "schema": []} {"input": "The long terminal repeat (LTR) region of HIV proviral DNA contains binding sites for nuclear factor kappa B (NF-kappa B ), and this transcriptional activator appears to regulate HIV activation.", "output": {"entities": {"dna": [{"text": "long terminal repeat (LTR) region", "start": 4, "end": 37}, {"text": "HIV proviral DNA", "start": 41, "end": 57}], "protein": [{"text": "nuclear factor kappa B", "start": 85, "end": 107}, {"text": "NF-kappa B", "start": 109, "end": 119}, {"text": "transcriptional activator", "start": 132, "end": 157}]}}, "schema": []} {"input": "Recent findings suggest an involvement of reactive oxygen species (ROS) in signal transduction pathways leading to NF-kappa B activation.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 115, "end": 125}]}}, "schema": []} {"input": "The present study was based on reports that antioxidants which eliminate ROS should block the activation of NF-kappa B and subsequently HIV transcription, and thus antioxidants can be used as therapeutic agents for AIDS.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 108, "end": 118}]}}, "schema": []} {"input": "Incubation of Jurkat T cells (1 x 10(6) cells/ml) with a natural thiol antioxidant, alpha-lipoic acid, prior to the stimulation of cells was found to inhibit NF-kappa B activation induced by tumor necrosis factor-alpha (25 ng/ml) or by phorbol 12-myristate 13-acetate (50 ng/ml).", "output": {"entities": {"cell_line": [{"text": "Jurkat T cells", "start": 14, "end": 28}], "protein": [{"text": "NF-kappa B", "start": 158, "end": 168}, {"text": "tumor necrosis factor-alpha", "start": 191, "end": 218}]}}, "schema": []} {"input": "The inhibitory action of alpha-lipoic acid was found to be very potent as only 4 mM was needed for a complete inhibition, whereas 20 mM was required for N-acetylcysteine.", "output": {"entities": {}}, "schema": []} {"input": "These results indicate that alpha-lipoic acid may be effective in AIDS therapeutics.", "output": {"entities": {}}, "schema": []} {"input": "Reticuloendotheliosis virus long terminal repeat elements are efficient promoters in cells of various species and tissue origin, including human lymphoid cells.", "output": {"entities": {"dna": [{"text": "Reticuloendotheliosis virus long terminal repeat elements", "start": 0, "end": 57}, {"text": "promoters", "start": 72, "end": 81}], "cell_type": [{"text": "human lymphoid cells", "start": 139, "end": 159}]}}, "schema": []} {"input": "Promiscuous transcriptional activity of the reticuloendotheliosis virus (REV) long terminal repeat (LTR) was detected in transient expression assays using LTR- chloramphenicol acetyltransferase -encoding gene chimeras, and cells of diverse species and tissue type; levels of expression from two different REV LTRs correlate with reports of pathogenicity of the respective viruses in vivo.", "output": {"entities": {"dna": [{"text": "reticuloendotheliosis virus (REV) long terminal repeat", "start": 44, "end": 98}, {"text": "LTR", "start": 100, "end": 103}, {"text": "LTR-", "start": 155, "end": 159}, {"text": "-encoding gene chimeras", "start": 194, "end": 217}, {"text": "REV LTRs", "start": 305, "end": 313}], "protein": [{"text": "chloramphenicol acetyltransferase", "start": 160, "end": 193}]}}, "schema": []} {"input": "REVs do not encode a transactivator targeted to the viral LTR, and cells infected with Marek's disease virus, a herpesvirus with an overlapping host range, do not express factors that preferentially enhance expression from REV or avian sarcoma/leukemia virus LTRs.", "output": {"entities": {"dna": [{"text": "viral LTR", "start": 52, "end": 61}, {"text": "avian sarcoma/leukemia virus LTRs", "start": 230, "end": 263}]}}, "schema": []} {"input": "REV LTRs work efficiently in human lymphoid cells, and are viable alternatives to promoters commonly used for expression of cloned genes.", "output": {"entities": {"dna": [{"text": "REV LTRs", "start": 0, "end": 8}, {"text": "promoters", "start": 82, "end": 91}, {"text": "cloned genes", "start": 124, "end": 136}], "cell_type": [{"text": "human lymphoid cells", "start": 29, "end": 49}]}}, "schema": []} {"input": "They may also prove useful in the identification of new, ubiquitous cellular transcription factors.", "output": {"entities": {"protein": [{"text": "ubiquitous cellular transcription factors", "start": 57, "end": 98}]}}, "schema": []} {"input": "A novel Ets-related transcription factor, Elf-1, binds to human immunodeficiency virus type 2 regulatory elements that are required for inducible trans activation in T cells.", "output": {"entities": {"protein": [{"text": "Ets-related transcription factor", "start": 8, "end": 40}, {"text": "Elf-1", "start": 42, "end": 47}], "dna": [{"text": "human immunodeficiency virus type 2 regulatory elements", "start": 58, "end": 113}], "cell_type": [{"text": "T cells", "start": 166, "end": 173}]}}, "schema": []} {"input": "Human immunodeficiency virus type 1 (HIV-1) and HIV-2 are structurally related retroviruses which both cause AIDS in humans.", "output": {"entities": {}}, "schema": []} {"input": "Although both viruses establish latency in quiescent human-peripheral-blood T cells, the asymptomatic phase of HIV-2 infection may be more prolonged than that of HIV-1.", "output": {"entities": {"cell_type": [{"text": "human-peripheral-blood T cells", "start": 53, "end": 83}]}}, "schema": []} {"input": "The latent phases of both HIV-1 and HIV-2 infection have been shown to be disrupted by T-cell activation, a process that requires host cell transcription factors.", "output": {"entities": {}}, "schema": []} {"input": "In the case of HIV-1, the transcription factor NF-kappa B is sufficient for inducible transcriptional activation.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 47, "end": 57}]}}, "schema": []} {"input": "In contrast, factors in addition to NF-kappa B are required to activate HIV-2 transcription in infected T cells.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 36, "end": 46}], "cell_type": [{"text": "infected T cells", "start": 95, "end": 111}]}}, "schema": []} {"input": "In this report, we demonstrate that a novel Ets-related transcription factor, Elf-1, binds specifically to two purine-rich motifs in the HIV-2 enhancer.", "output": {"entities": {"protein": [{"text": "Ets-related transcription factor", "start": 44, "end": 76}, {"text": "Elf-1", "start": 78, "end": 83}], "dna": [{"text": "two purine-rich motifs", "start": 107, "end": 129}, {"text": "HIV-2 enhancer", "start": 137, "end": 151}]}}, "schema": []} {"input": "Mutagenesis experiments demonstrated that these Elf-1 binding sites are required for induction of HIV-2 transcription following T-cell-receptor-mediated T-cell activation.", "output": {"entities": {"dna": [{"text": "Elf-1 binding sites", "start": 48, "end": 67}]}}, "schema": []} {"input": "Moreover, Elf-1 is the only factor present in activated T-cell nuclear extracts that binds to these sites in electrophoretic mobility shift assays.", "output": {"entities": {"protein": [{"text": "Elf-1", "start": 10, "end": 15}]}}, "schema": []} {"input": "Thus, Elf-1 is a novel transcription factor that appears to be required for the T-cell-receptor-mediated trans activation of HIV-2 gene expression.", "output": {"entities": {"protein": [{"text": "Elf-1", "start": 6, "end": 11}, {"text": "novel transcription factor", "start": 17, "end": 43}]}}, "schema": []} {"input": "These results may explain differences in the clinical spectra of diseases caused by HIV-1 and HIV-2 and may also have implications for the design of therapeutic approaches to HIV-2 infection.", "output": {"entities": {}}, "schema": []} {"input": "Okadaic acid is a potent inducer of AP-1, NF-kappa B, and tumor necrosis factor-alpha in human B lymphocytes.", "output": {"entities": {"protein": [{"text": "AP-1", "start": 36, "end": 40}, {"text": "NF-kappa B", "start": 42, "end": 52}, {"text": "tumor necrosis factor-alpha", "start": 58, "end": 85}], "cell_type": [{"text": "human B lymphocytes", "start": 89, "end": 108}]}}, "schema": []} {"input": "Treatment of human B lymphocytes with an optimal concentration of okadaic acid, an inhibitor of phosphatases 1 and 2A, resulted in the induction of the transcription factor, AP-1 and a marked increase in NF-kappa B levels.", "output": {"entities": {"cell_type": [{"text": "human B lymphocytes", "start": 13, "end": 32}], "protein": [{"text": "transcription factor", "start": 152, "end": 172}, {"text": "AP-1", "start": 174, "end": 178}, {"text": "NF-kappa B", "start": 204, "end": 214}]}}, "schema": []} {"input": "In contrast, no effect on the levels of the octamer binding proteins, Oct-1 or Oct-2, were found.", "output": {"entities": {"protein": [{"text": "octamer binding proteins", "start": 44, "end": 68}, {"text": "Oct-1", "start": 70, "end": 75}, {"text": "Oct-2", "start": 79, "end": 84}]}}, "schema": []} {"input": "Since both AP-1 and NF-kappa B have been reported to be important in the induction of the tumor necrosis factor-alpha (TNF-alpha) gene we examined the effects of okadaic acid on TNF-alpha mRNA levels.", "output": {"entities": {"protein": [{"text": "AP-1", "start": 11, "end": 15}, {"text": "NF-kappa B", "start": 20, "end": 30}, {"text": "tumor necrosis factor-alpha", "start": 90, "end": 117}], "dna": [{"text": "(TNF-alpha) gene", "start": 118, "end": 134}], "rna": [{"text": "TNF-alpha mRNA", "start": 178, "end": 192}]}}, "schema": []} {"input": "Treatment with okadaic acid resulted in a striking increase in TNF-alpha mRNA transcripts within 1 h of stimulation and large amounts of TNF-alpha were released into the culture media.", "output": {"entities": {"rna": [{"text": "TNF-alpha mRNA", "start": 63, "end": 77}], "protein": [{"text": "TNF-alpha", "start": 137, "end": 146}]}}, "schema": []} {"input": "Although okadaic acid provides a potent inductive signal for AP-1 and NF-kappa B it did not induce either B cell proliferation or immunoglobulin secretion.", "output": {"entities": {"protein": [{"text": "AP-1", "start": 61, "end": 65}, {"text": "NF-kappa B", "start": 70, "end": 80}, {"text": "immunoglobulin", "start": 130, "end": 144}]}}, "schema": []} {"input": "Heterodimerization and transcriptional activation in vitro by NF-kappa B proteins.", "output": {"entities": {"protein": [{"text": "NF-kappa B proteins", "start": 62, "end": 81}]}}, "schema": []} {"input": "The NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to regulation of genes involved in immune responsiveness and inflammation, as well as activation of the HIV long terminal repeat.", "output": {"entities": {"protein": [{"text": "NF-kappa B family", "start": 4, "end": 21}, {"text": "transcription proteins", "start": 25, "end": 47}, {"text": "rel related polypeptides", "start": 81, "end": 105}], "dna": [{"text": "HIV long terminal repeat", "start": 226, "end": 250}]}}, "schema": []} {"input": "In this study multiple NF-kappa B related polypeptides ranging from 85 to 45 kDa were examined for their capacity to interact with the PRDII regulatory element of interferon beta and were shown to possess distinct intrinsic DNA binding affinities for this NF-kappa B site and form multiple DNA binding homo- and hetero dimer complexes in co-renaturation experiments.", "output": {"entities": {"protein": [{"text": "NF-kappa B related polypeptides", "start": 23, "end": 54}], "dna": [{"text": "PRDII regulatory element", "start": 135, "end": 159}, {"text": "interferon beta", "start": 163, "end": 178}, {"text": "NF-kappa B site", "start": 256, "end": 271}]}}, "schema": []} {"input": "Furthermore, using DNA templates containing two copies of the PRDII domain linked to the rabbit beta globin gene, the purified polypeptides specifically stimulated NF-kappa B dependent transcription in an in vitro reconstitution assay as heterodimers but not as p50 homodimers.", "output": {"entities": {"dna": [{"text": "DNA templates", "start": 19, "end": 32}, {"text": "PRDII domain", "start": 62, "end": 74}, {"text": "rabbit beta globin gene", "start": 89, "end": 112}], "protein": [{"text": "NF-kappa B", "start": 164, "end": 174}, {"text": "p50 homodimers", "start": 262, "end": 276}]}}, "schema": []} {"input": "These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit functional diversification of a limited number of regulatory proteins.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 40, "end": 50}, {"text": "regulatory proteins", "start": 177, "end": 196}]}}, "schema": []} {"input": "c-myc mRNA expression in minor salivary glands of patients with Sjogren's syndrome.", "output": {"entities": {"rna": [{"text": "c-myc mRNA", "start": 0, "end": 10}]}}, "schema": []} {"input": "c-myc protooncogene is implicated in the pathogenesis of B cell lymphoid malignancies and high levels of c-myc mRNA expression are observed in activated blood mononuclear cells.", "output": {"entities": {"dna": [{"text": "c-myc protooncogene", "start": 0, "end": 19}], "rna": [{"text": "c-myc mRNA", "start": 105, "end": 115}], "cell_type": [{"text": "activated blood mononuclear cells", "start": 143, "end": 176}]}}, "schema": []} {"input": "Sjogren's syndrome (SS) is characterized by lymphocytic infiltrates of exocrine glands, remarkable B cell hyperreactivity and a strong predisposition to B cell neoplasia.", "output": {"entities": {"cell_type": [{"text": "lymphocytic infiltrates", "start": 44, "end": 67}]}}, "schema": []} {"input": "In this study, c-myc protooncogene mRNA expression in 29 labial minor salivary gland biopsies from patients with primary SS and 15 controls was examined using in situ hybridization histochemistry.", "output": {"entities": {"dna": [{"text": "c-myc protooncogene", "start": 15, "end": 34}], "rna": [{"text": "mRNA", "start": 35, "end": 39}]}}, "schema": []} {"input": "Two 40mer oligonucleotides from the 1st and the 2nd exon of the c-myc gene, labeled with 35S, were used as probes.", "output": {"entities": {"dna": [{"text": "c-myc gene", "start": 64, "end": 74}]}}, "schema": []} {"input": "To detect the origin of the cell hybridized with a c-myc probe, a combined immunochemistry in situ hybridization histochemistry technique was used.", "output": {"entities": {"dna": [{"text": "c-myc probe", "start": 51, "end": 62}]}}, "schema": []} {"input": "High c-myc mRNA expression was detected on acinar epithelial cells.", "output": {"entities": {"rna": [{"text": "c-myc mRNA", "start": 5, "end": 15}], "cell_type": [{"text": "acinar epithelial cells", "start": 43, "end": 66}]}}, "schema": []} {"input": "c-myc did not correlate with c-fos and c-jun protein expression.", "output": {"entities": {"protein": [{"text": "c-myc", "start": 0, "end": 5}, {"text": "c-fos", "start": 29, "end": 34}, {"text": "c-jun", "start": 39, "end": 44}]}}, "schema": []} {"input": "Stronger c-myc mRNA expression was detected in labial salivary glands of patients with longer disease duration (p less than or equal to 0.002) and more intense T lymphocyte infiltrates (p less than 0.05) although these patients revealed no hypergammaglobulinemia.", "output": {"entities": {"rna": [{"text": "c-myc mRNA", "start": 9, "end": 19}], "cell_type": [{"text": "T lymphocyte infiltrates", "start": 160, "end": 184}]}}, "schema": []} {"input": "No correlation was observed between c-myc mRNA and B lymphocyte monoclonicity or lymphoma.", "output": {"entities": {"rna": [{"text": "c-myc mRNA", "start": 36, "end": 46}]}}, "schema": []} {"input": "In conclusion, strong c-myc mRNA expression was observed on epithelial cells of labial salivary glands from patients with primary SS.", "output": {"entities": {"rna": [{"text": "c-myc mRNA", "start": 22, "end": 32}], "cell_type": [{"text": "epithelial cells", "start": 60, "end": 76}]}}, "schema": []} {"input": "Our findings may indicate the presence of a reactivated virus hosted in these cells.", "output": {"entities": {}}, "schema": []} {"input": "Corticosteroid receptors and lymphocyte subsets in mononuclear leukocytes in aging.", "output": {"entities": {"protein": [{"text": "Corticosteroid receptors", "start": 0, "end": 24}], "cell_type": [{"text": "lymphocyte subsets", "start": 29, "end": 47}, {"text": "mononuclear leukocytes", "start": 51, "end": 73}]}}, "schema": []} {"input": "Plasma cortisol and aldosterone levels and number of related receptors in mononuclear leukocytes were measured in 49 healthy aged subjects (62-97 yr) and in 21 adult controls (21-50 yr).", "output": {"entities": {"cell_type": [{"text": "mononuclear leukocytes", "start": 74, "end": 96}]}}, "schema": []} {"input": "In all subjects, in addition, lymphocyte subsets were determined as an index of corticosteroid action.", "output": {"entities": {"cell_type": [{"text": "lymphocyte subsets", "start": 30, "end": 48}]}}, "schema": []} {"input": "The mean number of type I and type II receptors was significantly lower in aged subjects than in controls (respectively, 198 +/- 96 and 272 +/- 97 receptors /cell for type I, and 1,794 +/- 803 and 3,339 +/- 918 for type II receptors ).", "output": {"entities": {"protein": [{"text": "receptors", "start": 147, "end": 156}, {"text": "type I", "start": 167, "end": 173}, {"text": "II receptors", "start": 220, "end": 232}]}}, "schema": []} {"input": "Plasma aldosterone and cortisol and lymphocyte subsets were not different in the two groups.", "output": {"entities": {"cell_type": [{"text": "lymphocyte subsets", "start": 36, "end": 54}]}}, "schema": []} {"input": "All of the parameters were also tested for correlation, and a significant inverse correlation was found between age and type I and type II receptors when all subjects were plotted and between aged and CD4 and age and CD4/CD8 in the aged group.", "output": {"entities": {"protein": [{"text": "type I", "start": 120, "end": 126}, {"text": "type II receptors", "start": 131, "end": 148}], "cell_type": [{"text": "CD4", "start": 201, "end": 204}, {"text": "CD4/CD8", "start": 217, "end": 224}]}}, "schema": []} {"input": "These data show that aged subjects have reductions of corticosteroid receptors that are not associated with increase of related steroids and that this situation probably represents a concomitant of the normal aging process.", "output": {"entities": {"protein": [{"text": "corticosteroid receptors", "start": 54, "end": 78}]}}, "schema": []} {"input": "T cell-specific negative regulation of transcription of the human cytokine IL-4.", "output": {"entities": {"protein": [{"text": "human cytokine IL-4", "start": 60, "end": 79}]}}, "schema": []} {"input": "IL-4 secreted by activated T cells is a pleiotropic cytokine affecting growth and differentiation of diverse cell types such as T cells, B cells, and mast cells.", "output": {"entities": {"protein": [{"text": "IL-4", "start": 0, "end": 4}, {"text": "pleiotropic cytokine", "start": 40, "end": 60}], "cell_type": [{"text": "activated T cells", "start": 17, "end": 34}, {"text": "T cells", "start": 128, "end": 135}, {"text": "B cells", "start": 137, "end": 144}, {"text": "mast cells", "start": 150, "end": 160}]}}, "schema": []} {"input": "We investigated the upstream regulatory elements of the human IL-4 promoter.", "output": {"entities": {"dna": [{"text": "upstream regulatory elements", "start": 20, "end": 48}, {"text": "human IL-4 promoter", "start": 56, "end": 75}]}}, "schema": []} {"input": "A novel T cell-specific negative regulatory element (NRE) composed of two protein-binding sites were mapped in the 5' flanking region of the IL-4 gene: -311CTCCCTTCT-303 (NRE-I) and -288CTTTTTGCTT-TGC-300 (NRE-II ).", "output": {"entities": {"dna": [{"text": "novel T cell-specific negative regulatory element", "start": 2, "end": 51}, {"text": "NRE", "start": 53, "end": 56}, {"text": "IL-4 gene", "start": 141, "end": 150}, {"text": "NRE-I", "start": 171, "end": 176}, {"text": "NRE-II", "start": 206, "end": 212}]}}, "schema": []} {"input": "A T cell-specific protein Neg-1 and a ubiquitous protein Neg-2 binding to NRE-I and NRE-II, respectively, were identified.", "output": {"entities": {"protein": [{"text": "T cell-specific protein", "start": 2, "end": 25}, {"text": "Neg-1", "start": 26, "end": 31}, {"text": "ubiquitous protein", "start": 38, "end": 56}, {"text": "Neg-2", "start": 57, "end": 62}], "dna": [{"text": "NRE-I", "start": 74, "end": 79}, {"text": "NRE-II", "start": 84, "end": 90}]}}, "schema": []} {"input": "Furthermore, a positive regulatory element was found 45 bp downstream of the NRE.", "output": {"entities": {"dna": [{"text": "positive regulatory element", "start": 15, "end": 42}, {"text": "45 bp downstream", "start": 53, "end": 69}, {"text": "NRE", "start": 77, "end": 80}]}}, "schema": []} {"input": "The enhancer activity of the PRE was completely suppressed when the NRE was present.", "output": {"entities": {"dna": [{"text": "PRE", "start": 29, "end": 32}, {"text": "NRE", "start": 68, "end": 71}]}}, "schema": []} {"input": "These data suggest that IL-4 promoter activity is normally down-regulated by an NRE via repression of the enhancer positive regulatory element.", "output": {"entities": {"dna": [{"text": "IL-4 promoter", "start": 24, "end": 37}, {"text": "NRE", "start": 80, "end": 83}, {"text": "enhancer positive regulatory element", "start": 106, "end": 142}]}}, "schema": []} {"input": "These data may have implications for the stringent control of IL-4 expression in T cells.", "output": {"entities": {"protein": [{"text": "IL-4", "start": 62, "end": 66}], "cell_type": [{"text": "T cells", "start": 81, "end": 88}]}}, "schema": []} {"input": "Interleukin 6-induced differentiation of a human B cell line into IgM-secreting plasma cells is mediated by c-fos.", "output": {"entities": {"cell_line": [{"text": "human B cell line", "start": 43, "end": 60}], "cell_type": [{"text": "IgM-secreting plasma cells", "start": 66, "end": 92}], "dna": [{"text": "c-fos", "start": 108, "end": 113}]}}, "schema": []} {"input": "The role of the protooncogene c-fos in interleukin (IL) 6 -induced B cell differentiation was assessed.", "output": {"entities": {"dna": [{"text": "protooncogene c-fos", "start": 16, "end": 35}], "protein": [{"text": "interleukin (IL) 6", "start": 39, "end": 57}]}}, "schema": []} {"input": "Treatment of SKW 6.4 cells with IL 6 induced a transient and early stimulation of c-fos sense mRNA expression.", "output": {"entities": {"protein": [{"text": "IL 6", "start": 32, "end": 36}], "rna": [{"text": "c-fos sense mRNA", "start": 82, "end": 98}]}}, "schema": []} {"input": "The effect appeared within 30 min and returned to basal levels after 2 h.", "output": {"entities": {}}, "schema": []} {"input": "The addition of antisense oligonucleotides to c-fos significantly inhibited IL 6 -induced IgM production by SKW 6.4 cells (p less than 0.001), whereas control oligonucleotides had no inhibitory effect.", "output": {"entities": {"dna": [{"text": "c-fos", "start": 46, "end": 51}], "protein": [{"text": "IL 6", "start": 76, "end": 80}, {"text": "IgM", "start": 90, "end": 93}], "cell_line": [{"text": "SKW 6.4 cells", "start": 108, "end": 121}]}}, "schema": []} {"input": "These results indicate that activation of c-fos is involved in IL 6 -induced differentiation of SKW 6.4 cells into IgM-secreting cells.", "output": {"entities": {"dna": [{"text": "c-fos", "start": 42, "end": 47}], "protein": [{"text": "IL 6", "start": 63, "end": 67}], "cell_line": [{"text": "SKW 6.4 cells", "start": 96, "end": 109}, {"text": "IgM-secreting cells", "start": 115, "end": 134}]}}, "schema": []} {"input": "Transcriptional regulation during T-cell development: the alpha TCR gene as a molecular model.", "output": {"entities": {"cell_type": [{"text": "T-cell", "start": 34, "end": 40}], "dna": [{"text": "alpha TCR gene", "start": 58, "end": 72}]}}, "schema": []} {"input": "The regulation of gene expression during lymphocyte differentiation is a complex process involving interactions between multiple positive and negative transcriptional regulatory elements.", "output": {"entities": {"cell_type": [{"text": "lymphocyte", "start": 41, "end": 51}]}}, "schema": []} {"input": "In this article, transcriptional regulation of the archetypal T-cell -specific gene, alpha TCR, is discussed.", "output": {"entities": {"dna": [{"text": "archetypal", "start": 51, "end": 61}, {"text": "-specific gene", "start": 69, "end": 83}, {"text": "alpha TCR", "start": 85, "end": 94}], "cell_type": [{"text": "T-cell", "start": 62, "end": 68}]}}, "schema": []} {"input": "Major recent developments, including the identification of novel families of transcription factors that regulate multiple T-cell genes during thymocyte ontogeny and T-cell activation, are described.", "output": {"entities": {"dna": [{"text": "transcription factors", "start": 77, "end": 98}, {"text": "genes", "start": 129, "end": 134}], "cell_type": [{"text": "T-cell", "start": 122, "end": 128}, {"text": "T-cell", "start": 165, "end": 171}]}}, "schema": []} {"input": "Photoaffinity labeling of plasma membrane receptors for aldosterone from human mononuclear leukocytes.", "output": {"entities": {"protein": [{"text": "plasma membrane receptors", "start": 26, "end": 51}], "cell_type": [{"text": "human mononuclear leukocytes", "start": 73, "end": 101}]}}, "schema": []} {"input": "Non-genomic effects of aldosterone on the sodium-proton-antiport have been shown in human mononuclear leukocytes which could be related to a new aldosterone membrane receptor.", "output": {"entities": {"protein": [{"text": "sodium-proton-antiport", "start": 42, "end": 64}, {"text": "aldosterone membrane receptor", "start": 145, "end": 174}], "cell_type": [{"text": "human mononuclear leukocytes", "start": 84, "end": 112}]}}, "schema": []} {"input": "In the present paper plasma membranes from human mononuclear leukocytes were covalently photolabeled with a [125I]-aldosterone derivative.", "output": {"entities": {"cell_type": [{"text": "human mononuclear leukocytes", "start": 43, "end": 71}]}}, "schema": []} {"input": "Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed significant aldosterone binding at a molecular weight of approximately 50000 Dalton which was absent with 1 microM cold aldosterone, but not cortisol in the binding media.", "output": {"entities": {}}, "schema": []} {"input": "The presence of the sulfhydryl agent dithiothreitol did not affect results suggesting the absence of disulfide bridges in the steroid binding domain of the receptor.", "output": {"entities": {"protein": [{"text": "disulfide bridges", "start": 101, "end": 118}, {"text": "steroid binding domain", "start": 126, "end": 148}]}}, "schema": []} {"input": "These data are the first to define the molecular weight of the membrane receptor for aldosterone.", "output": {"entities": {"protein": [{"text": "membrane receptor", "start": 63, "end": 80}]}}, "schema": []} {"input": "Redox status of cells influences constitutive or induced NF-kappa B translocation and HIV long terminal repeat activity in human T and monocytic cell lines.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 57, "end": 67}], "dna": [{"text": "HIV long terminal repeat", "start": 86, "end": 110}]}}, "schema": []} {"input": "We have tested the hypothesis that cellular activation events occurring in T lymphocytes and monocytes and mediated through translocation of the transcription factor NF-kappa B are dependent upon the constitutive redox status of these cells.", "output": {"entities": {"cell_type": [{"text": "T lymphocytes", "start": 75, "end": 88}, {"text": "monocytes", "start": 93, "end": 102}], "protein": [{"text": "transcription factor", "start": 145, "end": 165}, {"text": "NF-kappa B", "start": 166, "end": 176}]}}, "schema": []} {"input": "We used phenolic, lipid-soluble, chain-breaking antioxidants (butylated hydroxyanisole (BHA ), nordihydroquairetic acid, or alpha-tocopherol (vitamin E) to show that peroxyl radical scavenging in unstimulated and PMA- or TNF- stimulated cells blocks the functions depending on NF-kappa B activation.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 277, "end": 287}]}}, "schema": []} {"input": "BHA was found to suppress not only PMA- or TNF- induced, but also constitutive, HIV-enhancer activity concomitant to an inhibition of NF-kappa B binding activity in both lymphoblastoid T (J.Jhan) and monocytic (U937) cell lines.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 134, "end": 144}], "cell_line": [{"text": "lymphoblastoid T", "start": 170, "end": 186}, {"text": "J.Jhan", "start": 188, "end": 194}, {"text": "monocytic (", "start": 200, "end": 211}, {"text": "U937) cell lines", "start": 211, "end": 227}]}}, "schema": []} {"input": "This was also true for KBF (p50 homodimer) binding activity in U937 cells.", "output": {"entities": {"cell_line": [{"text": "U937 cells", "start": 63, "end": 73}]}}, "schema": []} {"input": "Secretion of TNF, the product of another NF-kappa B -dependent gene, was abolished by BHA in PMA-stimulated U937 cells.", "output": {"entities": {"protein": [{"text": "TNF", "start": 13, "end": 16}, {"text": "NF-kappa B", "start": 41, "end": 51}], "dna": [{"text": "-dependent gene", "start": 52, "end": 67}], "cell_line": [{"text": "PMA-stimulated U937 cells", "start": 93, "end": 118}]}}, "schema": []} {"input": "The anti-oxidative effect of BHA was accompanied by an increase in thiol, but not glutathione, content in stimulated and unstimulated T cell, whereas TNF stimulation itself barely modified the cellular thiol level.", "output": {"entities": {"cell_line": [{"text": "stimulated and unstimulated T cell", "start": 106, "end": 140}], "protein": [{"text": "TNF", "start": 150, "end": 153}]}}, "schema": []} {"input": "Oxidative stress obtained by the addition of H2O2 to the culture medium of J.Jhan or U937 cells could not by itself induce NF-kappa B activation.", "output": {"entities": {"cell_line": [{"text": "J.Jhan", "start": 75, "end": 81}, {"text": "U937 cells", "start": 85, "end": 95}], "protein": [{"text": "NF-kappa B", "start": 123, "end": 133}]}}, "schema": []} {"input": "These observations suggest that TNF and PMA do not lead to NF-kappa B activation through induction of changes in the cell redox status.", "output": {"entities": {"protein": [{"text": "TNF", "start": 32, "end": 35}, {"text": "PMA", "start": 40, "end": 43}, {"text": "NF-kappa B", "start": 59, "end": 69}]}}, "schema": []} {"input": "Rather, TNF and PMA can exert their effect only if cells are in an appropriate redox status, because prior modification toward reduction with BHA treatment prevents this activation.", "output": {"entities": {"protein": [{"text": "TNF", "start": 8, "end": 11}, {"text": "PMA", "start": 16, "end": 19}]}}, "schema": []} {"input": "It appears that a basal redox equilibrium tending toward oxidation is a prerequisite for full activation of transduction pathways regulating the activity of NF-kappa B -dependent genes.", "output": {"entities": {"dna": [{"text": "NF-kappa B -dependent genes", "start": 157, "end": 184}]}}, "schema": []} {"input": "Selection of optimal kappa B/Rel DNA-binding motifs: interaction of both subunits of NF-kappa B with DNA is required for transcriptional activation.", "output": {"entities": {"dna": [{"text": "kappa B/Rel DNA-binding motifs", "start": 21, "end": 51}], "protein": [{"text": "NF-kappa B", "start": 85, "end": 95}]}}, "schema": []} {"input": "Analysis of the p50 and p65 subunits of the NF-kappa B transcription factor complex has revealed that both proteins can interact with related DNA sequences through either homo- or hetero dimer formation.", "output": {"entities": {"protein": [{"text": "p50", "start": 16, "end": 19}, {"text": "p65 subunits", "start": 24, "end": 36}, {"text": "NF-kappa B transcription factor complex", "start": 44, "end": 83}], "dna": [{"text": "DNA sequences", "start": 142, "end": 155}]}}, "schema": []} {"input": "In addition, the product of the proto-oncogene c-rel can bind to similar DNA motifs by itself or as a heterodimer with p50 or p65.", "output": {"entities": {"dna": [{"text": "proto-oncogene c-rel", "start": 32, "end": 52}, {"text": "DNA motifs", "start": 73, "end": 83}], "protein": [{"text": "p50", "start": 119, "end": 122}, {"text": "p65", "start": 126, "end": 129}]}}, "schema": []} {"input": "However, these studies have used a limited number of known kappa B DNA motifs, and the question of the optimal DNA sequences preferred by each homodimer has not been addressed.", "output": {"entities": {"dna": [{"text": "kappa B DNA motifs", "start": 59, "end": 77}, {"text": "optimal DNA sequences", "start": 103, "end": 124}]}}, "schema": []} {"input": "Using purified recombinant p50, p65, and c-Rel proteins, optimal DNA-binding motifs were selected from a pool of random oligonucleotides.", "output": {"entities": {"protein": [{"text": "p50", "start": 27, "end": 30}, {"text": "p65", "start": 32, "end": 35}, {"text": "c-Rel proteins", "start": 41, "end": 55}], "dna": [{"text": "optimal DNA-binding motifs", "start": 57, "end": 83}]}}, "schema": []} {"input": "Alignment of the selected sequences allowed us to predict a consensus sequence for binding of the individual homodimeric Rel-related proteins, and DNA-protein binding analysis of the selected DNA sequences revealed sequence specificity of the proteins.", "output": {"entities": {"protein": [{"text": "homodimeric Rel-related proteins", "start": 109, "end": 141}], "dna": [{"text": "selected DNA sequences", "start": 183, "end": 205}]}}, "schema": []} {"input": "Contrary to previous assumptions, we observed that p65 homodimers can interact with a subset of DNA sequences not recognized by p50 homodimers.", "output": {"entities": {"protein": [{"text": "p65", "start": 51, "end": 54}, {"text": "p50 homodimers", "start": 128, "end": 142}], "dna": [{"text": "DNA sequences", "start": 96, "end": 109}]}}, "schema": []} {"input": "Differential binding affinities were also obtained with p50- and c-Rel- selected sequences.", "output": {"entities": {}}, "schema": []} {"input": "Using either a p50- or p65- selected kappa B motif, which displayed differential binding with respect to the other protein, little to no binding was observed with the heterodimeric NF-kappa B complex.", "output": {"entities": {"protein": [{"text": "heterodimeric NF-kappa B complex", "start": 167, "end": 199}]}}, "schema": []} {"input": "Similarly, in transfection experiments in which the selective kappa B binding sites were used to drive the expression of a chloramphenicol acetyltransferase reporter construct, the p65 -and p50 -selected motifs were activated only in the presence of p65 and p50/65 (a chimeric protein with the p50 DNA binding domain and p65 activation domain) expression vectors, respectively, and neither demonstrated a significant response to stimuli that induce NF-kappa B activity.", "output": {"entities": {"dna": [{"text": "selective kappa B binding sites", "start": 52, "end": 83}, {"text": "reporter construct", "start": 157, "end": 175}], "protein": [{"text": "chloramphenicol acetyltransferase", "start": 123, "end": 156}, {"text": "p65", "start": 181, "end": 184}, {"text": "p50", "start": 190, "end": 193}, {"text": "p65", "start": 250, "end": 253}, {"text": "p50/65", "start": 258, "end": 264}, {"text": "chimeric protein", "start": 268, "end": 284}, {"text": "p50 DNA binding domain", "start": 294, "end": 316}, {"text": "p65 activation domain", "start": 321, "end": 342}, {"text": "NF-kappa B", "start": 449, "end": 459}]}}, "schema": []} {"input": "These findings demonstrate that interaction of both subunits of the heterodimeric NF-kappa B complex with DNA is required for DNA binding and transcriptional activation and suggest that transcriptional activation mediated by the individual rel-related proteins will differ dramatically, depending on the specific kappa B motifs present.", "output": {"entities": {"protein": [{"text": "heterodimeric", "start": 68, "end": 81}, {"text": "NF-kappa B complex", "start": 82, "end": 100}, {"text": "rel-related proteins", "start": 240, "end": 260}], "dna": [{"text": "specific kappa B motifs", "start": 304, "end": 327}]}}, "schema": []} {"input": "NF-kappa B -dependent induction of the NF-kappa B p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 0, "end": 10}, {"text": "NF-kappa B", "start": 39, "end": 49}, {"text": "p50", "start": 50, "end": 53}], "dna": [{"text": "subunit gene promoter", "start": 54, "end": 75}], "cell_type": [{"text": "monocytic cells", "start": 153, "end": 168}]}}, "schema": []} {"input": "The molecular mechanisms underlying the sustained nuclear translocation of NF-kappa B observed in U937 monocytic cells chronically infected with human immunodeficiency virus (HIV) were studied.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 75, "end": 85}], "cell_line": [{"text": "U937", "start": 98, "end": 102}], "cell_type": [{"text": "monocytic cells", "start": 103, "end": 118}]}}, "schema": []} {"input": "The activity of the promoter regulating the synthesis of the p105 precursor of the NF-kappa B p50 subunit was enhanced in these cells.", "output": {"entities": {"dna": [{"text": "promoter", "start": 20, "end": 28}], "protein": [{"text": "p105 precursor", "start": 61, "end": 75}, {"text": "NF-kappa B", "start": 83, "end": 93}, {"text": "p50 subunit", "start": 94, "end": 105}]}}, "schema": []} {"input": "Deletions in this promoter indicated that this upregulation was mediated through the NF-kappa B- but not the AP-1-binding motif, by bona fide p50/p65 heterodimers.", "output": {"entities": {"dna": [{"text": "promoter", "start": 18, "end": 26}, {"text": "NF-kappa B-", "start": 85, "end": 96}, {"text": "AP-1-binding motif", "start": 109, "end": 127}], "protein": [{"text": "p50/p65 heterodimers", "start": 142, "end": 162}]}}, "schema": []} {"input": "Analysis of cytosolic extracts indicated that NF-kappa B levels were increased in HIV -infected cells.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 46, "end": 56}], "cell_type": [{"text": "HIV -infected cells", "start": 82, "end": 101}]}}, "schema": []} {"input": "In contrast to the transient NF-kappa B activation induced by phorbol ester, the permanent NF-kappa B translocation induced by HIV infection was not dependent on PKC isoenzymes alpha and beta as shown by the use of a specific inhibitor (GF 109203X ).", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 29, "end": 39}, {"text": "NF-kappa B", "start": 91, "end": 101}, {"text": "PKC isoenzymes", "start": 162, "end": 176}]}}, "schema": []} {"input": "These observations indicate that during chronic HIV infection of U937 cells, continuous NF-kappa B (p50/p65) translocation results in p105 promoter upregulation with subsequent cytosolic NF-kappa B accumulation, ready for further translocation.", "output": {"entities": {"cell_line": [{"text": "U937 cells", "start": 65, "end": 75}], "protein": [{"text": "NF-kappa B", "start": 88, "end": 98}, {"text": "p50/p65", "start": 100, "end": 107}, {"text": "NF-kappa B", "start": 187, "end": 197}], "dna": [{"text": "p105 promoter", "start": 134, "end": 147}]}}, "schema": []} {"input": "This HIV -mediated mechanism results in a self-perpetuating loop of NF-kappa B production.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 68, "end": 78}]}}, "schema": []} {"input": "Activation of NF-kappa B by interleukin 2 in human blood monocytes.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 14, "end": 24}, {"text": "interleukin 2", "start": 28, "end": 41}], "cell_type": [{"text": "human blood", "start": 45, "end": 56}, {"text": "monocytes", "start": 57, "end": 66}]}}, "schema": []} {"input": "We report here that interleukin 2 (IL-2) acts on human blood monocytes by enhancing binding activity of the transcription factor NF-kappa B to its consensus sequence in the 5' regulatory enhancer region of the IL-2 receptor alpha chain (p55 ).", "output": {"entities": {"protein": [{"text": "interleukin 2", "start": 20, "end": 33}, {"text": "IL-2", "start": 35, "end": 39}, {"text": "transcription factor NF-kappa B", "start": 108, "end": 139}, {"text": "IL-2", "start": 210, "end": 214}, {"text": "p55", "start": 237, "end": 240}], "cell_type": [{"text": "human blood", "start": 49, "end": 60}, {"text": "monocytes", "start": 61, "end": 70}], "dna": [{"text": "5' regulatory enhancer region", "start": 173, "end": 202}, {"text": "receptor alpha chain", "start": 215, "end": 235}]}}, "schema": []} {"input": "Similarly, IL-2 activates NF-kappa B in the human monocytic cell line U 937, but not in resting human T-cells.", "output": {"entities": {"protein": [{"text": "IL-2", "start": 11, "end": 15}, {"text": "NF-kappa B", "start": 26, "end": 36}], "cell_line": [{"text": "human monocytic cell line U 937", "start": 44, "end": 75}], "cell_type": [{"text": "resting human T-cells", "start": 88, "end": 109}]}}, "schema": []} {"input": "This effect is detectable within 15 min and peaks 1 h after exposure to IL-2.", "output": {"entities": {"protein": [{"text": "IL-2", "start": 72, "end": 76}]}}, "schema": []} {"input": "Enhanced NF-kappa B binding activity is followed by functional activation in that inducibility of the IL-2 receptor alpha chain is mediated by enhanced NF-kappa B binding and that a heterologous promoter containing the NF-kappa B consensus sequence (-291 to -245) of the IL-2 receptor alpha chain gene is activated.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 9, "end": 19}, {"text": "IL-2 receptor alpha chain", "start": 102, "end": 127}, {"text": "NF-kappa B", "start": 152, "end": 162}], "dna": [{"text": "NF-kappa B consensus sequence", "start": 219, "end": 248}, {"text": "-291 to -245", "start": 250, "end": 262}, {"text": "IL-2 receptor alpha chain gene", "start": 271, "end": 301}]}}, "schema": []} {"input": "In addition, IL-2 is capable of increasing transcript levels of the p50 gene coding for the p50 subunit of the NF-kappa B transcription factor, whereas mRNA levels of the p65 NF-kappa B gene remained unchanged.", "output": {"entities": {"protein": [{"text": "IL-2", "start": 13, "end": 17}, {"text": "p50", "start": 68, "end": 71}, {"text": "p50 subunit", "start": 92, "end": 103}, {"text": "NF-kappa B", "start": 111, "end": 121}, {"text": "p65", "start": 171, "end": 174}, {"text": "NF-kappa B", "start": 175, "end": 185}], "dna": [{"text": "gene", "start": 186, "end": 190}]}}, "schema": []} {"input": "Studies on the biological activity of triiodothyronine sulfate.", "output": {"entities": {}}, "schema": []} {"input": "Hepatic microsomes and isolated hepatocytes in short term culture desulfate T3 sulfate (T3SO4 ).", "output": {"entities": {"cell_type": [{"text": "Hepatic microsomes", "start": 0, "end": 18}, {"text": "isolated hepatocytes", "start": 23, "end": 43}]}}, "schema": []} {"input": "We, therefore, wished to determine whether T3SO4 could mimic the action of thyroid hormone in vitro.", "output": {"entities": {}}, "schema": []} {"input": "T3SO4 had no thyromimetic effect on the activity of Ca(2+)-ATPase in human erythrocyte membranes at doses up to 10,000 times the maximally effective dose of T3 (10(-10) mol/L).", "output": {"entities": {"protein": [{"text": "Ca(2+)-ATPase", "start": 52, "end": 65}]}}, "schema": []} {"input": "In GH4C1 pituitary cells, T3SO4 failed to displace [125I]T3 from nuclear receptors in intact cells or soluble preparations.", "output": {"entities": {"cell_line": [{"text": "GH4C1 pituitary cells", "start": 3, "end": 24}, {"text": "intact cells", "start": 86, "end": 98}], "protein": [{"text": "nuclear receptors", "start": 65, "end": 82}]}}, "schema": []} {"input": "Thus, T3SO4 was not directly thyromimetic in either an isolated human membrane system or a pituitary cell system in which nuclear receptor occupancy correlates with GH synthesis.", "output": {"entities": {}}, "schema": []} {"input": "Thyroid hormones inhibit [3H]glycosaminoglycan synthesis by cultured human dermal fibroblasts, and T3SO4 displayed about 0.5% the activity of T3 at 72 h.", "output": {"entities": {"cell_line": [{"text": "cultured human dermal fibroblasts", "start": 60, "end": 93}]}}, "schema": []} {"input": "Human fibroblasts contained roughly the same level of microsomal p-nitrophenyl sulfatase activity as that previously observed in hepatic microsomes.", "output": {"entities": {"cell_type": [{"text": "Human fibroblasts", "start": 0, "end": 17}, {"text": "hepatic microsomes", "start": 129, "end": 147}], "protein": [{"text": "p-nitrophenyl sulfatase", "start": 65, "end": 88}]}}, "schema": []} {"input": "Propylthiouracil (50 mumol/L) did not affect the action of T3SO4, suggesting that deiodination was not important for this activity of T3SO4.", "output": {"entities": {}}, "schema": []} {"input": "Thus, it appears T3SO4 has no intrinsic biological activity, but, under certain circumstances, may be reactivated by desulfation.", "output": {"entities": {}}, "schema": []} {"input": "Human T cell activation through the activation-inducer molecule/CD69 enhances the activity of transcription factor AP-1.", "output": {"entities": {"protein": [{"text": "activation-inducer molecule/CD69", "start": 36, "end": 68}, {"text": "transcription factor AP-1", "start": 94, "end": 119}]}}, "schema": []} {"input": "The induction of the AP-1 transcription factor has been ascribed to the early events leading to T cell differentiation and activation.", "output": {"entities": {"protein": [{"text": "AP-1 transcription factor", "start": 21, "end": 46}]}}, "schema": []} {"input": "We have studied the regulation of AP-1 activity in human peripheral blood T lymphocytes stimulated through the activation inducer molecule (AIM)/ CD69 activation pathway.", "output": {"entities": {"protein": [{"text": "AP-1", "start": 34, "end": 38}, {"text": "CD69", "start": 146, "end": 150}], "cell_type": [{"text": "human peripheral blood T lymphocytes", "start": 51, "end": 87}]}}, "schema": []} {"input": "Phorbol esters are required to induce AIM/CD69 cell-surface expression as well as for triggering the proliferation of T cells in conjunction with anti-AIM mAb.", "output": {"entities": {"protein": [{"text": "AIM/CD69", "start": 38, "end": 46}, {"text": "anti-AIM mAb", "start": 146, "end": 158}], "cell_type": [{"text": "T cells", "start": 118, "end": 125}]}}, "schema": []} {"input": "Mobility shift assays showed that addition of anti-AIM mAb to PMA -treated T lymphocytes markedly enhanced the binding activity of AP-1 to its cognate sequence, the phorbol ester response element.", "output": {"entities": {"protein": [{"text": "anti-AIM mAb", "start": 46, "end": 58}, {"text": "PMA", "start": 62, "end": 65}, {"text": "AP-1", "start": 131, "end": 135}], "cell_type": [{"text": "-treated T lymphocytes", "start": 66, "end": 88}], "dna": [{"text": "phorbol ester response element", "start": 165, "end": 195}]}}, "schema": []} {"input": "In contrast, anti-AIM mAb did not induce any change in the binding activity of NF-kappa B, a transcription factor whose activity is also regulated by protein kinase C.", "output": {"entities": {"protein": [{"text": "anti-AIM mAb", "start": 13, "end": 25}, {"text": "NF-kappa B", "start": 79, "end": 89}, {"text": "transcription factor", "start": 93, "end": 113}, {"text": "protein kinase C", "start": 150, "end": 166}]}}, "schema": []} {"input": "The increase in AP-1 -binding activity was accompanied by the marked stimulation of the transcription of c-fos but not that of c-jun.", "output": {"entities": {"protein": [{"text": "AP-1", "start": 16, "end": 20}, {"text": "c-fos", "start": 105, "end": 110}, {"text": "c-jun", "start": 127, "end": 132}]}}, "schema": []} {"input": "Blockade of the DNA-binding complexes with an anti-Fos mAb demonstrated a direct participation of c-Fos in the AP-1 complexes induced by anti-AIM mAb.", "output": {"entities": {"protein": [{"text": "DNA-binding complexes", "start": 16, "end": 37}, {"text": "anti-Fos mAb", "start": 46, "end": 58}, {"text": "c-Fos", "start": 98, "end": 103}, {"text": "AP-1 complexes", "start": 111, "end": 125}, {"text": "anti-AIM mAb", "start": 137, "end": 149}]}}, "schema": []} {"input": "Most of the AP-1 activity could be eliminated when the anti-AIM mAb was added to the culture medium in the presence of cycloheximide, suggesting that de novo protein synthesis is crucial for the induction of AP-1 -binding activity.", "output": {"entities": {"protein": [{"text": "AP-1", "start": 12, "end": 16}, {"text": "anti-AIM mAb", "start": 55, "end": 67}, {"text": "AP-1", "start": 208, "end": 212}]}}, "schema": []} {"input": "These data provide the evidence that activation of human peripheral blood T cells through the AIM activation pathway regulate the activity of AP-1.", "output": {"entities": {"cell_type": [{"text": "human peripheral blood T cells", "start": 51, "end": 81}], "protein": [{"text": "AP-1", "start": 142, "end": 146}]}}, "schema": []} {"input": "Therefore, this pathway appears as a crucial step in the initiation of early T cell activation events.", "output": {"entities": {}}, "schema": []} {"input": "Gangliosides suppress tumor necrosis factor production in human monocytes.", "output": {"entities": {"protein": [{"text": "tumor necrosis factor", "start": 22, "end": 43}], "cell_type": [{"text": "human", "start": 58, "end": 63}, {"text": "monocytes", "start": 64, "end": 73}]}}, "schema": []} {"input": "Both normal and malignant cells contain gangliosides as important cell membrane constituents that, after being shed, may influence cells of the immune system.", "output": {"entities": {}}, "schema": []} {"input": "We have studied the impact of gangliosides on the expression of TNF in blood monocytes and in the monocytic cell line Mono Mac 6.", "output": {"entities": {"protein": [{"text": "TNF", "start": 64, "end": 67}], "cell_type": [{"text": "blood monocytes", "start": 71, "end": 86}], "cell_line": [{"text": "monocytic cell line Mono Mac 6", "start": 98, "end": 128}]}}, "schema": []} {"input": "Although under standard culture conditions, bovine brain gangliosides (100 micrograms/ml) suppressed LPS-stimulated TNF production 5-fold in PBMC and 10-fold in Mono Mac 6 cells, suppression was more efficient under serum-free conditions.", "output": {"entities": {"protein": [{"text": "TNF", "start": 116, "end": 119}], "cell_type": [{"text": "PBMC", "start": 141, "end": 145}], "cell_line": [{"text": "Mono Mac 6 cells", "start": 161, "end": 177}]}}, "schema": []} {"input": "Looking at highly purified gangliosides, GD3, GD1a, GM3, GM2, and GM1 were all effective in reducing TNF production in PBMC, and in Mono Mac 6 by factor 10 to 50.", "output": {"entities": {"protein": [{"text": "TNF", "start": 101, "end": 104}], "cell_type": [{"text": "PBMC", "start": 119, "end": 123}], "cell_line": [{"text": "Mono Mac 6", "start": 132, "end": 142}]}}, "schema": []} {"input": "The suppressive activity was lost in molecules, lacking the sugar moiety or the lipid moiety.", "output": {"entities": {}}, "schema": []} {"input": "Gangliosides appear to act at an early step of activation in that TNF transcripts were reduced and the mobilization of the nuclear factor kappa B was blocked.", "output": {"entities": {"protein": [{"text": "TNF", "start": 66, "end": 69}, {"text": "nuclear factor kappa B", "start": 123, "end": 145}], "rna": [{"text": "transcripts", "start": 70, "end": 81}]}}, "schema": []} {"input": "Furthermore, in time kinetics, gangliosides were effective for up to 30 min after addition of LPS, but not thereafter.", "output": {"entities": {}}, "schema": []} {"input": "However, the expression of the CD14 Ag, a receptor molecule for LPS-LPS binding protein complexes, was unaffected by gangliosides.", "output": {"entities": {"protein": [{"text": "CD14 Ag", "start": 31, "end": 38}, {"text": "receptor molecule", "start": 42, "end": 59}, {"text": "LPS-LPS binding protein complexes", "start": 64, "end": 97}]}}, "schema": []} {"input": "Finally, when using Staphylococcus aureus or platelet activating factor as a stimulus, gangliosides were able to suppress TNF production in Mono Mac 6 cells by factor 5 to 10, as well.", "output": {"entities": {"protein": [{"text": "platelet activating factor", "start": 45, "end": 71}, {"text": "TNF", "start": 122, "end": 125}], "cell_line": [{"text": "Mono Mac 6 cells", "start": 140, "end": 156}]}}, "schema": []} {"input": "On the other hand, phorbol ester -induced production of O2- was similar in cells treated with and without gangliosides.", "output": {"entities": {}}, "schema": []} {"input": "Taken together, our data demonstrate that TNF gene expression in monocytes induced by different types of stimuli can be blocked by gangliosides at an early step of signal transduction.", "output": {"entities": {"protein": [{"text": "TNF", "start": 42, "end": 45}], "cell_type": [{"text": "monocytes", "start": 65, "end": 74}]}}, "schema": []} {"input": "A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site.", "output": {"entities": {"protein": [{"text": "mitogen-inducible gene product", "start": 8, "end": 38}, {"text": "p50/p105-NF-kappa B", "start": 50, "end": 69}], "dna": [{"text": "kappa B site", "start": 112, "end": 124}]}}, "schema": []} {"input": "A Rel-related, mitogen-inducible, kappa B-binding protein has been cloned as an immediate-early activation gene of human peripheral blood T cells.", "output": {"entities": {"protein": [{"text": "Rel-related, mitogen-inducible, kappa B-binding protein", "start": 2, "end": 57}], "dna": [{"text": "immediate-early activation gene", "start": 80, "end": 111}], "cell_type": [{"text": "human peripheral blood T cells", "start": 115, "end": 145}]}}, "schema": []} {"input": "The cDNA has an open reading frame of 900 amino acids capable of encoding a 97-kDa protein.", "output": {"entities": {"dna": [{"text": "cDNA", "start": 4, "end": 8}, {"text": "open reading frame", "start": 16, "end": 34}, {"text": "900 amino acids", "start": 38, "end": 53}], "protein": [{"text": "97-kDa protein", "start": 76, "end": 90}]}}, "schema": []} {"input": "This protein is most similar to the 105-kDa precursor polypeptide of p50-NF-kappa B.", "output": {"entities": {"protein": [{"text": "p50-NF-kappa B", "start": 69, "end": 83}]}}, "schema": []} {"input": "Like the 105-kDa precursor, it contains an amino-terminal Rel-related domain of about 300 amino acids and a carboxy-terminal domain containing six full cell cycle or ankyrin repeats.", "output": {"entities": {"protein": [{"text": "amino-terminal Rel-related domain", "start": 43, "end": 76}, {"text": "carboxy-terminal domain", "start": 108, "end": 131}, {"text": "full cell cycle", "start": 147, "end": 162}, {"text": "ankyrin repeats", "start": 166, "end": 181}]}}, "schema": []} {"input": "In vitro-translated proteins, truncated downstream of the Rel domain and excluding the repeats, bind kappa B sites.", "output": {"entities": {"protein": [{"text": "vitro-translated proteins", "start": 3, "end": 28}], "dna": [{"text": "Rel domain", "start": 58, "end": 68}, {"text": "kappa B sites", "start": 101, "end": 114}]}}, "schema": []} {"input": "We refer to the kappa B-binding, truncated protein as p50B by analogy with p50-NF-kappa B and to the full-length protein as p97.", "output": {"entities": {"protein": [{"text": "kappa B-binding, truncated protein", "start": 16, "end": 50}, {"text": "p50B", "start": 54, "end": 58}, {"text": "p50-NF-kappa B", "start": 75, "end": 89}, {"text": "p97", "start": 124, "end": 127}]}}, "schema": []} {"input": "p50B is able to form heteromeric kappa B-binding complexes with RelB, as well as with p65 and p50, the two subunits of NF-kappa B.", "output": {"entities": {"protein": [{"text": "p50B", "start": 0, "end": 4}, {"text": "heteromeric kappa B-binding complexes", "start": 21, "end": 58}, {"text": "RelB", "start": 64, "end": 68}, {"text": "p65", "start": 86, "end": 89}, {"text": "p50", "start": 94, "end": 97}, {"text": "NF-kappa B", "start": 119, "end": 129}]}}, "schema": []} {"input": "Transient-transfection experiments in embryonal carcinoma cells demonstrate a functional cooperation between p50B and RelB or p65 in transactivation of a reporter plasmid dependent on a kappa B site.", "output": {"entities": {"cell_line": [{"text": "embryonal carcinoma cells", "start": 38, "end": 63}], "protein": [{"text": "p50B", "start": 109, "end": 113}, {"text": "RelB", "start": 118, "end": 122}, {"text": "p65", "start": 126, "end": 129}], "dna": [{"text": "reporter plasmid", "start": 154, "end": 170}, {"text": "kappa B site", "start": 186, "end": 198}]}}, "schema": []} {"input": "The data imply the existence of a complex family of NF-kappa B -like transcription factors.", "output": {"entities": {"protein": [{"text": "NF-kappa B -like transcription factors", "start": 52, "end": 90}]}}, "schema": []} {"input": "Surrogate thyroglobulin receptors and T cell proliferation in Hashimoto's thyroiditis.", "output": {"entities": {"protein": [{"text": "thyroglobulin receptors", "start": 10, "end": 33}]}}, "schema": []} {"input": "Immunoglobulin molecules on the surface of a B lymphocyte are the endogenous \"receptors\" to which specific antigens bind.", "output": {"entities": {"protein": [{"text": "Immunoglobulin molecules", "start": 0, "end": 24}], "cell_type": [{"text": "B lymphocyte", "start": 45, "end": 57}]}}, "schema": []} {"input": "Studies in mice have shown that a monoclonal antibody, conjugated with palmitate to provide a lipid tail, can be inserted into the cell membrane to provide a \" surrogate\" antigen receptor.", "output": {"entities": {"protein": [{"text": "monoclonal antibody", "start": 34, "end": 53}, {"text": "surrogate\" antigen receptor", "start": 160, "end": 187}]}}, "schema": []} {"input": "We have investigated whether a palmitate conjugate of a human monoclonal antibody specific for thyroglobulin (TG) could function as a surrogate TG receptor on blood mononuclear cells separated into fractions enriched for T cells or depleted of T cells (non-T cells ).", "output": {"entities": {"protein": [{"text": "palmitate conjugate", "start": 31, "end": 50}, {"text": "human", "start": 56, "end": 61}, {"text": "monoclonal antibody", "start": 62, "end": 81}, {"text": "thyroglobulin", "start": 95, "end": 108}, {"text": "TG", "start": 110, "end": 112}, {"text": "surrogate", "start": 134, "end": 143}, {"text": "TG receptor", "start": 144, "end": 155}], "cell_type": [{"text": "blood mononuclear cells", "start": 159, "end": 182}, {"text": "T cells", "start": 221, "end": 228}, {"text": "T cells", "start": 244, "end": 251}, {"text": "non-T cells", "start": 253, "end": 264}]}}, "schema": []} {"input": "Using flow cytometry, we detected surrogate TG receptors on non-T (but not on T) cells from 11 of 11 individuals studied (5 Hashimoto patients and 6 control donors ).", "output": {"entities": {"protein": [{"text": "surrogate TG receptors", "start": 34, "end": 56}], "cell_type": [{"text": "non-T (but not on T) cells", "start": 60, "end": 86}]}}, "schema": []} {"input": "In contrast, endogenous TG receptors could only be detected on non- T cells from 1 of 3 Hashimoto patients and from 0 of 4 control donors.", "output": {"entities": {"protein": [{"text": "endogenous TG receptors", "start": 13, "end": 36}], "cell_type": [{"text": "non- T cells", "start": 63, "end": 75}]}}, "schema": []} {"input": "Because of the efficient binding of TG by surrogate receptors on non-T cells, we assessed the ability of such cells to present TG to T cells.", "output": {"entities": {"protein": [{"text": "TG", "start": 36, "end": 38}, {"text": "surrogate receptors", "start": 42, "end": 61}, {"text": "TG", "start": 127, "end": 129}], "cell_type": [{"text": "non-T cells", "start": 65, "end": 76}, {"text": "T cells", "start": 133, "end": 140}]}}, "schema": []} {"input": "Proliferation in response to TG was observed in T cells from only 1 of 5 Hashimoto patients.", "output": {"entities": {"protein": [{"text": "TG", "start": 29, "end": 31}], "cell_type": [{"text": "T cells", "start": 48, "end": 55}]}}, "schema": []} {"input": "This low frequency of response was no different from that previously detected using cultures of T cells and autologous dendritic cells.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 96, "end": 103}, {"text": "autologous dendritic cells", "start": 108, "end": 134}]}}, "schema": []} {"input": "Therefore, the successful generation of surrogate receptors on non-T cells is not associated with more efficient TG presentation of T cells.", "output": {"entities": {"protein": [{"text": "surrogate receptors", "start": 40, "end": 59}, {"text": "TG", "start": 113, "end": 115}], "cell_type": [{"text": "non-T cells", "start": 63, "end": 74}, {"text": "T cells", "start": 132, "end": 139}]}}, "schema": []} {"input": "Furthermore, the significance of the present study is that the T cells, not the antigen-presenting cells, are likely to be the limiting element in the T cell proliferative response to TG and other thyroid autoantigens.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 63, "end": 70}, {"text": "antigen-presenting cells", "start": 80, "end": 104}], "protein": [{"text": "TG", "start": 184, "end": 186}, {"text": "thyroid autoantigens", "start": 197, "end": 217}]}}, "schema": []} {"input": "Targeted degradation of c-Fos, but not v-Fos, by a phosphorylation-dependent signal on c-Jun.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 24, "end": 29}, {"text": "v-Fos", "start": 39, "end": 44}, {"text": "phosphorylation-dependent signal", "start": 51, "end": 83}, {"text": "c-Jun", "start": 87, "end": 92}]}}, "schema": []} {"input": "The proto-oncogene products c-Fos and c-Jun heterodimerize through their leucine zippers to form the AP-1 transcription factor.", "output": {"entities": {"protein": [{"text": "proto-oncogene products", "start": 4, "end": 27}, {"text": "c-Fos", "start": 28, "end": 33}, {"text": "c-Jun", "start": 38, "end": 43}, {"text": "leucine zippers", "start": 73, "end": 88}, {"text": "AP-1 transcription factor", "start": 101, "end": 126}]}}, "schema": []} {"input": "The transcriptional activity of the heterodimer is regulated by signal-dependent phosphorylation and dephosphorylation events.", "output": {"entities": {}}, "schema": []} {"input": "The stability of c-Fos was found to also be controlled by intracellular signal transduction.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 17, "end": 22}]}}, "schema": []} {"input": "In transient expression and in vitro degradation experiments, the stability of c-Fos was decreased when the protein was dimerized with phosphorylated c-Jun.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 79, "end": 84}, {"text": "phosphorylated c-Jun", "start": 135, "end": 155}]}}, "schema": []} {"input": "c-Jun protein isolated from phorbol ester-induced cells did not target c-Fos for degradation, which suggests that c-Fos is transiently stabilized after stimulation of cell growth.", "output": {"entities": {"protein": [{"text": "c-Jun", "start": 0, "end": 5}, {"text": "c-Fos", "start": 71, "end": 76}, {"text": "c-Fos", "start": 114, "end": 119}], "cell_line": [{"text": "phorbol ester-induced cells", "start": 28, "end": 55}]}}, "schema": []} {"input": "v-Fos protein, the retroviral counterpart of c-Fos, was not susceptible to degradation targeted by c-Jun.", "output": {"entities": {"protein": [{"text": "v-Fos protein", "start": 0, "end": 13}, {"text": "c-Fos", "start": 45, "end": 50}, {"text": "c-Jun", "start": 99, "end": 104}]}}, "schema": []} {"input": "The regulation of the human tumor necrosis factor alpha promoter region in macrophage, T cell, and B cell lines.", "output": {"entities": {"dna": [{"text": "human tumor necrosis factor alpha promoter region", "start": 22, "end": 71}], "cell_line": [{"text": "macrophage", "start": 75, "end": 85}, {"text": "T cell", "start": 87, "end": 93}, {"text": "B cell lines", "start": 99, "end": 111}]}}, "schema": []} {"input": "The 1311-base pair human tumor necrosis factor (TNF) alpha promoter region was fused to the luciferase (Luc) reporter gene and studied in a transient transfection system in three TNF producing cell lines, the U937 macrophage cell line, the MLA 144 T cell line, and the 729-6 B cell line.", "output": {"entities": {"dna": [{"text": "1311-base pair human tumor necrosis factor (TNF) alpha promoter region", "start": 4, "end": 74}, {"text": "luciferase (Luc) reporter gene", "start": 92, "end": 122}], "cell_line": [{"text": "TNF producing cell lines", "start": 179, "end": 203}, {"text": "U937 macrophage cell line", "start": 209, "end": 234}, {"text": "MLA 144 T cell line", "start": 240, "end": 259}, {"text": "729-6 B cell line", "start": 269, "end": 286}]}}, "schema": []} {"input": "This full length promoter construct can be induced by phorbol 13-myristate acetate (PMA) in each of these cell types.", "output": {"entities": {}}, "schema": []} {"input": "Analysis of a series of 5'-truncations showed several peaks of basal and PMA induced activity suggesting the presence of several positive and negative regulatory elements.", "output": {"entities": {"dna": [{"text": "5'-truncations", "start": 24, "end": 38}, {"text": "positive", "start": 129, "end": 137}, {"text": "negative regulatory elements", "start": 142, "end": 170}]}}, "schema": []} {"input": "A PMA responsive element was localized to a region between -95 and -36 bp relative to the transcription start site.", "output": {"entities": {"dna": [{"text": "PMA responsive element", "start": 2, "end": 24}, {"text": "-95 and -36 bp", "start": 59, "end": 73}, {"text": "transcription start site", "start": 90, "end": 114}]}}, "schema": []} {"input": "Within this region, single AP-2- and AP-1- like consensus sequences were noted.", "output": {"entities": {}}, "schema": []} {"input": "These AP-2 and AP-1 sites were each modified with a double point mutation.", "output": {"entities": {"dna": [{"text": "AP-2", "start": 6, "end": 10}, {"text": "AP-1 sites", "start": 15, "end": 25}]}}, "schema": []} {"input": "A modest (20-50%) reduction in TNF promoter activity was observed with the AP-2 site mutation.", "output": {"entities": {"dna": [{"text": "TNF promoter", "start": 31, "end": 43}, {"text": "AP-2 site mutation", "start": 75, "end": 93}]}}, "schema": []} {"input": "However, mutation of the AP-1 site markedly diminished both the basal and PMA-activated promoter activity.", "output": {"entities": {"dna": [{"text": "AP-1 site", "start": 25, "end": 34}]}}, "schema": []} {"input": "Also co-transfections of the wild-type promoter construct with an AP-1/c-jun expression vector resulted in augmented basal and PMA -induced promoter activity.", "output": {"entities": {"dna": [{"text": "wild-type promoter construct", "start": 29, "end": 57}, {"text": "AP-1/c-jun expression vector", "start": 66, "end": 94}]}}, "schema": []} {"input": "Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication.", "output": {"entities": {"protein": [{"text": "transdominant Rev protein", "start": 21, "end": 46}], "cell_type": [{"text": "human T cells", "start": 50, "end": 63}]}}, "schema": []} {"input": "The human immunodeficiency virus (HIV) Rev protein is essential for viral structural protein expression (Gag, Pol, and Env) and, hence, for viral replication.", "output": {"entities": {"protein": [{"text": "Rev protein", "start": 39, "end": 50}, {"text": "Gag", "start": 105, "end": 108}, {"text": "Pol", "start": 110, "end": 113}, {"text": "Env", "start": 119, "end": 122}]}}, "schema": []} {"input": "In transient transfection assays, mutant forms of Rev have been identified that inhibit wild-type Rev activity and therefore suppress viral replication.", "output": {"entities": {"protein": [{"text": "Rev", "start": 50, "end": 53}, {"text": "Rev", "start": 98, "end": 101}]}}, "schema": []} {"input": "To determine whether such transdominant Rev proteins could provide long-term protection against HIV infection without affecting T cell function, T leukemia cell lines were stably transduced with a retroviral vector encoding a transdominant mutant of the Rev protein, M10.", "output": {"entities": {"protein": [{"text": "transdominant Rev proteins", "start": 26, "end": 52}, {"text": "Rev protein", "start": 254, "end": 265}, {"text": "M10", "start": 267, "end": 270}], "cell_line": [{"text": "T leukemia cell lines", "start": 145, "end": 166}], "dna": [{"text": "retroviral vector", "start": 197, "end": 214}]}}, "schema": []} {"input": "While all the M10 -expressing cell lines remained infectable by HIV-1, these same cells failed to support a productive replication cycle when infected with a cloned isolate of HIV-1.", "output": {"entities": {"cell_line": [{"text": "M10 -expressing cell lines", "start": 14, "end": 40}]}}, "schema": []} {"input": "In addition, two out of three M10 -expressing CEM clones were also resistant to highly productive infection by a heterogeneous HIV-1 pool.", "output": {"entities": {"cell_line": [{"text": "M10 -expressing CEM clones", "start": 30, "end": 56}]}}, "schema": []} {"input": "Expression of M10 did not affect induction of HIV transcription mediated by the kappa B regulatory element or Tat.", "output": {"entities": {"protein": [{"text": "M10", "start": 14, "end": 17}, {"text": "Tat", "start": 110, "end": 113}], "dna": [{"text": "kappa B regulatory element", "start": 80, "end": 106}]}}, "schema": []} {"input": "Importantly, constitutive expression of Rev M10 did not alter the secretion of interleukin 2 in response to mitogen stimulation of EL-4 and Jurkat cells.", "output": {"entities": {"protein": [{"text": "Rev M10", "start": 40, "end": 47}, {"text": "interleukin 2", "start": 79, "end": 92}], "cell_line": [{"text": "EL-4", "start": 131, "end": 135}, {"text": "Jurkat cells", "start": 140, "end": 152}]}}, "schema": []} {"input": "The inhibition of HIV infection in cells stably expressing a transdominant Rev protein, in the absence of any deleterious effect on T cell function, suggests that such a strategy could provide a therapeutic effect in the T lymphocytes of acquired immunodeficiency syndrome patients.", "output": {"entities": {"protein": [{"text": "transdominant Rev protein", "start": 61, "end": 86}], "cell_type": [{"text": "T lymphocytes", "start": 221, "end": 234}]}}, "schema": []} {"input": "Simple derivation of TFIID-dependent RNA polymerase II transcription systems from Schizosaccharomyces pombe and other organisms, and factors required for transcriptional activation.", "output": {"entities": {"protein": [{"text": "RNA polymerase II", "start": 37, "end": 54}]}}, "schema": []} {"input": "Resolution of whole cell extract through two chromatographic steps yields a single protein fraction requiring only the addition of TFIID for the initiation of transcription at RNA polymerase II promoters.", "output": {"entities": {"protein": [{"text": "TFIID", "start": 131, "end": 136}, {"text": "RNA polymerase II", "start": 176, "end": 193}], "dna": [{"text": "promoters", "start": 194, "end": 203}]}}, "schema": []} {"input": "This approach allows the convenient generation of RNA polymerase II transcription systems from Saccharomyces cerevisiae, human lymphocytes, and Schizosaccharomyces pombe.", "output": {"entities": {"protein": [{"text": "RNA polymerase II", "start": 50, "end": 67}], "cell_type": [{"text": "human lymphocytes", "start": 121, "end": 138}]}}, "schema": []} {"input": "TFIIDs from all three organisms are interchangeable among all three systems.", "output": {"entities": {"protein": [{"text": "TFIIDs", "start": 0, "end": 6}]}}, "schema": []} {"input": "The S. cerevisiae and Sch. pombe systems support effects of acidic activator proteins, provided a further protein fraction from S. cerevisiae is supplied.", "output": {"entities": {"protein": [{"text": "acidic activator proteins", "start": 60, "end": 85}]}}, "schema": []} {"input": "This further fraction is distinct from the mediator of transcriptional activation described previously and represents a second component in addition to general initiation factors that may facilitate a response to acidic activators.", "output": {"entities": {"protein": [{"text": "general initiation factors", "start": 152, "end": 178}, {"text": "acidic activators", "start": 213, "end": 230}]}}, "schema": []} {"input": "Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 14, "end": 19}]}}, "schema": []} {"input": "The present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 132, "end": 137}], "cell_line": [{"text": "U-937 leukemia cells", "start": 185, "end": 205}]}}, "schema": []} {"input": "The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression.", "output": {"entities": {"protein": [{"text": "Mac-1 cell surface antigen", "start": 174, "end": 200}, {"text": "c-myc transcripts", "start": 236, "end": 253}], "dna": [{"text": "tumor necrosis factor gene", "start": 276, "end": 302}]}}, "schema": []} {"input": "This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h.", "output": {"entities": {"rna": [{"text": "c-jun mRNA", "start": 87, "end": 97}]}}, "schema": []} {"input": "Similar effects were obtained for the c-fos gene.", "output": {"entities": {"dna": [{"text": "c-fos gene", "start": 38, "end": 48}]}}, "schema": []} {"input": "Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 50, "end": 55}], "cell_line": [{"text": "U-937 cells", "start": 73, "end": 84}]}}, "schema": []} {"input": "c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid -induced c-jun transcription.", "output": {"entities": {"rna": [{"text": "c-jun mRNA", "start": 0, "end": 10}], "dna": [{"text": "c-jun", "start": 187, "end": 192}]}}, "schema": []} {"input": "The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid -induced cells.", "output": {"entities": {"rna": [{"text": "c-jun mRNA", "start": 17, "end": 27}], "cell_line": [{"text": "okadaic acid -induced cells", "start": 74, "end": 101}]}}, "schema": []} {"input": "In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts.", "output": {"entities": {"protein": [{"text": "c-jun transcripts", "start": 118, "end": 135}]}}, "schema": []} {"input": "Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 62, "end": 67}]}}, "schema": []} {"input": "Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element.", "output": {"entities": {"dna": [{"text": "c-jun gene", "start": 50, "end": 60}, {"text": "c-jun promoter (positions -132/+170)-reporter gene constructs", "start": 122, "end": 183}, {"text": "AP-1 element", "start": 211, "end": 223}], "protein": [{"text": "Jun/AP-1", "start": 79, "end": 87}]}}, "schema": []} {"input": "(ABSTRACT TRUNCATED AT 250 WORDS)", "output": {"entities": {}}, "schema": []} {"input": "Mitogen stimulation of T-cells increases c-Fos and c-Jun protein levels, AP-1 binding and AP-1 transcriptional activity.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 41, "end": 46}, {"text": "c-Jun", "start": 51, "end": 56}]}}, "schema": []} {"input": "We have analysed the effect of mitogenic lectins on c-Fos and c-Jun protein levels as well as on activator protein-1 (AP-1) binding and enhancer activity in Jurkat T-cells.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 52, "end": 57}, {"text": "c-Jun", "start": 62, "end": 67}]}}, "schema": []} {"input": "Both c-Fos and c-Jun protein levels were increased after Con A and PHA stimulation.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 5, "end": 10}, {"text": "c-Jun", "start": 15, "end": 20}]}}, "schema": []} {"input": "Since T-cell stimulation increases both intracellular Ca2+ and cAMP levels and activates protein kinase C (PKC), the possible involvement of these intracellular messengers in c-Fos and c-Jun induction was tested.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 175, "end": 180}, {"text": "c-Jun", "start": 185, "end": 190}]}}, "schema": []} {"input": "PMA, which directly activates PKC, mimicked the effect of the lectins on c-Fos and c-Jun, but elevation of either intracellular Ca2+ or cAMP levels had little or no effect.", "output": {"entities": {"protein": [{"text": "c-Jun", "start": 83, "end": 88}]}}, "schema": []} {"input": "The mitogen-induced increase of c-Fos and c-Jun immunoreactivity was inhibited by H-7, a kinase inhibitor with relatively high specificity for PKC, and less efficiently by H-8, a structurally related kinase inhibitor less active on PKC, but more active on cyclic nucleotide-dependent kinases.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 32, "end": 37}, {"text": "c-Jun", "start": 42, "end": 47}]}}, "schema": []} {"input": "Con A stimulation was found to increase both binding of AP-1 to the AP-1 consensus sequence, TRE, and AP-1 enhancer activity, in Jurkat cells.", "output": {"entities": {"cell_line": [{"text": "Jurkat cells", "start": 129, "end": 141}]}}, "schema": []} {"input": "PMA was also found to increase the AP-1 enhancer activity, whereas elevation of Ca2+ or cAMP had only minor effects.", "output": {"entities": {}}, "schema": []} {"input": "We conclude that stimulation with mitogenic lectins is sufficient to increase both c-Fos and c-Jun protein levels, AP-1 binding and AP-1 enhancer activity in Jurkat cells and that they act via mechanisms that could involve the activation of PKC.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 83, "end": 88}, {"text": "c-Jun", "start": 93, "end": 98}], "cell_line": [{"text": "Jurkat cells", "start": 158, "end": 170}]}}, "schema": []} {"input": "An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals.", "output": {"entities": {"dna": [{"text": "11-base-pair DNA sequence motif", "start": 3, "end": 34}, {"text": "human interleukin 4 gene", "start": 60, "end": 84}]}}, "schema": []} {"input": "We have identified a DNA segment that confers responsiveness to antigen stimulation signals on the human interleukin (IL) 4 gene in Jurkat cells.", "output": {"entities": {"dna": [{"text": "DNA segment", "start": 21, "end": 32}, {"text": "human interleukin (IL) 4 gene", "start": 99, "end": 128}], "cell_line": [{"text": "Jurkat cells", "start": 132, "end": 144}]}}, "schema": []} {"input": "The human IL-4 gene, of 10 kilobases, is composed of four exons and three introns.", "output": {"entities": {"dna": [{"text": "human IL-4 gene", "start": 4, "end": 19}, {"text": "exons", "start": 58, "end": 63}, {"text": "introns", "start": 74, "end": 81}]}}, "schema": []} {"input": "A cis-acting element (P sequence) resides in the 5' upstream region; no additional DNA segments with enhancer activity were identified in the human IL-4 gene.", "output": {"entities": {"dna": [{"text": "cis-acting element", "start": 2, "end": 20}, {"text": "P sequence", "start": 22, "end": 32}, {"text": "5' upstream region", "start": 49, "end": 67}, {"text": "DNA segments", "start": 83, "end": 95}, {"text": "human IL-4 gene", "start": 142, "end": 157}]}}, "schema": []} {"input": "For further mapping purposes, a fusion promoter was constructed with the granulocyte/macrophage colony-stimulating factor basic promoter containing 60 base pairs of sequence upstream from the cap site of the mouse granulocyte/macrophage colony-stimulating factor gene and various lengths of the 5' upstream sequence of the IL-4 gene.", "output": {"entities": {"dna": [{"text": "fusion promoter", "start": 32, "end": 47}, {"text": "granulocyte/macrophage colony-stimulating factor basic promoter", "start": 73, "end": 136}, {"text": "60 base pairs of sequence", "start": 148, "end": 173}, {"text": "cap site", "start": 192, "end": 200}, {"text": "gene", "start": 263, "end": 267}, {"text": "5' upstream sequence", "start": 295, "end": 315}, {"text": "IL-4 gene", "start": 323, "end": 332}], "protein": [{"text": "mouse granulocyte/macrophage colony-stimulating factor", "start": 208, "end": 262}]}}, "schema": []} {"input": "The P sequence was located between positions -79 and -69 relative to the transcription start site of the human IL-4 gene, and this location was confirmed by base-substitution mutations.", "output": {"entities": {"dna": [{"text": "P sequence", "start": 4, "end": 14}, {"text": "transcription start site", "start": 73, "end": 97}, {"text": "human", "start": 105, "end": 110}, {"text": "IL-4 gene", "start": 111, "end": 120}]}}, "schema": []} {"input": "The plasmids carrying multiple copies of the P sequence showed higher responsiveness to the stimulation.", "output": {"entities": {"dna": [{"text": "P sequence", "start": 45, "end": 55}]}}, "schema": []} {"input": "The binding protein (s) that recognize the P sequence of the IL-4 gene were identified by DNA-mobility-shift assays.", "output": {"entities": {"protein": [{"text": "binding protein", "start": 4, "end": 19}], "dna": [{"text": "P sequence", "start": 43, "end": 53}, {"text": "IL-4 gene", "start": 61, "end": 70}]}}, "schema": []} {"input": "The binding of NF(P) (a DNA binding protein that specifically recognizes the P sequence) to the P sequence was abolished when oligonucleotides carrying base substitutions were used, indicating that the NF(P) interaction is sequence-specific and that binding specificity of the protein paralleled the sequence requirements for IL-4 expression in vivo.", "output": {"entities": {"protein": [{"text": "NF(P)", "start": 15, "end": 20}, {"text": "DNA binding protein", "start": 24, "end": 43}, {"text": "NF(P)", "start": 202, "end": 207}, {"text": "IL-4", "start": 326, "end": 330}], "dna": [{"text": "P sequence", "start": 77, "end": 87}, {"text": "P sequence", "start": 96, "end": 106}]}}, "schema": []} {"input": "The P sequence does not share homology with the 5' upstream sequence of the IL-2 gene, even though surrounding sequences of the IL-4 gene share high homology with the IL-2 gene.", "output": {"entities": {"dna": [{"text": "P sequence", "start": 4, "end": 14}, {"text": "5' upstream sequence", "start": 48, "end": 68}, {"text": "IL-2 gene", "start": 76, "end": 85}, {"text": "IL-4 gene", "start": 128, "end": 137}, {"text": "IL-2 gene", "start": 167, "end": 176}]}}, "schema": []} {"input": "We conclude that a different set of proteins recognize IL-2 and IL-4 genes.", "output": {"entities": {"protein": [{"text": "proteins", "start": 36, "end": 44}]}}, "schema": []} {"input": "Leukotriene B4 stimulates c-fos and c-jun gene transcription and AP-1 binding activity in human monocytes.", "output": {"entities": {"protein": [{"text": "AP-1", "start": 65, "end": 69}], "cell_type": [{"text": "human monocytes", "start": 90, "end": 105}]}}, "schema": []} {"input": "We have examined the effect of leukotriene B4 (LTB4 ), a potent lipid proinflammatory mediator, on the expression of the proto-oncogenes c-jun and c-fos.", "output": {"entities": {"protein": [{"text": "proinflammatory mediator", "start": 70, "end": 94}]}}, "schema": []} {"input": "In addition, we looked at the modulation of nuclear factors binding specifically to the AP-1 element after LTB4 stimulation.", "output": {"entities": {"protein": [{"text": "nuclear factors", "start": 44, "end": 59}], "dna": [{"text": "AP-1 element", "start": 88, "end": 100}]}}, "schema": []} {"input": "LTB4 increased the expression of the c-fos gene in a time- and concentration-dependent manner.", "output": {"entities": {"dna": [{"text": "c-fos gene", "start": 37, "end": 47}]}}, "schema": []} {"input": "The c-jun mRNA, which is constitutively expressed in human peripheral-blood monocytes at relatively high levels, was also slightly augmented by LTB4, although to a much lower extent than c-fos.", "output": {"entities": {"rna": [{"text": "c-jun mRNA", "start": 4, "end": 14}], "cell_type": [{"text": "human peripheral-blood monocytes", "start": 53, "end": 85}], "dna": [{"text": "c-fos", "start": 187, "end": 192}]}}, "schema": []} {"input": "The kinetics of expression of the two genes were also slightly different, with c-fos mRNA reaching a peak at 15 min after stimulation and c-jun at 30 min.", "output": {"entities": {"rna": [{"text": "c-fos mRNA", "start": 79, "end": 89}], "dna": [{"text": "c-jun", "start": 138, "end": 143}]}}, "schema": []} {"input": "Both messages rapidly declined thereafter.", "output": {"entities": {}}, "schema": []} {"input": "Stability of the c-fos and c-jun mRNA was not affected by LTB4, as assessed after actinomycin D treatment.", "output": {"entities": {"dna": [{"text": "c-fos", "start": 17, "end": 22}], "rna": [{"text": "c-jun mRNA", "start": 27, "end": 37}]}}, "schema": []} {"input": "Nuclear transcription studies in vitro showed that LTB4 increased the transcription of the c-fos gene 7-fold and the c-jun gene 1.4-fold.", "output": {"entities": {"dna": [{"text": "c-fos gene", "start": 91, "end": 101}, {"text": "c-jun gene", "start": 117, "end": 127}]}}, "schema": []} {"input": "Resting monocytes contained nuclear factors binding to the AP-1 element, but stimulation of monocytes with LTB4 induced greater AP-1 -binding activity of nuclear proteins.", "output": {"entities": {"cell_type": [{"text": "Resting monocytes", "start": 0, "end": 17}, {"text": "monocytes", "start": 92, "end": 101}], "protein": [{"text": "nuclear factors", "start": 28, "end": 43}, {"text": "AP-1", "start": 128, "end": 132}, {"text": "nuclear proteins", "start": 154, "end": 170}], "dna": [{"text": "AP-1 element", "start": 59, "end": 71}]}}, "schema": []} {"input": "These results indicate that LTB4 may regulate the production of different cytokines by modulating the yield and/or the function of transcription factors such as AP-1 -binding proto-oncogene products.", "output": {"entities": {"protein": [{"text": "cytokines", "start": 74, "end": 83}, {"text": "transcription factors", "start": 131, "end": 152}, {"text": "AP-1", "start": 161, "end": 165}, {"text": "proto-oncogene products", "start": 175, "end": 198}]}}, "schema": []} {"input": "Modulation of normal erythroid differentiation by the endogenous thyroid hormone and retinoic acid receptors: a possible target for v-erbA oncogene action.", "output": {"entities": {"protein": [{"text": "retinoic acid receptors", "start": 85, "end": 108}], "dna": [{"text": "v-erbA oncogene", "start": 132, "end": 147}]}}, "schema": []} {"input": "The v-erbA oncogene, a mutated version of the thyroid hormone receptor alpha (c-erbA/TR-alpha ), inhibits erythroid differentiation and constitutively represses transcription of certain erythrocyte genes, suggesting a normal function of the proto-oncogene c-erbA in erythropoiesis.", "output": {"entities": {"dna": [{"text": "v-erbA oncogene", "start": 4, "end": 19}, {"text": "erythrocyte genes", "start": 186, "end": 203}, {"text": "proto-oncogene c-erbA", "start": 241, "end": 262}], "protein": [{"text": "thyroid hormone receptor alpha", "start": 46, "end": 76}, {"text": "c-erbA/TR-alpha", "start": 78, "end": 93}]}}, "schema": []} {"input": "Here we demonstrate that the endogenous thyroid hormone receptor alpha (c-erbA/TR-alpha) and the closely related retinoic acid receptor alpha (RAR-alpha) play a role in the regulation of normal erythroid differentiation.", "output": {"entities": {"protein": [{"text": "thyroid hormone receptor alpha", "start": 40, "end": 70}, {"text": "c-erbA/TR-alpha", "start": 72, "end": 87}, {"text": "retinoic acid receptor alpha", "start": 113, "end": 141}, {"text": "RAR-alpha", "start": 143, "end": 152}]}}, "schema": []} {"input": "Retinoic acid (RA) distinctly modulated the erythroid differentiation program of normal erythroid progenitors and erythroblasts reversibly transformed by a conditional tyrosine kinase oncogene.", "output": {"entities": {"cell_type": [{"text": "normal erythroid progenitors", "start": 81, "end": 109}], "dna": [{"text": "tyrosine kinase oncogene", "start": 168, "end": 192}]}}, "schema": []} {"input": "When added pulsewise to immature cells, differentiation was accelerated while more mature cells underwent premature cell death.", "output": {"entities": {"cell_type": [{"text": "immature cells", "start": 24, "end": 38}, {"text": "mature cells", "start": 83, "end": 95}]}}, "schema": []} {"input": "Thyroid hormone (T3) alone caused similar but weaker effects.", "output": {"entities": {}}, "schema": []} {"input": "Interestingly, T3 strongly enhanced the action of RA, suggesting cooperative action of the two receptors in modulating erythroid differentiation.", "output": {"entities": {}}, "schema": []} {"input": "Expression of the human RAR-alpha in receptor-negative erythroblasts conferred RA -induced regulation of differentiation to the otherwise unresponsive cells, thus showing that the RAR-alpha is essential for the RA effect.", "output": {"entities": {"protein": [{"text": "human", "start": 18, "end": 23}, {"text": "RAR-alpha", "start": 24, "end": 33}, {"text": "RAR-alpha", "start": 180, "end": 189}], "cell_line": [{"text": "receptor-negative erythroblasts", "start": 37, "end": 68}], "cell_type": [{"text": "unresponsive cells", "start": 138, "end": 156}]}}, "schema": []} {"input": "Likewise, enhanced expression of exogenous c-erbA/TR-alpha in erythroblasts rendered them susceptible to modulation of differentiation by T3, suggesting a similar function of both receptors.", "output": {"entities": {"protein": [{"text": "exogenous c-erbA/TR-alpha", "start": 33, "end": 58}], "cell_type": [{"text": "erythroblasts", "start": 62, "end": 75}]}}, "schema": []} {"input": "Activation of lymphokine genes in T cells: role of cis-acting DNA elements that respond to T cell activation signals.", "output": {"entities": {"dna": [{"text": "lymphokine genes", "start": 14, "end": 30}, {"text": "cis-acting DNA elements", "start": 51, "end": 74}], "cell_type": [{"text": "T cells", "start": 34, "end": 41}]}}, "schema": []} {"input": "Activation of T cells is initiated by the recognition of antigen on antigen presenting cells to exert the effector functions in immune and inflammatory responses.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 14, "end": 21}, {"text": "antigen presenting cells", "start": 68, "end": 92}], "protein": [{"text": "antigen", "start": 57, "end": 64}]}}, "schema": []} {"input": "Two types of helper T cell (Th) clones (Th1 and Th2) are defined on the basis of different patterns of cytokine (lymphokine) secretion.", "output": {"entities": {"cell_line": [{"text": "helper T cell (Th) clones", "start": 13, "end": 38}, {"text": "Th1", "start": 40, "end": 43}, {"text": "Th2", "start": 48, "end": 51}], "protein": [{"text": "cytokine", "start": 103, "end": 111}, {"text": "lymphokine", "start": 113, "end": 123}]}}, "schema": []} {"input": "They determine the outcome of an antigenic response toward humoral or cell-mediated immunity.", "output": {"entities": {}}, "schema": []} {"input": "Although lymphokine genes are coordinately regulated upon antigen stimulation, they are regulated by the mechanisms common to all as well as those which are unique to each gene.", "output": {"entities": {"protein": [{"text": "lymphokine", "start": 9, "end": 19}], "dna": [{"text": "genes", "start": 20, "end": 25}]}}, "schema": []} {"input": "For most lymphokine genes, a combination of phorbol esters (phorbol 12-myristate 13 acetate, PMA) and calcium ionophores (A23187) is required for their maximal induction.", "output": {"entities": {"dna": [{"text": "lymphokine genes", "start": 9, "end": 25}]}}, "schema": []} {"input": "Yet phorbol ester alone or calcium ionophore alone produce several lymphokines.", "output": {"entities": {"protein": [{"text": "lymphokines", "start": 67, "end": 78}]}}, "schema": []} {"input": "The production of the granulocyte-macrophage colony stimulating factor (GM-CSF) is completely dependent on the two signals.", "output": {"entities": {"protein": [{"text": "granulocyte-macrophage colony stimulating factor", "start": 22, "end": 70}, {"text": "GM-CSF", "start": 72, "end": 78}]}}, "schema": []} {"input": "We have previously found a cis-acting region spanning the GM-CSF promoter region (positions -95 to +27) that confers inducibility to reporter genes in transient transfection assays.", "output": {"entities": {"dna": [{"text": "cis-acting region", "start": 27, "end": 44}, {"text": "GM-CSF promoter region", "start": 58, "end": 80}, {"text": "reporter genes", "start": 133, "end": 147}]}}, "schema": []} {"input": "Further analysis identified three elements required for efficient induction, referred to as GM2, GC-box and conserved lymphokine element (CLE0 ).", "output": {"entities": {"dna": [{"text": "GM2", "start": 92, "end": 95}, {"text": "GC-box", "start": 97, "end": 103}, {"text": "conserved", "start": 108, "end": 117}, {"text": "element", "start": 129, "end": 136}, {"text": "CLE0", "start": 138, "end": 142}], "protein": [{"text": "lymphokine", "start": 118, "end": 128}]}}, "schema": []} {"input": "GM2 defines a binding site for protein(s) whose binding is inducible by PMA.", "output": {"entities": {"dna": [{"text": "GM2", "start": 0, "end": 3}, {"text": "binding site", "start": 14, "end": 26}]}}, "schema": []} {"input": "One protein, NF-GM2 is similar to the transcription factor NF-kB.", "output": {"entities": {"protein": [{"text": "NF-GM2", "start": 13, "end": 19}, {"text": "transcription factor", "start": 38, "end": 58}, {"text": "NF-kB", "start": 59, "end": 64}]}}, "schema": []} {"input": "GC-box is a binding site for constitutively bound proteins.", "output": {"entities": {"dna": [{"text": "GC-box", "start": 0, "end": 6}, {"text": "binding site", "start": 12, "end": 24}], "protein": [{"text": "constitutively bound proteins", "start": 29, "end": 58}]}}, "schema": []} {"input": "CLEO defines a binding site for protein(s) whose optimum binding is stimulated by PMA and A23187.", "output": {"entities": {"dna": [{"text": "binding site", "start": 15, "end": 27}]}}, "schema": []} {"input": "Viral trans-activators such as Tax (human T cell leukemia virus-1, HTLV-1) and E2 (bovine papilloma virus, BPV) proteins are other agents which activate lymphokine gene expression by bypassing T cell receptor (TCR) mediated signaling.", "output": {"entities": {"protein": [{"text": "Viral trans-activators", "start": 0, "end": 22}, {"text": "Tax", "start": 31, "end": 34}, {"text": "E2", "start": 79, "end": 81}, {"text": "T cell receptor", "start": 193, "end": 208}, {"text": "TCR", "start": 210, "end": 213}], "dna": [{"text": "lymphokine gene", "start": 153, "end": 168}]}}, "schema": []} {"input": "The trans-activation domain of E2 and Tax is interchangeable although they have no obvious sequence homology between them.", "output": {"entities": {"protein": [{"text": "E2", "start": 31, "end": 33}, {"text": "Tax", "start": 38, "end": 41}]}}, "schema": []} {"input": "The viral trans-activators appear to target specific DNA binding protein such as NF-kB and Sp1 to cis-acting DNA site and promote lymphokine gene expression without TCR -mediated stimulation.", "output": {"entities": {"protein": [{"text": "viral trans-activators", "start": 4, "end": 26}, {"text": "DNA binding protein", "start": 53, "end": 72}, {"text": "NF-kB", "start": 81, "end": 86}, {"text": "Sp1", "start": 91, "end": 94}, {"text": "TCR", "start": 165, "end": 168}], "dna": [{"text": "cis-acting DNA site", "start": 98, "end": 117}, {"text": "lymphokine gene", "start": 130, "end": 145}]}}, "schema": []} {"input": "Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency.", "output": {"entities": {"dna": [{"text": "Pit-1 gene", "start": 17, "end": 27}]}}, "schema": []} {"input": "Pit-1 is a pituitary-specific transcription factor that binds to and transactivates promoters of growth hormone and prolactin genes.", "output": {"entities": {"protein": [{"text": "Pit-1", "start": 0, "end": 5}, {"text": "pituitary-specific transcription factor", "start": 11, "end": 50}], "dna": [{"text": "promoters", "start": 84, "end": 93}]}}, "schema": []} {"input": "In three unrelated Japanese children with combined pituitary hormone deficiency, we identified three point mutations in the Pit-1 gene, Pro24Leu, Arg143Gln, and Arg271Trp, located on the major transactivation region, POU-specific domain, and POU-homeodomain, respectively.", "output": {"entities": {"protein": [{"text": "Pit-1", "start": 124, "end": 129}], "dna": [{"text": "gene", "start": 130, "end": 134}, {"text": "Pro24Leu", "start": 136, "end": 144}, {"text": "Arg143Gln", "start": 146, "end": 155}, {"text": "Arg271Trp", "start": 161, "end": 170}, {"text": "major transactivation region", "start": 187, "end": 215}, {"text": "POU-specific domain", "start": 217, "end": 236}, {"text": "POU-homeodomain", "start": 242, "end": 257}]}}, "schema": []} {"input": "Activation of protein kinase C and elevation of cAMP interact synergistically to raise c-Fos and AP-1 activity in Jurkat cells.", "output": {"entities": {"protein": [{"text": "protein kinase C", "start": 14, "end": 30}, {"text": "c-Fos", "start": 87, "end": 92}, {"text": "AP-1", "start": 97, "end": 101}]}}, "schema": []} {"input": "We have earlier found that in Jurkat cells activation of protein kinase C (PKC) enhances the cyclic adenosine monophosphate (cAMP) accumulation induced by adenosine receptor stimulation or activation of Gs.", "output": {"entities": {"protein": [{"text": "protein kinase C", "start": 57, "end": 73}, {"text": "PKC", "start": 75, "end": 78}, {"text": "Gs", "start": 203, "end": 205}]}}, "schema": []} {"input": "Here we have therefore examined the effect of the phorbol ester PMA (phorbol 12-myristate 13-acetate) which stimulates PKC and a combination of the adenosine receptor agonist NECA (5'-(N-ethyl)-carboxamido adenosine) and forskolin to raise cAMP, on the levels of c-Fos and Jun and on the binding and transcriptional activity of the transcription factor, activator protein-1 (AP-1 ).", "output": {"entities": {"protein": [{"text": "PKC", "start": 119, "end": 122}, {"text": "adenosine receptor", "start": 148, "end": 166}, {"text": "c-Fos", "start": 263, "end": 268}, {"text": "Jun", "start": 273, "end": 276}, {"text": "transcription factor", "start": 332, "end": 352}, {"text": "activator protein-1", "start": 354, "end": 373}, {"text": "AP-1", "start": 375, "end": 379}]}}, "schema": []} {"input": "PMA treatment caused a concentration- and time-dependent increase in both c-Fos and Jun immunoreactivity in contrast to cAMP elevation that had only a slight effect.", "output": {"entities": {}}, "schema": []} {"input": "Both PMA and the combination of NECA and forskolin acted together either to increase (c-Fos) or decrease (Jun) protein levels as well as increasing AP-1 binding, as judged by gel-shift assay, and AP-1 transcriptional activity.", "output": {"entities": {"protein": [{"text": "c-Fos", "start": 86, "end": 91}, {"text": "Jun", "start": 106, "end": 109}, {"text": "AP-1", "start": 148, "end": 152}, {"text": "AP-1", "start": 196, "end": 200}]}}, "schema": []} {"input": "Furthermore there was a clear-cut synergy between the PKC stimulator and the cAMP elevating agents.", "output": {"entities": {"protein": [{"text": "PKC", "start": 54, "end": 57}]}}, "schema": []} {"input": "The results demonstrate that the simultaneous activation of PKC and elevation of cAMP leads to an enhanced AP-1 transcriptional activity in a T-leukemia cell line, suggesting that the previously observed interaction between the parallel signal transduction pathways may have functional consequences at the level of gene transcription.", "output": {"entities": {"protein": [{"text": "PKC", "start": 60, "end": 63}, {"text": "AP-1", "start": 107, "end": 111}], "cell_line": [{"text": "T-leukemia cell line", "start": 142, "end": 162}]}}, "schema": []} {"input": "Inhibition of anti-CD3 monoclonal antibody -induced T-cell proliferation by dexamethasone, isoproterenol, or prostaglandin E2 either alone or in combination.", "output": {"entities": {"protein": [{"text": "anti-CD3 monoclonal antibody", "start": 14, "end": 42}]}}, "schema": []} {"input": "1.", "output": {"entities": {}}, "schema": []} {"input": "The purpose of these studies was to investigate the modulation of the proliferation of human T cells obtained from peripheral blood by dexamethasone (DEX ), isoproterenol (ISO ), and prostaglandin E2 (PGE2 ).", "output": {"entities": {"cell_type": [{"text": "human T cells", "start": 87, "end": 100}]}}, "schema": []} {"input": "The former two substances interact with T cells via the glucocorticoid and beta-adrenergic receptors respectively.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 40, "end": 47}]}}, "schema": []} {"input": "When occupied by their natural ligands, glucocorticosteroids and catecholamines, these receptors have a role in modulating T-cell function during stress.", "output": {"entities": {}}, "schema": []} {"input": "During the inflammatory response increased levels of PGE2 bind to their receptors on T cells and thus alter responsiveness.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 85, "end": 92}]}}, "schema": []} {"input": "Proliferation of T cells was induced by immobilized anti-CD3 monoclonal antibody (mAb) in the presence or absence of an additional costimulatory signal delivered by anti-CD28 mAb.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 17, "end": 24}], "protein": [{"text": "anti-CD3 monoclonal antibody", "start": 52, "end": 80}, {"text": "mAb", "start": 82, "end": 85}, {"text": "anti-CD28 mAb", "start": 165, "end": 178}]}}, "schema": []} {"input": "2.", "output": {"entities": {}}, "schema": []} {"input": "Various physiologic concentrations of DEX, ISO, or PGE2 were added at the time of initiation of the cultures and subsequent proliferation of the unstimulated T cells was determined.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 158, "end": 165}]}}, "schema": []} {"input": "The results demonstrate that physiologic concentrations of all three of these agents inhibit the anti-CD3 mAb -induced proliferation of T cells.", "output": {"entities": {"protein": [{"text": "anti-CD3 mAb", "start": 97, "end": 109}], "cell_type": [{"text": "T cells", "start": 136, "end": 143}]}}, "schema": []} {"input": "3.", "output": {"entities": {}}, "schema": []} {"input": "Although DEX and PGE2 were equipotent in suppressing T-cell proliferation, ISO was much less effective.", "output": {"entities": {}}, "schema": []} {"input": "4.", "output": {"entities": {}}, "schema": []} {"input": "Because concomitant elevations in the peripheral levels of these substances may occur, experiments were performed to determine the T-cell inhibitory effects of DEX together with either PGE2 or ISO.", "output": {"entities": {}}, "schema": []} {"input": "Synergistic suppression of T-cell proliferation was observed when various concentrations of DEX and PGE2, but not DEX and ISO, were added to cultures.", "output": {"entities": {}}, "schema": []} {"input": "This synergistic suppression could not be explained by an increase in cAMP accumulation in T cells stimulated with DEX and PGE2.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 91, "end": 98}]}}, "schema": []} {"input": "5.", "output": {"entities": {}}, "schema": []} {"input": "Finally, the addition of anti-CD28 mAb to anti-CD3 mAb-stimulated T cells overcame much of the suppression of proliferation induced by PGE2 or ISO but less so than that induced by DEX.", "output": {"entities": {"protein": [{"text": "anti-CD28 mAb", "start": 25, "end": 38}], "cell_type": [{"text": "anti-CD3 mAb-stimulated T cells", "start": 42, "end": 73}]}}, "schema": []} {"input": "In vivo footprint analysis of the HLA-DRA gene promoter: cell-specific interaction at the octamer site and up-regulation of X box binding by interferon gamma.", "output": {"entities": {"dna": [{"text": "HLA-DRA gene promoter", "start": 34, "end": 55}, {"text": "octamer site", "start": 90, "end": 102}], "protein": [{"text": "interferon gamma", "start": 141, "end": 157}]}}, "schema": []} {"input": "Analysis of the major histocompatibility complex class II gene promoter DRA has previously identified at least five cis-acting regions required for maximal expression.", "output": {"entities": {"protein": [{"text": "major histocompatibility complex class II", "start": 16, "end": 57}], "dna": [{"text": "gene promoter", "start": 58, "end": 71}, {"text": "DRA", "start": 72, "end": 75}, {"text": "cis-acting regions", "start": 116, "end": 134}]}}, "schema": []} {"input": "We have examined the DRA promoter for protein-DNA interactions in the intact cell, which may mediate transcriptional activation.", "output": {"entities": {"dna": [{"text": "DRA promoter", "start": 21, "end": 33}], "cell_type": [{"text": "intact cell", "start": 70, "end": 81}]}}, "schema": []} {"input": "Using in vivo genomic footprinting we identified interactions in B-cell lines at the octamer site and the Y, X1, and X2 boxes.", "output": {"entities": {"cell_line": [{"text": "B-cell lines", "start": 65, "end": 77}], "dna": [{"text": "octamer site", "start": 85, "end": 97}]}}, "schema": []} {"input": "Class II antigen expressing T-cell lines maintained contacts identical to B-cell lines, while class II-negative T-cell lines exhibited no interactions.", "output": {"entities": {"cell_line": [{"text": "Class II antigen expressing T-cell lines", "start": 0, "end": 40}, {"text": "B-cell lines", "start": 74, "end": 86}, {"text": "class II-negative T-cell lines", "start": 94, "end": 124}]}}, "schema": []} {"input": "In lymphoid cell lines, the octamer site is occupied and required for maximal expression.", "output": {"entities": {"cell_line": [{"text": "lymphoid cell lines", "start": 3, "end": 22}], "dna": [{"text": "octamer site", "start": 28, "end": 40}]}}, "schema": []} {"input": "This is most likely due to the presence of the lymphoid-specific OTF-2 factor.", "output": {"entities": {"protein": [{"text": "lymphoid-specific OTF-2 factor", "start": 47, "end": 77}]}}, "schema": []} {"input": "In contrast, the class II-positive nonlymphoid glioblastoma cell line does not exhibit interactions at the octamer site despite the presence of the ubiquitous OTF-1 factor and an open binding site.", "output": {"entities": {"cell_line": [{"text": "class II-positive nonlymphoid glioblastoma cell line", "start": 17, "end": 69}], "dna": [{"text": "octamer site", "start": 107, "end": 119}, {"text": "open binding site", "start": 179, "end": 196}], "protein": [{"text": "ubiquitous OTF-1 factor", "start": 148, "end": 171}]}}, "schema": []} {"input": "Thus, the DRA promoter discriminates against OTF-1 activation at the level of DNA binding in the glioblastoma line.", "output": {"entities": {"dna": [{"text": "DRA promoter", "start": 10, "end": 22}], "protein": [{"text": "OTF-1", "start": 45, "end": 50}], "cell_line": [{"text": "glioblastoma line", "start": 97, "end": 114}]}}, "schema": []} {"input": "Interferon gamma induces class II expression in this glioblastoma cell line and, in parallel, up-regulates X1 and X2 box protein-DNA interactions, while all other interactions remain unchanged.", "output": {"entities": {"protein": [{"text": "Interferon gamma", "start": 0, "end": 16}], "cell_line": [{"text": "glioblastoma cell line", "start": 53, "end": 75}]}}, "schema": []} {"input": "These results suggest that interferon gamma functions on a poised promoter by altering weak, nonproductive interactions at the X boxes to strong interactions.", "output": {"entities": {"protein": [{"text": "interferon gamma", "start": 27, "end": 43}], "dna": [{"text": "poised promoter", "start": 59, "end": 74}, {"text": "X boxes", "start": 127, "end": 134}]}}, "schema": []} {"input": "These findings provide direct in vivo evidence to strongly suggest that the modulation of X1 and X2 interactions is an important constituent of the interferon gamma induction pathway.", "output": {"entities": {"dna": [{"text": "X1", "start": 90, "end": 92}, {"text": "X2", "start": 97, "end": 99}], "protein": [{"text": "interferon gamma", "start": 148, "end": 164}]}}, "schema": []} {"input": "Estrogen binding sites in peripheral blood monocytes and effects of danazol on their sites in vitro.", "output": {"entities": {"cell_type": [{"text": "peripheral blood monocytes", "start": 26, "end": 52}]}}, "schema": []} {"input": "1.", "output": {"entities": {}}, "schema": []} {"input": "This study was designed to investigate the presence of estrogen type I (high affinity, low capacity) and type II (low affinity, high capacity) binding sites in human peripheral blood monocytes and the effects of danazol on these sites.", "output": {"entities": {"cell_type": [{"text": "peripheral blood monocytes", "start": 166, "end": 192}]}}, "schema": []} {"input": "2.", "output": {"entities": {}}, "schema": []} {"input": "These two types of estrogen binding sites existed in human peripheral blood monocytes.", "output": {"entities": {"cell_type": [{"text": "human peripheral blood monocytes", "start": 53, "end": 85}]}}, "schema": []} {"input": "3.", "output": {"entities": {}}, "schema": []} {"input": "Danazol bound to these sites in high concentration (10(-6) M, clinical serum concentration during danazol therapy) and decreased the number of both sites.", "output": {"entities": {}}, "schema": []} {"input": "4.", "output": {"entities": {}}, "schema": []} {"input": "It is suggested that danazol has an anti-estrogenic action to the monocytes through the competition and suppression of estrogen binding sites as seen in the estrogen target organ.", "output": {"entities": {}}, "schema": []} {"input": "A microtitre assay system for glucocorticoid receptors: decreased receptor concentration in myocardial infarction.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 30, "end": 54}]}}, "schema": []} {"input": "A major difficulty in determination of glucocorticoid receptor sites is the very complicated assay procedure.", "output": {"entities": {}}, "schema": []} {"input": "Therefore, we describe a microtitre assay system for glucocorticoid receptors which is a whole-cell competitive binding radioassay using [3H]-dexamethasone as radioligand.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 53, "end": 77}]}}, "schema": []} {"input": "This modification of a previously described protocol simplifies and reduces laboratory work and allows assay reproducibility to be controlled more reliably.", "output": {"entities": {}}, "schema": []} {"input": "Thus enabled to perform the test on multiple blood samples in parallel, we investigated cardiac infarction patients over a 12-day period to test if glucocorticoid receptor binding is altered in this'stressful' disease.", "output": {"entities": {"cell_type": [{"text": "blood samples", "start": 45, "end": 58}], "protein": [{"text": "glucocorticoid receptor", "start": 148, "end": 171}]}}, "schema": []} {"input": "On the first day of the disease, glucocorticoid receptor capacity was significantly decreased without alteration of the receptor-ligand affinity, whereas on days 4 and 12 the number of receptor sites was normal again.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 33, "end": 56}]}}, "schema": []} {"input": "This result fits well into the general observation of stress-induced down-regulation of immune responses.", "output": {"entities": {}}, "schema": []} {"input": "SRC-related proto-oncogenes and transcription factors in primary human T cells: modulation by cyclosporin A and FK506.", "output": {"entities": {"dna": [{"text": "SRC-related proto-oncogenes", "start": 0, "end": 27}], "protein": [{"text": "transcription factors", "start": 32, "end": 53}], "cell_type": [{"text": "human T cells", "start": 65, "end": 78}]}}, "schema": []} {"input": "Activation of T lymphocytes induces transcription of genes encoding for lymphokines.", "output": {"entities": {"cell_type": [{"text": "T lymphocytes", "start": 14, "end": 27}], "dna": [{"text": "genes", "start": 53, "end": 58}], "protein": [{"text": "lymphokines", "start": 72, "end": 83}]}}, "schema": []} {"input": "Interleukin-2 (IL-2) gene expression is controlled transcriptionally by the cooperative activity of specific trans-activating factors that bind to the IL-2 enhancer.", "output": {"entities": {"protein": [{"text": "Interleukin-2", "start": 0, "end": 13}, {"text": "trans-activating factors", "start": 109, "end": 133}], "dna": [{"text": "(IL-2) gene", "start": 14, "end": 25}, {"text": "IL-2 enhancer", "start": 151, "end": 164}]}}, "schema": []} {"input": "Cyclosporin A (CsA) and FK506 inhibit the production of IL-2 in T lymphocytes at the level of gene transcription.", "output": {"entities": {"protein": [{"text": "IL-2", "start": 56, "end": 60}], "cell_type": [{"text": "T lymphocytes", "start": 64, "end": 77}]}}, "schema": []} {"input": "A member of the src gene family, the lymphocyte-specific protein tyrosine kinase, p56lck, has been implicated in IL-2 production.", "output": {"entities": {"dna": [{"text": "src gene family", "start": 16, "end": 31}], "protein": [{"text": "lymphocyte-specific protein tyrosine kinase", "start": 37, "end": 80}, {"text": "p56lck", "start": 82, "end": 88}, {"text": "IL-2", "start": 113, "end": 117}]}}, "schema": []} {"input": "CsA was found not to inhibit lck gene expression, nor the activity of the lck gene product.", "output": {"entities": {"protein": [{"text": "lck", "start": 29, "end": 32}, {"text": "lck gene product", "start": 74, "end": 90}]}}, "schema": []} {"input": "However, CsA and FK506 inhibit the appearance of DNA binding activity of factors that bind to the NF-AT and AP-1 sites in the IL-2 enhancer.", "output": {"entities": {"dna": [{"text": "NF-AT", "start": 98, "end": 103}, {"text": "AP-1 sites", "start": 108, "end": 118}, {"text": "IL-2 enhancer", "start": 126, "end": 139}]}}, "schema": []} {"input": "Since the induction of NF-AT and AP-1 is induced by the same stimuli that stimulate IL-2 production, these results indicate that the immunosuppressant action of CsA and FK506 is exerted at the level of these trans-activating factors.", "output": {"entities": {"protein": [{"text": "NF-AT", "start": 23, "end": 28}, {"text": "AP-1", "start": 33, "end": 37}, {"text": "IL-2", "start": 84, "end": 88}, {"text": "trans-activating factors", "start": 208, "end": 232}]}}, "schema": []} {"input": "The AP-1 site at -150 bp, but not the NF-kappa B site, is likely to represent the major target of protein kinase C in the interleukin 2 promoter.", "output": {"entities": {"dna": [{"text": "AP-1 site", "start": 4, "end": 13}, {"text": "-150 bp", "start": 17, "end": 24}, {"text": "NF-kappa B site", "start": 38, "end": 53}, {"text": "promoter", "start": 136, "end": 144}], "protein": [{"text": "protein kinase C", "start": 98, "end": 114}, {"text": "interleukin 2", "start": 122, "end": 135}]}}, "schema": []} {"input": "Stimulation of T cells with antigen results in activation of several kinases, including protein kinase C (PKC ), that may mediate the later induction of activation-related genes.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 15, "end": 22}], "protein": [{"text": "kinases", "start": 69, "end": 76}, {"text": "protein kinase C", "start": 88, "end": 104}, {"text": "PKC", "start": 106, "end": 109}]}}, "schema": []} {"input": "We have examined the potential role of PKC in induction of the interleukin 2 (IL-2) gene in T cells stimulated through the T cell receptor/CD3 complex.", "output": {"entities": {"protein": [{"text": "PKC", "start": 39, "end": 42}, {"text": "T cell receptor/CD3 complex", "start": 123, "end": 150}], "dna": [{"text": "interleukin 2 (IL-2) gene", "start": 63, "end": 88}], "cell_type": [{"text": "T cells", "start": 92, "end": 99}]}}, "schema": []} {"input": "We have previously shown that prolonged treatment of the untransformed T cell clone Ar-5 with phorbol esters results in downmodulation of the alpha and beta isozymes of PKC, and abrogates induction of IL-2 mRNA and protein.", "output": {"entities": {"cell_line": [{"text": "T cell clone Ar-5", "start": 71, "end": 88}], "protein": [{"text": "PKC", "start": 169, "end": 172}, {"text": "protein", "start": 215, "end": 222}], "rna": [{"text": "IL-2 mRNA", "start": 201, "end": 210}]}}, "schema": []} {"input": "Here we show that phorbol ester treatment also abolishes induction of chloramphenicol acetyltransferase activity in Ar-5 cells transfected with a plasmid containing the IL-2 promoter linked to this reporter gene.", "output": {"entities": {"protein": [{"text": "chloramphenicol acetyltransferase", "start": 70, "end": 103}], "cell_line": [{"text": "Ar-5 cells", "start": 116, "end": 126}], "dna": [{"text": "plasmid", "start": 146, "end": 153}, {"text": "IL-2 promoter", "start": 169, "end": 182}, {"text": "reporter gene", "start": 198, "end": 211}]}}, "schema": []} {"input": "The IL-2 promoter contains binding sites for nuclear factors including NFAT-1, Oct, NF-kappa B, and AP-1, which are all potentially sensitive to activation of PKC.", "output": {"entities": {"dna": [{"text": "IL-2 promoter", "start": 4, "end": 17}, {"text": "binding sites", "start": 27, "end": 40}], "protein": [{"text": "nuclear factors", "start": 45, "end": 60}, {"text": "NFAT-1", "start": 71, "end": 77}, {"text": "Oct", "start": 79, "end": 82}, {"text": "NF-kappa B", "start": 84, "end": 94}, {"text": "AP-1", "start": 100, "end": 104}, {"text": "PKC", "start": 159, "end": 162}]}}, "schema": []} {"input": "We show that induction of a trimer of the NFAT and Oct sites is not sensitive to phorbol ester treatment, and that mutations in the NF-kappa B site have no effect on inducibility of the IL-2 promoter.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 132, "end": 142}], "dna": [{"text": "site", "start": 143, "end": 147}, {"text": "IL-2 promoter", "start": 186, "end": 199}]}}, "schema": []} {"input": "In contrast, mutations in the AP-1 site located at -150 bp almost completely abrogate induction of the IL-2 promoter, and appearance of an inducible nuclear factor binding to this site is sensitive to PKC depletion.", "output": {"entities": {"dna": [{"text": "AP-1 site", "start": 30, "end": 39}, {"text": "-150 bp", "start": 51, "end": 58}, {"text": "IL-2 promoter", "start": 103, "end": 116}], "protein": [{"text": "inducible nuclear factor", "start": 139, "end": 163}, {"text": "PKC", "start": 201, "end": 204}]}}, "schema": []} {"input": "Moreover, cotransfections with c-fos and c-jun expression plasmids markedly enhance induction of the IL-2 promoter in minimally stimulated T cells.", "output": {"entities": {"dna": [{"text": "IL-2 promoter", "start": 101, "end": 114}], "cell_line": [{"text": "minimally stimulated", "start": 118, "end": 138}], "cell_type": [{"text": "T cells", "start": 139, "end": 146}]}}, "schema": []} {"input": "Our results indicate that the AP-1 site at -150 bp represents a major, if not the only, site of PKC responsiveness in the IL-2 promoter.", "output": {"entities": {"dna": [{"text": "AP-1 site", "start": 30, "end": 39}, {"text": "-150 bp", "start": 43, "end": 50}, {"text": "IL-2 promoter", "start": 122, "end": 135}], "protein": [{"text": "PKC", "start": 96, "end": 99}]}}, "schema": []} {"input": "[Effect of antihypertensive therapy with captopril on gluco- and mineralo corticoid receptors of peripheral blood lymphocytes in hypertensive patients of various age]", "output": {"entities": {"cell_type": [{"text": "peripheral blood lymphocytes", "start": 97, "end": 125}]}}, "schema": []} {"input": "Binding of 3H-dexamethasone and 3H-aldosterone by peripheral lymphocyte receptors was investigated in healthy persons and hypertensive patients before and after 2-week captopril treatment.", "output": {"entities": {"protein": [{"text": "peripheral lymphocyte receptors", "start": 50, "end": 81}]}}, "schema": []} {"input": "The number of glucocorticoid and mineralocorticoid binding sites was increased in hypertensives vs normotensives.", "output": {"entities": {"protein": [{"text": "glucocorticoid and", "start": 14, "end": 32}, {"text": "mineralocorticoid binding sites", "start": 33, "end": 64}]}}, "schema": []} {"input": "The treatment with the ACE inhibitor captopril led to activation of hormone-receptor interactions.", "output": {"entities": {}}, "schema": []} {"input": "There was a more marked rise of the number of receptors in middle-aged (44-55 years) hypertensives vs elderly (61-80 years) subjects after captopril treatment.", "output": {"entities": {"protein": [{"text": "receptors", "start": 46, "end": 55}]}}, "schema": []} {"input": "The use of interferon-gamma-treated U937 cells in chemiluminescence assays to detect red cell, platelet and granulocyte antibodies of potential clinical significance.", "output": {"entities": {"cell_line": [{"text": "interferon-gamma-treated U937 cells", "start": 11, "end": 46}]}}, "schema": []} {"input": "The chemiluminescent (CL) response of interferon-gamma-treated U937 (IFN-U937) cells to sensitized target cells has been used to detect red cell, platelet and granulocyte antibodies.", "output": {"entities": {"cell_line": [{"text": "interferon-gamma-treated U937 (", "start": 38, "end": 69}, {"text": "IFN-U937) cells", "start": 69, "end": 84}], "protein": [{"text": "red cell", "start": 136, "end": 144}, {"text": "platelet", "start": 146, "end": 154}, {"text": "granulocyte antibodies", "start": 159, "end": 181}]}}, "schema": []} {"input": "A clone of U937 cells was selected which expressed Fc receptor I (Fc gamma RI) and which, after incubation with IFN-gamma for 72 h, was capable of generating high levels of lucigenin-enhanced CL.", "output": {"entities": {"cell_line": [{"text": "U937 cells", "start": 11, "end": 21}], "protein": [{"text": "Fc receptor I", "start": 51, "end": 64}, {"text": "Fc gamma RI", "start": 66, "end": 77}, {"text": "IFN-gamma", "start": 112, "end": 121}]}}, "schema": []} {"input": "The CL responses of IFN-U937 cells and peripheral blood human monocytes to sensitized red cells, platelets or granulocytes were then compared.", "output": {"entities": {"cell_line": [{"text": "IFN-U937 cells", "start": 20, "end": 34}], "cell_type": [{"text": "peripheral blood human monocytes", "start": 39, "end": 71}, {"text": "sensitized red cells", "start": 75, "end": 95}, {"text": "platelets", "start": 97, "end": 106}, {"text": "granulocytes", "start": 110, "end": 122}]}}, "schema": []} {"input": "Assays using monocytes or IFN-U937 cells were of comparable sensitivity for detection of antibodies against all three types of target cell.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 13, "end": 22}], "cell_line": [{"text": "IFN-U937 cells", "start": 26, "end": 40}], "protein": [{"text": "antibodies", "start": 89, "end": 99}]}}, "schema": []} {"input": "In addition, the use of IFN-U937 cells reduced interassay variation and simplified assay performance.", "output": {"entities": {"cell_line": [{"text": "IFN-U937 cells", "start": 24, "end": 38}]}}, "schema": []} {"input": "The potential clinical usefulness of these CL assays was suggested by the ability of both monocytes and IFN-U937 cells to respond to red cells, platelets or granulocytes sensitized with sera from pregnant women whose babies had either haemolytic disease of the newborn (HDN ), alloimmune thrombocytopenia or alloimmune neutropenia respectively.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 90, "end": 99}, {"text": "red cells", "start": 133, "end": 142}, {"text": "platelets", "start": 144, "end": 153}, {"text": "granulocytes", "start": 157, "end": 169}], "cell_line": [{"text": "IFN-U937 cells", "start": 104, "end": 118}]}}, "schema": []} {"input": "In addition, monocytes and IFN-U937 cells both responded to red cells sensitized with antibodies against a variety of specificities of assumed (although not documented) clinical significance for blood transfusion recipients.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 13, "end": 22}, {"text": "red cells", "start": 60, "end": 69}], "cell_line": [{"text": "IFN-U937 cells", "start": 27, "end": 41}], "protein": [{"text": "antibodies", "start": 86, "end": 96}]}}, "schema": []} {"input": "In contrast, monocytes and IFN-U937 cells responded only weakly to red cells sensitized with either anti-D in sera from mothers of babies unaffected by HDN, or with antisera containing high titre antibodies with specificities not normally associated with significantly reduced red cell survival.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 13, "end": 22}, {"text": "red cells", "start": 67, "end": 76}, {"text": "red cell", "start": 277, "end": 285}], "cell_line": [{"text": "IFN-U937 cells", "start": 27, "end": 41}], "protein": [{"text": "anti-D", "start": 100, "end": 106}, {"text": "high titre antibodies", "start": 185, "end": 206}]}}, "schema": []} {"input": "Ablation of transplanted HTLV-I Tax-transformed tumors in mice by antisense inhibition of NF-kappa B [published erratum appears in Science 1993 Mar 12;259(5101):1523]", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 90, "end": 100}]}}, "schema": []} {"input": "Mice transgenic for the human T cell leukemia virus (HTLV-I) Tax gene develop fibroblastic tumors that express NF-kappa B-inducible early genes.", "output": {"entities": {"dna": [{"text": "human T cell leukemia virus (HTLV-I)", "start": 24, "end": 60}, {"text": "gene", "start": 65, "end": 69}, {"text": "NF-kappa B-inducible early genes", "start": 111, "end": 143}], "protein": [{"text": "Tax", "start": 61, "end": 64}]}}, "schema": []} {"input": "In vitro inhibition of NF-kappa B expression by antisense oligodeoxynucleotides (ODNs) inhibited growth of these culture-adapted Tax-transformed fibroblasts as well as an HTLV-I -transformed human lymphocyte line.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 23, "end": 33}], "cell_line": [{"text": "culture-adapted Tax-transformed fibroblasts", "start": 113, "end": 156}, {"text": "HTLV-I -transformed human lymphocyte line", "start": 171, "end": 212}]}}, "schema": []} {"input": "In contrast, antisense inhibition of Tax itself had no apparent effect on cell growth.", "output": {"entities": {"protein": [{"text": "Tax", "start": 37, "end": 40}]}}, "schema": []} {"input": "Mice treated with antisense to NF-kappa B ODNs showed rapid regression of transplanted fibrosarcomas.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 31, "end": 41}]}}, "schema": []} {"input": "This suggests that NF-kappa B expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I -associated disease.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 19, "end": 29}]}}, "schema": []} {"input": "Membrane receptors for aldosterone: a novel pathway for mineralocorticoid action.", "output": {"entities": {"protein": [{"text": "Membrane receptors", "start": 0, "end": 18}]}}, "schema": []} {"input": "Rapid nongenomic in vitro effects of aldosterone on intracellular electrolytes, cell volume, and Na(+)-H+ antiport have been found in human mononuclear leukocytes (HML ).", "output": {"entities": {"protein": [{"text": "Na(+)-H+ antiport", "start": 97, "end": 114}], "cell_type": [{"text": "human mononuclear leukocytes", "start": 134, "end": 162}, {"text": "HML", "start": 164, "end": 167}]}}, "schema": []} {"input": "Binding of 125I-labeled aldosterone to plasma membranes of HML shares important features with these functional data.", "output": {"entities": {"cell_type": [{"text": "HML", "start": 59, "end": 62}]}}, "schema": []} {"input": "This includes a very low apparent dissociation constant (Kd) of 0.1 nM for both aldosterone and the effect on the Na(+)-H(+)-antiport, a high turnover rate, and the almost exclusive binding selectivity for aldosterone.", "output": {"entities": {"protein": [{"text": "Na(+)-H(+)-antiport", "start": 114, "end": 133}]}}, "schema": []} {"input": "Dexamethasone, RU 26988, corticosterone, ouabain, amiloride, and 18-hydroxyprogesterone were inactive as ligands.", "output": {"entities": {}}, "schema": []} {"input": "Deoxycorticosterone acetate had an intermediate activity with an apparent Kd of 100 nM.", "output": {"entities": {}}, "schema": []} {"input": "These findings are the first to demonstrate membrane binding of aldosterone being compatible with major aspects of its nongenomic effects.", "output": {"entities": {}}, "schema": []} {"input": "Leukotriene B4 transcriptionally activates interleukin-6 expression involving NK-chi B and NF-IL6.", "output": {"entities": {"protein": [{"text": "interleukin-6", "start": 43, "end": 56}, {"text": "NK-chi B", "start": 78, "end": 86}, {"text": "NF-IL6", "start": 91, "end": 97}]}}, "schema": []} {"input": "Leukotriene B4 (LTB4) is a notable participant in inflammation and chemotaxis.", "output": {"entities": {}}, "schema": []} {"input": "It is, however, still unclear whether LTB4 acts in this regard directly or indirectly by stimulating the release of chemotactic and inflammatory cytokines.", "output": {"entities": {"protein": [{"text": "inflammatory cytokines", "start": 132, "end": 154}]}}, "schema": []} {"input": "Here we report that LTB4 induces synthesis of interleukin (IL)-6 by human blood monocytes through transcriptional activation of the IL-6 gene.", "output": {"entities": {"protein": [{"text": "interleukin (IL)-6", "start": 46, "end": 64}, {"text": "IL-6", "start": 132, "end": 136}], "cell_type": [{"text": "human blood monocytes", "start": 68, "end": 89}], "dna": [{"text": "gene", "start": 137, "end": 141}]}}, "schema": []} {"input": "We furthermore demonstrate that this process involves activation of the transcription factor NF-chi B and, to a lesser extent, of NF-IL6, while the activity of the transcription factor AP-1, shown to otherwise confer IL-6 inducibility, appeared to be unaffected by LTB4.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 72, "end": 92}, {"text": "NF-chi B", "start": 93, "end": 101}, {"text": "NF-IL6", "start": 130, "end": 136}, {"text": "transcription factor", "start": 164, "end": 184}, {"text": "AP-1", "start": 185, "end": 189}, {"text": "IL-6", "start": 217, "end": 221}]}}, "schema": []} {"input": "Involvement of NF-chi B and NF-IL6 in induction of IL-6 transcription by monocytes was demonstrated using deleted forms of the IL-6 promoter.", "output": {"entities": {"protein": [{"text": "NF-chi B", "start": 15, "end": 23}, {"text": "NF-IL6", "start": 28, "end": 34}, {"text": "IL-6", "start": 51, "end": 55}, {"text": "IL-6", "start": 127, "end": 131}], "dna": [{"text": "promoter", "start": 132, "end": 140}]}}, "schema": []} {"input": "Activation of the IL-6 promoter by LTB4 was not only associated with accumulation of the respective transcripts but resulted in synthesis of functional IL-6 protein as well.", "output": {"entities": {"dna": [{"text": "IL-6 promoter", "start": 18, "end": 31}], "protein": [{"text": "IL-6 protein", "start": 152, "end": 164}]}}, "schema": []} {"input": "In addition, LTB4 mediated transactivation of a heterologous promoter construct containing the NF-chi B or the NF-IL6 enhancer, but not the AP-1 enhancer.", "output": {"entities": {"dna": [{"text": "heterologous promoter construct", "start": 48, "end": 79}, {"text": "NF-IL6 enhancer", "start": 111, "end": 126}, {"text": "AP-1 enhancer", "start": 140, "end": 153}], "protein": [{"text": "NF-chi B", "start": 95, "end": 103}]}}, "schema": []} {"input": "The signaling events mediating this effect appeared to involve the release of H2O2, since LTB4 failed to induce NF-chi B or NF-IL6 in the presence of the scavenger of H2O2, N-acetyl-L-cysteine.", "output": {"entities": {"protein": [{"text": "NF-chi B", "start": 112, "end": 120}, {"text": "NF-IL6", "start": 124, "end": 130}]}}, "schema": []} {"input": "Bcl-2: a repressor of lymphocyte death.", "output": {"entities": {"protein": [{"text": "Bcl-2", "start": 0, "end": 5}], "cell_type": [{"text": "lymphocyte", "start": 22, "end": 32}]}}, "schema": []} {"input": "The genes and mechanisms that control programmed cell death are currently the subject of intense study.", "output": {"entities": {}}, "schema": []} {"input": "The bcl-2 gene, a repressor of lymphocyte death, is perhaps the best understood of the programmed cell death associated genes.", "output": {"entities": {"dna": [{"text": "bcl-2 gene", "start": 4, "end": 14}], "cell_type": [{"text": "lymphocyte", "start": 31, "end": 41}]}}, "schema": []} {"input": "Here, Stanley Korsmeyer provides a brief overview of bcl-2, concentrating on its roles in B- and T- cell development and in oncogenesis.", "output": {"entities": {"protein": [{"text": "bcl-2", "start": 53, "end": 58}]}}, "schema": []} {"input": "Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes.", "output": {"entities": {"protein": [{"text": "IgG Fc receptors", "start": 50, "end": 66}], "cell_type": [{"text": "B lymphocytes", "start": 70, "end": 83}]}}, "schema": []} {"input": "B lymphocytes and macrophages express closely related immunoglobulin G (IgG) Fc receptors (Fc gamma RII) that differ only in the structures of their cytoplasmic domains.", "output": {"entities": {"cell_type": [{"text": "B lymphocytes", "start": 0, "end": 13}], "protein": [{"text": "immunoglobulin G (", "start": 54, "end": 72}, {"text": "IgG) Fc receptors", "start": 72, "end": 89}, {"text": "Fc gamma RII", "start": 91, "end": 103}, {"text": "cytoplasmic domains", "start": 149, "end": 168}]}}, "schema": []} {"input": "Because of cell type-specific alternative messenger RNA splicing, B-cell Fc gamma RII contains an insertion of 47 amino acids that participates in determining receptor function in these cells.", "output": {"entities": {"protein": [{"text": "B-cell", "start": 66, "end": 72}, {"text": "Fc gamma RII", "start": 73, "end": 85}]}}, "schema": []} {"input": "Transfection of an Fc gamma RII -negative B-cell line with complementary DNA's encoding the two splice products and various receptor mutants indicated that the insertion was responsible for preventing both Fc gamma RII -mediated endocytosis and Fc gamma RII -mediated antigen presentation.", "output": {"entities": {"protein": [{"text": "Fc gamma RII", "start": 19, "end": 31}, {"text": "Fc gamma RII", "start": 206, "end": 218}, {"text": "Fc gamma RII", "start": 245, "end": 257}], "cell_line": [{"text": "-negative B-cell line", "start": 32, "end": 53}]}}, "schema": []} {"input": "The insertion was not required for Fc gamma RII to modulate surface immunoglobulin -triggered B-cell activation.", "output": {"entities": {"protein": [{"text": "Fc gamma RII", "start": 35, "end": 47}, {"text": "surface immunoglobulin", "start": 60, "end": 82}]}}, "schema": []} {"input": "Instead, regulation of activation involved a region of the cytoplasmic domain common to both the lymphocyte and macrophage receptor isoforms.", "output": {"entities": {"protein": [{"text": "cytoplasmic domain", "start": 59, "end": 77}]}}, "schema": []} {"input": "In contrast, the insertion did contribute to the formation of caps in response to receptor cross-linking, consistent with suggestions that the lymphocyte but not macrophage form of the receptor can associate with the detergent-insoluble cytoskeleton.", "output": {"entities": {}}, "schema": []} {"input": "[Age-related changes in glucocorticoid and mineralocorticoid receptors in lymphocytes of healthy persons and patients with hypertension]", "output": {"entities": {"cell_type": [{"text": "lymphocytes", "start": 74, "end": 85}]}}, "schema": []} {"input": "It has been found that the number of glucocorticoid receptors in lymphocytes of the peripheral blood of healthy elderly subjects increases, while the number of mineralocorticoid receptors decreases.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 37, "end": 61}], "cell_type": [{"text": "lymphocytes", "start": 65, "end": 76}]}}, "schema": []} {"input": "The mechanisms of hormone-receptor interactions in hypertension are activated: the number of glucocorticoid and mineralocorticoid binding sites grows in hypertensive patients.", "output": {"entities": {}}, "schema": []} {"input": "Still a more essential rise in the number of receptors is observed in mid-age hypertensive patients than in elderly ones.", "output": {"entities": {}}, "schema": []} {"input": "The mechanism of action of cyclosporin A and FK506.", "output": {"entities": {}}, "schema": []} {"input": "CsA and FK506 are powerful suppressors of the immune system, most notably of T cells.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 77, "end": 84}]}}, "schema": []} {"input": "They act at a point in activation that lies between receptor ligation and the transcription of early genes.", "output": {"entities": {"dna": [{"text": "early genes", "start": 95, "end": 106}]}}, "schema": []} {"input": "Here, Stuart Schreiber and Gerald Crabtree review recent findings that indicate CsA and FK506 operate as prodrugs: they bind endogenous intracellular receptors, the immunophilins, and the resulting complex targets the protein phosphatase, calcineurin, to exert the immunosuppressive effect.", "output": {"entities": {"protein": [{"text": "endogenous intracellular receptors", "start": 125, "end": 159}, {"text": "immunophilins", "start": 165, "end": 178}, {"text": "protein phosphatase,", "start": 218, "end": 238}, {"text": "calcineurin", "start": 239, "end": 250}]}}, "schema": []} {"input": "Induction of monocytic differentiation and NF-kappa B -like activities by human immunodeficiency virus 1 infection of myelomonoblastic cells.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 43, "end": 53}], "cell_type": [{"text": "myelomonoblastic cells", "start": 118, "end": 140}]}}, "schema": []} {"input": "The effects of human immunodeficiency virus 1 (HIV-1) infection on cellular differentiation and NF-kappa B DNA binding activity have been investigated in a new model of myeloid differentiation.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 96, "end": 106}]}}, "schema": []} {"input": "PLB-985 cells represent a bipotential myelomonoblastic cell population capable of either granulocytic or monocytic differentiation after induction with appropriate inducers.", "output": {"entities": {"cell_line": [{"text": "PLB-985 cells", "start": 0, "end": 13}, {"text": "bipotential myelomonoblastic cell population", "start": 26, "end": 70}]}}, "schema": []} {"input": "By virtue of the presence of CD4 on the cell surface, PLB-985 cells were chronically infected with HIV-1 strain IIIB.", "output": {"entities": {"protein": [{"text": "CD4", "start": 29, "end": 32}], "cell_line": [{"text": "PLB-985 cells", "start": 54, "end": 67}]}}, "schema": []} {"input": "PLB-IIIB cells clearly possessed a more monocytic phenotype than the parental myeloblasts, as determined by differential staining, increased expression of the myeloid-specific surface markers, and transcription of the c-fms proto-oncogene.", "output": {"entities": {"cell_line": [{"text": "PLB-IIIB cells", "start": 0, "end": 14}], "cell_type": [{"text": "parental myeloblasts", "start": 69, "end": 89}], "protein": [{"text": "myeloid-specific surface markers", "start": 159, "end": 191}], "dna": [{"text": "c-fms proto-oncogene", "start": 218, "end": 238}]}}, "schema": []} {"input": "NF-kappa B binding activity was inducible by tumor necrosis factor and phorbol myristate acetate in PLB-985.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 0, "end": 10}, {"text": "tumor necrosis factor", "start": 45, "end": 66}], "cell_line": [{"text": "PLB-985", "start": 100, "end": 107}]}}, "schema": []} {"input": "However, in PLB-IIIB cells, constitutive expression of a novel NF-kappa B complex was detected, composed of proteins ranging between 70 and 110 kD.", "output": {"entities": {"cell_line": [{"text": "PLB-IIIB cells", "start": 12, "end": 26}], "protein": [{"text": "NF-kappa B complex", "start": 63, "end": 81}, {"text": "proteins", "start": 108, "end": 116}]}}, "schema": []} {"input": "These proteins interacted specifically with the symmetric NF-kappa B site from the interferon beta (IFN-beta) promoter.", "output": {"entities": {"protein": [{"text": "proteins", "start": 6, "end": 14}], "dna": [{"text": "symmetric NF-kappa B site", "start": 48, "end": 73}, {"text": "interferon beta (IFN-beta) promoter", "start": 83, "end": 118}]}}, "schema": []} {"input": "Mutations affecting the 5' guanine residues of the kappa B site were unable to compete for these NF-kappa B -related proteins.", "output": {"entities": {"dna": [{"text": "5' guanine residues", "start": 24, "end": 43}, {"text": "kappa B site", "start": 51, "end": 63}], "protein": [{"text": "NF-kappa B -related proteins", "start": 97, "end": 125}]}}, "schema": []} {"input": "Inducibility of endogenous IFN-beta and IFN-alpha RNA was also increased in PLB-IIIB cells.", "output": {"entities": {"cell_line": [{"text": "PLB-IIIB cells", "start": 76, "end": 90}]}}, "schema": []} {"input": "These studies indicate that HIV-1 infection of myelomonoblastic cells may select for a more mature monocytic phenotype and that unique subunit associations of NF-kappa B DNA binding proteins may contribute to differential NF-kappa B -mediated gene expression.", "output": {"entities": {"cell_type": [{"text": "myelomonoblastic cells", "start": 47, "end": 69}], "protein": [{"text": "NF-kappa B DNA binding proteins", "start": 159, "end": 190}, {"text": "NF-kappa B", "start": 222, "end": 232}]}}, "schema": []} {"input": "Cortisol receptor resistance: the variability of its clinical presentation and response to treatment.", "output": {"entities": {}}, "schema": []} {"input": "Primary (partial) cortisol receptor resistance was previously reported in a total of 7 patients and 14 asymptomatic family members.", "output": {"entities": {"protein": [{"text": "cortisol receptor", "start": 18, "end": 35}]}}, "schema": []} {"input": "Its occurrence is considered to be extremely rare.", "output": {"entities": {}}, "schema": []} {"input": "In the present study we report on 6 patients (2 males and 4 females) with the syndrome.", "output": {"entities": {}}, "schema": []} {"input": "The first male patient presented with mild hypertension.", "output": {"entities": {}}, "schema": []} {"input": "Hydrochlorothiazide therapy resulted in life-threatening hypokalemia.", "output": {"entities": {}}, "schema": []} {"input": "The second male patient had slight hypertension without hypokalemia.", "output": {"entities": {}}, "schema": []} {"input": "All four female patients presented between the age of 20-30 yr with acne, hirsutism, and irregular menstruations.", "output": {"entities": {}}, "schema": []} {"input": "Low dose dexamethasone therapy (1-1.5 mg/day) was of clinical benefit in these patients.", "output": {"entities": {}}, "schema": []} {"input": "All patients showed insufficient suppression of serum cortisol concentrations in the overnight 1-mg dexamethasone test.", "output": {"entities": {}}, "schema": []} {"input": "The diurnal rhythm of ACTH and cortisol was intact, albeit at an elevated level.", "output": {"entities": {}}, "schema": []} {"input": "There was a normal increase in ACTH, cortisol, and GH (except in one obese patient) in response to insulin-induced hypoglycemia, while cortisol production was elevated in three patients.", "output": {"entities": {}}, "schema": []} {"input": "Circulating adrenal androgen levels were increased in all patients.", "output": {"entities": {}}, "schema": []} {"input": "Glucocorticoid receptors were investigated in a whole cell dexamethasone binding assay in mononuclear leukocytes.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptors", "start": 0, "end": 24}], "cell_type": [{"text": "mononuclear leukocytes", "start": 90, "end": 112}]}}, "schema": []} {"input": "In the first male patient, the number of receptors was very low, while the affinity was lower than that in controls.", "output": {"entities": {}}, "schema": []} {"input": "A lowered affinity to dexamethasone was found in one female patient, while a lowered number of receptors was found in three patients.", "output": {"entities": {}}, "schema": []} {"input": "In the second male patient, no abnormalities were found.", "output": {"entities": {}}, "schema": []} {"input": "As a bioassay for glucocorticoid action we also measured dexamethasone suppressibility of mitogen-stimulated incorporation of [3H]thymidine in mononuclear leukocytes.", "output": {"entities": {"cell_type": [{"text": "mononuclear leukocytes", "start": 143, "end": 165}]}}, "schema": []} {"input": "In the male patient with normal receptor status, dexamethasone suppressibility of [3H]thymidine incorporation was significantly lower than that in healthy controls with respect to both maximal suppression and IC50.", "output": {"entities": {}}, "schema": []} {"input": "Partial cortisol receptor resistance might be less rare than previously thought.", "output": {"entities": {}}, "schema": []} {"input": "In the six patients presented, at least three different forms can be recognized.", "output": {"entities": {}}, "schema": []} {"input": "Therapy with dexamethasone was successful in female patients with acne and hirsutism, as the secondary increase in the production of adrenal androgens was effectively controlled.", "output": {"entities": {}}, "schema": []} {"input": "The development of functionally responsive T cells.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 43, "end": 50}]}}, "schema": []} {"input": "The work reviewed in this article separates T cell development into four phases.", "output": {"entities": {}}, "schema": []} {"input": "First is an expansion phase prior to TCR rearrangement, which appears to be correlated with programming of at least some response genes for inducibility.", "output": {"entities": {"protein": [{"text": "TCR", "start": 37, "end": 40}]}}, "schema": []} {"input": "This phase can occur to some extent outside of the thymus.", "output": {"entities": {}}, "schema": []} {"input": "However, the profound T cell deficit of nude mice indicates that the thymus is by far the most potent site for inducing the expansion per se, even if other sites can induce some response acquisition.", "output": {"entities": {}}, "schema": []} {"input": "Second is a controlled phase of TCR gene rearrangement.", "output": {"entities": {"dna": [{"text": "TCR gene", "start": 32, "end": 40}]}}, "schema": []} {"input": "The details of the regulatory mechanism that selects particular loci for rearrangement are still not known.", "output": {"entities": {"dna": [{"text": "loci", "start": 64, "end": 68}]}}, "schema": []} {"input": "It seems that the rearrangement of the TCR gamma loci in the gamma delta lineage may not always take place at a developmental stage strictly equivalent to the rearrangement of TCR beta in the alpha beta lineage, and it is not clear just how early the two lineages diverge.", "output": {"entities": {"dna": [{"text": "TCR gamma loci", "start": 39, "end": 53}, {"text": "TCR beta", "start": 176, "end": 184}], "cell_type": [{"text": "gamma delta lineage", "start": 61, "end": 80}, {"text": "alpha beta lineage", "start": 192, "end": 210}]}}, "schema": []} {"input": "In the TCR alpha beta lineage, however, the final gene rearrangement events are accompanied by rapid proliferation and an interruption in cellular response gene inducibility.", "output": {"entities": {"cell_type": [{"text": "TCR alpha beta lineage,", "start": 7, "end": 30}]}}, "schema": []} {"input": "The loss of conventional responsiveness is probably caused by alterations at the level of signaling, and may be a manifestation of the physiological state that is a precondition for selection.", "output": {"entities": {}}, "schema": []} {"input": "Third is the complex process of selection.", "output": {"entities": {}}, "schema": []} {"input": "Whereas peripheral T cells can undergo forms of positive selection (by antigen-driven clonal expansion) and negative selection (by abortive stimulation leading to anergy or death), neither is exactly the same phenomenon that occurs in the thymic cortex.", "output": {"entities": {"cell_type": [{"text": "peripheral", "start": 8, "end": 18}, {"text": "T cells", "start": 19, "end": 26}]}}, "schema": []} {"input": "Negative selection in the cortex appears to be a suicidal inversion of antigen responsiveness: instead of turning on IL-2 expression, the activated cell destroys its own chromatin.", "output": {"entities": {"protein": [{"text": "IL-2", "start": 117, "end": 121}], "cell_type": [{"text": "activated cell", "start": 138, "end": 152}], "dna": [{"text": "chromatin", "start": 170, "end": 179}]}}, "schema": []} {"input": "The genes that need to be induced for this response are not yet identified, but it is unquestionably a form of activation.", "output": {"entities": {}}, "schema": []} {"input": "It is interesting that in humans and rats, cortical thymocytes undergoing negative selection can still induce IL-2R alpha expression and even be rescued in vitro, if exogenous IL-2 is provided.", "output": {"entities": {"cell_type": [{"text": "cortical thymocytes", "start": 43, "end": 62}], "protein": [{"text": "IL-2R alpha", "start": 110, "end": 121}, {"text": "exogenous IL-2", "start": 166, "end": 180}]}}, "schema": []} {"input": "Perhaps murine thymocytes are denied this form of rescue because they shut off IL-2R beta chain expression at an earlier stage or because they may be uncommonly Bcl-2 deficient (cf. Sentman et al., 1991; Strasser et al., 1991).", "output": {"entities": {"cell_type": [{"text": "murine thymocytes", "start": 8, "end": 25}], "protein": [{"text": "IL-2R beta chain", "start": 79, "end": 95}, {"text": "Bcl-2", "start": 161, "end": 166}]}}, "schema": []} {"input": "Even so, medullary thymocytes remain at least partially susceptible to negative selection even as they continue to mature.", "output": {"entities": {"cell_type": [{"text": "medullary thymocytes", "start": 9, "end": 29}]}}, "schema": []} {"input": "I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding.", "output": {"entities": {"protein": [{"text": "I kappa B/MAD-3", "start": 0, "end": 15}, {"text": "NF-kappa B p65", "start": 57, "end": 71}, {"text": "transactivation domain", "start": 89, "end": 111}, {"text": "NF-kappa B p65", "start": 123, "end": 137}]}}, "schema": []} {"input": "The active nuclear form of the NF-kappa B transcription factor complex is composed of two DNA binding subunits, NF-kappa B p65 and NF-kappa B p50, both of which share extensive N-terminal sequence homology with the v-rel oncogene product.", "output": {"entities": {"protein": [{"text": "NF-kappa B transcription factor complex", "start": 31, "end": 70}, {"text": "DNA binding subunits", "start": 90, "end": 110}, {"text": "NF-kappa B p65", "start": 112, "end": 126}, {"text": "NF-kappa B p50", "start": 131, "end": 145}, {"text": "v-rel oncogene product", "start": 215, "end": 237}]}}, "schema": []} {"input": "The NF-kappa B p65 subunit provides the transactivation activity in this complex and serves as an intracellular receptor for a cytoplasmic inhibitor of NF-kappa B, termed I kappa B.", "output": {"entities": {"protein": [{"text": "NF-kappa B p65 subunit", "start": 4, "end": 26}, {"text": "NF-kappa B", "start": 152, "end": 162}]}}, "schema": []} {"input": "In contrast, NF-kappa B p50 alone fails to stimulate kappa B-directed transcription, and based on prior in vitro studies, is not directly regulated by I kappa B.", "output": {"entities": {"protein": [{"text": "NF-kappa B p50", "start": 13, "end": 27}, {"text": "I kappa B", "start": 151, "end": 160}]}}, "schema": []} {"input": "To investigate the molecular basis for the critical regulatory interaction between NF-kappa B and I kappa B/MAD-3, a series of human NF-kappa B p65 mutants was identified that functionally segregated DNA binding, I kappa B -mediated inhibition, and I kappa B -induced nuclear exclusion of this transcription factor.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 83, "end": 93}, {"text": "I kappa B/MAD-3", "start": 98, "end": 113}, {"text": "human", "start": 127, "end": 132}, {"text": "NF-kappa B p65 mutants", "start": 133, "end": 155}, {"text": "I kappa B", "start": 213, "end": 222}, {"text": "I kappa B", "start": 249, "end": 258}, {"text": "transcription factor", "start": 294, "end": 314}]}}, "schema": []} {"input": "Results from in vivo expression studies performed with these NF-kappa B p65 mutants revealed the following: 1) I kappa B/MAD-3 completely inhibits NF-kappa B p65 -dependent transcriptional activation mediated through the human immunodeficiency virus type 1 kappa B enhancer in human T lymphocytes, 2) the binding of I kappa B/MAD-3 to NF-kappa B p65 is sufficient to retarget NF-kappa B p65 from the nucleus to the cytoplasm, 3) selective deletion of the functional nuclear localization signal present in the Rel homology domain of NF-kappa B p65 disrupts its ability to engage I kappa B/MAD-3, and 4) the unique C-terminus of NF-kappa B p65 attenuates its own nuclear localization and contains sequences that are required for I kappa B -mediated inhibition of NF-kappa B p65 DNA binding activity.", "output": {"entities": {"protein": [{"text": "NF-kappa B p65 mutants", "start": 61, "end": 83}, {"text": "I kappa B/MAD-3", "start": 111, "end": 126}, {"text": "NF-kappa B p65", "start": 147, "end": 161}, {"text": "I kappa B/MAD-3", "start": 316, "end": 331}, {"text": "NF-kappa B p65", "start": 335, "end": 349}, {"text": "NF-kappa B p65", "start": 376, "end": 390}, {"text": "Rel homology domain", "start": 509, "end": 528}, {"text": "NF-kappa B p65", "start": 532, "end": 546}, {"text": "I kappa B/MAD-3", "start": 578, "end": 593}, {"text": "C-terminus", "start": 613, "end": 623}, {"text": "NF-kappa B p65", "start": 627, "end": 641}, {"text": "I kappa B", "start": 727, "end": 736}, {"text": "NF-kappa B p65", "start": 761, "end": 775}], "dna": [{"text": "human immunodeficiency virus type 1 kappa B enhancer", "start": 221, "end": 273}], "cell_type": [{"text": "human T lymphocytes", "start": 277, "end": 296}]}}, "schema": []} {"input": "Together, these findings suggest that the nuclear localization signal and transactivation domain of NF-kappa B p65 constitute a bipartite system that is critically involved in the inhibitory function of I kappa B/MAD-3.", "output": {"entities": {"protein": [{"text": "transactivation domain", "start": 74, "end": 96}, {"text": "NF-kappa B p65", "start": 100, "end": 114}, {"text": "I kappa B/MAD-3", "start": 203, "end": 218}]}}, "schema": []} {"input": "Unexpectedly, our in vivo studies also demonstrate that I kappa B/MAD-3 binds directly to NF-kappa B p50.", "output": {"entities": {"protein": [{"text": "I kappa B/MAD-3", "start": 56, "end": 71}, {"text": "NF-kappa B p50", "start": 90, "end": 104}]}}, "schema": []} {"input": "This interaction is functional as it leads to retargeting of NF-kappa B p50 from the nucleus to the cytoplasm.", "output": {"entities": {"protein": [{"text": "NF-kappa B p50", "start": 61, "end": 75}]}}, "schema": []} {"input": "However, no loss of DNA binding activity is observed, presumably reflecting the unique C-terminal domain that is distinct from that present in NF-kappa B p65.", "output": {"entities": {"protein": [{"text": "C-terminal domain", "start": 87, "end": 104}, {"text": "NF-kappa B p65", "start": 143, "end": 157}]}}, "schema": []} {"input": "Characterization of a new tissue-specific transcription factor binding to the simian virus 40 enhancer TC-II (NF-kappa B) element.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 42, "end": 62}], "dna": [{"text": "simian virus 40 enhancer TC-II (NF-kappa B) element", "start": 78, "end": 129}]}}, "schema": []} {"input": "We have biochemically and functionally characterized a new transcription factor, NP-TCII, which is present in nuclei from unstimulated T and B lymphocytes but is not found in nonhematopoietic cells.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 59, "end": 79}, {"text": "NP-TCII", "start": 81, "end": 88}], "cell_line": [{"text": "unstimulated T and", "start": 122, "end": 140}, {"text": "B lymphocytes", "start": 141, "end": 154}], "cell_type": [{"text": "nonhematopoietic cells", "start": 175, "end": 197}]}}, "schema": []} {"input": "This factor has a DNA-binding specificity similar to that of NF-kappa B but is unrelated to this or other Rel proteins by functional and biochemical criteria.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 61, "end": 71}, {"text": "Rel proteins", "start": 106, "end": 118}]}}, "schema": []} {"input": "It can also be distinguished from other previously described lymphocyte-specific DNA-binding proteins.", "output": {"entities": {"protein": [{"text": "lymphocyte-specific DNA-binding proteins", "start": 61, "end": 101}]}}, "schema": []} {"input": "The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-kappa B -mediated inhibition.", "output": {"entities": {"protein": [{"text": "candidate oncoprotein Bcl-3", "start": 4, "end": 31}, {"text": "p50/NF-kappa B", "start": 52, "end": 66}]}}, "schema": []} {"input": "The candidate oncogene bcl-3 was discovered as a translocation into the immunoglobulin alpha-locus in some cases of B-cell chronic lymphocytic leukaemias.", "output": {"entities": {"dna": [{"text": "candidate oncogene bcl-3", "start": 4, "end": 28}, {"text": "immunoglobulin alpha-locus", "start": 72, "end": 98}]}}, "schema": []} {"input": "The protein Bcl-3 contains seven so-called ankyrin repeats.", "output": {"entities": {"protein": [{"text": "protein Bcl-3", "start": 4, "end": 17}, {"text": "ankyrin repeats", "start": 43, "end": 58}]}}, "schema": []} {"input": "Similar repeat motifs are found in a number of diverse regulatory proteins but the motifs of Bcl-3 are most closely related to those found in I kappa B proteins in which the ankyrin repeat domain is thought to be directly involved in inhibition of NF-kappa B activity.", "output": {"entities": {"protein": [{"text": "repeat motifs", "start": 8, "end": 21}, {"text": "diverse regulatory proteins", "start": 47, "end": 74}, {"text": "Bcl-3", "start": 93, "end": 98}, {"text": "I kappa B proteins", "start": 142, "end": 160}, {"text": "ankyrin repeat", "start": 174, "end": 188}, {"text": "NF-kappa B", "start": 248, "end": 258}]}}, "schema": []} {"input": "No biological function has yet been described for Bcl-3, but it was noted recently that Bcl-3 interferes with DNA-binding of the p50 subunit of NF-kappa B in vitro.", "output": {"entities": {"protein": [{"text": "Bcl-3", "start": 50, "end": 55}, {"text": "Bcl-3", "start": 88, "end": 93}, {"text": "p50 subunit", "start": 129, "end": 140}, {"text": "NF-kappa B", "start": 144, "end": 154}]}}, "schema": []} {"input": "Here we demonstrate that Bcl-3 can aid kappa B site -dependent transcription in vivo by counteracting the inhibitory effects of p50/NF-kappa B homodimers.", "output": {"entities": {"protein": [{"text": "Bcl-3", "start": 25, "end": 30}, {"text": "p50/NF-kappa B homodimers", "start": 128, "end": 153}], "dna": [{"text": "kappa B site", "start": 39, "end": 51}]}}, "schema": []} {"input": "Bcl-3 may therefore aid activation of select NF-kappa B -regulated genes, including those of the human immunodeficiency virus.", "output": {"entities": {"protein": [{"text": "Bcl-3", "start": 0, "end": 5}, {"text": "NF-kappa B", "start": 45, "end": 55}], "dna": [{"text": "-regulated genes", "start": 56, "end": 72}]}}, "schema": []} {"input": "[Mechanism of action of steroid hormones. I. Estrogens]", "output": {"entities": {}}, "schema": []} {"input": "The steroid hormone are very versatile molecules: although they are related among them by their chemical structure, they have very diverse functions and including antagonic.", "output": {"entities": {}}, "schema": []} {"input": "Their action mechanism is not completely cleared.", "output": {"entities": {}}, "schema": []} {"input": "The estrogens participate in the regulation of practically all the reproductive and sexual events of the female, although the intracellular actions by which they take place are not well known and the proposed models do not adequately satisfy the questions.", "output": {"entities": {}}, "schema": []} {"input": "Currently it is accepted the existence of a cytoplasmic and/or nuclear receptor, without explaining satisfactorily how the hormones come to the nucleus.", "output": {"entities": {}}, "schema": []} {"input": "The endocrine events that are rapidly expressed (seconds) are due to a possible interaction with cellular membrane.", "output": {"entities": {}}, "schema": []} {"input": "The purpose of this review is to analyze and concilliate the reported data on the mechanism of action of estrogens.", "output": {"entities": {}}, "schema": []} {"input": "Reduced susceptibility to HIV-1 infection of ethyl-methanesulfonate-treated CEM subclones correlates with a blockade in their protein kinase C signaling pathway.", "output": {"entities": {"cell_line": [{"text": "ethyl-methanesulfonate-treated CEM subclones", "start": 45, "end": 89}], "protein": [{"text": "protein kinase C", "start": 126, "end": 142}]}}, "schema": []} {"input": "We have described the isolation of chemically induced CEM subclones that express CD4 receptors and bind soluble gp120, yet show a markedly reduced susceptibility to infection with HIV-1.", "output": {"entities": {"cell_line": [{"text": "CEM subclones", "start": 54, "end": 67}], "protein": [{"text": "CD4 receptors", "start": 81, "end": 94}, {"text": "gp120", "start": 112, "end": 117}]}}, "schema": []} {"input": "Two subclones were found to have an abnormal response to the protein kinase C (PKC) activator PMA.", "output": {"entities": {"protein": [{"text": "protein kinase C", "start": 61, "end": 77}, {"text": "PKC", "start": 79, "end": 82}]}}, "schema": []} {"input": "PMA treatment induced CD3 and CD25 (IL-2R) receptors on the parental line and on other ethyl-methanesulfonate-derived subclones, but not on these two mutants.", "output": {"entities": {"cell_line": [{"text": "ethyl-methanesulfonate-derived subclones", "start": 87, "end": 127}]}}, "schema": []} {"input": "Direct assays of PKC activity were conducted.", "output": {"entities": {"protein": [{"text": "PKC", "start": 17, "end": 20}]}}, "schema": []} {"input": "Total cellular PKC enzymatic activity was found to be normal in these subclones.", "output": {"entities": {"protein": [{"text": "PKC", "start": 15, "end": 18}]}}, "schema": []} {"input": "PMA -induced CD4 down-modulation occurred normally.", "output": {"entities": {"protein": [{"text": "CD4", "start": 13, "end": 16}]}}, "schema": []} {"input": "In addition, activation of c-raf kinase was normal.", "output": {"entities": {"protein": [{"text": "c-raf kinase", "start": 27, "end": 39}]}}, "schema": []} {"input": "Since HIV-1 long terminal repeat contains two functional nuclear factor kB (NF-kB) regulatory elements, we studied the ability of PMA to induce NF-kB binding activity by different assays.", "output": {"entities": {"dna": [{"text": "HIV-1 long terminal repeat", "start": 6, "end": 32}, {"text": "nuclear factor kB (NF-kB) regulatory elements", "start": 57, "end": 102}], "protein": [{"text": "NF-kB", "start": 144, "end": 149}]}}, "schema": []} {"input": "Chloramphenicol acetyl transferase (CAT) assays using the HIV-1 (-139)long terminal repeat-CAT construct showed no PMA induction of CAT activity in these subclones (unlike the parental line and other subclones).", "output": {"entities": {"protein": [{"text": "Chloramphenicol acetyl transferase", "start": 0, "end": 34}, {"text": "CAT", "start": 36, "end": 39}, {"text": "CAT", "start": 132, "end": 135}], "dna": [{"text": "HIV-1 (-139)long terminal repeat-CAT construct", "start": 58, "end": 104}]}}, "schema": []} {"input": "Okadaic acid, an inhibitor of phosphatases 1 and 2A, did not overcome the defect in these subclones.", "output": {"entities": {}}, "schema": []} {"input": "Gel retardation assays, using a 32P-probe containing the HIV-1 NF-kB probe and nuclear extracts from PMA -treated cells, showed significantly reduced induction of nuclear NF-kB binding proteins in these two subclones compared with wild type CEM and a control subclone.", "output": {"entities": {"protein": [{"text": "NF-kB", "start": 63, "end": 68}, {"text": "nuclear NF-kB binding proteins", "start": 163, "end": 193}, {"text": "wild type", "start": 231, "end": 240}, {"text": "CEM", "start": 241, "end": 244}], "cell_type": [{"text": "PMA -treated cells", "start": 101, "end": 119}]}}, "schema": []} {"input": "Deoxycholate treatment of cytoplasmic extracts from these subclones released much reduced NF-kB binding proteins from their cytoplasmic pools.", "output": {"entities": {"protein": [{"text": "NF-kB binding proteins", "start": 90, "end": 112}]}}, "schema": []} {"input": "Thus, reduced levels of PKC -induced nuclear NF-kB activity in two T cell subclones did not affect their normal cell growth, but correlated with a pronounced reduction in their susceptibility to HIV-1 infection.", "output": {"entities": {"protein": [{"text": "PKC", "start": 24, "end": 27}, {"text": "NF-kB", "start": 45, "end": 50}]}}, "schema": []} {"input": "Nuclear factor of activated T cells contains Fos and Jun.", "output": {"entities": {"protein": [{"text": "Nuclear factor", "start": 0, "end": 14}, {"text": "Fos", "start": 45, "end": 48}, {"text": "Jun", "start": 53, "end": 56}], "cell_type": [{"text": "activated T cells", "start": 18, "end": 35}]}}, "schema": []} {"input": "The nuclear factor NF-AT (ref. 1) is induced in T cells stimulated through the T-cell receptor/CD3 complex, and is required for interleukin-2 (IL-2) gene induction.", "output": {"entities": {"protein": [{"text": "nuclear factor NF-AT", "start": 4, "end": 24}, {"text": "T-cell receptor/CD3 complex", "start": 79, "end": 106}, {"text": "interleukin-2", "start": 128, "end": 141}], "cell_type": [{"text": "T cells", "start": 48, "end": 55}], "dna": [{"text": "(IL-2) gene", "start": 142, "end": 153}]}}, "schema": []} {"input": "Although NF-AT has not been cloned or purified, there is evidence that it is a major target for immunosuppression by cyclosporin A (CsA) and FK506 (refs 2-7).", "output": {"entities": {"protein": [{"text": "NF-AT", "start": 9, "end": 14}]}}, "schema": []} {"input": "NF-AT induction may require two activation-dependent events: the CsA -sensitive translocation of a pre-existing component and the CsA -resistant synthesis of a nuclear component.", "output": {"entities": {"protein": [{"text": "NF-AT", "start": 0, "end": 5}, {"text": "nuclear component", "start": 160, "end": 177}]}}, "schema": []} {"input": "Here we report that the newly synthesized nuclear component of NF-AT is the transcription factor AP-1.", "output": {"entities": {"protein": [{"text": "nuclear component", "start": 42, "end": 59}, {"text": "NF-AT", "start": 63, "end": 68}, {"text": "transcription factor", "start": 76, "end": 96}, {"text": "AP-1", "start": 97, "end": 101}]}}, "schema": []} {"input": "We show that the inducible nuclear form of NF-AT contains Fos and Jun proteins.", "output": {"entities": {"protein": [{"text": "NF-AT", "start": 43, "end": 48}, {"text": "Fos", "start": 58, "end": 61}, {"text": "Jun", "start": 66, "end": 69}]}}, "schema": []} {"input": "Furthermore, we identify a pre-existing NF-AT -binding factor that is present in hypotonic extracts of unstimulated T cells.", "output": {"entities": {"protein": [{"text": "pre-existing NF-AT -binding factor", "start": 27, "end": 61}], "cell_type": [{"text": "unstimulated", "start": 103, "end": 115}, {"text": "T cells", "start": 116, "end": 123}]}}, "schema": []} {"input": "On the basis of binding, reconstitution and cotransfection experiments, we propose that activation of NF-AT occurs in at least two stages: a CsA -sensitive stage involving modification and/or translocation of the pre-existing NF-AT complex, and a CsA -insensitive stage involving the addition of newly synthesized Fos or Fos/Jun proteins to the pre-existing complex.", "output": {"entities": {"protein": [{"text": "NF-AT", "start": 102, "end": 107}, {"text": "NF-AT complex", "start": 226, "end": 239}, {"text": "Fos", "start": 314, "end": 317}, {"text": "Fos/Jun proteins", "start": 321, "end": 337}, {"text": "pre-existing complex", "start": 345, "end": 365}]}}, "schema": []} {"input": "A lymphoid cell-specific nuclear factor containing c-Rel-like proteins preferentially interacts with interleukin-6 kappa B-related motifs whose activities are repressed in lymphoid cells.", "output": {"entities": {"protein": [{"text": "lymphoid cell-specific nuclear factor", "start": 2, "end": 39}, {"text": "c-Rel-like proteins", "start": 51, "end": 70}], "dna": [{"text": "interleukin-6 kappa B-related motifs", "start": 101, "end": 137}], "cell_type": [{"text": "lymphoid cells", "start": 172, "end": 186}]}}, "schema": []} {"input": "The proto-oncoprotein c-Rel is a member of the nuclear factor kappa B transcription factor family, which includes the p50 and p65 subunits of nuclear factor kappa B.", "output": {"entities": {"protein": [{"text": "proto-oncoprotein c-Rel", "start": 4, "end": 27}, {"text": "nuclear factor kappa B transcription factor family", "start": 47, "end": 97}, {"text": "p50", "start": 118, "end": 121}, {"text": "p65 subunits", "start": 126, "end": 138}, {"text": "nuclear factor kappa B", "start": 142, "end": 164}]}}, "schema": []} {"input": "We show here that c-Rel binds to kappa B sites as homodimers as well as heterodimers with p50.", "output": {"entities": {"protein": [{"text": "c-Rel", "start": 18, "end": 23}, {"text": "homodimers", "start": 50, "end": 60}, {"text": "heterodimers", "start": 72, "end": 84}, {"text": "p50", "start": 90, "end": 93}], "dna": [{"text": "kappa B sites", "start": 33, "end": 46}]}}, "schema": []} {"input": "These homodimers and heterodimers show distinct DNA-binding specificities and affinities for various kappa B motifs.", "output": {"entities": {"protein": [{"text": "homodimers", "start": 6, "end": 16}, {"text": "heterodimers", "start": 21, "end": 33}], "dna": [{"text": "kappa B motifs", "start": 101, "end": 115}]}}, "schema": []} {"input": "In particular, the c-Rel homodimer has a high affinity for interleukin-6 (IL-6) and beta interferon kappa B sites.", "output": {"entities": {"protein": [{"text": "c-Rel homodimer", "start": 19, "end": 34}, {"text": "interleukin-6", "start": 59, "end": 72}, {"text": "IL-6", "start": 74, "end": 78}], "dna": [{"text": "beta interferon", "start": 84, "end": 99}, {"text": "kappa B sites", "start": 100, "end": 113}]}}, "schema": []} {"input": "In spite of its association with p50 in vitro, however, we found a lymphoid cell-specific nuclear factor in vivo that contains c-Rel but not p50 epitopes; this factor, termed IL-6 kappa B binding factor II, appears to contain the c-Rel homodimer and preferentially recognizes several IL-6 kappa B-related kappa B motifs.", "output": {"entities": {"protein": [{"text": "p50", "start": 33, "end": 36}, {"text": "lymphoid cell-specific nuclear factor", "start": 67, "end": 104}, {"text": "c-Rel", "start": 127, "end": 132}, {"text": "p50 epitopes", "start": 141, "end": 153}, {"text": "IL-6 kappa B binding factor II", "start": 175, "end": 205}, {"text": "c-Rel homodimer", "start": 230, "end": 245}, {"text": "IL-6", "start": 284, "end": 288}], "dna": [{"text": "kappa B-related kappa B motifs", "start": 289, "end": 319}]}}, "schema": []} {"input": "Although it has been previously shown that the IL-6 kappa B motif functions as a potent IL-1/tumor necrosis factor-responsive element in nonlymphoid cells, its activity was found to be repressed in lymphoid cells such as a Jurkat T-cell line.", "output": {"entities": {"dna": [{"text": "IL-6 kappa B motif", "start": 47, "end": 65}, {"text": "IL-1/tumor necrosis factor-responsive element", "start": 88, "end": 133}], "cell_type": [{"text": "nonlymphoid cells", "start": 137, "end": 154}, {"text": "lymphoid cells", "start": 198, "end": 212}], "cell_line": [{"text": "Jurkat T-cell line", "start": 223, "end": 241}]}}, "schema": []} {"input": "We also present evidence that IL-6 kappa B binding factor II functions as a repressor specific for IL-6 kappa B-related kappa B motifs in lymphoid cells.", "output": {"entities": {"protein": [{"text": "IL-6 kappa B binding factor II", "start": 30, "end": 60}], "dna": [{"text": "IL-6 kappa B-related", "start": 99, "end": 119}, {"text": "kappa B motifs", "start": 120, "end": 134}], "cell_type": [{"text": "lymphoid cells", "start": 138, "end": 152}]}}, "schema": []} {"input": "Cortisol resistance in acquired immunodeficiency syndrome.", "output": {"entities": {}}, "schema": []} {"input": "This study concerns 9 iv drug abusers with acquired immunodeficiency syndrome (AIDS) who developed hypercortisolism without the clinical signs or metabolic consequences of hypercortisolism.", "output": {"entities": {}}, "schema": []} {"input": "All patients were characterized by an Addisonian picture (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis ).", "output": {"entities": {}}, "schema": []} {"input": "An acquired form of peripheral resistance to glucocorticoids was suspected.", "output": {"entities": {}}, "schema": []} {"input": "We, therefore, examined glucocorticoid receptor characteristics on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which is one of the effects of glucocorticoid receptor activation.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 24, "end": 47}, {"text": "glucocorticoid receptor", "start": 224, "end": 247}], "cell_type": [{"text": "mononuclear leukocytes", "start": 67, "end": 89}]}}, "schema": []} {"input": "Glucocorticoid receptor density was increased in AIDS patients with an Addisonian picture (group 1; 16.2 +/- 9.4 fmol/million cells) compared to values in 12 AIDS patients without an Addisonian picture (group 2; 6.05 +/- 2.6 fmol/million cells; P less than 0.01) and sex- and age-matched controls (3.15 +/- 2.3 fmol/million cells; P less than 0.01).", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptor", "start": 0, "end": 23}]}}, "schema": []} {"input": "The affinity of glucocorticoid receptors (Kd) was strikingly decreased (9.36 +/- 3.44 nM in group 1; 3.2 +/- 1.5 nM in group 2; 2.0 +/- 0.8 nM in controls; P less than 0.01).", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 16, "end": 40}]}}, "schema": []} {"input": "[3H]Thymidine incorporation was decreased dose-dependently by dexamethasone in controls and patients; the effect was significantly blunted (P less than 0.05) in group 1 patients, which suggests that activation of glucocorticoid receptor is impaired as a result of the glucocorticoid receptor abnormality.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 213, "end": 236}, {"text": "glucocorticoid receptor", "start": 268, "end": 291}]}}, "schema": []} {"input": "In conclusion, AIDS patients with hypercortisolism and clinical features of peripheral resistance to glucocorticoids are characterized by abnormal glucocorticoid receptors on lymphocytes.", "output": {"entities": {"protein": [{"text": "abnormal glucocorticoid receptors", "start": 138, "end": 171}], "cell_type": [{"text": "lymphocytes", "start": 175, "end": 186}]}}, "schema": []} {"input": "Resistance to glucocorticoids implies a complex change in immune-endocrine function, which may be important in the course of immunodeficiency syndrome.", "output": {"entities": {}}, "schema": []} {"input": "A novel primer extension method to detect the number of CAG repeats in the androgen receptor gene in families with X-linked spinal and bulbar muscular atrophy.", "output": {"entities": {"dna": [{"text": "androgen receptor gene", "start": 75, "end": 97}]}}, "schema": []} {"input": "X-linked spinal and bulbar muscular atrophy (SBMA), an adult-onset form of motor neuron disease, was recently reported to be caused by amplification of the CAG repeats in the androgen receptor gene.", "output": {"entities": {"dna": [{"text": "androgen receptor gene", "start": 175, "end": 197}]}}, "schema": []} {"input": "We report here a simple and rapid strategy to detect the precise number of the CAGs.", "output": {"entities": {}}, "schema": []} {"input": "After the DNA fragment containing the CAG repeats is amplified by the polymerase chain reaction, a primer extension is carried out; the extension of the end-labelled reverse primer adjacent to 3' end of CAG repeats stops at the first T after CAG repeats with the incorporation of dideoxy ATP in the reaction mixture.", "output": {"entities": {"dna": [{"text": "DNA fragment", "start": 10, "end": 22}, {"text": "CAG repeats", "start": 38, "end": 49}, {"text": "end-labelled reverse primer", "start": 153, "end": 180}, {"text": "3' end", "start": 193, "end": 199}, {"text": "CAG repeats", "start": 203, "end": 214}, {"text": "CAG repeats", "start": 242, "end": 253}]}}, "schema": []} {"input": "The resultant primer products are analysed by denaturing polyacrylamide gel electrophoresis and autoradiography.", "output": {"entities": {"dna": [{"text": "primer products", "start": 14, "end": 29}]}}, "schema": []} {"input": "This method could be quite useful to detect not only CAG repeats in SBMA but also other polymorphic dinucleotide and trinucleotide repeats.", "output": {"entities": {"dna": [{"text": "CAG repeats", "start": 53, "end": 64}, {"text": "polymorphic dinucleotide", "start": 88, "end": 112}, {"text": "trinucleotide repeats", "start": 117, "end": 138}]}}, "schema": []} {"input": "Cellular immune and cytokine pathways resulting in tissue factor expression and relevance to septic shock.", "output": {"entities": {"protein": [{"text": "tissue factor", "start": 51, "end": 64}]}}, "schema": []} {"input": "Cells of monocyte lineage serve as effector cells in the cellular immune response.", "output": {"entities": {"cell_type": [{"text": "effector cells", "start": 35, "end": 49}]}}, "schema": []} {"input": "In addition, they respond to LPS and cytokines with activation and expression of inflammatory effector gene products similar to those elicited by the antigen driven response.", "output": {"entities": {"protein": [{"text": "inflammatory effector gene products", "start": 81, "end": 116}]}}, "schema": []} {"input": "The response to antigen proceeds at the T helper cell level through two independent forms of cellular collaboration, contact and lymphokine.", "output": {"entities": {"cell_type": [{"text": "T helper cell", "start": 40, "end": 53}], "protein": [{"text": "lymphokine", "start": 129, "end": 139}]}}, "schema": []} {"input": "We review the control of expression of the Tissue Factor (TF) gene and the function of the TF protein.", "output": {"entities": {"protein": [{"text": "Tissue Factor", "start": 43, "end": 56}, {"text": "TF", "start": 58, "end": 60}, {"text": "TF protein", "start": 91, "end": 101}], "dna": [{"text": "(", "start": 57, "end": 58}, {"text": ") gene", "start": 60, "end": 66}]}}, "schema": []} {"input": "The enhanced initiation of transcription of the TF gene appears to require engagement of a 56 bp LPS Response Element, an enhancer that is engaged by both AP-1 type heterodimeric complexes as well as NF kappa B like heterodimeric complexes.", "output": {"entities": {"dna": [{"text": "TF gene", "start": 48, "end": 55}, {"text": "LPS Response Element", "start": 97, "end": 117}], "protein": [{"text": "AP-1 type heterodimeric complexes", "start": 155, "end": 188}, {"text": "NF kappa B like heterodimeric complexes", "start": 200, "end": 239}]}}, "schema": []} {"input": "Dissociation of NF kappa B from Ig kappa B by cytokine and LPS stimulation, and possibly activated T cells, may represent a common pathway to induction of the TF and other inflammatory genes.", "output": {"entities": {"protein": [{"text": "NF kappa B", "start": 16, "end": 26}, {"text": "Ig kappa B", "start": 32, "end": 42}, {"text": "TF", "start": 159, "end": 161}], "cell_type": [{"text": "activated T cells", "start": 89, "end": 106}]}}, "schema": []} {"input": "Enhancement of expression of TF is observed upon adhesion of Mo to endothelial cells and extracellular matrix proteins, as well as upon engagement of leukocyte integrins.", "output": {"entities": {"protein": [{"text": "TF", "start": 29, "end": 31}, {"text": "leukocyte integrins", "start": 150, "end": 169}], "cell_type": [{"text": "endothelial cells", "start": 67, "end": 84}]}}, "schema": []} {"input": "The biological effects that follow from expression of TF by vascular cells have been resolved by analysis of function aided by the use of recombinant full length TF and truncated surface domain of TF.", "output": {"entities": {"protein": [{"text": "TF", "start": 54, "end": 56}, {"text": "recombinant full length TF", "start": 138, "end": 164}, {"text": "truncated surface domain", "start": 169, "end": 193}, {"text": "TF", "start": 197, "end": 199}]}}, "schema": []} {"input": "The rules of assembly of the cognate ligands of TF, namely the zymogen plasma factors VII and the serine protease factor VIIa, with the soluble surface domain of TF in free solution, in the presence of phospholipid surfaces and cell surface and of the anchored TF molecule have been described.", "output": {"entities": {"protein": [{"text": "TF", "start": 48, "end": 50}, {"text": "zymogen plasma factors VII", "start": 63, "end": 89}, {"text": "serine protease factor VIIa", "start": 98, "end": 125}, {"text": "soluble surface domain", "start": 136, "end": 158}, {"text": "TF", "start": 162, "end": 164}, {"text": "anchored TF molecule", "start": 252, "end": 272}]}}, "schema": []} {"input": "It is evident that assembly of the surface domain of TF with VIIa to form the binary TF.VIIa complex induces a significant increase in the Kcat of the catalytic domain of VIIa for small peptidyl substrates and more profoundly for protein substrate.", "output": {"entities": {"protein": [{"text": "surface domain", "start": 35, "end": 49}, {"text": "TF", "start": 53, "end": 55}, {"text": "VIIa", "start": 61, "end": 65}, {"text": "TF.VIIa complex", "start": 85, "end": 100}, {"text": "catalytic domain", "start": 151, "end": 167}, {"text": "VIIa", "start": 171, "end": 175}, {"text": "protein substrate", "start": 230, "end": 247}]}}, "schema": []} {"input": "This provides substantial evidence for an allosteric effect on the catalytic cleft of VIIa that is imparted by binding to TF, its cognate catalytic cofactor.", "output": {"entities": {"protein": [{"text": "VIIa", "start": 86, "end": 90}, {"text": "TF", "start": 122, "end": 124}, {"text": "cofactor", "start": 148, "end": 156}]}}, "schema": []} {"input": "It is also evident that the TF.VIIa complex is proteolytically active and can activate the zymogen plasma factor X to the serine protease Xa in free solution, inferring that extended substrate recognition by induced structural loci of the TF.VIIa complex are created from either or both proteins to constitute a new recognition structure.", "output": {"entities": {"protein": [{"text": "TF.VIIa complex", "start": 28, "end": 43}, {"text": "zymogen plasma factor X", "start": 91, "end": 114}, {"text": "serine protease Xa", "start": 122, "end": 140}, {"text": "TF.VIIa complex", "start": 239, "end": 254}, {"text": "new recognition structure", "start": 312, "end": 337}]}}, "schema": []} {"input": "It is also evident that association of X with charged phospholipid surfaces enhances the proteolytic activation of this zymogen by increasing recognition and susceptibility of the sessile peptide bond deduced from the markedly decreased Km and increased Kcat.", "output": {"entities": {"protein": [{"text": "X", "start": 39, "end": 40}, {"text": "zymogen", "start": 120, "end": 127}]}}, "schema": []} {"input": "Phorbol ester reduces constitutive nuclear NF kappa B and inhibits HIV-1 production in mature human monocytic cells.", "output": {"entities": {"protein": [{"text": "constitutive nuclear", "start": 22, "end": 42}, {"text": "NF kappa B", "start": 43, "end": 53}], "cell_type": [{"text": "mature human", "start": 87, "end": 99}, {"text": "monocytic cells", "start": 100, "end": 115}]}}, "schema": []} {"input": "NF kappa B is a potent mediator of specific gene expression in human monocytes and has been shown to play a role in transcription of the HIV-1 genome in promonocytic leukemias.", "output": {"entities": {"protein": [{"text": "NF kappa B", "start": 0, "end": 10}]}}, "schema": []} {"input": "There is little information available on the response of NF kappa B to cytokines in normal human monocytes.", "output": {"entities": {"protein": [{"text": "NF kappa B", "start": 57, "end": 67}, {"text": "cytokines", "start": 71, "end": 80}], "cell_type": [{"text": "normal human monocytes", "start": 84, "end": 106}]}}, "schema": []} {"input": "We have used a 32P-labeled oligonucleotide derived from human immunodeficiency virus (HIV-1) long terminal repeat, which contains a tandem repeat of the NF kappa B binding sequence, as a probe in a gel retardation assay to study this transcription factor.", "output": {"entities": {"dna": [{"text": "human immunodeficiency virus (HIV-1) long terminal repeat", "start": 56, "end": 113}, {"text": "tandem repeat", "start": 132, "end": 145}, {"text": "NF kappa B binding sequence", "start": 153, "end": 180}], "protein": [{"text": "transcription factor", "start": 234, "end": 254}]}}, "schema": []} {"input": "Using this assay, we have detected NF kappa B in extracts of nuclei from normal human monocytes.", "output": {"entities": {"protein": [{"text": "NF kappa B", "start": 35, "end": 45}], "cell_type": [{"text": "normal human monocytes", "start": 73, "end": 95}]}}, "schema": []} {"input": "Treatment of normal monocytes with 12-0-tetradecanoyl phorbol-13-acetate (TPA) for 4-24 h caused the complete disappearance of NF kappa B from nuclear extracts of monocytes.", "output": {"entities": {"cell_type": [{"text": "normal monocytes", "start": 13, "end": 29}], "protein": [{"text": "NF kappa B", "start": 127, "end": 137}]}}, "schema": []} {"input": "A similar result was obtained with the mature monocytic leukemia cell line THP-1.", "output": {"entities": {"cell_line": [{"text": "mature monocytic leukemia cell line", "start": 39, "end": 74}, {"text": "THP-1", "start": 75, "end": 80}]}}, "schema": []} {"input": "The constitutive transcription factor SP1 was unaffected by addition of TPA.", "output": {"entities": {"protein": [{"text": "constitutive transcription factor", "start": 4, "end": 37}, {"text": "SP1", "start": 38, "end": 41}]}}, "schema": []} {"input": "The disappearance of NF kappa B from the nucleus was concentration dependent between 10 and 50 ng/ml of phorbol ester.", "output": {"entities": {"protein": [{"text": "NF kappa B", "start": 21, "end": 31}]}}, "schema": []} {"input": "In THP-1 cells, TPA also induced a new, faster-migrating NF kappa B species not induced in monocytes.", "output": {"entities": {"protein": [{"text": "faster-migrating NF kappa B species", "start": 40, "end": 75}], "cell_type": [{"text": "monocytes", "start": 91, "end": 100}]}}, "schema": []} {"input": "Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NF kappa B.", "output": {"entities": {"protein": [{"text": "nuclear", "start": 161, "end": 168}, {"text": "NF kappa B", "start": 169, "end": 179}]}}, "schema": []} {"input": "Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 25, "end": 34}], "protein": [{"text": "reverse transcriptase", "start": 101, "end": 122}]}}, "schema": []} {"input": "These results are in striking contrast to the increase in nuclear NF kappa B and HIV-1 replication induced by phorbol esters in promonocytic leukemia cells U937 and HL-60, and emphasize the importance of studying cytokine regulation of HIV-1 in normal monocytes.", "output": {"entities": {"protein": [{"text": "NF kappa B", "start": 66, "end": 76}, {"text": "cytokine", "start": 213, "end": 221}], "cell_line": [{"text": "promonocytic leukemia cells U937", "start": 128, "end": 160}, {"text": "HL-60", "start": 165, "end": 170}], "cell_type": [{"text": "normal monocytes", "start": 245, "end": 261}]}}, "schema": []} {"input": "A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 69, "end": 92}, {"text": "endothelial-leukocyte adhesion molecule 1", "start": 161, "end": 202}, {"text": "intercellular adhesion molecule 1", "start": 207, "end": 240}], "cell_type": [{"text": "endothelial cells", "start": 125, "end": 142}]}}, "schema": []} {"input": "Corticosteroids are the preeminent antiinflammatory agents although the molecular mechanisms that impart their efficacy have not been defined.", "output": {"entities": {}}, "schema": []} {"input": "The endothelium plays a critical role in inflammation by directing circulating leukocytes into extravascular tissues by expressing adhesive molecules for leukocytes [e.g., endothelial-leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion molecule 1 (ICAM-1 )].", "output": {"entities": {"cell_type": [{"text": "circulating leukocytes", "start": 67, "end": 89}, {"text": "leukocytes", "start": 154, "end": 164}], "protein": [{"text": "adhesive molecules", "start": 131, "end": 149}, {"text": "endothelial-leukocyte adhesion molecule 1", "start": 172, "end": 213}, {"text": "ELAM-1", "start": 215, "end": 221}, {"text": "intercellular adhesion molecule 1", "start": 227, "end": 260}, {"text": "ICAM-1", "start": 262, "end": 268}]}}, "schema": []} {"input": "We therefore determined whether corticosteroids suppress inflammation by inhibiting endothelial expression of adhesion molecules for neutrophils (polymorphonuclear leukocytes ).", "output": {"entities": {"protein": [{"text": "adhesion molecules", "start": 110, "end": 128}], "cell_type": [{"text": "neutrophils", "start": 133, "end": 144}, {"text": "polymorphonuclear", "start": 146, "end": 163}, {"text": "leukocytes", "start": 164, "end": 174}]}}, "schema": []} {"input": "Preincubation of endothelial cells with endotoxin [lipopolysaccharide (LPS ), 1 microgram/ml] led to a 4-fold increase in subsequent adherence of polymorphonuclear leukocytes (P < 0.0001, n = 10) to endothelial cells, an increase that was markedly attenuated when endothelial cells were treated with dexamethasone (IC50 < 1 nM, P < 0.0001, n = 6 or 7) during preincubation with LPS.", "output": {"entities": {"cell_type": [{"text": "endothelial cells", "start": 17, "end": 34}, {"text": "polymorphonuclear leukocytes", "start": 146, "end": 174}, {"text": "endothelial cells", "start": 199, "end": 216}, {"text": "endothelial cells", "start": 264, "end": 281}]}}, "schema": []} {"input": "Moreover, the steroid receptor agonist cortisol (10 microM), but not its inactive metabolite tetrahydrocortisol (10 microM), diminished LPS -induced endothelial cell adhesiveness.", "output": {"entities": {"protein": [{"text": "steroid receptor", "start": 14, "end": 30}]}}, "schema": []} {"input": "Further evidence that the action of dexamethasone was mediated through ligation of corticosteroid receptors [human glucocorticoid receptors (hGRs )] was provided by experiments utilizing the steroid antagonist RU-486.", "output": {"entities": {"protein": [{"text": "corticosteroid receptors", "start": 83, "end": 107}, {"text": "human glucocorticoid receptors", "start": 109, "end": 139}, {"text": "hGRs", "start": 141, "end": 145}]}}, "schema": []} {"input": "RU-486 (10 microM), which prevents translocation of ligated hGR to the nucleus by inhibiting dissociation of hGR from heat shock protein 90, completely aborted the effect of dexamethasone on adhesiveness of endothelial cells (P < 0.0005, n = 3).", "output": {"entities": {"protein": [{"text": "hGR", "start": 60, "end": 63}, {"text": "hGR", "start": 109, "end": 112}], "cell_type": [{"text": "endothelial cells", "start": 207, "end": 224}]}}, "schema": []} {"input": "Treatment of endothelial cells with LPS (1 microgram/ml) stimulated transcription of ELAM-1, as shown by Northern blot analysis, and expression of membrane-associated ELAM-1 and ICAM-1, as shown by quantitative immunofluorescence (both P < 0.001, n = 9).", "output": {"entities": {"cell_type": [{"text": "endothelial cells", "start": 13, "end": 30}], "protein": [{"text": "ELAM-1", "start": 85, "end": 91}, {"text": "membrane-associated", "start": 147, "end": 166}, {"text": "ELAM-1", "start": 167, "end": 173}, {"text": "ICAM-1", "start": 178, "end": 184}]}}, "schema": []} {"input": "Dexamethasone markedly inhibited LPS -stimulated accumulation of mRNA for ELAM-1 and expression of ELAM-1 and ICAM-1 (IC50 < 10 nM, both P < 0.001, n = 4-9); inhibition of expression by dexamethasone was reversed by RU-486 (both P < 0.005, n = 4-6).", "output": {"entities": {"protein": [{"text": "ELAM-1", "start": 74, "end": 80}, {"text": "ELAM-1", "start": 99, "end": 105}, {"text": "ICAM-1", "start": 110, "end": 116}]}}, "schema": []} {"input": "As in the adhesion studies, cortisol but not tetrahydrocortisol inhibited expression of ELAM-1 and ICAM-1 (both P < 0.005, n = 3 or 4).", "output": {"entities": {"protein": [{"text": "ELAM-1", "start": 88, "end": 94}, {"text": "ICAM-1", "start": 99, "end": 105}]}}, "schema": []} {"input": "In contrast, sodium salicylate (1 mM) inhibited neither adhesion nor expression of these adhesion molecules.", "output": {"entities": {"protein": [{"text": "adhesion molecules", "start": 89, "end": 107}]}}, "schema": []} {"input": "These studies suggest that antagonism by dexamethasone of endotoxin -induced inflammation is a specific instance of the general biological principle that the glucocorticoid receptor is a hormone-dependent regulator of transcription.", "output": {"entities": {"protein": [{"text": "endotoxin", "start": 58, "end": 67}, {"text": "glucocorticoid receptor", "start": 158, "end": 181}]}}, "schema": []} {"input": "Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis.", "output": {"entities": {"dna": [{"text": "Pax-5", "start": 0, "end": 5}], "protein": [{"text": "transcription factor", "start": 18, "end": 38}, {"text": "BSAP", "start": 39, "end": 43}], "cell_type": [{"text": "B lymphocytes", "start": 64, "end": 77}]}}, "schema": []} {"input": "BSAP has been identified previously as a transcription factor that is expressed at early, but not late, stages of B-cell differentiation.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 0, "end": 4}, {"text": "transcription factor", "start": 41, "end": 61}]}}, "schema": []} {"input": "Biochemical purification and cDNA cloning has now revealed that BSAP belongs to the family of paired domain proteins.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 64, "end": 68}, {"text": "paired domain proteins", "start": 94, "end": 116}]}}, "schema": []} {"input": "BSAP is encoded by the Pax-5 gene and has been highly conserved between human and mouse.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 0, "end": 4}], "dna": [{"text": "Pax-5 gene", "start": 23, "end": 33}]}}, "schema": []} {"input": "An intact paired domain was shown to be both necessary and sufficient for DNA binding of BSAP.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 89, "end": 93}]}}, "schema": []} {"input": "Binding studies with several BSAP recognition sequences demonstrated that the sequence specificity of BSAP differs from that of the distantly related paired domain protein Pax-1.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 29, "end": 33}, {"text": "BSAP", "start": 102, "end": 106}, {"text": "paired domain protein Pax-1", "start": 150, "end": 177}], "dna": [{"text": "recognition sequences", "start": 34, "end": 55}]}}, "schema": []} {"input": "During embryogenesis, the BSAP gene is transiently expressed in the mesencephalon and spinal cord with a spatial and temporal expression pattern that is distinct from that of other Pax genes in the developing central nervous system (CNS ).", "output": {"entities": {"dna": [{"text": "BSAP gene", "start": 26, "end": 35}, {"text": "Pax genes", "start": 181, "end": 190}]}}, "schema": []} {"input": "Later, the expression of the BSAP gene shifts to the fetal liver where it correlates with the onset of B lymphopoiesis.", "output": {"entities": {"dna": [{"text": "BSAP gene", "start": 29, "end": 38}]}}, "schema": []} {"input": "BSAP expression persists in B lymphocytes and is also seen in the testis of the adult mouse.", "output": {"entities": {"protein": [{"text": "BSAP", "start": 0, "end": 4}], "cell_type": [{"text": "B lymphocytes", "start": 28, "end": 41}]}}, "schema": []} {"input": "All of this evidence indicates that the transcription factor BSAP may not only play an important role in B-cell differentiation but also in neural development and spermatogenesis.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 40, "end": 60}, {"text": "BSAP", "start": 61, "end": 65}]}}, "schema": []} {"input": "Cell cycle-dependent initiation and lineage-dependent abrogation of GATA-1 expression in pure differentiating hematopoietic progenitors.", "output": {"entities": {"protein": [{"text": "GATA-1", "start": 68, "end": 74}], "cell_type": [{"text": "pure differentiating hematopoietic progenitors", "start": 89, "end": 135}]}}, "schema": []} {"input": "The programmed activation/repression of transcription factors in early hematopoietic differentiation has not yet been explored.", "output": {"entities": {"protein": [{"text": "transcription factors", "start": 40, "end": 61}]}}, "schema": []} {"input": "The DNA-binding protein GATA-1 is required for normal erythroid development and regulates erythroid-expressed genes in maturing erythroblasts.", "output": {"entities": {"protein": [{"text": "DNA-binding protein", "start": 4, "end": 23}, {"text": "GATA-1", "start": 24, "end": 30}], "dna": [{"text": "erythroid-expressed genes", "start": 90, "end": 115}], "cell_type": [{"text": "maturing erythroblasts", "start": 119, "end": 141}]}}, "schema": []} {"input": "We analyzed GATA-1 expression in early human adult hematopoiesis by using an in vitro system in which \"pure\" early hematopoietic progenitors are induced to gradual and synchronized differentiation selectively along the erythroid or granulocyte-macrophage pathway by differential treatment with hematopoietic growth factors.", "output": {"entities": {"protein": [{"text": "GATA-1", "start": 12, "end": 18}], "cell_type": [{"text": "early hematopoietic progenitors", "start": 109, "end": 140}]}}, "schema": []} {"input": "The GATA-1 gene, though virtually silent in quiescent progenitors, is activated after entrance into the cell cycle upon stimulation with hematopoietic growth factors.", "output": {"entities": {"dna": [{"text": "GATA-1 gene", "start": 4, "end": 15}], "cell_type": [{"text": "quiescent progenitors", "start": 44, "end": 65}]}}, "schema": []} {"input": "Subsequently, increasing expression along the erythroid pathway contrasts with an abrupt downregulation in the granulocyte-macrophage lineage.", "output": {"entities": {"cell_type": [{"text": "granulocyte-macrophage lineage", "start": 111, "end": 141}]}}, "schema": []} {"input": "These results suggest a microenvironment-directed, two-step model for GATA-1 expression in differentiating hematopoietic progenitors that involves (i) cycle-dependent initiation and (ii) lineage-dependent maintenance or suppression.", "output": {"entities": {"protein": [{"text": "GATA-1", "start": 70, "end": 76}], "cell_type": [{"text": "differentiating hematopoietic progenitors", "start": 91, "end": 132}]}}, "schema": []} {"input": "Hypothetically, on/off switches of lineage-restricted transactivators may underlie the binary fate decisions of hematopoietic progenitors.", "output": {"entities": {"protein": [{"text": "lineage-restricted transactivators", "start": 35, "end": 69}], "cell_type": [{"text": "hematopoietic progenitors", "start": 112, "end": 137}]}}, "schema": []} {"input": "Specific NF-kappa B subunits act in concert with Tat to stimulate human immunodeficiency virus type 1 transcription.", "output": {"entities": {"protein": [{"text": "NF-kappa B subunits", "start": 9, "end": 28}, {"text": "Tat", "start": 49, "end": 52}]}}, "schema": []} {"input": "NF-kappa B is a protein complex which functions in concert with the tat-I gene product to stimulate human immunodeficiency virus (HIV) transcription.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 0, "end": 10}, {"text": "protein complex", "start": 16, "end": 31}, {"text": "tat-I gene product", "start": 68, "end": 86}]}}, "schema": []} {"input": "To determine whether specific members of the NF-kappa B family contribute to this effect, we have examined the abilities of different NF-kappa B subunits to act with Tat-I to stimulate transcription of HIV in Jurkat T-leukemia cells.", "output": {"entities": {"protein": [{"text": "NF-kappa B family", "start": 45, "end": 62}, {"text": "NF-kappa B subunits", "start": 134, "end": 153}, {"text": "Tat-I", "start": 166, "end": 171}], "cell_type": [{"text": "Jurkat T-leukemia cells", "start": 209, "end": 232}]}}, "schema": []} {"input": "We have found that the p49(100) DNA binding subunit, together with p65, can act in concert with Tat-I to stimulate the expression of HIV -CAT plasmid.", "output": {"entities": {"protein": [{"text": "p49(100) DNA binding subunit", "start": 23, "end": 51}, {"text": "p65", "start": 67, "end": 70}, {"text": "Tat-I", "start": 96, "end": 101}], "dna": [{"text": "HIV -CAT plasmid", "start": 133, "end": 149}]}}, "schema": []} {"input": "Little effect was observed with 50-kDa forms of p105 NF-kappa B or rel, in combination with p65 or full-length c-rel, which do not stimulate the HIV enhancer in these cells.", "output": {"entities": {"protein": [{"text": "50-kDa forms", "start": 32, "end": 44}, {"text": "p105", "start": 48, "end": 52}, {"text": "NF-kappa B", "start": 53, "end": 63}, {"text": "rel", "start": 67, "end": 70}, {"text": "p65", "start": 92, "end": 95}, {"text": "full-length c-rel", "start": 99, "end": 116}], "dna": [{"text": "HIV enhancer", "start": 145, "end": 157}]}}, "schema": []} {"input": "These findings suggest that the combination of p49(100) and p65 NF-kappa B can act in concert with the tat-I gene product to stimulate the synthesis of HIV RNA.", "output": {"entities": {"protein": [{"text": "p49(100)", "start": 47, "end": 55}, {"text": "p65", "start": 60, "end": 63}, {"text": "NF-kappa B", "start": 64, "end": 74}, {"text": "tat-I gene product", "start": 103, "end": 121}], "rna": [{"text": "HIV RNA", "start": 152, "end": 159}]}}, "schema": []} {"input": "Stable expression of HB24, a diverged human homeobox gene, in T lymphocytes induces genes involved in T cell activation and growth.", "output": {"entities": {"dna": [{"text": "HB24", "start": 21, "end": 25}, {"text": "diverged human homeobox gene", "start": 29, "end": 57}]}}, "schema": []} {"input": "A diverged homeobox gene, HB24, which is known to be induced following lymphocyte activation, was introduced into Jurkat T cells under the control of a constitutive promoter.", "output": {"entities": {"dna": [{"text": "diverged homeobox gene", "start": 2, "end": 24}, {"text": "HB24", "start": 26, "end": 30}, {"text": "constitutive promoter", "start": 152, "end": 173}], "cell_line": [{"text": "Jurkat T cells", "start": 114, "end": 128}]}}, "schema": []} {"input": "Stable transfectants of HB24 were established that expressed high levels of HB24 mRNA and possessed an altered phenotype suggestive of activated T cells.", "output": {"entities": {"dna": [{"text": "HB24", "start": 24, "end": 28}], "rna": [{"text": "HB24 mRNA", "start": 76, "end": 85}], "cell_type": [{"text": "activated T cells", "start": 135, "end": 152}]}}, "schema": []} {"input": "A number of genes known to be induced following T cell activation and associated with cell growth were increased in the transfectants, including c-fos, c-myc, c-myb, HLA-DR, lck, NF-kappa B, interleukin-2 and interleukin-2 receptor alpha (IL-2R alpha ).", "output": {"entities": {"cell_line": [{"text": "transfectants", "start": 120, "end": 133}], "dna": [{"text": "c-fos", "start": 145, "end": 150}, {"text": "c-myc", "start": 152, "end": 157}, {"text": "c-myb", "start": 159, "end": 164}, {"text": "HLA-DR", "start": 166, "end": 172}, {"text": "lck", "start": 174, "end": 177}, {"text": "interleukin-2", "start": 191, "end": 204}, {"text": "interleukin-2 receptor alpha", "start": 209, "end": 237}, {"text": "IL-2R alpha", "start": 239, "end": 250}], "protein": [{"text": "NF-kappa B", "start": 179, "end": 189}]}}, "schema": []} {"input": "Analysis of IL-2R alpha expression by transient transfection of IL-2R alpha promoter constructs into the HB24 transfectants revealed constitutive expression (about 60% of phytohemagglutinin- and phorbol ester- activated Jurkat cells) that was dependent on the kappa B site in the IL-2R alpha promoter.", "output": {"entities": {"protein": [{"text": "IL-2R alpha", "start": 12, "end": 23}], "dna": [{"text": "IL-2R alpha promoter constructs", "start": 64, "end": 95}, {"text": "kappa B site", "start": 260, "end": 272}, {"text": "IL-2R alpha promoter", "start": 280, "end": 300}], "cell_line": [{"text": "HB24 transfectants", "start": 105, "end": 123}]}}, "schema": []} {"input": "Furthermore, as a consequence of the increased HB24 mRNA levels, the Jurkat HB24 transfectants proliferated more rapidly than control cell lines.", "output": {"entities": {"rna": [{"text": "HB24 mRNA", "start": 47, "end": 56}], "cell_line": [{"text": "Jurkat HB24 transfectants", "start": 69, "end": 94}, {"text": "control cell lines", "start": 126, "end": 144}]}}, "schema": []} {"input": "Thus, stable expression of HB24 confers an activation phenotype on a human T cell line, implicating this gene as an important transcriptional factor during T cell activation and growth.", "output": {"entities": {"dna": [{"text": "HB24", "start": 27, "end": 31}], "cell_line": [{"text": "human T cell line", "start": 69, "end": 86}], "protein": [{"text": "transcriptional factor", "start": 126, "end": 148}]}}, "schema": []} {"input": "Functional interaction between the two zinc finger domains of the v-erb A oncoprotein.", "output": {"entities": {"protein": [{"text": "zinc finger domains", "start": 39, "end": 58}, {"text": "v-erb A oncoprotein", "start": 66, "end": 85}]}}, "schema": []} {"input": "The v-erb A oncogene of avian erythroblastosis virus is a mutated and virally transduced copy of a host cell gene encoding a thyroid hormone receptor.", "output": {"entities": {"dna": [{"text": "v-erb A oncogene", "start": 4, "end": 20}, {"text": "host cell gene", "start": 99, "end": 113}], "protein": [{"text": "thyroid hormone receptor", "start": 125, "end": 149}]}}, "schema": []} {"input": "The protein expressed by the v-erb A oncogene binds to DNA and acts as a dominant negative inhibitor of both the thyroid hormone receptor and the closely related retinoic acid receptor.", "output": {"entities": {"dna": [{"text": "v-erb A oncogene", "start": 29, "end": 45}, {"text": "DNA", "start": 55, "end": 58}], "protein": [{"text": "thyroid hormone receptor", "start": 113, "end": 137}, {"text": "retinoic acid receptor", "start": 162, "end": 184}]}}, "schema": []} {"input": "The v-erb A protein has sustained two amino acid alterations within its DNA-binding domain relative to that of c-erb A, one of which, at serine 61, is known to be important for v-erb A function in the neoplastic cell.", "output": {"entities": {"protein": [{"text": "v-erb A protein", "start": 4, "end": 19}, {"text": "DNA-binding domain", "start": 72, "end": 90}, {"text": "c-erb A", "start": 111, "end": 118}, {"text": "v-erb A", "start": 177, "end": 184}], "cell_type": [{"text": "neoplastic cell", "start": 201, "end": 216}]}}, "schema": []} {"input": "We report here that the second alteration, at threonine 78, also plays an important, although more indirect, role: alteration of the sequence at threonine 78 such that it resembles that of c-erb A can act as an intragenic suppressor and can partially restore function to a v-erb A protein rendered defective due to a mutation at position 61.", "output": {"entities": {"protein": [{"text": "c-erb A", "start": 189, "end": 196}, {"text": "v-erb A protein", "start": 273, "end": 288}, {"text": "position 61", "start": 329, "end": 340}]}}, "schema": []} {"input": "Threonine 78 lies within the D-box of the v-erb A protein, a region thought to mediate receptor-receptor dimerizations, and is not in physical proximity to the serine at position 61.", "output": {"entities": {"protein": [{"text": "D-box", "start": 29, "end": 34}, {"text": "v-erb A protein", "start": 42, "end": 57}, {"text": "position 61", "start": 170, "end": 181}]}}, "schema": []} {"input": "It therefore appears that an indirect interaction occurs between these two sites and that this interaction is crucial for v-erb A function.", "output": {"entities": {"protein": [{"text": "v-erb A", "start": 122, "end": 129}]}}, "schema": []} {"input": "cis-acting sequences required for inducible interleukin-2 enhancer function bind a novel Ets-related protein, Elf-1.", "output": {"entities": {"dna": [{"text": "cis-acting sequences", "start": 0, "end": 20}, {"text": "interleukin-2 enhancer", "start": 44, "end": 66}], "protein": [{"text": "Ets-related protein", "start": 89, "end": 108}, {"text": "Elf-1", "start": 110, "end": 115}]}}, "schema": []} {"input": "The recent definition of a consensus DNA binding sequence for the Ets family of transcription factors has allowed the identification of potential Ets binding sites in the promoters and enhancers of many inducible T-cell genes.", "output": {"entities": {"dna": [{"text": "DNA binding sequence", "start": 37, "end": 57}, {"text": "Ets binding sites", "start": 146, "end": 163}, {"text": "promoters", "start": 171, "end": 180}, {"text": "enhancers", "start": 185, "end": 194}, {"text": "inducible T-cell genes", "start": 203, "end": 225}], "protein": [{"text": "Ets family", "start": 66, "end": 76}, {"text": "transcription factors", "start": 80, "end": 101}]}}, "schema": []} {"input": "In the studies described in this report, we have identified two potential Ets binding sites, EBS1 and EBS2, which are conserved in both the human and murine interleukin-2 enhancers.", "output": {"entities": {"dna": [{"text": "Ets binding sites", "start": 74, "end": 91}, {"text": "EBS1", "start": 93, "end": 97}, {"text": "EBS2", "start": 102, "end": 106}]}}, "schema": []} {"input": "Within the human enhancer, these two sites are located within the previously defined DNase I footprints, NFAT-1 and NFIL-2B, respectively.", "output": {"entities": {"dna": [{"text": "human enhancer", "start": 11, "end": 25}, {"text": "NFAT-1", "start": 105, "end": 111}, {"text": "NFIL-2B", "start": 116, "end": 123}], "protein": [{"text": "DNase I", "start": 85, "end": 92}]}}, "schema": []} {"input": "Electrophoretic mobility shift and methylation interference analyses demonstrated that EBS1 and EBS2 are essential for the formation of the NFAT-1 and NFIL-2B nuclear protein complexes.", "output": {"entities": {"dna": [{"text": "EBS1", "start": 87, "end": 91}, {"text": "EBS2", "start": 96, "end": 100}], "protein": [{"text": "NFAT-1 and NFIL-2B nuclear protein complexes", "start": 140, "end": 184}]}}, "schema": []} {"input": "Furthermore, in vitro mutagenesis experiments demonstrated that inducible interleukin-2 enhancer function requires the presence of either EBS1 or EBS2.", "output": {"entities": {"dna": [{"text": "interleukin-2 enhancer", "start": 74, "end": 96}, {"text": "EBS1", "start": 138, "end": 142}, {"text": "EBS2", "start": 146, "end": 150}]}}, "schema": []} {"input": "Two well-characterized Ets family members, Ets-1 and Ets-2, are reciprocally expressed during T-cell activation.", "output": {"entities": {"protein": [{"text": "Ets family members", "start": 23, "end": 41}, {"text": "Ets-1", "start": 43, "end": 48}, {"text": "Ets-2", "start": 53, "end": 58}]}}, "schema": []} {"input": "Surprisingly, however, neither of these proteins bound in vitro to EBS1 or EBS2.", "output": {"entities": {"dna": [{"text": "EBS1", "start": 67, "end": 71}, {"text": "EBS2", "start": 75, "end": 79}]}}, "schema": []} {"input": "We therefore screened a T-cell cDNA library under low-stringency conditions with a probe from the DNA binding domain of Ets-1 and isolated a novel Ets family member, Elf-1.", "output": {"entities": {"dna": [{"text": "T-cell cDNA", "start": 24, "end": 35}], "protein": [{"text": "DNA binding domain", "start": 98, "end": 116}, {"text": "Ets-1", "start": 120, "end": 125}, {"text": "novel", "start": 141, "end": 146}, {"text": "Ets family member", "start": 147, "end": 164}, {"text": "Elf-1", "start": 166, "end": 171}]}}, "schema": []} {"input": "Elf-1 contains a DNA binding domain that is nearly identical to that of E74, the ecdysone-inducible Drosophila transcription factor required for metamorphosis (hence the name Elf-1, for E74-like factor 1 ).", "output": {"entities": {"protein": [{"text": "Elf-1", "start": 0, "end": 5}, {"text": "DNA binding domain", "start": 17, "end": 35}, {"text": "E74", "start": 72, "end": 75}, {"text": "ecdysone-inducible Drosophila transcription factor", "start": 81, "end": 131}, {"text": "Elf-1", "start": 175, "end": 180}, {"text": "E74-like factor 1", "start": 186, "end": 203}]}}, "schema": []} {"input": "Elf-1 bound specifically to both EBS1 and EBS2 in electrophoretic mobility shift assays.", "output": {"entities": {"protein": [{"text": "Elf-1", "start": 0, "end": 5}], "dna": [{"text": "EBS1", "start": 33, "end": 37}, {"text": "EBS2", "start": 42, "end": 46}]}}, "schema": []} {"input": "It also bound to the purine-rich CD3R element from the human immunodeficiency virus type 2 long terminal repeat, which is required for inducible virus expression in response to signalling through the T-cell receptor.", "output": {"entities": {"dna": [{"text": "purine-rich CD3R element", "start": 21, "end": 45}, {"text": "human immunodeficiency virus type 2 long terminal repeat", "start": 55, "end": 111}], "protein": [{"text": "T-cell receptor", "start": 200, "end": 215}]}}, "schema": []} {"input": "Taken together, these results demonstrate that multiple Ets family members with apparently distinct DNA binding specificities regulate differential gene expression in resting and activated T cells.", "output": {"entities": {"protein": [{"text": "multiple Ets family members", "start": 47, "end": 74}]}}, "schema": []} {"input": "Binding of erythroid and non-erythroid nuclear proteins to the silencer of the human epsilon-globin-encoding gene.", "output": {"entities": {"dna": [{"text": "silencer", "start": 63, "end": 71}, {"text": "human epsilon-globin-encoding gene", "start": 79, "end": 113}]}}, "schema": []} {"input": "To clarify the molecular mechanisms involved in the developmental control of hemoglobin-encoding genes we have been studying the expression of these genes in human cells in continuous culture.", "output": {"entities": {"dna": [{"text": "hemoglobin-encoding genes", "start": 77, "end": 102}, {"text": "genes", "start": 149, "end": 154}], "cell_type": [{"text": "human cells", "start": 158, "end": 169}]}}, "schema": []} {"input": "We have previously reported the presence of a transcriptional control element with the properties of a silencer extending from -392 to -177 bp relative to the cap site of the human epsilon-globin-encoding gene [Cao et al., Proc.Natl.Acad.Sci.USA 86 (1989) 5306-5309].", "output": {"entities": {"dna": [{"text": "transcriptional control element", "start": 46, "end": 77}, {"text": "silencer", "start": 103, "end": 111}, {"text": "-392 to -177 bp", "start": 127, "end": 142}, {"text": "cap site", "start": 159, "end": 167}, {"text": "human epsilon-globin-encoding gene", "start": 175, "end": 209}]}}, "schema": []} {"input": "We also showed that this silencer has stronger inhibitory activity in HeLa cells, as compared to K562 human erythroleukemia cells.", "output": {"entities": {"dna": [{"text": "silencer", "start": 25, "end": 33}], "cell_line": [{"text": "HeLa cells", "start": 70, "end": 80}, {"text": "K562 human erythroleukemia cells", "start": 97, "end": 129}]}}, "schema": []} {"input": "Using deletion mutants and cis-cloned synthetic oligodeoxyribonucleotides in transient expression assays, nucleotide sequences responsible for this effect have now been further delimited to 44 bp located from -294 to -251 bp.", "output": {"entities": {"dna": [{"text": "deletion mutants", "start": 6, "end": 22}, {"text": "-294 to -251 bp", "start": 209, "end": 224}]}}, "schema": []} {"input": "Gel electrophoresis mobility shift assays and DNaseI footprinting assays demonstrate that these negative regulatory sequences are recognized differently by proteins present in nuclear extracts obtained from HeLa and K562 cells.", "output": {"entities": {"protein": [{"text": "DNaseI", "start": 46, "end": 52}, {"text": "proteins", "start": 156, "end": 164}], "cell_line": [{"text": "HeLa", "start": 207, "end": 211}, {"text": "K562 cells", "start": 216, "end": 226}]}}, "schema": []} {"input": "Two binding proteins are detected in K562 nuclear extracts, while only one is found in extracts from HeLa cells.", "output": {"entities": {"cell_line": [{"text": "HeLa cells", "start": 101, "end": 111}]}}, "schema": []} {"input": "Possible mechanisms by which these proteins may regulate transcription of the epsilon-globin-encoding gene in erythroid and non-erythroid cells are discussed.", "output": {"entities": {"dna": [{"text": "epsilon-globin-encoding gene", "start": 78, "end": 106}], "cell_type": [{"text": "erythroid and", "start": 110, "end": 123}, {"text": "non-erythroid cells", "start": 124, "end": 143}]}}, "schema": []} {"input": "Calcitriol: a hematolymphopoietrope? [editorial]", "output": {"entities": {}}, "schema": []} {"input": "A MEDLINE search of the English-language literature was conducted using the indexing terms' immunology, calcitriol and vitamin D' to identify studies indicating a role for calcitriol as a primary immunomodulator.", "output": {"entities": {}}, "schema": []} {"input": "Sixty-six papers published between January 1956 and June 1991 were identified.", "output": {"entities": {}}, "schema": []} {"input": "Forty-five of these reports are cited in this review.", "output": {"entities": {}}, "schema": []} {"input": "The data strongly suggest an endocrine, autocrine and/or paracrine role for calcitriol in immune regulation.", "output": {"entities": {}}, "schema": []} {"input": "No unifying hypothesis has yet emerged explaining this collection of data.", "output": {"entities": {}}, "schema": []} {"input": "This paper provides a brief review of immune properties currently attributed to calcitriol.", "output": {"entities": {}}, "schema": []} {"input": "Transcription of the hypersensitive site HS2 enhancer in erythroid cells.", "output": {"entities": {"dna": [{"text": "hypersensitive site HS2 enhancer", "start": 21, "end": 53}], "cell_type": [{"text": "erythroid cells", "start": 57, "end": 72}]}}, "schema": []} {"input": "In the human genome, the erythroid-specific hypersensitive site HS2 enhancer regulates the transcription of the downstream beta-like globin genes 10-50 kilobases away.", "output": {"entities": {"dna": [{"text": "human genome", "start": 7, "end": 19}, {"text": "erythroid-specific hypersensitive site HS2 enhancer", "start": 25, "end": 76}, {"text": "downstream beta-like globin genes", "start": 112, "end": 145}, {"text": "10-50 kilobases", "start": 146, "end": 161}]}}, "schema": []} {"input": "The mechanism of HS2 enhancer function is not known.", "output": {"entities": {"dna": [{"text": "HS2 enhancer", "start": 17, "end": 29}]}}, "schema": []} {"input": "The present study employs RNA protection assays to analyze the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids.", "output": {"entities": {"dna": [{"text": "HS2 enhancer", "start": 93, "end": 105}, {"text": "transfected recombinant", "start": 109, "end": 132}, {"text": "(", "start": 167, "end": 168}, {"text": ") plasmids", "start": 171, "end": 181}], "protein": [{"text": "chloramphenicol acetyltransferase", "start": 133, "end": 166}, {"text": "CAT", "start": 168, "end": 171}]}}, "schema": []} {"input": "In erythroid K562 cells in which the HS2 enhancer is active, the HS2 sequence directs the synthesis of long enhancer transcripts that are initiated apparently from within the enhancer and elongated through the intervening DNA into the cis-linked CAT gene.", "output": {"entities": {"cell_line": [{"text": "erythroid K562 cells", "start": 3, "end": 23}], "dna": [{"text": "HS2 enhancer", "start": 37, "end": 49}, {"text": "HS2 sequence", "start": 65, "end": 77}, {"text": "enhancer", "start": 175, "end": 183}, {"text": "cis-linked CAT gene", "start": 235, "end": 254}]}}, "schema": []} {"input": "In nonerythroid HL-60 cells in which the HS2 enhancer is inactive, long enhancer transcripts are not detectable.", "output": {"entities": {"cell_line": [{"text": "nonerythroid HL-60 cells", "start": 3, "end": 27}], "dna": [{"text": "HS2 enhancer", "start": 41, "end": 53}], "rna": [{"text": "long enhancer transcripts", "start": 67, "end": 92}]}}, "schema": []} {"input": "Splitting the HS2 enhancer between two tandem Ap1 sites abolishes the synthesis of a group of long enhancer transcripts and results in loss of enhancer function and transcriptional silencing of the cis-linked CAT gene.", "output": {"entities": {"dna": [{"text": "HS2 enhancer", "start": 14, "end": 26}, {"text": "tandem Ap1 sites", "start": 39, "end": 55}, {"text": "cis-linked CAT gene", "start": 198, "end": 217}], "rna": [{"text": "long enhancer transcripts", "start": 94, "end": 119}]}}, "schema": []} {"input": "In directing the synthesis of RNA through the intervening DNA and the gene by a tracking and transcription mechanism, the HS2 enhancer may (i) open up the chromatin structure of a gene domain and (ii) deliver enhancer binding proteins to the promoter sequence where they may stimulate the transcription of the gene at the cap site.", "output": {"entities": {"rna": [{"text": "RNA", "start": 30, "end": 33}], "dna": [{"text": "DNA", "start": 58, "end": 61}, {"text": "HS2 enhancer", "start": 122, "end": 134}, {"text": "chromatin structure", "start": 155, "end": 174}, {"text": "gene domain", "start": 180, "end": 191}, {"text": "cap site", "start": 322, "end": 330}], "protein": [{"text": "enhancer binding proteins", "start": 209, "end": 234}]}}, "schema": []} {"input": "Characterization of a novel T lymphocyte protein which binds to a site related to steroid/thyroid hormone receptor response elements in the negative regulatory sequence of the human immunodeficiency virus long terminal repeat.", "output": {"entities": {"protein": [{"text": "novel T lymphocyte protein", "start": 22, "end": 48}], "dna": [{"text": "steroid/thyroid hormone receptor response elements", "start": 82, "end": 132}, {"text": "negative regulatory sequence", "start": 140, "end": 168}, {"text": "human immunodeficiency virus long terminal repeat", "start": 176, "end": 225}]}}, "schema": []} {"input": "We have previously identified a T lymphocyte protein which binds to a site within the LTR of the human immunodeficiency virus type 1 (HIV-1) and exerts an inhibitory effect on virus gene expression.", "output": {"entities": {"protein": [{"text": "T lymphocyte protein", "start": 32, "end": 52}], "dna": [{"text": "LTR", "start": 86, "end": 89}]}}, "schema": []} {"input": "The palindromic site (site B) recognized by this protein is related to the palindromic binding sites of members of the steroid/thyroid hormone receptor family.", "output": {"entities": {"dna": [{"text": "palindromic site", "start": 4, "end": 20}, {"text": "site B", "start": 22, "end": 28}, {"text": "palindromic binding sites", "start": 75, "end": 100}], "protein": [{"text": "steroid/thyroid hormone receptor family", "start": 119, "end": 158}]}}, "schema": []} {"input": "Here we characterize the T cell protein binding to this site as a 100 kD protein which is most abundant in T cells and which binds to site B as a 200 kD complex.", "output": {"entities": {"protein": [{"text": "T cell protein", "start": 25, "end": 39}, {"text": "200 kD complex", "start": 146, "end": 160}], "cell_type": [{"text": "T cells", "start": 107, "end": 114}], "dna": [{"text": "site B", "start": 134, "end": 140}]}}, "schema": []} {"input": "This protein is distinct from other members of the steroid/thyroid hormone receptor family including the COUP protein which has a closely related DNA binding specificity.", "output": {"entities": {"protein": [{"text": "steroid/thyroid hormone receptor family", "start": 51, "end": 90}, {"text": "COUP protein", "start": 105, "end": 117}]}}, "schema": []} {"input": "TAR -independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation.", "output": {"entities": {"dna": [{"text": "TAR", "start": 0, "end": 3}], "protein": [{"text": "Tat", "start": 36, "end": 39}]}}, "schema": []} {"input": "The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy.", "output": {"entities": {"protein": [{"text": "Tat protein", "start": 4, "end": 15}]}}, "schema": []} {"input": "Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter.", "output": {"entities": {"protein": [{"text": "Tat", "start": 0, "end": 3}], "dna": [{"text": "viral promoter", "start": 119, "end": 133}]}}, "schema": []} {"input": "This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS ), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes.", "output": {"entities": {}}, "schema": []} {"input": "Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of all HIV-1 mRNAs.", "output": {"entities": {"protein": [{"text": "Tat", "start": 54, "end": 57}], "rna": [{"text": "RNA target", "start": 74, "end": 84}, {"text": "TAR", "start": 92, "end": 95}, {"text": "transactivation responsive", "start": 97, "end": 123}, {"text": "HIV-1 mRNAs", "start": 172, "end": 183}]}}, "schema": []} {"input": "This interaction is believed to be an important component of the mechanism of transactivation.", "output": {"entities": {}}, "schema": []} {"input": "In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR -independent pathway.", "output": {"entities": {"cell_line": [{"text": "CNS-derived cells", "start": 46, "end": 63}], "protein": [{"text": "Tat", "start": 64, "end": 67}], "dna": [{"text": "TAR", "start": 109, "end": 112}]}}, "schema": []} {"input": "A Tat -responsive element is found upstream within the viral promoter that in glial-derived cell lines allows transactivation in the absence of TAR.", "output": {"entities": {"dna": [{"text": "Tat -responsive element", "start": 2, "end": 25}, {"text": "viral promoter", "start": 55, "end": 69}], "cell_line": [{"text": "glial-derived cell lines", "start": 78, "end": 102}], "rna": [{"text": "TAR", "start": 144, "end": 147}]}}, "schema": []} {"input": "Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat -responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-kappa B domain.", "output": {"entities": {"dna": [{"text": "hybrid promoter constructs", "start": 21, "end": 47}, {"text": "Tat -responsive element", "start": 86, "end": 109}, {"text": "viral long terminal repeat", "start": 147, "end": 173}, {"text": "LTR", "start": 175, "end": 178}, {"text": "HIV-1 enhancer", "start": 209, "end": 223}, {"text": "NF-kappa B domain", "start": 228, "end": 245}]}}, "schema": []} {"input": "DNA band-shift analysis reveals NF-kappa B binding activity in glial cells that differs from that present in T lymphoid cells.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 32, "end": 42}], "cell_type": [{"text": "T lymphoid cells", "start": 109, "end": 125}]}}, "schema": []} {"input": "Further, we observe that TAR-deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen.", "output": {"entities": {"dna": [{"text": "TAR-deleted mutants", "start": 25, "end": 44}], "cell_type": [{"text": "glial cells", "start": 97, "end": 108}], "protein": [{"text": "viral p24 antigen", "start": 162, "end": 179}]}}, "schema": []} {"input": "(ABSTRACT TRUNCATED AT 250 WORDS)", "output": {"entities": {}}, "schema": []} {"input": "Transcription factor AP-2 activates gene expression of HTLV-I.", "output": {"entities": {"protein": [{"text": "Transcription factor AP-2", "start": 0, "end": 25}]}}, "schema": []} {"input": "The HTLV-I LTR contains three conserved regulatory elements known as 21 base pair repeats which are required for stimulation of gene expression by the transactivator protein tax.", "output": {"entities": {"dna": [{"text": "HTLV-I LTR", "start": 4, "end": 14}, {"text": "regulatory elements", "start": 40, "end": 59}, {"text": "21 base pair repeats", "start": 69, "end": 89}], "protein": [{"text": "transactivator protein", "start": 151, "end": 173}, {"text": "tax", "start": 174, "end": 177}]}}, "schema": []} {"input": "Mutagenesis indicates that the 21 bp repeats can be subdivided into three motifs, A, B and C, each of which influences the level of tax activation.", "output": {"entities": {"dna": [{"text": "21 bp repeats", "start": 31, "end": 44}, {"text": "A", "start": 82, "end": 83}, {"text": "B", "start": 85, "end": 86}, {"text": "C", "start": 91, "end": 92}], "protein": [{"text": "tax", "start": 132, "end": 135}]}}, "schema": []} {"input": "The A site in the 21 bp repeat has strong homology with previously described binding sites for the transcription factor AP-2.", "output": {"entities": {"dna": [{"text": "A site", "start": 4, "end": 10}, {"text": "21 bp repeat", "start": 18, "end": 30}, {"text": "binding sites", "start": 77, "end": 90}], "protein": [{"text": "transcription factor AP-2", "start": 99, "end": 124}]}}, "schema": []} {"input": "We demonstrated that AP-2 mRNA was present in T-lymphocytes and that cellular factors from both non-transformed and transformed T-lymphocytes specifically bound to the consensus motif for AP-2 in each 21 bp.", "output": {"entities": {"rna": [{"text": "AP-2 mRNA", "start": 21, "end": 30}], "cell_type": [{"text": "T-lymphocytes", "start": 46, "end": 59}, {"text": "T-lymphocytes", "start": 128, "end": 141}], "dna": [{"text": "consensus motif", "start": 168, "end": 183}], "protein": [{"text": "AP-2", "start": 188, "end": 192}]}}, "schema": []} {"input": "To determine the role of AP-2 in the regulation of the HTLV-I LTR gene expression, we used an AP-2 cDNA in DNA binding and transient expression assays.", "output": {"entities": {"protein": [{"text": "AP-2", "start": 25, "end": 29}, {"text": "AP-2", "start": 94, "end": 98}], "dna": [{"text": "HTLV-I LTR", "start": 55, "end": 65}, {"text": "cDNA", "start": 99, "end": 103}]}}, "schema": []} {"input": "Gel retardation and methylation interference studies revealed that bacterially produced AP-2 bound specifically and with high affinity to all three 21 bp repeats, and that it required the core sequence AGGC for specific binding.", "output": {"entities": {"protein": [{"text": "bacterially produced", "start": 67, "end": 87}, {"text": "AP-2", "start": 88, "end": 92}], "dna": [{"text": "21 bp repeats", "start": 148, "end": 161}, {"text": "core sequence", "start": 188, "end": 201}]}}, "schema": []} {"input": "Binding of AP-2 prevented the subsequent binding of members of the CREB/ATF family to an adjacent regulatory motif in the 21 bp repeat.", "output": {"entities": {"protein": [{"text": "AP-2", "start": 11, "end": 15}, {"text": "CREB/ATF family", "start": 67, "end": 82}], "dna": [{"text": "adjacent regulatory motif", "start": 89, "end": 114}, {"text": "21 bp repeat", "start": 122, "end": 134}]}}, "schema": []} {"input": "Transfection of an AP-2 expression construct into T-lymphocytes activated gene expression from the HTLV-I LTR.", "output": {"entities": {"dna": [{"text": "AP-2 expression construct", "start": 19, "end": 44}, {"text": "HTLV-I LTR", "start": 99, "end": 109}], "cell_type": [{"text": "T-lymphocytes", "start": 50, "end": 63}]}}, "schema": []} {"input": "At least two 21 bp repeats were required for high levels of AP-2 activation and mutagenesis of the AP-2 consensus binding sequences in the 21 bp repeats eliminate this activation.", "output": {"entities": {"dna": [{"text": "21 bp repeats", "start": 13, "end": 26}, {"text": "consensus binding sequences", "start": 104, "end": 131}, {"text": "21 bp repeats", "start": 139, "end": 152}], "protein": [{"text": "AP-2", "start": 60, "end": 64}, {"text": "AP-2", "start": 99, "end": 103}]}}, "schema": []} {"input": "(ABSTRACT TRUNCATED AT 250 WORDS)", "output": {"entities": {}}, "schema": []} {"input": "Activation of the human immunodeficiency virus type 1 enhancer is not dependent on NFAT-1.", "output": {"entities": {"dna": [{"text": "human immunodeficiency virus type 1 enhancer", "start": 18, "end": 62}], "protein": [{"text": "NFAT-1", "start": 83, "end": 89}]}}, "schema": []} {"input": "The function of a putative NFAT-1 site in the human immunodeficiency virus type 1 enhancer has been analyzed.", "output": {"entities": {"dna": [{"text": "putative NFAT-1 site", "start": 18, "end": 38}, {"text": "human immunodeficiency virus type 1 enhancer", "start": 46, "end": 90}]}}, "schema": []} {"input": "Activation by the T-cell antigen receptor is minimal in Jurkat cells and is mediated by the kappa B sites.", "output": {"entities": {"protein": [{"text": "T-cell antigen receptor", "start": 18, "end": 41}], "cell_line": [{"text": "Jurkat cells", "start": 56, "end": 68}], "dna": [{"text": "kappa B sites", "start": 92, "end": 105}]}}, "schema": []} {"input": "The putative NFAT-1 region is not required for the response to anti-CD3 or to mitogens in T-cell, B-cell, or monocyte/macrophage leukemia lines, nor is it a cis-acting negative regulatory element.", "output": {"entities": {"dna": [{"text": "putative", "start": 4, "end": 12}, {"text": "region", "start": 20, "end": 26}, {"text": "cis-acting negative regulatory element", "start": 157, "end": 195}], "protein": [{"text": "NFAT-1", "start": 13, "end": 19}, {"text": "anti-CD3", "start": 63, "end": 71}, {"text": "mitogens", "start": 78, "end": 86}], "cell_line": [{"text": "T-cell", "start": 90, "end": 96}, {"text": "B-cell", "start": 98, "end": 104}, {"text": "monocyte/macrophage leukemia lines", "start": 109, "end": 143}]}}, "schema": []} {"input": "The B cell-specific nuclear factor OTF-2 positively regulates transcription of the human class II transplantation gene, DRA.", "output": {"entities": {"protein": [{"text": "B cell-specific nuclear factor", "start": 4, "end": 34}, {"text": "OTF-2", "start": 35, "end": 40}], "dna": [{"text": "human class II transplantation gene", "start": 83, "end": 118}, {"text": "DRA", "start": 120, "end": 123}]}}, "schema": []} {"input": "The promoter of the major histocompatibility class II gene DRA contains an octamer element (ATTTGCAT) that is required for efficient DRA expression in B cells.", "output": {"entities": {"dna": [{"text": "major histocompatibility class II gene", "start": 20, "end": 58}, {"text": "DRA", "start": 59, "end": 62}, {"text": "octamer element", "start": 75, "end": 90}, {"text": "DRA", "start": 133, "end": 136}], "cell_type": [{"text": "B cells", "start": 151, "end": 158}]}}, "schema": []} {"input": "Several DNA-binding proteins are known to bind this sequence.", "output": {"entities": {"protein": [{"text": "DNA-binding proteins", "start": 8, "end": 28}]}}, "schema": []} {"input": "The best characterized are the B cell-specific OTF-2 and the ubiquitous OTF-1.", "output": {"entities": {"protein": [{"text": "B cell-specific OTF-2", "start": 31, "end": 52}, {"text": "OTF-1", "start": 72, "end": 77}]}}, "schema": []} {"input": "This report directly demonstrates that OTF-2 but not OTF-1 regulates the DRA gene.", "output": {"entities": {"protein": [{"text": "OTF-2", "start": 39, "end": 44}, {"text": "OTF-1", "start": 53, "end": 58}], "dna": [{"text": "DRA gene", "start": 73, "end": 81}]}}, "schema": []} {"input": "In vitro transcription analysis using protein fractions enriched for the octamer-binding protein OTF-2 demonstrate a positive functional role for OTF-2 in DRA gene transcription.", "output": {"entities": {"protein": [{"text": "OTF-2", "start": 97, "end": 102}, {"text": "OTF-2", "start": 146, "end": 151}], "dna": [{"text": "DRA gene", "start": 155, "end": 163}]}}, "schema": []} {"input": "In contrast, OTF-1 -enriched protein fractions did not affect DRA gene transcription although it functionally enhanced the transcription of another gene.", "output": {"entities": {"protein": [{"text": "OTF-1 -enriched protein fractions", "start": 13, "end": 46}], "dna": [{"text": "DRA gene", "start": 62, "end": 70}]}}, "schema": []} {"input": "Recombinant OTF-2 protein produced by in vitro transcription /translation could also enhance DRA gene transcription in vitro.", "output": {"entities": {"protein": [{"text": "Recombinant", "start": 0, "end": 11}, {"text": "OTF-2 protein", "start": 12, "end": 25}], "dna": [{"text": "DRA gene", "start": 93, "end": 101}]}}, "schema": []} {"input": "In vivo transient transfection studies utilizing an OTF-2 expression vector resulted in similar findings: that OTF-2 protein enhanced DRA gene transcription, and that this effect requires an intact octamer element.", "output": {"entities": {"dna": [{"text": "OTF-2 expression vector", "start": 52, "end": 75}, {"text": "DRA gene", "start": 134, "end": 142}, {"text": "octamer element", "start": 198, "end": 213}], "protein": [{"text": "OTF-2 protein", "start": 111, "end": 124}]}}, "schema": []} {"input": "Together these results constitute the first direct evidence of a positive role for the lymphoid-specific octamer-binding factor in DRA gene transcription.", "output": {"entities": {"protein": [{"text": "lymphoid-specific octamer-binding factor", "start": 87, "end": 127}]}}, "schema": []} {"input": "Interferon-gamma potentiates the antiviral activity and the expression of interferon-stimulated genes induced by interferon-alpha in U937 cells.", "output": {"entities": {"protein": [{"text": "Interferon-gamma", "start": 0, "end": 16}], "dna": [{"text": "interferon-stimulated genes", "start": 74, "end": 101}], "cell_line": [{"text": "interferon-alpha in U937 cells", "start": 113, "end": 143}]}}, "schema": []} {"input": "Binding of type I interferon (IFN-alpha/beta) to specific receptors results in the rapid transcriptional activation, independent of protein synthesis, of IFN-alpha-stimulated genes (ISGs) in human fibroblasts and HeLa and Daudi cell lines.", "output": {"entities": {"protein": [{"text": "type I interferon (IFN-alpha/beta) to specific receptors", "start": 11, "end": 67}], "dna": [{"text": "IFN-alpha-stimulated genes", "start": 154, "end": 180}, {"text": "ISGs", "start": 182, "end": 186}], "cell_type": [{"text": "human fibroblasts", "start": 191, "end": 208}], "cell_line": [{"text": "HeLa", "start": 213, "end": 217}, {"text": "Daudi cell lines", "start": 222, "end": 238}]}}, "schema": []} {"input": "The binding of ISGF3 (IFN-stimulated gene factor 3) to the conserved IFN-stimulated response element (ISRE) results in transcriptional activation.", "output": {"entities": {"protein": [{"text": "ISGF3", "start": 15, "end": 20}, {"text": "IFN-stimulated gene factor 3", "start": 22, "end": 50}], "dna": [{"text": "IFN-stimulated response element", "start": 69, "end": 100}, {"text": "ISRE", "start": 102, "end": 106}]}}, "schema": []} {"input": "This factor is composed of a DNA-binding protein (ISGF3 gamma ), which normally is present in the cytoplasm, and other IFN-alpha-activated proteins which preexist as latent cytoplasmic precursors (ISGF3 alpha ).", "output": {"entities": {"protein": [{"text": "DNA-binding protein", "start": 29, "end": 48}, {"text": "ISGF3 gamma", "start": 50, "end": 61}, {"text": "IFN-alpha-activated proteins", "start": 119, "end": 147}, {"text": "latent cytoplasmic precursors", "start": 166, "end": 195}, {"text": "ISGF3 alpha", "start": 197, "end": 208}]}}, "schema": []} {"input": "We have found that ISG expression in the monocytic U937 cell line differs from most cell lines previously examined.", "output": {"entities": {"cell_line": [{"text": "monocytic U937 cell line", "start": 41, "end": 65}, {"text": "cell lines", "start": 84, "end": 94}]}}, "schema": []} {"input": "U937 cells express both type I and type II IFN receptors, but only IFN-alpha is capable of inducing antiviral protection in these cells.", "output": {"entities": {"cell_line": [{"text": "U937 cells", "start": 0, "end": 10}], "protein": [{"text": "type I and type II IFN receptors", "start": 24, "end": 56}, {"text": "IFN-alpha", "start": 67, "end": 76}]}}, "schema": []} {"input": "Pretreatment with IFN-gamma potentiates the IFN-alpha -induced protection, but IFN-gamma alone does not have any antiviral activity.", "output": {"entities": {"protein": [{"text": "IFN-gamma", "start": 18, "end": 27}, {"text": "IFN-alpha", "start": 44, "end": 53}, {"text": "IFN-gamma", "start": 79, "end": 88}]}}, "schema": []} {"input": "ISG15 mRNA accumulation in U937 cells is not detectable before 6 h of IFN-alpha treatment, peaks at 24 h, and requires protein synthesis.", "output": {"entities": {"rna": [{"text": "ISG15 mRNA", "start": 0, "end": 10}], "cell_line": [{"text": "U937 cells", "start": 27, "end": 37}], "protein": [{"text": "IFN-alpha", "start": 70, "end": 79}]}}, "schema": []} {"input": "Although IFN-gamma alone does not induce ISG expression, IFN-gamma pretreatment markedly increases and hastens ISG expression and transcriptional induction.", "output": {"entities": {"protein": [{"text": "IFN-gamma", "start": 9, "end": 18}, {"text": "IFN-gamma", "start": 57, "end": 66}]}}, "schema": []} {"input": "Nuclear extracts assayed for the presence of ISRE binding factors by electrophoretic mobility shift assays show that ISGF3 is induced by IFN-alpha within 6 h from undetectable basal levels in untreated U937 cells.", "output": {"entities": {"dna": [{"text": "ISRE", "start": 45, "end": 49}], "protein": [{"text": "binding factors", "start": 50, "end": 65}, {"text": "ISGF3", "start": 117, "end": 122}, {"text": "IFN-alpha", "start": 137, "end": 146}], "cell_line": [{"text": "U937 cells", "start": 202, "end": 212}]}}, "schema": []} {"input": "Activation of ISGF3 alpha, the latent component of ISGF3, occurs rapidly.", "output": {"entities": {"protein": [{"text": "ISGF3 alpha", "start": 14, "end": 25}, {"text": "ISGF3", "start": 51, "end": 56}]}}, "schema": []} {"input": "However, the increase in ISGF3 activity ultimately correlates with the accumulation of ISGF3 gamma induced by IFN-alpha or IFN-gamma.", "output": {"entities": {"protein": [{"text": "ISGF3", "start": 25, "end": 30}, {"text": "ISGF3 gamma", "start": 87, "end": 98}, {"text": "IFN-alpha", "start": 110, "end": 119}, {"text": "IFN-gamma", "start": 123, "end": 132}]}}, "schema": []} {"input": "(ABSTRACT TRUNCATED AT 250 WORDS)", "output": {"entities": {}}, "schema": []} {"input": "Single point estimation of glucocorticoid receptors in lymphocytes of normal subjects and of children under long term glucocorticoid treatment.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 27, "end": 51}], "cell_type": [{"text": "lymphocytes", "start": 55, "end": 66}]}}, "schema": []} {"input": "A single point assay of glucocorticoid receptors (GR) in human lymphocytes based on the measurement of specific dexamethasone binding has been developed and compared with a common multi-point Scatchard analysis.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 24, "end": 48}, {"text": "GR", "start": 50, "end": 52}], "cell_type": [{"text": "lymphocytes", "start": 63, "end": 74}]}}, "schema": []} {"input": "The assay conditions-concentration of the ligand 20 nmol/l, incubation time 2 h and the cell count 2-6 mil.", "output": {"entities": {}}, "schema": []} {"input": "cells/tube in the assay volume 0.25 ml were found to be optimal.", "output": {"entities": {}}, "schema": []} {"input": "An attempt was also undertaken to use a cell harvester for the separation of cells from unbound ligand.", "output": {"entities": {}}, "schema": []} {"input": "Though specifically bound dexamethasone measured by whole-cell assay and that using cell harvester correlated well, almost by one order lower values obtained with the latter method render it non-applicable for receptor quantitation.", "output": {"entities": {}}, "schema": []} {"input": "The results from 9 healthy volunteers (average GR concentration 7131 +/- 1256 sites/cell) correlated excellently with those obtained by the Scatchard analysis.", "output": {"entities": {"protein": [{"text": "GR", "start": 47, "end": 49}]}}, "schema": []} {"input": "The single point assay has been also applied for determination of GH in 10 children treated with large doses of prednisone.", "output": {"entities": {}}, "schema": []} {"input": "The average values from healthy volunteers did not differ significantly from those found in these children, though much broader range was found in patients.", "output": {"entities": {}}, "schema": []} {"input": "Glucocorticoid receptor and inhibition of 3-O-methyl-D-glucose uptake by glucocorticoids in peripheral blood leukocytes from normal humans: correlation between receptor level and hormone effect in vitro.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptor", "start": 0, "end": 23}], "cell_type": [{"text": "peripheral blood leukocytes", "start": 92, "end": 119}]}}, "schema": []} {"input": "We have measured the glucocorticoid receptor concentration in mononuclear and polymorphonuclear leukocytes, both of which were isolated from peripheral blood from ten healthy male volunteers.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 21, "end": 44}], "cell_type": [{"text": "mononuclear", "start": 62, "end": 73}, {"text": "polymorphonuclear leukocytes", "start": 78, "end": 106}]}}, "schema": []} {"input": "In parallel, the inhibitory effect of dexamethasone on 3-O-methyl-D-glucose uptake was assayed in the corresponding mononuclear leukocytes.", "output": {"entities": {"cell_type": [{"text": "mononuclear leukocytes", "start": 116, "end": 138}]}}, "schema": []} {"input": "The glucocorticoid receptor levels in mononuclear leukocytes correlated with those in polymorphonuclear leukocytes, and there was a linear relationship between the cellular glucocorticoid receptor levels and glucocorticoid -mediated inhibition of the uptake of 3-O-methyl-D-glucose in mononuclear leukocytes.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 4, "end": 27}, {"text": "glucocorticoid receptor", "start": 173, "end": 196}], "cell_type": [{"text": "mononuclear leukocytes", "start": 38, "end": 60}, {"text": "polymorphonuclear leukocytes", "start": 86, "end": 114}, {"text": "mononuclear leukocytes", "start": 285, "end": 307}]}}, "schema": []} {"input": "When mononuclear leukocytes were incubated in the presence of 8-bromo-cAMP, cellular glucocorticoid receptor levels increased and a more pronounced inhibitory effect of dexamethasone was observed on the transport of 3-O-methyl-D-glucose.", "output": {"entities": {"cell_type": [{"text": "mononuclear leukocytes", "start": 5, "end": 27}], "protein": [{"text": "glucocorticoid receptor", "start": 85, "end": 108}]}}, "schema": []} {"input": "We conclude that the cellular glucocorticoid receptor levels in peripheral blood leukocytes reflect in vitro responsiveness to glucocorticoids in mononuclear leukocytes from healthy males, and that the individual responsiveness may alter upon changes in the cellular levels of glucocorticoid receptor.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 30, "end": 53}, {"text": "glucocorticoid receptor", "start": 277, "end": 300}], "cell_type": [{"text": "peripheral blood leukocytes", "start": 64, "end": 91}, {"text": "mononuclear leukocytes", "start": 146, "end": 168}]}}, "schema": []} {"input": "Transcription factor activation and functional stimulation of human monocytes.", "output": {"entities": {"protein": [{"text": "Transcription factor", "start": 0, "end": 20}], "cell_type": [{"text": "human monocytes", "start": 62, "end": 77}]}}, "schema": []} {"input": "Activation of expression of genes encoding transcription factors: c-fos and c-jun and formation of AP1 transcriptional complex in human monocytes was investigated.", "output": {"entities": {"dna": [{"text": "genes", "start": 28, "end": 33}, {"text": "c-fos", "start": 66, "end": 71}, {"text": "c-jun", "start": 76, "end": 81}], "protein": [{"text": "transcription factors", "start": 43, "end": 64}, {"text": "AP1 transcriptional complex", "start": 99, "end": 126}], "cell_type": [{"text": "human monocytes", "start": 130, "end": 145}]}}, "schema": []} {"input": "It was found that lipopolysaccharide induced strongly both c-fos and c-jun expression as well as AP1 formation.", "output": {"entities": {"dna": [{"text": "c-fos", "start": 59, "end": 64}, {"text": "c-jun", "start": 69, "end": 74}], "protein": [{"text": "AP1", "start": 97, "end": 100}]}}, "schema": []} {"input": "Interferon gamma activated strongly c-fos and weakly c-jun and AP1.", "output": {"entities": {"protein": [{"text": "Interferon gamma", "start": 0, "end": 16}, {"text": "AP1", "start": 63, "end": 66}], "dna": [{"text": "c-fos", "start": 36, "end": 41}, {"text": "c-jun", "start": 53, "end": 58}]}}, "schema": []} {"input": "Tumor necrosis factor induced slightly c-fos and had almost no effect on c-jun and AP1.", "output": {"entities": {"protein": [{"text": "Tumor necrosis factor", "start": 0, "end": 21}, {"text": "AP1", "start": 83, "end": 86}], "dna": [{"text": "c-fos", "start": 39, "end": 44}, {"text": "c-jun", "start": 73, "end": 78}]}}, "schema": []} {"input": "The data suggest that differences in functional responses elicited in monocytes by all three factors may be dependent on different routes on nuclear signalling employed by the factors.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 70, "end": 79}], "protein": [{"text": "factors", "start": 93, "end": 100}, {"text": "factors", "start": 176, "end": 183}]}}, "schema": []} {"input": "Regulation of interleukin-1 beta production by glucocorticoids in human monocytes: the mechanism of action depends on the activation signal.", "output": {"entities": {"protein": [{"text": "interleukin-1 beta", "start": 14, "end": 32}], "cell_type": [{"text": "human monocytes", "start": 66, "end": 81}]}}, "schema": []} {"input": "Glucocorticoids are known to downregulate interleukin-1 beta production in monocytic cells by two different mechanims: direct inhibition of the gene transcription and destabilization of the preformed interleukin-1 beta mRNA.", "output": {"entities": {"protein": [{"text": "interleukin-1 beta", "start": 42, "end": 60}, {"text": "interleukin-1 beta", "start": 200, "end": 218}], "cell_type": [{"text": "monocytic cells", "start": 75, "end": 90}], "rna": [{"text": "mRNA", "start": 219, "end": 223}]}}, "schema": []} {"input": "Now we have examined the effect of the nature of the monocyte activating signal on these two inhibitory mechanims.", "output": {"entities": {}}, "schema": []} {"input": "When human monocytes were preincubated with dexamethasone for 1 hour and then stimulated either with bacterial lipopolysaccharide or phorbol myristate, it was found that dexamethasone inhibited the lipopolysaccharide-induced interleukin-1 beta protein production, but the phorbol myristate -induced production was increased 3-10 fold.", "output": {"entities": {"cell_type": [{"text": "human monocytes", "start": 5, "end": 20}], "protein": [{"text": "interleukin-1 beta", "start": 225, "end": 243}]}}, "schema": []} {"input": "This difference was also seen at the mRNA level.", "output": {"entities": {}}, "schema": []} {"input": "When dexamethasone was added to the cultures 3 hours after the stimulators, it clearly decreased the interleukin-1 beta mRNA levels regardless of the stimulator used (although the effect was clearly weaker on the PMA-induced mRNA ).", "output": {"entities": {"rna": [{"text": "interleukin-1 beta mRNA", "start": 101, "end": 124}, {"text": "PMA-induced mRNA", "start": 213, "end": 229}]}}, "schema": []} {"input": "Thus these data suggest that the phorbol myristate-induced signal (prolonged protein kinase C activation ?) cannot be inhibited by prior incubation with dexamethasone and it also protects the induced mRNA for the degradative action of dexamethasone.", "output": {"entities": {"protein": [{"text": "protein kinase C", "start": 77, "end": 93}], "rna": [{"text": "induced mRNA", "start": 192, "end": 204}]}}, "schema": []} {"input": "Nuclear transcription factors that bind to elements of the IL-2 promoter.", "output": {"entities": {"protein": [{"text": "Nuclear transcription factors", "start": 0, "end": 29}], "dna": [{"text": "IL-2 promoter", "start": 59, "end": 72}]}}, "schema": []} {"input": "Induction requirements in primary human T cells.", "output": {"entities": {"cell_type": [{"text": "primary human T cells", "start": 26, "end": 47}]}}, "schema": []} {"input": "Prior studies have identified several elements that contribute to the activity of the IL-2 promoter in the stimulated T cell line, Jurkat.", "output": {"entities": {"dna": [{"text": "IL-2 promoter", "start": 86, "end": 99}], "cell_line": [{"text": "T cell line", "start": 118, "end": 129}, {"text": "Jurkat", "start": 131, "end": 137}]}}, "schema": []} {"input": "The sites and their corresponding nuclear binding factors include: NF-kappa B, AP-1, AP-3, OCT-1, and NF-AT.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 67, "end": 77}, {"text": "AP-1", "start": 79, "end": 83}, {"text": "AP-3", "start": 85, "end": 89}, {"text": "OCT-1", "start": 91, "end": 96}, {"text": "NF-AT", "start": 102, "end": 107}]}}, "schema": []} {"input": "The latter \" nuclear factor for activated T cells \" likely contributes to the tissue specificity of IL-2 gene expression.", "output": {"entities": {"protein": [{"text": "nuclear factor for", "start": 13, "end": 31}, {"text": "IL-2", "start": 100, "end": 104}], "cell_line": [{"text": "activated T cells", "start": 32, "end": 49}], "dna": [{"text": "gene", "start": 105, "end": 109}]}}, "schema": []} {"input": "Using electrophoretic mobility shift assays, we have studied these transcription factors in primary T cells from human blood to verify their presence in a physiologic setting and to identify the signals that stimulate factor activity.", "output": {"entities": {"protein": [{"text": "transcription factors", "start": 67, "end": 88}], "cell_type": [{"text": "primary T cells", "start": 92, "end": 107}]}}, "schema": []} {"input": "All factors are induced in the nuclei of T cells upon activation with mitogens but not with exogenous IL-2 growth factor.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 41, "end": 48}], "protein": [{"text": "mitogens", "start": 70, "end": 78}, {"text": "exogenous IL-2 growth factor", "start": 92, "end": 120}]}}, "schema": []} {"input": "However, the signaling requirements and sensitivity to protein synthesis inhibitors differ considerably.", "output": {"entities": {}}, "schema": []} {"input": "Only the activities for NF-AT and AP-1 sites require two signals for optimal induction, i.e., PMA plus either lectin or antibody to the CD3 or CD28 surface molecules.", "output": {"entities": {"protein": [{"text": "lectin", "start": 110, "end": 116}, {"text": "antibody", "start": 120, "end": 128}, {"text": "CD3", "start": 136, "end": 139}, {"text": "CD28 surface molecules", "start": 143, "end": 165}]}}, "schema": []} {"input": "Other factors are induced by lectin, antibody, and/or PMA alone.", "output": {"entities": {"protein": [{"text": "lectin", "start": 29, "end": 35}, {"text": "antibody", "start": 37, "end": 45}]}}, "schema": []} {"input": "After appropriate stimulation, both NF-AT and AP-1 are peculiarly sensitive to the protein synthesis inhibitor anisomycin.", "output": {"entities": {"protein": [{"text": "NF-AT", "start": 36, "end": 41}, {"text": "AP-1", "start": 46, "end": 50}]}}, "schema": []} {"input": "Our data correlate the activity of NF-AT and AP-1 in gel shift assays with the two signals requirements for IL-2 gene expression.", "output": {"entities": {"protein": [{"text": "NF-AT", "start": 35, "end": 40}, {"text": "AP-1", "start": 45, "end": 49}], "dna": [{"text": "IL-2 gene", "start": 108, "end": 117}]}}, "schema": []} {"input": "NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 0, "end": 10}, {"text": "Tax protein", "start": 53, "end": 64}], "cell_type": [{"text": "T cells", "start": 23, "end": 30}]}}, "schema": []} {"input": "The effect of constitutive Tax expression on the interaction of NF-kappa B with its recognition sequence and on NF-kappa B -dependent gene expression was examined in T lymphoid Jurkat cell lines (19D and 9J) stably transformed with a Tax expression vector.", "output": {"entities": {"protein": [{"text": "Tax", "start": 27, "end": 30}, {"text": "NF-kappa B", "start": 64, "end": 74}, {"text": "NF-kappa B", "start": 112, "end": 122}], "dna": [{"text": "recognition sequence", "start": 84, "end": 104}, {"text": "Tax expression vector", "start": 234, "end": 255}], "cell_line": [{"text": "T lymphoid Jurkat cell lines", "start": 166, "end": 194}, {"text": "19D", "start": 196, "end": 199}, {"text": "9J", "start": 204, "end": 206}]}}, "schema": []} {"input": "Tax expressing T cell lines contained a constitutive level of NF-kappa B binding activity, detectable by mobility shift assay and uv cross-linking using a palindromic NF-kappa B probe homologous to the interferon beta PRDII site.", "output": {"entities": {"protein": [{"text": "Tax", "start": 0, "end": 3}, {"text": "NF-kappa B", "start": 62, "end": 72}], "cell_line": [{"text": "expressing T cell lines", "start": 4, "end": 27}], "dna": [{"text": "palindromic NF-kappa B probe", "start": 155, "end": 183}, {"text": "interferon beta PRDII site", "start": 202, "end": 228}]}}, "schema": []} {"input": "In Jurkat and NC2.10 induction with phorbol esters resulted in the appearance of new DNA binding proteins of 85, 75, and 54 kDa, whereas in Tax expressing cells the 85-kDa protein and a 92-kDa DNA binding protein were constitutively induced.", "output": {"entities": {"protein": [{"text": "DNA binding proteins", "start": 85, "end": 105}, {"text": "Tax", "start": 140, "end": 143}, {"text": "85-kDa protein", "start": 165, "end": 179}, {"text": "92-kDa DNA binding protein", "start": 186, "end": 212}], "cell_line": [{"text": "expressing cells", "start": 144, "end": 160}]}}, "schema": []} {"input": "Expression of Tax protein in 19D and 9J resulted in transcription of the endogenous NF-kappa B -dependent granulocyte-macrophage colony stimulating factor gene and increased basal level expression of transfected NF-kappa B -regulated promoters.", "output": {"entities": {"protein": [{"text": "Tax protein", "start": 14, "end": 25}, {"text": "NF-kappa B", "start": 212, "end": 222}], "cell_line": [{"text": "19D", "start": 29, "end": 32}, {"text": "9J", "start": 37, "end": 39}], "dna": [{"text": "endogenous NF-kappa B -dependent granulocyte-macrophage colony stimulating factor gene", "start": 73, "end": 159}, {"text": "-regulated promoters", "start": 223, "end": 243}]}}, "schema": []} {"input": "Nonetheless transcription of both the endogenous and the transfected gene was inducible by PMA treatment.", "output": {"entities": {}}, "schema": []} {"input": "Tax expression in Jurkat T cells may alter the stoichiometry of NF-kappa B DNA binding proteins and thus change the expression of NF-kappa B -regulated promoters.", "output": {"entities": {"protein": [{"text": "Tax", "start": 0, "end": 3}, {"text": "NF-kappa B", "start": 64, "end": 74}, {"text": "DNA binding proteins", "start": 75, "end": 95}, {"text": "NF-kappa B", "start": 130, "end": 140}], "cell_line": [{"text": "Jurkat T cells", "start": 18, "end": 32}], "dna": [{"text": "-regulated promoters", "start": 141, "end": 161}]}}, "schema": []} {"input": "A nuclear factor NF-GM2 that interacts with a regulatory region of the GM-CSF gene essential for its induction in responses to T-cell activation: purification from human T-cell leukemia line Jurkat cells and similarity to NF-kappa B.", "output": {"entities": {"protein": [{"text": "nuclear factor", "start": 2, "end": 16}, {"text": "NF-GM2", "start": 17, "end": 23}, {"text": "NF-kappa B", "start": 222, "end": 232}], "dna": [{"text": "regulatory region", "start": 46, "end": 63}, {"text": "GM-CSF gene", "start": 71, "end": 82}], "cell_line": [{"text": "T-cell leukemia line Jurkat cells", "start": 170, "end": 203}]}}, "schema": []} {"input": "Activation of T cells by antigen, lectin, or a combination of phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) leads to the induction of genes for a set of lymphokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF ).", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 14, "end": 21}], "protein": [{"text": "lectin", "start": 34, "end": 40}, {"text": "lymphokines", "start": 173, "end": 184}, {"text": "granulocyte-macrophage colony-stimulating factor", "start": 196, "end": 244}, {"text": "GM-CSF", "start": 246, "end": 252}]}}, "schema": []} {"input": "We demonstrated in earlier studies that the upstream region of the mouse GM-CSF promoter at positions between -95 and -73 is essential for transcriptional activation in response to PMA/A23187.", "output": {"entities": {"dna": [{"text": "upstream region", "start": 44, "end": 59}, {"text": "mouse", "start": 67, "end": 72}, {"text": "promoter", "start": 80, "end": 88}, {"text": "-95 and -73", "start": 110, "end": 121}], "protein": [{"text": "GM-CSF", "start": 73, "end": 79}]}}, "schema": []} {"input": "This region contains two DNA-binding motifs, GM2 and GC-box.", "output": {"entities": {"dna": [{"text": "DNA-binding motifs", "start": 25, "end": 43}, {"text": "GM2", "start": 45, "end": 48}, {"text": "GC-box", "start": 53, "end": 59}]}}, "schema": []} {"input": "The GM2 sequence (GGTAGTTCCC) is recognized by an inducible factor NF-GM2; the other (CCGCCC) by constitutive factors A1, A2, and B.", "output": {"entities": {"dna": [{"text": "GM2 sequence", "start": 4, "end": 16}], "protein": [{"text": "inducible factor NF-GM2", "start": 50, "end": 73}, {"text": "constitutive factors", "start": 97, "end": 117}, {"text": "A1", "start": 118, "end": 120}, {"text": "A2", "start": 122, "end": 124}, {"text": "B", "start": 130, "end": 131}]}}, "schema": []} {"input": "To elucidate the mechanism of GM-CSF gene activation, we have purified the inducible factor NF-GM2 from the nuclear extract of stimulated Jurkat cells on the basis of specific DNA-binding activity.", "output": {"entities": {"protein": [{"text": "GM-CSF", "start": 30, "end": 36}, {"text": "inducible factor NF-GM2", "start": 75, "end": 98}], "cell_line": [{"text": "Jurkat cells", "start": 138, "end": 150}]}}, "schema": []} {"input": "The purified NF-GM2 consists of 50 (p50) and 65 kDa (p65) polypeptides and has a binding activity specific for both the GM-CSF and immunoglobulin kappa (GGAAAGTCCC) enhancers.", "output": {"entities": {"protein": [{"text": "NF-GM2", "start": 13, "end": 19}, {"text": "p50", "start": 36, "end": 39}, {"text": "p65", "start": 53, "end": 56}, {"text": "GM-CSF", "start": 120, "end": 126}], "dna": [{"text": "immunoglobulin kappa (GGAAAGTCCC) enhancers", "start": 131, "end": 174}]}}, "schema": []} {"input": "Electrophoretically purified p50 alone can form a protein-DNA complex, but in the mixture, p50 associates preferentially with p65 to form the NF-GM2 complex.", "output": {"entities": {"protein": [{"text": "p50", "start": 29, "end": 32}, {"text": "protein-DNA complex", "start": 50, "end": 69}, {"text": "p50", "start": 91, "end": 94}, {"text": "p65", "start": 126, "end": 129}, {"text": "NF-GM2 complex", "start": 142, "end": 156}]}}, "schema": []} {"input": "In addition, p65 gave per se, with low affinity, a protein-DNA complex that migrated more slowly than native NF-GM2 complex.", "output": {"entities": {"protein": [{"text": "p65", "start": 13, "end": 16}, {"text": "protein-DNA complex", "start": 51, "end": 70}, {"text": "NF-GM2 complex", "start": 109, "end": 123}]}}, "schema": []} {"input": "Furthermore, an antiserum against KBF1 (identical to 50 kDa NF-kappa B protein) reacted with the p50 of NF-GM2, indicating that the NF-GM2 polypeptide cannot be immunologically differentiated from the 50 kDa subunit of NF-kappa B.", "output": {"entities": {"protein": [{"text": "KBF1", "start": 34, "end": 38}, {"text": "50 kDa NF-kappa B protein", "start": 53, "end": 78}, {"text": "p50", "start": 97, "end": 100}, {"text": "NF-GM2", "start": 104, "end": 110}, {"text": "NF-GM2 polypeptide", "start": 132, "end": 150}, {"text": "50 kDa subunit", "start": 201, "end": 215}, {"text": "NF-kappa B", "start": 219, "end": 229}]}}, "schema": []} {"input": "The purified NF-GM2 activated in vitro transcription from the kappa B enhancer, while it failed to stimulate transcription from the GM-CSF promoter harboring the GM2 sequence.", "output": {"entities": {"protein": [{"text": "NF-GM2", "start": 13, "end": 19}], "dna": [{"text": "kappa B enhancer", "start": 62, "end": 78}, {"text": "GM-CSF promoter", "start": 132, "end": 147}, {"text": "GM2 sequence", "start": 162, "end": 174}]}}, "schema": []} {"input": "This suggests that the activation mechanism of the GM-CSF gene through the GM2/GC-box sequence is different from that of genes carrying the kappa B enhancer alone.", "output": {"entities": {"dna": [{"text": "GM-CSF gene", "start": 51, "end": 62}, {"text": "GM2/GC-box sequence", "start": 75, "end": 94}, {"text": "kappa B enhancer", "start": 140, "end": 156}]}}, "schema": []} {"input": "Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B -like activity.", "output": {"entities": {"dna": [{"text": "immediate-early gene", "start": 23, "end": 43}], "cell_type": [{"text": "adherent monocytes", "start": 55, "end": 73}], "protein": [{"text": "I kappa B", "start": 87, "end": 96}]}}, "schema": []} {"input": "We have cloned a group of cDNAs representing mRNAs that are rapidly induced following adherence of human monocytes.", "output": {"entities": {"dna": [{"text": "cDNAs", "start": 26, "end": 31}], "rna": [{"text": "mRNAs", "start": 45, "end": 50}], "cell_type": [{"text": "human monocytes", "start": 99, "end": 114}]}}, "schema": []} {"input": "One of the induced transcripts (MAD-3) encodes a protein of 317 amino acids with one domain containing five tandem repeats of the cdc10/ankyrin motif, which is 60% similar (46% identical) to the ankyrin repeat region of the precursor of NF-kappa B /KBF1 p50.", "output": {"entities": {"rna": [{"text": "MAD-3", "start": 32, "end": 37}], "protein": [{"text": "five tandem repeats", "start": 103, "end": 122}, {"text": "cdc10/ankyrin motif", "start": 130, "end": 149}, {"text": "ankyrin repeat region", "start": 195, "end": 216}, {"text": "NF-kappa B", "start": 237, "end": 247}, {"text": "/KBF1 p50", "start": 248, "end": 257}]}}, "schema": []} {"input": "The C-terminus has a putative protein kinase C phosphorylation site.", "output": {"entities": {"protein": [{"text": "C-terminus", "start": 4, "end": 14}, {"text": "protein kinase C phosphorylation site", "start": 30, "end": 67}]}}, "schema": []} {"input": "In vitro translated MAD-3 protein was found to specifically inhibit the DNA-binding activity of the p50/p65 NF-kappa B complex but not that of the p50/p50 KBF1 factor or of other DNA-binding proteins.", "output": {"entities": {"protein": [{"text": "MAD-3 protein", "start": 20, "end": 33}, {"text": "p50/p65 NF-kappa B complex", "start": 100, "end": 126}, {"text": "p50/p50 KBF1 factor", "start": 147, "end": 166}, {"text": "DNA-binding proteins", "start": 179, "end": 199}]}}, "schema": []} {"input": "The MAD-3 cDNA encodes an I kappa B-like protein that is likely to be involved in regulation of transcriptional responses to NF-kappa B, including adhesion-dependent pathways of monocyte activation.", "output": {"entities": {"dna": [{"text": "MAD-3 cDNA", "start": 4, "end": 14}], "protein": [{"text": "I kappa B-like protein", "start": 26, "end": 48}, {"text": "NF-kappa B", "start": 125, "end": 135}]}}, "schema": []} {"input": "Cortivazol mediated induction of glucocorticoid receptor messenger ribonucleic acid in wild-type and dexamethasone -resistant human leukemic (CEM) cells.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 33, "end": 56}], "rna": [{"text": "messenger ribonucleic acid", "start": 57, "end": 83}], "cell_line": [{"text": "wild-type", "start": 87, "end": 96}, {"text": "dexamethasone -resistant human leukemic (CEM) cells", "start": 101, "end": 152}]}}, "schema": []} {"input": "Cortivazol is a phenylpyrazolo glucocorticoid of high potency and unusual structure.", "output": {"entities": {}}, "schema": []} {"input": "In both wild-type and highly dexamethasone (dex)-resistant clones of the human leukemic cell line CEM, exposure to cortivazol leads to cell death.", "output": {"entities": {"cell_line": [{"text": "wild-type", "start": 8, "end": 17}, {"text": "dexamethasone (dex)-resistant clones", "start": 29, "end": 65}, {"text": "human leukemic cell line CEM", "start": 73, "end": 101}]}}, "schema": []} {"input": "It has been shown recently that in wild-type CEM cells but not in a dex-resistant, glucocorticoid receptor (GR)-defective clone ICR-27 TK-3, dex induces GR mRNA.", "output": {"entities": {"cell_line": [{"text": "wild-type CEM cells", "start": 35, "end": 54}, {"text": "dex-resistant,", "start": 68, "end": 82}, {"text": "(GR)-defective clone", "start": 107, "end": 127}, {"text": "ICR-27 TK-3", "start": 128, "end": 139}], "protein": [{"text": "glucocorticoid receptor", "start": 83, "end": 106}], "rna": [{"text": "GR mRNA", "start": 153, "end": 160}]}}, "schema": []} {"input": "To test the hypothesis that cortivazol acts in dex -resistant cells by making use of the residual GR found there, wild-type and dex -resistant clones were treated with various concentrations of cortivazol and induction of GR mRNA was studied.", "output": {"entities": {"cell_line": [{"text": "dex -resistant cells", "start": 47, "end": 67}, {"text": "dex -resistant clones", "start": 128, "end": 149}], "protein": [{"text": "GR", "start": 98, "end": 100}], "rna": [{"text": "GR mRNA", "start": 222, "end": 229}]}}, "schema": []} {"input": "Cortivazol significantly induced GR mRNA in the normal CEM-C7 as well as in two classes of dex -resistant clones, although the dex -resistant clones needed at least 10 times more cortivazol than the normal cells for significant GR mRNA induction.", "output": {"entities": {"rna": [{"text": "GR mRNA", "start": 33, "end": 40}, {"text": "mRNA", "start": 231, "end": 235}], "cell_line": [{"text": "normal CEM-C7", "start": 48, "end": 61}, {"text": "dex -resistant clones", "start": 91, "end": 112}, {"text": "dex -resistant clones", "start": 127, "end": 148}], "cell_type": [{"text": "normal cells", "start": 199, "end": 211}], "protein": [{"text": "GR", "start": 228, "end": 230}]}}, "schema": []} {"input": "Increased levels of GR mRNA were noticed as early as 3 h after treatment.", "output": {"entities": {"rna": [{"text": "GR mRNA", "start": 20, "end": 27}]}}, "schema": []} {"input": "A general correlation between induction of GR mRNA and lysis of the normal and dex -resistant cells was found.", "output": {"entities": {"protein": [{"text": "GR", "start": 43, "end": 45}], "rna": [{"text": "mRNA", "start": 46, "end": 50}], "cell_line": [{"text": "dex -resistant cells", "start": 79, "end": 99}]}}, "schema": []} {"input": "Positive induction of GR mRNA might be one of the earliest crucial steps in the lysis of normal and dex-resistant CEM cells, or might serve as a marker for the process.", "output": {"entities": {"rna": [{"text": "GR mRNA", "start": 22, "end": 29}]}}, "schema": []} {"input": "However, the lysis pathway in the dex -resistant cells is defective in that dex -resistant clones needed significantly more cortivazol than the normal cells for lysis of the cells.", "output": {"entities": {"cell_line": [{"text": "dex -resistant cells", "start": 34, "end": 54}, {"text": "dex -resistant clones", "start": 76, "end": 97}, {"text": "normal cells", "start": 144, "end": 156}]}}, "schema": []} {"input": "HIV enhancer activity perpetuated by NF-kappa B induction on infection of monocytes [see comments]", "output": {"entities": {"dna": [{"text": "HIV enhancer", "start": 0, "end": 12}], "protein": [{"text": "NF-kappa B", "start": 37, "end": 47}], "cell_type": [{"text": "monocytes", "start": 74, "end": 83}]}}, "schema": []} {"input": "Permissiveness to replication of human immunodeficiency virus (HIV) differs in T lymphocytes and macrophages.", "output": {"entities": {"cell_type": [{"text": "T lymphocytes", "start": 79, "end": 92}, {"text": "macrophages", "start": 97, "end": 108}]}}, "schema": []} {"input": "In T cells, HIV transcription is poorly detected in vivo.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 3, "end": 10}]}}, "schema": []} {"input": "Cloned, normal T lymphocytes show very little, if any, basal activity of the HIV enhancer and low nuclear expression of NF-kappa B, a potent transcriptional activator of the HIV enhancer.", "output": {"entities": {"cell_type": [{"text": "T lymphocytes", "start": 15, "end": 28}], "dna": [{"text": "HIV enhancer", "start": 77, "end": 89}, {"text": "HIV enhancer", "start": 174, "end": 186}], "protein": [{"text": "NF-kappa B", "start": 120, "end": 130}, {"text": "potent transcriptional activator", "start": 134, "end": 166}]}}, "schema": []} {"input": "In contrast, fixed tissue macrophages express detectable HIV proteins, indicating permanent virus transcription.", "output": {"entities": {"cell_type": [{"text": "macrophages", "start": 26, "end": 37}], "protein": [{"text": "HIV proteins", "start": 57, "end": 69}]}}, "schema": []} {"input": "One explanation for the perpetuation of virus infection in macrophages could be sustained nuclear NF-kappa B expression.", "output": {"entities": {"cell_type": [{"text": "macrophages", "start": 59, "end": 70}], "protein": [{"text": "NF-kappa B", "start": 98, "end": 108}]}}, "schema": []} {"input": "However, the U937 monocytic cell line, which is fully permissive to HIV replication, is known to express only low levels of nuclear NF-kappa B.", "output": {"entities": {"cell_line": [{"text": "U937 monocytic cell line", "start": 13, "end": 37}], "protein": [{"text": "nuclear NF-kappa B", "start": 124, "end": 142}]}}, "schema": []} {"input": "We show here that chronic HIV infection results in both induction of a nuclear factor with antigenic properties indistinguishable from those of NF-kappa B and permanently increased HIV enhancer activity.", "output": {"entities": {"protein": [{"text": "nuclear factor", "start": 71, "end": 85}, {"text": "NF-kappa B", "start": 144, "end": 154}], "dna": [{"text": "HIV enhancer", "start": 181, "end": 193}]}}, "schema": []} {"input": "This phenomenon, which is independent of tumour necrosis factor, is associated with HIV replication, and is thus likely to explain at least in part the perpetuation of HIV infection in monocytes.", "output": {"entities": {"protein": [{"text": "tumour necrosis factor", "start": 41, "end": 63}], "cell_type": [{"text": "monocytes", "start": 185, "end": 194}]}}, "schema": []} {"input": "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B [published erratum appears in Science 1991 Oct 4;254(5028):11]", "output": {"entities": {"dna": [{"text": "rel-related human cDNA", "start": 15, "end": 37}], "protein": [{"text": "65-kD subunit", "start": 67, "end": 80}, {"text": "NF-kappa B", "start": 84, "end": 94}]}}, "schema": []} {"input": "A DNA probe that spanned a domain conserved among the proto-oncogene c-rel, the Drosophila morphogen dorsal, and the p50 DNA binding subunit of NF-kappa B was generated from Jurkat T cell complementary DNA with the polymerase chain reaction (PCR) and degenerate oligonucleotides.", "output": {"entities": {"dna": [{"text": "DNA probe", "start": 2, "end": 11}, {"text": "proto-oncogene c-rel", "start": 54, "end": 74}, {"text": "Jurkat T cell complementary DNA", "start": 174, "end": 205}], "protein": [{"text": "Drosophila morphogen dorsal", "start": 80, "end": 107}, {"text": "p50 DNA binding subunit", "start": 117, "end": 140}, {"text": "NF-kappa B", "start": 144, "end": 154}]}}, "schema": []} {"input": "This probe was used to identify a rel-related complementary DNA that hybridized to a 2.6-kilobase messenger RNA present in human T and B lymphocytes.", "output": {"entities": {"dna": [{"text": "rel-related complementary DNA", "start": 34, "end": 63}], "rna": [{"text": "2.6-kilobase messenger RNA", "start": 85, "end": 111}]}}, "schema": []} {"input": "In vitro transcription and translation of the complementary DNA resulted in the synthesis of a protein with an apparent molecular size of 65 kilodaltons (kD).", "output": {"entities": {"dna": [{"text": "complementary DNA", "start": 46, "end": 63}], "protein": [{"text": "65 kilodaltons", "start": 138, "end": 152}]}}, "schema": []} {"input": "The translated protein showed weak DNA binding with a specificity for the kappa B binding motif.", "output": {"entities": {"dna": [{"text": "kappa B binding motif", "start": 74, "end": 95}]}}, "schema": []} {"input": "This protein-DNA complex comigrated with the complex obtained with the purified human p65 NF-kappa B subunit and binding was inhibited by I kappa B-alpha and -beta proteins.", "output": {"entities": {"protein": [{"text": "protein-DNA complex", "start": 5, "end": 24}, {"text": "purified human p65 NF-kappa B subunit", "start": 71, "end": 108}, {"text": "I kappa B-alpha", "start": 138, "end": 153}, {"text": "-beta proteins", "start": 158, "end": 172}]}}, "schema": []} {"input": "In addition, the 65-kD protein associated with the p50 subunit of NF-kappa B and the kappa B probe to form a complex with the same electrophoretic mobility as the NF-kappa B -DNA complex.", "output": {"entities": {"protein": [{"text": "65-kD protein", "start": 17, "end": 30}, {"text": "p50 subunit", "start": 51, "end": 62}, {"text": "NF-kappa B", "start": 66, "end": 76}, {"text": "NF-kappa B -DNA complex", "start": 163, "end": 186}], "dna": [{"text": "kappa B probe", "start": 85, "end": 98}]}}, "schema": []} {"input": "Therefore the rel-related 65-kD protein may represent the p65 subunit of the active NF-kappa B transcription factor complex.", "output": {"entities": {"protein": [{"text": "rel-related 65-kD protein", "start": 14, "end": 39}, {"text": "p65 subunit", "start": 58, "end": 69}, {"text": "active NF-kappa B transcription factor complex", "start": 77, "end": 123}]}}, "schema": []} {"input": "The human myelomonocytic cell line U-937 as a model for studying alterations in steroid-induced monokine gene expression: marked enhancement of lipopolysaccharide-stimulated interleukin-1 beta messenger RNA levels by 1,25-dihydroxyvitamin D3.", "output": {"entities": {"cell_line": [{"text": "human myelomonocytic cell line U-937", "start": 4, "end": 40}], "rna": [{"text": "lipopolysaccharide-stimulated interleukin-1 beta messenger RNA", "start": 144, "end": 206}]}}, "schema": []} {"input": "The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3 ], is a potent regulator of human monocyte/macrophage function in vitro.", "output": {"entities": {}}, "schema": []} {"input": "To establish a model for 1,25-(OH)2D3 regulation of human monocyte monokine synthesis, three human cell lines (U-937, THP-1, and HL-60) were examined for: 1) the presence of functional 1,25-(OH)2D3 receptors; 2) the accumulation of interleukin-1 beta (IL-1 beta) mRNA and IL-1 beta protein in response to lipopolysaccharide (LPS ); and 3) the regulation of this response by 1,25-(OH)2D3.", "output": {"entities": {"cell_line": [{"text": "human cell lines", "start": 93, "end": 109}, {"text": "U-937", "start": 111, "end": 116}, {"text": "THP-1", "start": 118, "end": 123}, {"text": "HL-60", "start": 129, "end": 134}], "rna": [{"text": "interleukin-1 beta (", "start": 232, "end": 252}, {"text": ") mRNA", "start": 261, "end": 267}], "protein": [{"text": "IL-1 beta", "start": 252, "end": 261}, {"text": "IL-1 beta protein", "start": 272, "end": 289}]}}, "schema": []} {"input": "All three cell lines expressed vitamin D receptor and had increased levels of IL-1 beta mRNA in response to LPS.", "output": {"entities": {"rna": [{"text": "IL-1 beta mRNA", "start": 78, "end": 92}]}}, "schema": []} {"input": "Preincubation of cells with 1,25-(OH)2D3 augmented IL-1 beta mRNA levels only in U-937 and HL-60 cells.", "output": {"entities": {"protein": [{"text": "IL-1 beta", "start": 51, "end": 60}], "rna": [{"text": "mRNA", "start": 61, "end": 65}], "cell_line": [{"text": "U-937", "start": 81, "end": 86}, {"text": "HL-60", "start": 91, "end": 96}]}}, "schema": []} {"input": "From these data, and taking into consideration their state of differentiation and relative ease of culture, U-937 was chosen over HL-60 and THP-1 as the cell line we further characterized.", "output": {"entities": {"cell_line": [{"text": "U-937", "start": 108, "end": 113}, {"text": "HL-60", "start": 130, "end": 135}, {"text": "THP-1", "start": 140, "end": 145}]}}, "schema": []} {"input": "In U-937 cells, optimum time and dose of pretreatment with 1,25-(OH)2D3 were determined to be 12-24 h at a receptor saturating concentration of 1,25-(OH)2D3 (10 nM).", "output": {"entities": {"cell_line": [{"text": "U-937 cells", "start": 3, "end": 14}]}}, "schema": []} {"input": "Preincubation of cells with 1,25-(OH)2D3 had no effect on the time course of IL-1 beta mRNA appearance in response to LPS.", "output": {"entities": {"protein": [{"text": "IL-1 beta", "start": 77, "end": 86}], "rna": [{"text": "mRNA", "start": 87, "end": 91}]}}, "schema": []} {"input": "However, exposure of U-937 cells to 1,25-(OH)2D3 increased by 200% the level of IL-1 beta mRNA detected and decreased by three orders of magnitude the concentration of LPS required to achieve steady state mRNA levels equivalent to those observed in U-937 cells not preincubated with the hormone.2+o", "output": {"entities": {"cell_line": [{"text": "U-937 cells", "start": 21, "end": 32}, {"text": "U-937 cells", "start": 249, "end": 260}], "protein": [{"text": "IL-1 beta", "start": 80, "end": 89}], "rna": [{"text": "mRNA", "start": 90, "end": 94}]}}, "schema": []} {"input": "Regulation of M-CSF expression by M-CSF: role of protein kinase C and transcription factor NF kappa B.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 14, "end": 19}, {"text": "M-CSF", "start": 34, "end": 39}, {"text": "protein kinase C", "start": 49, "end": 65}, {"text": "transcription factor NF kappa B", "start": 70, "end": 101}]}}, "schema": []} {"input": "Macrophage-colony-stimulating factor (M-CSF ), also referred to as CSF-1, regulates the survival, growth, differentiation and functional activity of monocytes by binding to a single class of high-affinity cell surface receptors, known to be the product of the c-fms protooncogene.", "output": {"entities": {"protein": [{"text": "Macrophage-colony-stimulating factor", "start": 0, "end": 36}, {"text": "M-CSF", "start": 38, "end": 43}, {"text": "CSF-1", "start": 67, "end": 72}, {"text": "high-affinity cell surface receptors", "start": 191, "end": 227}], "cell_type": [{"text": "monocytes", "start": 149, "end": 158}], "dna": [{"text": "c-fms protooncogene", "start": 260, "end": 279}]}}, "schema": []} {"input": "The detection of both M-CSF and c-fms expression by cells of the monocyte lineage has suggested that M-CSF may act by an autocrine mechanism.", "output": {"entities": {"cell_type": [{"text": "monocyte lineage", "start": 65, "end": 81}], "protein": [{"text": "M-CSF", "start": 101, "end": 106}]}}, "schema": []} {"input": "Interestingly, it has been shown that M-CSF can induce the expression of its own gene.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 38, "end": 43}]}}, "schema": []} {"input": "Although sensitivity to M-CSF can be modulated by regulation of receptor expression and function, M-CSF responsiveness is largely determined at a postreceptor level.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 24, "end": 29}, {"text": "M-CSF", "start": 98, "end": 103}]}}, "schema": []} {"input": "To date, little is known about the intracellular pathway of M-CSF signal transduction.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 60, "end": 65}]}}, "schema": []} {"input": "We have therefore investigated the changes in protein kinase C (PKC) activity upon exposure of monocytes to M-CSF.", "output": {"entities": {"protein": [{"text": "protein kinase C", "start": 46, "end": 62}, {"text": "PKC", "start": 64, "end": 67}, {"text": "M-CSF", "start": 108, "end": 113}], "cell_type": [{"text": "monocytes", "start": 95, "end": 104}]}}, "schema": []} {"input": "We show that M-CSF activates and translocates PKC.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 13, "end": 18}, {"text": "PKC", "start": 46, "end": 49}]}}, "schema": []} {"input": "Inhibition of PKC by the isoquinoline derivative H7 abolishes induction of M-CSF by M-CSF.", "output": {"entities": {"protein": [{"text": "PKC", "start": 14, "end": 17}, {"text": "M-CSF", "start": 75, "end": 80}, {"text": "M-CSF", "start": 84, "end": 89}]}}, "schema": []} {"input": "Furthermore, activation of PKC was pertussis-toxin-sensitive and was associated with the detection of an NF kappa B protein in nuclear extracts of M-CSF -induced blood monocytes but not in monocytes exposed to medium treatment only.", "output": {"entities": {"protein": [{"text": "PKC", "start": 27, "end": 30}, {"text": "NF kappa B protein", "start": 105, "end": 123}], "cell_line": [{"text": "M-CSF -induced blood monocytes", "start": 147, "end": 177}], "cell_type": [{"text": "monocytes", "start": 189, "end": 198}]}}, "schema": []} {"input": "The results suggest that M-CSF induction of M-CSF involves G proteins, PKC and NF kappa B.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 25, "end": 30}, {"text": "M-CSF", "start": 44, "end": 49}, {"text": "G proteins", "start": 59, "end": 69}, {"text": "PKC", "start": 71, "end": 74}, {"text": "NF kappa B", "start": 79, "end": 89}]}}, "schema": []} {"input": "Clone pAT 133 identifies a gene that encodes another human member of a class of growth factor-induced genes with almost identical zinc-finger domains.", "output": {"entities": {"dna": [{"text": "Clone pAT 133", "start": 0, "end": 13}, {"text": "growth factor-induced genes", "start": 80, "end": 107}], "protein": [{"text": "zinc-finger domains", "start": 130, "end": 149}]}}, "schema": []} {"input": "We report the structure and regulation of a gene represented by clone pAT 133, which is induced upon transition from a resting state (G0) through the early phase of the cell cycle (G1 ).", "output": {"entities": {"dna": [{"text": "clone pAT 133", "start": 64, "end": 77}]}}, "schema": []} {"input": "The pAT 133 gene is immediately induced, with FOS -like kinetics, in human T cells and in fibroblasts.", "output": {"entities": {"dna": [{"text": "pAT 133 gene", "start": 4, "end": 16}], "protein": [{"text": "FOS", "start": 46, "end": 49}], "cell_type": [{"text": "human T cells", "start": 69, "end": 82}, {"text": "fibroblasts", "start": 90, "end": 101}]}}, "schema": []} {"input": "Primary structure analysis showed that the encoded protein contains three tandem zinc-finger sequences of the type Cys2-Xaa12-His2.", "output": {"entities": {"protein": [{"text": "tandem", "start": 74, "end": 80}, {"text": "zinc-finger sequences", "start": 81, "end": 102}, {"text": "Cys2-Xaa12-His2", "start": 115, "end": 130}]}}, "schema": []} {"input": "This zinc-finger region, which is thought to bind DNA in a sequence-specific manner, is similar (greater than 80% on the amino acid level) to two previously described transcription factors pAT 225/EGR1 and pAT 591/EGR2.", "output": {"entities": {"protein": [{"text": "zinc-finger region", "start": 5, "end": 23}, {"text": "transcription factors", "start": 167, "end": 188}, {"text": "pAT 225/EGR1", "start": 189, "end": 201}, {"text": "591/EGR2", "start": 210, "end": 218}]}}, "schema": []} {"input": "Except for the conserved zinc-finger domains, the amino acid sequences of the three proteins are distinct.", "output": {"entities": {"protein": [{"text": "zinc-finger domains", "start": 25, "end": 44}, {"text": "amino acid sequences", "start": 50, "end": 70}]}}, "schema": []} {"input": "This structural similarity suggests that the pAT 133 gene encodes a transcription factor with a specific biological function.", "output": {"entities": {"dna": [{"text": "pAT 133 gene", "start": 45, "end": 57}], "protein": [{"text": "transcription factor", "start": 68, "end": 88}]}}, "schema": []} {"input": "Comparing the regulation of these related zinc-finger -encoding genes showed coordinate induction upon mitogenic stimulation of resting T lymphocytes and of resting fibroblasts.", "output": {"entities": {"dna": [{"text": "zinc-finger -encoding genes", "start": 42, "end": 69}], "cell_type": [{"text": "resting T lymphocytes", "start": 128, "end": 149}, {"text": "resting fibroblasts", "start": 157, "end": 176}]}}, "schema": []} {"input": "However, upon transition from a proliferating (G1) to a resting state of the cell cycle the three genes were differently regulated.", "output": {"entities": {}}, "schema": []} {"input": "In human histiocytic U937 cells mRNA of clone pAT 133 was constitutively expressed, whereas mRNA of pAT 225/EGR1 was induced upon induction of terminal differentiation.", "output": {"entities": {"rna": [{"text": "human histiocytic U937 cells mRNA", "start": 3, "end": 36}, {"text": "mRNA", "start": 92, "end": 96}], "protein": [{"text": "pAT 225/EGR1", "start": 100, "end": 112}]}}, "schema": []} {"input": "In contrast mRNA representing pAT 591/EGR2 was not expressed in these cells.", "output": {"entities": {"protein": [{"text": "591/EGR2", "start": 34, "end": 42}]}}, "schema": []} {"input": "This difference in gene regulation suggests distinct biological roles in the control of cell proliferation for the respective proteins.", "output": {"entities": {}}, "schema": []} {"input": "v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII.", "output": {"entities": {"protein": [{"text": "v-erbA", "start": 0, "end": 6}, {"text": "c-erbA", "start": 48, "end": 54}], "cell_type": [{"text": "erythroid cell", "start": 67, "end": 81}], "dna": [{"text": "erbA target gene", "start": 120, "end": 136}, {"text": "CAII", "start": 137, "end": 141}]}}, "schema": []} {"input": "The v-erbA oncoprotein represents a retrovirus-transduced oncogenic version of the thyroid hormone (T3/T4) receptor c-erbA (type alpha).", "output": {"entities": {"protein": [{"text": "v-erbA oncoprotein", "start": 4, "end": 22}, {"text": "thyroid hormone (T3/T4) receptor", "start": 83, "end": 115}, {"text": "c-erbA (type alpha)", "start": 116, "end": 135}]}}, "schema": []} {"input": "It contributes to virus-induced erythroleukemia by efficiently arresting differentiation of red cell progenitors and by suppressing transcription of erythrocyte-specific genes.", "output": {"entities": {"cell_type": [{"text": "red cell progenitors", "start": 92, "end": 112}], "dna": [{"text": "erythrocyte-specific genes", "start": 149, "end": 175}]}}, "schema": []} {"input": "Here, we show that v-erbA and c-erbA bind directly to sequences within the promoter of the erythrocyte-specific carbonic anhydrase II (CAII ), a gene whose transcription is efficiently suppressed by v-erbA.", "output": {"entities": {"protein": [{"text": "v-erbA", "start": 19, "end": 25}, {"text": "c-erbA", "start": 30, "end": 36}, {"text": "erythrocyte-specific carbonic anhydrase II", "start": 91, "end": 133}, {"text": "v-erbA", "start": 199, "end": 205}], "dna": [{"text": "promoter", "start": 75, "end": 83}, {"text": "CAII", "start": 135, "end": 139}]}}, "schema": []} {"input": "This erbA-binding site confers thyroid hormone responsiveness to a heterologous promoter in transient expression experiments and is a target for efficient down-regulation of CAII transcription by the v-erbA oncoprotein.", "output": {"entities": {"dna": [{"text": "erbA-binding site", "start": 5, "end": 22}, {"text": "heterologous promoter", "start": 67, "end": 88}, {"text": "CAII", "start": 174, "end": 178}], "protein": [{"text": "v-erbA oncoprotein", "start": 200, "end": 218}]}}, "schema": []} {"input": "In stably transformed erythroblasts coexpressing the v-erbA oncoprotein and the c-erbA/T3 receptor at an approximately equimolar ratio, c-erbA activity is dominant over v-erbA.", "output": {"entities": {"cell_line": [{"text": "stably transformed erythroblasts", "start": 3, "end": 35}], "protein": [{"text": "v-erbA oncoprotein", "start": 53, "end": 71}, {"text": "c-erbA/T3 receptor", "start": 80, "end": 98}, {"text": "c-erbA", "start": 136, "end": 142}, {"text": "v-erbA", "start": 169, "end": 175}]}}, "schema": []} {"input": "T3 efficiently induced erythroid differentiation in these cells, thus overcoming the v-erbA -mediated differentiation arrest.", "output": {"entities": {"protein": [{"text": "v-erbA", "start": 85, "end": 91}]}}, "schema": []} {"input": "Likewise, T3 activated CAII transcription as well as transient expression of a T3 -responsive reporter gene containing the CAII -specific erbA-binding site.", "output": {"entities": {"dna": [{"text": "CAII", "start": 23, "end": 27}, {"text": "T3 -responsive reporter gene", "start": 79, "end": 107}, {"text": "CAII -specific erbA-binding site", "start": 123, "end": 155}]}}, "schema": []} {"input": "The c-erbA -dependent activation of this CAII reporter construct could only be suppressed by very high amounts of v-erbA.", "output": {"entities": {"protein": [{"text": "c-erbA", "start": 4, "end": 10}, {"text": "v-erbA", "start": 114, "end": 120}], "dna": [{"text": "CAII reporter construct", "start": 41, "end": 64}]}}, "schema": []} {"input": "Our results suggest that overexpression of v-erbA is required for its function as an oncoprotein.", "output": {"entities": {"protein": [{"text": "v-erbA", "start": 43, "end": 49}, {"text": "oncoprotein", "start": 85, "end": 96}]}}, "schema": []} {"input": "Anti-CD2 receptor antibodies activate the HIV long terminal repeat in T lymphocytes.", "output": {"entities": {"protein": [{"text": "Anti-CD2 receptor antibodies", "start": 0, "end": 28}], "dna": [{"text": "HIV long terminal repeat", "start": 42, "end": 66}], "cell_type": [{"text": "T lymphocytes", "start": 70, "end": 83}]}}, "schema": []} {"input": "The CD2 T lymphocyte glycoprotein surface molecule mediates both cell to cell adhesion and T cell activation, two processes that are involved in the spread of HIV infection.", "output": {"entities": {"protein": [{"text": "CD2 T lymphocyte glycoprotein surface molecule", "start": 4, "end": 50}]}}, "schema": []} {"input": "Treatment of chronically HIV-infected PBMC with anti-CD2 mAb has been shown to induce the expression of infectious virus from these cultures.", "output": {"entities": {"cell_line": [{"text": "chronically HIV-infected PBMC", "start": 13, "end": 42}], "protein": [{"text": "anti-CD2 mAb", "start": 48, "end": 60}]}}, "schema": []} {"input": "In this study we investigated the mechanisms whereby anti-CD2 antibodies stimulate viral production.", "output": {"entities": {"protein": [{"text": "anti-CD2 antibodies", "start": 53, "end": 72}]}}, "schema": []} {"input": "We demonstrate that treatment of transiently transfected T lymphocytes with anti-CD2 antibodies results in activation of the HIV long terminal repeat.", "output": {"entities": {"cell_type": [{"text": "T lymphocytes", "start": 57, "end": 70}], "protein": [{"text": "anti-CD2 antibodies", "start": 76, "end": 95}], "dna": [{"text": "HIV long terminal repeat", "start": 125, "end": 149}]}}, "schema": []} {"input": "Furthermore, CAT assays using mutated HIV long terminal repeat -CAT constructs and gel shift assays demonstrate that this activation is dependent on the NF-kappa B enhancer.", "output": {"entities": {"protein": [{"text": "CAT", "start": 13, "end": 16}], "dna": [{"text": "HIV long terminal repeat -CAT constructs", "start": 38, "end": 78}, {"text": "NF-kappa B enhancer", "start": 153, "end": 172}]}}, "schema": []} {"input": "These studies suggest that interaction of CD2 with its natural ligand, LFA-3, may play a role in regulation of HIV expression.", "output": {"entities": {"protein": [{"text": "CD2", "start": 42, "end": 45}, {"text": "LFA-3", "start": 71, "end": 76}]}}, "schema": []} {"input": "Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1.", "output": {"entities": {"protein": [{"text": "NF-kappa B transcription factor", "start": 92, "end": 123}]}}, "schema": []} {"input": "Hydrogen peroxide and oxygen radicals are agents commonly produced during inflammatory processes.", "output": {"entities": {}}, "schema": []} {"input": "In this study, we show that micromolar concentrations of H2O2 can induce the expression and replication of HIV-1 in a human T cell line.", "output": {"entities": {"cell_line": [{"text": "human T cell line", "start": 118, "end": 135}]}}, "schema": []} {"input": "The effect is mediated by the NF-kappa B transcription factor which is potently and rapidly activated by an H2O2 treatment of cells from its inactive cytoplasmic form.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 30, "end": 40}, {"text": "transcription factor", "start": 41, "end": 61}, {"text": "inactive cytoplasmic form", "start": 141, "end": 166}]}}, "schema": []} {"input": "N-acetyl-L-cysteine (NAC ), a well characterized antioxidant which counteracts the effects of reactive oxygen intermediates (ROI) in living cells, prevented the activation of NF-kappa B by H2O2.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 175, "end": 185}]}}, "schema": []} {"input": "NAC and other thiol compounds also blocked the activation of NF-kappa B by cycloheximide, double-stranded RNA, calcium ionophore, TNF-alpha, active phorbol ester, interleukin-1, lipopolysaccharide and lectin.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 61, "end": 71}, {"text": "TNF-alpha", "start": 130, "end": 139}, {"text": "interleukin-1", "start": 163, "end": 176}, {"text": "lectin", "start": 201, "end": 207}], "rna": [{"text": "double-stranded RNA", "start": 90, "end": 109}]}}, "schema": []} {"input": "This suggests that diverse agents thought to activate NF-kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 54, "end": 64}]}}, "schema": []} {"input": "ROI appear to serve as messengers mediating directly or indirectly the release of the inhibitory subunit I kappa B from NF-kappa B.", "output": {"entities": {"protein": [{"text": "inhibitory subunit", "start": 86, "end": 104}, {"text": "I kappa B", "start": 105, "end": 114}, {"text": "NF-kappa B", "start": 120, "end": 130}]}}, "schema": []} {"input": "Inhibition of transcription factors belonging to the rel/ NF-kappa B family by a transdominant negative mutant.", "output": {"entities": {"protein": [{"text": "transcription factors", "start": 14, "end": 35}, {"text": "rel/ NF-kappa B family", "start": 53, "end": 75}, {"text": "transdominant negative mutant", "start": 81, "end": 110}]}}, "schema": []} {"input": "The KBF1 factor, which binds to the enhancer A located in the promoter of the mouse MHC class I gene H-2Kb, is indistinguishable from the p50 DNA binding subunit of the transcription factor NF-kappa B, which regulates a series of genes involved in immune and inflammatory responses.", "output": {"entities": {"protein": [{"text": "KBF1 factor", "start": 4, "end": 15}, {"text": "p50 DNA binding subunit", "start": 138, "end": 161}, {"text": "transcription factor", "start": 169, "end": 189}, {"text": "NF-kappa B", "start": 190, "end": 200}], "dna": [{"text": "enhancer A", "start": 36, "end": 46}, {"text": "promoter", "start": 62, "end": 70}, {"text": "mouse MHC class I gene", "start": 78, "end": 100}, {"text": "H-2Kb", "start": 101, "end": 106}]}}, "schema": []} {"input": "The KBF1/p50 factor binds as a homodimer but can also form heterodimers with the products of other members of the same family, like the c-rel and v-rel (proto)oncogenes.", "output": {"entities": {"protein": [{"text": "KBF1/p50 factor", "start": 4, "end": 19}, {"text": "homodimer", "start": 31, "end": 40}, {"text": "heterodimers", "start": 59, "end": 71}]}}, "schema": []} {"input": "The dimerization domain of KBF1/p50 is contained between amino acids 201 and 367.", "output": {"entities": {"protein": [{"text": "dimerization domain", "start": 4, "end": 23}, {"text": "KBF1/p50", "start": 27, "end": 35}, {"text": "between amino acids 201 and 367", "start": 49, "end": 80}]}}, "schema": []} {"input": "A mutant of KBF1/p50 (delta SP ), unable to bind to DNA but able to form homo- or heterodimers, has been constructed.", "output": {"entities": {"protein": [{"text": "KBF1/p50", "start": 12, "end": 20}, {"text": "delta SP", "start": 22, "end": 30}, {"text": "heterodimers", "start": 82, "end": 94}]}}, "schema": []} {"input": "This protein reduces or abolishes in vitro the DNA binding activity of wild-type proteins of the same family (KBF1/p50, c- and v- rel ).", "output": {"entities": {"protein": [{"text": "wild-type proteins", "start": 71, "end": 89}, {"text": "KBF1/p50", "start": 110, "end": 118}]}}, "schema": []} {"input": "This mutant also functions in vivo as a trans-acting dominant negative regulator: the transcriptional inducibility of the HIV long terminal repeat (which contains two potential NF-kappa B binding sites) by phorbol ester (PMA) is inhibited when it is co-transfected into CD4+ T cells with the delta SP mutant.", "output": {"entities": {"protein": [{"text": "trans-acting dominant negative regulator", "start": 40, "end": 80}, {"text": "NF-kappa B", "start": 177, "end": 187}, {"text": "delta SP", "start": 292, "end": 300}], "dna": [{"text": "HIV long terminal repeat", "start": 122, "end": 146}], "cell_line": [{"text": "CD4+ T cells", "start": 270, "end": 282}]}}, "schema": []} {"input": "Similarly the basal as well as TNF or IL1-induced activity of the MHC class I H-2Kb promoter can be inhibited by this mutant in two different cell lines.", "output": {"entities": {"protein": [{"text": "TNF", "start": 31, "end": 34}], "dna": [{"text": "MHC class I H-2Kb promoter", "start": 66, "end": 92}], "cell_line": [{"text": "cell lines", "start": 142, "end": 152}]}}, "schema": []} {"input": "These results constitute the first formal demonstration that these genes are regulated by members of the rel/ NF-kappa B family.", "output": {"entities": {"protein": [{"text": "rel/ NF-kappa B family", "start": 105, "end": 127}]}}, "schema": []} {"input": "Tissue-specific expression of the platelet GPIIb gene.", "output": {"entities": {"dna": [{"text": "platelet GPIIb gene", "start": 34, "end": 53}]}}, "schema": []} {"input": "One of the major objectives in the study of thrombogenesis is to determine the mechanisms by which a hematopoietic progenitor is activated and committed to the megakaryocytic lineage.", "output": {"entities": {"cell_type": [{"text": "hematopoietic progenitor", "start": 101, "end": 125}, {"text": "megakaryocytic lineage", "start": 160, "end": 182}]}}, "schema": []} {"input": "Recent development of primary cultures of human megakaryocytes and the molecular cloning of genes that are specific to this lineage offer the possibility of getting some insights into the genetic mechanisms that control megakaryocytopoiesis.", "output": {"entities": {"cell_line": [{"text": "primary cultures", "start": 22, "end": 38}, {"text": "human megakaryocytes", "start": 42, "end": 62}]}}, "schema": []} {"input": "One gene of interest is the glycoprotein IIb (GPIIb) gene; GPIIb, the alpha subunit of the platelet cytoadhesin GPIIb-IIIa, is produced in megakaryocytes at an early stage of the differentiation, whereas the other subunit of this complex, GPIIIa, is expressed in other cells.", "output": {"entities": {"dna": [{"text": "glycoprotein IIb (GPIIb) gene", "start": 28, "end": 57}, {"text": "GPIIb", "start": 59, "end": 64}], "protein": [{"text": "alpha subunit", "start": 70, "end": 83}, {"text": "platelet cytoadhesin GPIIb-IIIa", "start": 91, "end": 122}, {"text": "GPIIIa", "start": 239, "end": 245}], "cell_line": [{"text": "megakaryocytes", "start": 139, "end": 153}]}}, "schema": []} {"input": "For these reasons, the 5'-flanking region of the GPIIb gene was used to identify the regions that interact with DNA-binding nuclear factors.", "output": {"entities": {"dna": [{"text": "5'-flanking region", "start": 23, "end": 41}, {"text": "GPIIb gene", "start": 49, "end": 59}], "protein": [{"text": "DNA-binding nuclear factors", "start": 112, "end": 139}]}}, "schema": []} {"input": "A fragment extending from -643 to +33 is capable of controlling the tissue-specific expression of the CAT gene in transfection experiments.", "output": {"entities": {"dna": [{"text": "-643 to +33", "start": 26, "end": 37}, {"text": "CAT gene", "start": 102, "end": 110}]}}, "schema": []} {"input": "Within this region, we have identified several sequences that are implicated in DNA protein interactions as shown in DNAse I footprints and gel mobility shift assays.", "output": {"entities": {"protein": [{"text": "DNAse I", "start": 117, "end": 124}]}}, "schema": []} {"input": "One region, centered at -54, is similar to a nuclear factor E1-binding site, and a region located at position -233 contains a CCAAT motif.", "output": {"entities": {"dna": [{"text": "nuclear factor E1-binding site", "start": 45, "end": 75}, {"text": "CCAAT motif", "start": 126, "end": 137}]}}, "schema": []} {"input": "Two domains centered at positions -345 and -540, respectively, bind proteins that are present in megakaryocytic cells and nonrelated cells as well.", "output": {"entities": {"cell_line": [{"text": "megakaryocytic cells", "start": 97, "end": 117}], "cell_type": [{"text": "nonrelated cells", "start": 122, "end": 138}]}}, "schema": []} {"input": "Finally, two other domains, located at positions -460 and -510, interact with proteins that are only present in megakaryocytic cells.", "output": {"entities": {"cell_line": [{"text": "megakaryocytic cells", "start": 112, "end": 132}]}}, "schema": []} {"input": "In addition, deletion of the region containing these two domains results in a significant decrease of the promoter activity.", "output": {"entities": {"dna": [{"text": "promoter", "start": 106, "end": 114}]}}, "schema": []} {"input": "It is very likely that these domains bind megakaryocyte-specific nuclear proteins acting as positive transcription factors.", "output": {"entities": {"protein": [{"text": "megakaryocyte-specific nuclear proteins", "start": 42, "end": 81}, {"text": "positive", "start": 92, "end": 100}, {"text": "transcription factors", "start": 101, "end": 122}]}}, "schema": []} {"input": "Lymphocyte glucocorticoid receptor binding during depression and after clinical recovery.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 11, "end": 34}]}}, "schema": []} {"input": "Lymphocyte glucocorticoid receptor binding parameters were studied in 15 severely depressed patients during depression and after clinical recovery, and in 15 healthy controls.", "output": {"entities": {"protein": [{"text": "Lymphocyte glucocorticoid receptor", "start": 0, "end": 34}]}}, "schema": []} {"input": "There was no difference in glucocorticoid receptor number or affinity between depressed patients and recovered or control subjects.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 27, "end": 50}]}}, "schema": []} {"input": "Afternoon ACTH and cortisol concentrations did not differ significantly between the three groups.", "output": {"entities": {}}, "schema": []} {"input": "No relationship could be established between glucocorticoid receptor binding and antidepressant medication.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 45, "end": 68}]}}, "schema": []} {"input": "These data support the view of an impaired ligand-induced plasticity of glucocorticoid receptor regulation rather than the hypothesis of decreased glucocorticoid receptor numbers during depression.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 72, "end": 95}, {"text": "glucocorticoid receptor", "start": 147, "end": 170}]}}, "schema": []} {"input": "Every enhancer works with every promoter for all the combinations tested: could new regulatory pathways evolve by enhancer shuffling?", "output": {"entities": {"dna": [{"text": "promoter", "start": 32, "end": 40}]}}, "schema": []} {"input": "The promoters and enhancers of cell type-specific genes are often conserved in evolution, and hence one might expect that a given enhancer has evolved to work best with its own promoter.", "output": {"entities": {"dna": [{"text": "promoters", "start": 4, "end": 13}, {"text": "enhancers", "start": 18, "end": 27}, {"text": "enhancer", "start": 130, "end": 138}, {"text": "promoter", "start": 177, "end": 185}]}}, "schema": []} {"input": "While this expectation may be realized in some cases, we have not found evidence for it.", "output": {"entities": {}}, "schema": []} {"input": "A total of 27 combinations of different promoters and enhancers were tested by transfection into cultured cells.", "output": {"entities": {"dna": [{"text": "promoters", "start": 40, "end": 49}, {"text": "enhancers", "start": 54, "end": 63}], "cell_line": [{"text": "cultured cells", "start": 97, "end": 111}]}}, "schema": []} {"input": "We found that the relative efficiency of the enhancers is approximately the same, irrespective of the type of promoter used, i.e., there was no strong preference for any given enhancer/ promoter combination.", "output": {"entities": {"dna": [{"text": "enhancers", "start": 45, "end": 54}, {"text": "promoter", "start": 110, "end": 118}, {"text": "promoter", "start": 186, "end": 194}]}}, "schema": []} {"input": "Notably, we do not see particularly strong transcription when the immunoglobulin kappa enhancer (or the immunoglobulin heavy chain enhancer) is used to activate a kappa gene promoter.", "output": {"entities": {"dna": [{"text": "immunoglobulin kappa enhancer", "start": 66, "end": 95}, {"text": "enhancer", "start": 131, "end": 139}, {"text": "promoter", "start": 174, "end": 182}], "protein": [{"text": "immunoglobulin heavy chain", "start": 104, "end": 130}]}}, "schema": []} {"input": "We propose that a generally permissive enhancer/ promoter interaction is of evolutionary benefit for higher eukaryotes: by enhancer shuffling, genes could be easily brought under a new type of inducibility/cell type specificity.", "output": {"entities": {"dna": [{"text": "promoter", "start": 49, "end": 57}]}}, "schema": []} {"input": "Towards a molecular understanding of T-cell differentiation.", "output": {"entities": {}}, "schema": []} {"input": "Lymphoid differentiation is one of the best studied examples of mammalian development.", "output": {"entities": {}}, "schema": []} {"input": "Here Hans Clevers and Michael Owen describe how the cloning of the genes that encode T-cell-specific membrane proteins allows the identification of transcription factors that control the expression of these T-cell genes.", "output": {"entities": {"protein": [{"text": "T-cell-specific membrane proteins", "start": 85, "end": 118}, {"text": "transcription factors", "start": 148, "end": 169}], "dna": [{"text": "T-cell genes", "start": 207, "end": 219}]}}, "schema": []} {"input": "Such transcription factors play a key role in the development of the mature T-cell phenotype by functioning as'master regulators of T-cell differentiation'.", "output": {"entities": {"protein": [{"text": "transcription factors", "start": 5, "end": 26}]}}, "schema": []} {"input": "A study on the circadian rhythm of glucocorticoid receptor.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 35, "end": 58}]}}, "schema": []} {"input": "Circadian rhythm in glucocorticoid receptor (GR) was studied in the rat liver and human peripheral leukocytes.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 20, "end": 43}, {"text": "GR", "start": 45, "end": 47}], "cell_type": [{"text": "rat liver", "start": 68, "end": 77}, {"text": "human peripheral leukocytes", "start": 82, "end": 109}]}}, "schema": []} {"input": "For rats exposed to a natural environmental photic cycle or a 12L:12D artificial light regime, peak values of hepatic GR were detected between 23:00 and 02:00 h.", "output": {"entities": {"protein": [{"text": "hepatic GR", "start": 110, "end": 120}]}}, "schema": []} {"input": "Except for a 4-hour advancement of the peak, a similar circadian rhythm of hepatic GR was detected in rats reared under a reversed lighting regimen (12D:12L; lights on between 18:30 and 06:30 h).", "output": {"entities": {"protein": [{"text": "hepatic GR", "start": 75, "end": 85}]}}, "schema": []} {"input": "In human leukocytes, the peak value of GR was found to parallel that of plasma cortisol with high and low values detected at 04:00-08:00 h and 23:00-24:00 h, respectively.", "output": {"entities": {"cell_type": [{"text": "human leukocytes", "start": 3, "end": 19}], "protein": [{"text": "GR", "start": 39, "end": 41}]}}, "schema": []} {"input": "In patients suffering from Cushing's syndrome, the circadian rhythm of plasma cortisol either disappeared or was inverted while that of GR did not significantly deviate from the normal subjects.", "output": {"entities": {"protein": [{"text": "GR", "start": 136, "end": 138}]}}, "schema": []} {"input": "For apoplexic patients with lesions localized to the base of the brain as indicated by computerized tomography, the diurnal variation of GR was abolished.", "output": {"entities": {"protein": [{"text": "GR", "start": 137, "end": 139}]}}, "schema": []} {"input": "Conversely, diurnal rhythmicity persisted in apoplexy patients whose lesions were in the cerebral cortex.", "output": {"entities": {}}, "schema": []} {"input": "Thus, we postulated that the circadian modification of GR was independent of the diurnal fluctuations in plasma cortisol level or the circadian variations in environmental lighting and that the rhythmicity might be regulated by the' circadian pacemaker' located in the human basal brain.", "output": {"entities": {"protein": [{"text": "GR", "start": 55, "end": 57}]}}, "schema": []} {"input": "These diurnal variations in GR might serve to coordinate the reactivity of the target cells to cortisol because the diurnal rhythms of a GR -mediated response, the fractional inhibition of chemotactic migration rate of polymorphonuclear leukocytes by cortisol, were found to be synchronous with those of GR.", "output": {"entities": {"protein": [{"text": "GR", "start": 28, "end": 30}, {"text": "GR", "start": 137, "end": 139}, {"text": "GR", "start": 304, "end": 306}], "cell_type": [{"text": "target cells", "start": 79, "end": 91}, {"text": "polymorphonuclear leukocytes", "start": 219, "end": 247}]}}, "schema": []} {"input": "Transcription factor requirements for U2 snRNA -encoding gene activation in B lymphoid cells.", "output": {"entities": {"protein": [{"text": "Transcription factor", "start": 0, "end": 20}], "rna": [{"text": "U2 snRNA", "start": 38, "end": 46}], "cell_type": [{"text": "B lymphoid cells", "start": 76, "end": 92}]}}, "schema": []} {"input": "Transcription of a human U2 small nuclear RNA(snRNA)-encoding gene in HeLa cells requires a distal enhancer element, which is composed of one octamer motif (Oct) and three Sp 1-binding sites.", "output": {"entities": {"dna": [{"text": "U2 small nuclear RNA(snRNA)-encoding gene", "start": 25, "end": 66}, {"text": "distal enhancer element", "start": 92, "end": 115}, {"text": "octamer motif", "start": 142, "end": 155}, {"text": "Oct", "start": 157, "end": 160}, {"text": "Sp 1-binding sites", "start": 172, "end": 190}], "cell_line": [{"text": "HeLa cells", "start": 70, "end": 80}]}}, "schema": []} {"input": "To study the transcription factor requirement in B-cells, different U2 enhancer constructions were transfected into the lymphoid cell line, BJA-B.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 13, "end": 33}], "cell_type": [{"text": "B-cells", "start": 49, "end": 56}], "dna": [{"text": "U2 enhancer constructions", "start": 68, "end": 93}], "cell_line": [{"text": "lymphoid cell line", "start": 120, "end": 138}, {"text": "BJA-B", "start": 140, "end": 145}]}}, "schema": []} {"input": "The results showed that the activation of U2 snRNA transcription in B-cells also requires an enhancer comprising both the Oct and at least one Sp 1-binding site.", "output": {"entities": {"cell_type": [{"text": "B-cells", "start": 68, "end": 75}], "dna": [{"text": "Oct", "start": 122, "end": 125}, {"text": "Sp 1-binding site", "start": 143, "end": 160}]}}, "schema": []} {"input": "Deletion of all the Sp 1-binding sites from the enhancer reduces transcription by 80-90% in HeLa, as well as in BJA-B cells, whereas the removal of the octamer-binding site reduces transcription to levels below detection in both cell types.", "output": {"entities": {"dna": [{"text": "Sp 1-binding sites", "start": 20, "end": 38}, {"text": "enhancer", "start": 48, "end": 56}, {"text": "octamer-binding site", "start": 152, "end": 172}], "cell_line": [{"text": "BJA-B cells", "start": 112, "end": 123}]}}, "schema": []} {"input": "Enhancers containing a single Oct have, nevertheless, the capacity to partially activate U2 snRNA transcription in both HeLa cells, in which only OTF-1 is expressed, and in BJA-B cells in which OTF-2 is the predominantly expressed octamer-binding factor.", "output": {"entities": {"dna": [{"text": "Oct", "start": 30, "end": 33}], "rna": [{"text": "U2 snRNA", "start": 89, "end": 97}], "cell_line": [{"text": "HeLa cells", "start": 120, "end": 130}, {"text": "BJA-B cells", "start": 173, "end": 184}], "protein": [{"text": "OTF-2", "start": 194, "end": 199}, {"text": "octamer-binding factor", "start": 231, "end": 253}]}}, "schema": []} {"input": "The most likely interpretation of our results is that both the ubiquitous transcription factor, OTF-1, and the B-cell-specific transcription factor, OTF-2, can activate U2 snRNA transcription.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 74, "end": 94}, {"text": "OTF-1", "start": 96, "end": 101}, {"text": "B-cell-specific", "start": 111, "end": 126}, {"text": "transcription factor", "start": 127, "end": 147}, {"text": "OTF-2", "start": 149, "end": 154}], "rna": [{"text": "U2 snRNA", "start": 169, "end": 177}]}}, "schema": []} {"input": "The results also revealed a similar functional cooperation between the transcription factors which bind to the Oct and the adjacent Sp 1-binding site in BJA-B cells, as has been observed in HeLa cells, since a template which contains a weak binding site for OTFs expresses wild-type levels of U2 snRNA in both cell types when the weak octamer-binding site is combined with a Sp 1-binding site.", "output": {"entities": {"dna": [{"text": "Oct", "start": 111, "end": 114}, {"text": "Sp 1-binding site", "start": 132, "end": 149}, {"text": "OTFs", "start": 258, "end": 262}, {"text": "octamer-binding site", "start": 335, "end": 355}, {"text": "Sp 1-binding site", "start": 375, "end": 392}], "cell_line": [{"text": "BJA-B cells", "start": 153, "end": 164}, {"text": "HeLa cells", "start": 190, "end": 200}], "rna": [{"text": "U2 snRNA", "start": 293, "end": 301}]}}, "schema": []} {"input": "One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter.", "output": {"entities": {"dna": [{"text": "kB-like proto-enhancer element", "start": 67, "end": 97}, {"text": "interleukin 2 promoter", "start": 107, "end": 129}]}}, "schema": []} {"input": "The inducible, T cell-specific enhancers of murine and human Interleukin 2 (Il-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif.", "output": {"entities": {"dna": [{"text": "T cell-specific enhancers", "start": 15, "end": 40}, {"text": "murine and human Interleukin 2 (Il-2) genes", "start": 44, "end": 87}, {"text": "kB-like sequence", "start": 100, "end": 116}, {"text": "essential cis-acting enhancer motif", "start": 135, "end": 170}]}}, "schema": []} {"input": "When cloned in multiple copies this so-called TCEd (distal T cell element) acts as an inducible proto-enhancer element in E14 T lymphoma cells, but not in HeLa cells.", "output": {"entities": {"dna": [{"text": "TCEd", "start": 46, "end": 50}, {"text": "distal T cell element", "start": 52, "end": 73}, {"text": "proto-enhancer element", "start": 96, "end": 118}], "cell_line": [{"text": "E14 T lymphoma cells", "start": 122, "end": 142}, {"text": "HeLa cells", "start": 155, "end": 165}]}}, "schema": []} {"input": "In extracts of induced, Il-2 secreting El4 cells three individual protein factors bind to TCEd DNA.", "output": {"entities": {"cell_line": [{"text": "Il-2 secreting El4 cells", "start": 24, "end": 48}], "protein": [{"text": "protein factors", "start": 66, "end": 81}], "dna": [{"text": "TCEd DNA", "start": 90, "end": 98}]}}, "schema": []} {"input": "The binding of the most prominent factor, named TCF-1 (T cell factor 1 ), is correlated with the proto-enhancer activity of TCEd.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 48, "end": 53}, {"text": "T cell factor 1", "start": 55, "end": 70}], "dna": [{"text": "TCEd", "start": 124, "end": 128}]}}, "schema": []} {"input": "TCF-1 consists of two polypeptides of about 50 kD and 105 kD; the former seems to be related to the 50 kD polypeptide of NF-kB.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 0, "end": 5}, {"text": "50 kD polypeptide", "start": 100, "end": 117}, {"text": "NF-kB", "start": 121, "end": 126}]}}, "schema": []} {"input": "Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA.", "output": {"entities": {"protein": [{"text": "Purified NF-kB", "start": 0, "end": 14}, {"text": "TCF-1", "start": 53, "end": 58}, {"text": "NF-kB", "start": 79, "end": 84}], "dna": [{"text": "TCEd", "start": 43, "end": 47}, {"text": "TCEd", "start": 88, "end": 92}]}}, "schema": []} {"input": "The conversion of the TCEd to a'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the'converted' TCEd motifs in HeLa cells.", "output": {"entities": {"dna": [{"text": "TCEd", "start": 22, "end": 26}, {"text": "'perfect' NF-kB binding site", "start": 31, "end": 59}, {"text": "TCEd DNA", "start": 99, "end": 107}, {"text": "'converted' TCEd motifs", "start": 164, "end": 187}], "protein": [{"text": "NF-kB", "start": 90, "end": 95}], "cell_line": [{"text": "HeLa cells", "start": 191, "end": 201}]}}, "schema": []} {"input": "Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and HeLa cells.", "output": {"entities": {"dna": [{"text": "GGGATTTCACC motif", "start": 69, "end": 86}], "cell_line": [{"text": "El4 cells", "start": 165, "end": 174}, {"text": "HeLa cells", "start": 179, "end": 189}]}}, "schema": []} {"input": "These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the Il-2 gene.", "output": {"entities": {"dna": [{"text": "TCEd", "start": 71, "end": 75}, {"text": "Il-2 gene", "start": 144, "end": 153}]}}, "schema": []} {"input": "An erythroid specific enhancer upstream to the gene encoding the cell-type specific transcription factor GATA-1.", "output": {"entities": {"dna": [{"text": "erythroid specific enhancer", "start": 3, "end": 30}], "protein": [{"text": "cell-type specific transcription factor", "start": 65, "end": 104}, {"text": "GATA-1", "start": 105, "end": 111}]}}, "schema": []} {"input": "The transcription factor GATA-1 is expressed in a subset of hemopoietic cells, where it mediates the cell-type specific expression of several genes.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 4, "end": 24}, {"text": "GATA-1", "start": 25, "end": 31}], "cell_type": [{"text": "hemopoietic cells", "start": 60, "end": 77}]}}, "schema": []} {"input": "We have cloned the mouse and human GATA-1 genes.", "output": {"entities": {"dna": [{"text": "GATA-1 genes", "start": 35, "end": 47}]}}, "schema": []} {"input": "A region upstream to the first exon, and highly conserved between mouse and man, acts as an erythroid specific enhancer in transient assays, if linked to the GATA-1 or to the SV40 promoter.", "output": {"entities": {"dna": [{"text": "erythroid specific enhancer", "start": 92, "end": 119}, {"text": "SV40 promoter", "start": 175, "end": 188}], "protein": [{"text": "GATA-1", "start": 158, "end": 164}]}}, "schema": []} {"input": "The activity of the enhancer is almost completely dependent on the integrity of a dimeric GATA-1 binding site.", "output": {"entities": {"dna": [{"text": "dimeric GATA-1 binding site", "start": 82, "end": 109}]}}, "schema": []} {"input": "Demonstration of a 1,25-dihydroxyvitamin D3 -responsive protein in human lymphocytes: immunologic crossreactivity and inverse regulation with the vitamin D receptor.", "output": {"entities": {"protein": [{"text": "1,25-dihydroxyvitamin D3 -responsive protein", "start": 19, "end": 63}, {"text": "vitamin D receptor", "start": 146, "end": 164}], "cell_type": [{"text": "human lymphocytes", "start": 67, "end": 84}]}}, "schema": []} {"input": "Using Western blot analysis with a monoclonal antibody recognizing a 17-amino acid epitope of the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 ]receptor, we have detected two crossreacting proteins in activated normal human lymphocytes.", "output": {"entities": {"protein": [{"text": "monoclonal antibody", "start": 35, "end": 54}, {"text": "17-amino acid epitope", "start": 69, "end": 90}, {"text": "1,25-dihydroxyvitamin D3 [1,25(OH)2D3 ]receptor", "start": 98, "end": 145}, {"text": "crossreacting proteins", "start": 168, "end": 190}], "cell_type": [{"text": "activated normal human lymphocytes", "start": 194, "end": 228}]}}, "schema": []} {"input": "The smaller of the two proteins (50 kDa) was indistinguishable from the classical 1,25(OH)2D3 receptor and, similar to the classical 1,25(OH)2D3 receptor, was upregulated in a dose-dependent fashion by 1,25(OH)2D3.", "output": {"entities": {"protein": [{"text": "50 kDa", "start": 33, "end": 39}, {"text": "1,25(OH)2D3 receptor", "start": 82, "end": 102}, {"text": "1,25(OH)2D3 receptor", "start": 133, "end": 153}]}}, "schema": []} {"input": "The larger crossreacting protein exhibited an electrophoretic mobility of 80 kDa, was localized in the cell cytosol, and appeared to be specific for activated lymphocytes since it was not detected in several other human cells including monocytes.", "output": {"entities": {"protein": [{"text": "80 kDa", "start": 74, "end": 80}], "cell_type": [{"text": "activated lymphocytes", "start": 149, "end": 170}, {"text": "human cells", "start": 214, "end": 225}, {"text": "monocytes", "start": 236, "end": 245}]}}, "schema": []} {"input": "More strikingly, the 80-kDa protein was downregulated in a dose-dependent fashion by 1,25(OH)2D3; this effect was independent of the mode of lymphocyte activation and specific for the 1,25(OH)2D3 metabolite of vitamin D3.", "output": {"entities": {"protein": [{"text": "80-kDa protein", "start": 21, "end": 35}]}}, "schema": []} {"input": "However, two potent immunosuppressive agents, glucocorticoids and cyclosporin A, also inhibited the 80-kDa protein.", "output": {"entities": {"protein": [{"text": "80-kDa protein", "start": 100, "end": 114}]}}, "schema": []} {"input": "Regulation of glucocorticoid receptors in human mononuclear cells: effects of glucocorticoid treatment, Cushing's disease and ketoconazole.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 14, "end": 38}], "cell_type": [{"text": "human mononuclear cells", "start": 42, "end": 65}]}}, "schema": []} {"input": "Glucocorticoid receptors (GcR) were determined by a whole cell assay in human mononulear leukocytes (hMNL) from control subjects, patients receiving glucocorticoid therapy for systemic diseases and Cushing's disease patients with or without ketoconazole therapy.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptors", "start": 0, "end": 24}, {"text": "GcR", "start": 26, "end": 29}], "cell_type": [{"text": "human mononulear leukocytes", "start": 72, "end": 99}, {"text": "hMNL", "start": 101, "end": 105}]}}, "schema": []} {"input": "Prolonged corticosteroid treatment resulted in down-regulation of GcR, while the mean level of GcR in Cushing's disease was normal.", "output": {"entities": {"protein": [{"text": "GcR", "start": 66, "end": 69}, {"text": "GcR", "start": 95, "end": 98}]}}, "schema": []} {"input": "In this group, however, receptor levels and morning plasma cortisol values showed a negative correlation, indicating a subtle down-regulatory effect.", "output": {"entities": {}}, "schema": []} {"input": "Furthermore, GcR were unaltered after these patients received ketoconazole, in spite of a marked reduction in morning plasma cortisol and urinary free cortisol.", "output": {"entities": {"protein": [{"text": "GcR", "start": 13, "end": 16}]}}, "schema": []} {"input": "We also observed that ketoconazole was a weak competitor of GcR in intact cells, although it significantly inhibited [3H] dexamethasone binding in cytosolic preparations from rat tissues.", "output": {"entities": {"protein": [{"text": "GcR", "start": 60, "end": 63}], "cell_type": [{"text": "intact cells", "start": 67, "end": 79}]}}, "schema": []} {"input": "The results suggested that GcR in hMNL are down-regulated by synthetic steroids given in vivo, but they showed very mild down-regulation in hypercortisolemic patients suffering from Cushing's disease.", "output": {"entities": {"protein": [{"text": "GcR", "start": 27, "end": 30}], "cell_type": [{"text": "hMNL", "start": 34, "end": 38}]}}, "schema": []} {"input": "Finally, we did not observed either up-regulation or antagonism of GcR by ketoconazole treatment, at the time that cortisol levels of patients with Cushing's disease were reduced.", "output": {"entities": {"protein": [{"text": "GcR", "start": 67, "end": 70}]}}, "schema": []} {"input": "This indicates that the beneficial effects of ketoconazole in Cushing's disease are due to adrenal cortisol suppression and not to interaction with GcR of target cells, and that the process of GcR regulation in hMNL is a complex phenomenon awaiting further elucidation.", "output": {"entities": {"protein": [{"text": "GcR", "start": 148, "end": 151}, {"text": "GcR", "start": 193, "end": 196}], "cell_type": [{"text": "target cells", "start": 155, "end": 167}, {"text": "hMNL", "start": 211, "end": 215}]}}, "schema": []} {"input": "HTLV-1 Tax induces expression of various immediate early serum responsive genes.", "output": {"entities": {"protein": [{"text": "HTLV-1 Tax", "start": 0, "end": 10}], "dna": [{"text": "immediate early serum responsive genes", "start": 41, "end": 79}]}}, "schema": []} {"input": "Human T-cell leukemia virus type 1 (HTLV-1) is an etiological agent of adult T-cell leukemia (ATL ).", "output": {"entities": {}}, "schema": []} {"input": "We showed here by mobility-shift assay that T-cell lines transformed with the virus contained high levels of AP-1 activities.", "output": {"entities": {"cell_line": [{"text": "T-cell lines", "start": 44, "end": 56}], "protein": [{"text": "AP-1", "start": 109, "end": 113}]}}, "schema": []} {"input": "Consistent with this result, these cell lines expressed increased levels of mRNAs encoding the AP-1 proteins, c-Fos, Fra-1, c-Jun, JunB, and JunD.", "output": {"entities": {"rna": [{"text": "mRNAs", "start": 76, "end": 81}], "protein": [{"text": "AP-1 proteins", "start": 95, "end": 108}, {"text": "c-Fos", "start": 110, "end": 115}, {"text": "Fra-1", "start": 117, "end": 122}, {"text": "c-Jun", "start": 124, "end": 129}, {"text": "JunB", "start": 131, "end": 135}, {"text": "JunD", "start": 141, "end": 145}]}}, "schema": []} {"input": "Previously, transcription of the c-fos gene has been reported to be transactivated by the viral transcription factor, Tax1.", "output": {"entities": {"dna": [{"text": "c-fos gene", "start": 33, "end": 43}], "protein": [{"text": "viral transcription factor", "start": 90, "end": 116}, {"text": "Tax1", "start": 118, "end": 122}]}}, "schema": []} {"input": "By using the human T-cell line (JPX-9 ), in which expression of the Tax1 is inducible, we showed that expression of mRNAs for Fra-1, c-Jun, and JunD was also transactivated by Tax1.", "output": {"entities": {"cell_line": [{"text": "human T-cell line", "start": 13, "end": 30}, {"text": "JPX-9", "start": 32, "end": 37}], "protein": [{"text": "Tax1", "start": 68, "end": 72}, {"text": "Fra-1", "start": 126, "end": 131}, {"text": "c-Jun", "start": 133, "end": 138}, {"text": "JunD", "start": 144, "end": 148}, {"text": "Tax1", "start": 176, "end": 180}], "rna": [{"text": "mRNAs", "start": 116, "end": 121}]}}, "schema": []} {"input": "Moreover, Tax1 activated expression of two other transcription factors having zinc finger motifs, Egr-1 and Egr-2, in the same cells.", "output": {"entities": {"protein": [{"text": "Tax1", "start": 10, "end": 14}, {"text": "transcription factors", "start": 49, "end": 70}, {"text": "zinc finger motifs", "start": 78, "end": 96}, {"text": "Egr-1", "start": 98, "end": 103}, {"text": "Egr-2", "start": 108, "end": 113}]}}, "schema": []} {"input": "The Tax1 -inducible transcription factors identified here are encoded by the members of immediate early genes under the control of growth signals.", "output": {"entities": {"protein": [{"text": "Tax1 -inducible transcription factors", "start": 4, "end": 41}], "dna": [{"text": "immediate early genes", "start": 88, "end": 109}]}}, "schema": []} {"input": "Thus, Tax1 was suggested to replace growth signals, at least in part, by this mechanism.", "output": {"entities": {"protein": [{"text": "Tax1", "start": 6, "end": 10}]}}, "schema": []} {"input": "Glucocorticoid receptor characteristics in monocytes of patients with corticosteroid -resistant bronchial asthma.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptor", "start": 0, "end": 23}], "cell_type": [{"text": "monocytes", "start": 43, "end": 52}]}}, "schema": []} {"input": "The mechanism of corticosteroid resistance in bronchial asthma has been studied by determining the rank order of potency for different corticosteroids in inhibiting the generation of a 3 kD molecule from peripheral blood monocytes isolated from corticosteroid-sensitive (CS) and corticosteroid-resistant (CR) asthmatic subjects, which augments leukotriene B4 (LTB4) generation by human neutrophils (PMN) stimulated by calcium ionophore.", "output": {"entities": {"cell_type": [{"text": "peripheral blood monocytes", "start": 204, "end": 230}, {"text": "human neutrophils", "start": 380, "end": 397}, {"text": "PMN", "start": 399, "end": 402}], "protein": [{"text": "LTB4", "start": 360, "end": 364}]}}, "schema": []} {"input": "In addition, binding studies with (3H) dexamethasone have been performed to determine the dissociation constant (Kd) and receptor numbers (Ro) in the monocytes of these two groups of subjects.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 150, "end": 159}]}}, "schema": []} {"input": "The concentration of corticosteroid producing 50% inhibition (IC50) was 600 nM, 70 nM, and 0.5 nM for hydrocortisone, methylprednisolone, and dexamethasone, respectively, in monocytes from CS individuals.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 174, "end": 183}]}}, "schema": []} {"input": "There was only weak inhibition of the generation of enhancing activity by the corticosteroids in the CR asthmatic individuals.", "output": {"entities": {}}, "schema": []} {"input": "The dexamethasone Kd was 2.45 +/- 0.58 nM (mean +/- SEM, n = 6) in the CS group and 1.6 +/- 0.35 nM (mean +/- SEM, n = 6) in the CR group of patients (p = 0.14).", "output": {"entities": {}}, "schema": []} {"input": "The Ro in the CS group was 3,605 +/- 984 binding sites per nucleus (mean +/- SEM, n = 6) and 4,757 +/- 692 binding sites per nucleus (mean +/- SEM, n = 6) in the CR group (p = 0.23).", "output": {"entities": {}}, "schema": []} {"input": "These findings indicate that corticosteroid resistance in bronchial asthma cannot be explained by abnormalities in corticosteroid receptor characteristics.", "output": {"entities": {}}, "schema": []} {"input": "Vitamin D receptor expression in human lymphocytes.", "output": {"entities": {"protein": [{"text": "Vitamin D receptor", "start": 0, "end": 18}], "cell_type": [{"text": "human lymphocytes", "start": 33, "end": 50}]}}, "schema": []} {"input": "Signal requirements and characterization by western blots and DNA sequencing.", "output": {"entities": {}}, "schema": []} {"input": "The signals controlling the expression of the receptor protein for 1 alpha,25-dihydroxyvitamin D3 in normal human lymphocytes and the relationship of this protein to the classical vitamin D receptor were examined.", "output": {"entities": {"protein": [{"text": "receptor protein", "start": 46, "end": 62}, {"text": "classical vitamin D receptor", "start": 170, "end": 198}], "cell_type": [{"text": "human lymphocytes", "start": 108, "end": 125}]}}, "schema": []} {"input": "Lymphocytes activated with the OKT3 antibody to the T-cell antigen receptor expressed fewer binding sites as compared to lymphocytes that were activated by the polyclonal activator phytohemagglutinin (PHA ).", "output": {"entities": {"cell_type": [{"text": "Lymphocytes", "start": 0, "end": 11}, {"text": "lymphocytes", "start": 121, "end": 132}], "protein": [{"text": "OKT3 antibody", "start": 31, "end": 44}, {"text": "T-cell antigen receptor", "start": 52, "end": 75}, {"text": "phytohemagglutinin", "start": 181, "end": 199}, {"text": "PHA", "start": 201, "end": 204}]}}, "schema": []} {"input": "However, combination of OKT3 and phorbol myristate acetate produced a concentration of binding sites similar to the PHA -activated cells.", "output": {"entities": {"protein": [{"text": "OKT3", "start": 24, "end": 28}, {"text": "PHA", "start": 116, "end": 119}], "cell_line": [{"text": "-activated cells", "start": 120, "end": 136}]}}, "schema": []} {"input": "The receptor from OKT3 and OKT3 + phorbol myristate acetate -activated lymphocytes exhibited decreased binding to DNA-cellulose compared to PHA -activated lymphocytes.", "output": {"entities": {"protein": [{"text": "OKT3", "start": 18, "end": 22}, {"text": "OKT3", "start": 27, "end": 31}], "cell_type": [{"text": "-activated", "start": 60, "end": 70}, {"text": "lymphocytes", "start": 71, "end": 82}, {"text": "PHA -activated lymphocytes", "start": 140, "end": 166}]}}, "schema": []} {"input": "In lymphocytes activated either by PHA or OKT3 (but not in resting cells ), a 50-kDa species cross-reacting with a monoclonal antibody against the intestinal vitamin D receptor was detected.", "output": {"entities": {"cell_type": [{"text": "lymphocytes", "start": 3, "end": 14}, {"text": "resting cells", "start": 59, "end": 72}], "protein": [{"text": "PHA", "start": 35, "end": 38}, {"text": "OKT3", "start": 42, "end": 46}, {"text": "50-kDa species", "start": 78, "end": 92}, {"text": "monoclonal antibody", "start": 115, "end": 134}, {"text": "intestinal vitamin D receptor", "start": 147, "end": 176}]}}, "schema": []} {"input": "Finally, RNA from activated lymphocytes was amplified by polymerase chain reaction using oligonucleotide primers flanking the 196 base pair long region encoding the DNA-binding domain of the human intestinal receptor.", "output": {"entities": {"rna": [{"text": "RNA", "start": 9, "end": 12}], "cell_type": [{"text": "activated", "start": 18, "end": 27}, {"text": "lymphocytes", "start": 28, "end": 39}], "dna": [{"text": "196 base pair long region", "start": 126, "end": 151}], "protein": [{"text": "DNA-binding domain", "start": 165, "end": 183}, {"text": "human intestinal receptor", "start": 191, "end": 216}]}}, "schema": []} {"input": "The amplified product showed an identical nucleotide sequence to the DNA-binding domain of the human intestinal receptor.", "output": {"entities": {"dna": [{"text": "identical nucleotide sequence", "start": 32, "end": 61}], "protein": [{"text": "DNA-binding domain", "start": 69, "end": 87}, {"text": "human intestinal receptor", "start": 95, "end": 120}]}}, "schema": []} {"input": "These findings suggest that expression of the 1,25-(OH)2D3 receptor in lymphocytes is triggered by distinct and contingent signals, and that the protein and the mRNA encoding it are identical to the classical vitamin D receptor.", "output": {"entities": {"protein": [{"text": "1,25-(OH)2D3 receptor", "start": 46, "end": 67}, {"text": "classical", "start": 199, "end": 208}, {"text": "vitamin D receptor", "start": 209, "end": 227}], "cell_type": [{"text": "lymphocytes", "start": 71, "end": 82}], "rna": [{"text": "mRNA", "start": 161, "end": 165}]}}, "schema": []} {"input": "Comparison of constitutive and inducible transcriptional enhancement mediated by kappa B-related sequences: modulation of activity in B cells by human T-cell leukemia virus type I tax gene.", "output": {"entities": {"dna": [{"text": "kappa B-related sequences", "start": 81, "end": 106}, {"text": "human T-cell leukemia virus type I tax gene", "start": 145, "end": 188}], "cell_type": [{"text": "B cells", "start": 134, "end": 141}]}}, "schema": []} {"input": "The kappa B sequence (GGGACTTTCC) binds a factor, NF-kappa B, that is constitutively found in its functional, DNA binding form only in B lymphocytes.", "output": {"entities": {"dna": [{"text": "kappa B sequence", "start": 4, "end": 20}], "protein": [{"text": "NF-kappa B", "start": 50, "end": 60}], "cell_type": [{"text": "B lymphocytes", "start": 135, "end": 148}]}}, "schema": []} {"input": "A factor with apparently indistinguishable sequence specificity can be induced in many other cell types, where it is used to regulate inducible gene expression.", "output": {"entities": {}}, "schema": []} {"input": "For example, kappa B-related sequences have been shown to be important for the transcription of a few inducible genes, such as the interleukin 2 receptor alpha-chain gene and the beta-interferon gene.", "output": {"entities": {"dna": [{"text": "kappa B-related sequences", "start": 13, "end": 38}, {"text": "interleukin 2 receptor alpha-chain gene", "start": 131, "end": 170}, {"text": "gene", "start": 195, "end": 199}], "protein": [{"text": "beta-interferon", "start": 179, "end": 194}]}}, "schema": []} {"input": "However, these genes are not constitutively active in B lymphocytes, suggesting that other regulatory mechanisms must play a role in determining the patterns of expression.", "output": {"entities": {"cell_type": [{"text": "B lymphocytes", "start": 54, "end": 67}]}}, "schema": []} {"input": "We have investigated the constitutive and inducible transcriptional activity mediated by five kappa B-related sequence elements in two different cell types.", "output": {"entities": {"dna": [{"text": "kappa B-related sequence elements", "start": 94, "end": 127}]}}, "schema": []} {"input": "We show that in S194 plasma cells the activity of each element correlates well with the relative affinity of B-cell-derived NF-kappa B for that element.", "output": {"entities": {"cell_line": [{"text": "S194 plasma cells", "start": 16, "end": 33}], "protein": [{"text": "B-cell-derived NF-kappa B", "start": 109, "end": 134}]}}, "schema": []} {"input": "This leads to significantly lower transcription enhancement by sites derived from the interleukin 2 receptor or T-cell receptor genes in S194 cells.", "output": {"entities": {"protein": [{"text": "interleukin 2 receptor", "start": 86, "end": 108}], "dna": [{"text": "T-cell receptor genes", "start": 112, "end": 133}], "cell_line": [{"text": "S194 cells", "start": 137, "end": 147}]}}, "schema": []} {"input": "However, in either EL-4 (T) cells or S194 cells, both lower-affinity sites can be significantly induced by the tax gene product of human T-cell leukemia virus type I, showing that NF-kappa B activity can be modulated even in a B-cell line that constitutively expresses this factor.", "output": {"entities": {"cell_line": [{"text": "EL-4 (T) cells", "start": 19, "end": 33}, {"text": "S194 cells", "start": 37, "end": 47}, {"text": "B-cell line", "start": 227, "end": 238}], "protein": [{"text": "tax gene product", "start": 111, "end": 127}, {"text": "NF-kappa B", "start": 180, "end": 190}]}}, "schema": []} {"input": "Specific depletion of the B-cell population induced by aberrant expression of human interferon regulatory factor 1 gene in transgenic mice.", "output": {"entities": {"cell_line": [{"text": "B-cell population", "start": 26, "end": 43}], "protein": [{"text": "human interferon regulatory factor 1", "start": 78, "end": 114}], "dna": [{"text": "gene", "start": 115, "end": 119}]}}, "schema": []} {"input": "Interferons (IFNs) are well known both as antiviral proteins and as potent regulators of cell growth and differentiation.", "output": {"entities": {"protein": [{"text": "Interferons", "start": 0, "end": 11}, {"text": "IFNs", "start": 13, "end": 17}, {"text": "antiviral proteins", "start": 42, "end": 60}]}}, "schema": []} {"input": "In fact, IFNs inhibit growth of various normal and transformed cell types.", "output": {"entities": {"protein": [{"text": "IFNs", "start": 9, "end": 13}], "cell_type": [{"text": "normal", "start": 40, "end": 46}, {"text": "transformed cell types", "start": 51, "end": 73}]}}, "schema": []} {"input": "Previously, a nuclear factor, IRF-1 (interferon regulatory factor 1 ), which binds to type I IFN and some IFN -inducible gene promoters, was identified and cloned.", "output": {"entities": {"protein": [{"text": "nuclear factor", "start": 14, "end": 28}, {"text": "IRF-1", "start": 30, "end": 35}, {"text": "interferon regulatory factor 1", "start": 37, "end": 67}], "dna": [{"text": "type I IFN", "start": 86, "end": 96}, {"text": "IFN -inducible gene promoters", "start": 106, "end": 135}]}}, "schema": []} {"input": "Since the IRF-1 gene is both virus and IFN inducible, an intriguing issue is raised as to whether the IRF-1 gene is functioning in IFN -mediated regulation of cell growth and differentiation.", "output": {"entities": {"protein": [{"text": "IRF-1", "start": 10, "end": 15}, {"text": "IFN", "start": 39, "end": 42}, {"text": "IRF-1", "start": 102, "end": 107}, {"text": "IFN", "start": 131, "end": 134}], "dna": [{"text": "gene", "start": 108, "end": 112}]}}, "schema": []} {"input": "In this study, we generated transgenic mice carrying the human IRF-1 gene linked to the human immunoglobulin heavy-chain enhancer.", "output": {"entities": {"dna": [{"text": "human IRF-1 gene", "start": 57, "end": 73}, {"text": "human immunoglobulin heavy-chain enhancer", "start": 88, "end": 129}]}}, "schema": []} {"input": "In the transgenic mice, all the lymphoid tissues examined showed a dramatic reduction in the number of B lymphocytes (B cells ).", "output": {"entities": {"cell_type": [{"text": "B lymphocytes", "start": 103, "end": 116}, {"text": "B cells", "start": 118, "end": 125}]}}, "schema": []} {"input": "Preparation and analysis of bone marrow cells from the chimeric mice indicated that the bone marrow is the effective site for specific depletion of the B-cell population.", "output": {"entities": {"cell_type": [{"text": "bone marrow cells", "start": 28, "end": 45}, {"text": "B-cell population", "start": 152, "end": 169}]}}, "schema": []} {"input": "In fact, transgenic bone marrow cells cocultured with a bone marrow-derived stromal cell line revealed an altered B-cell maturation pattern.", "output": {"entities": {"cell_line": [{"text": "transgenic bone marrow cells", "start": 9, "end": 37}, {"text": "bone marrow-derived stromal cell line", "start": 56, "end": 93}], "cell_type": [{"text": "B-cell", "start": 114, "end": 120}]}}, "schema": []} {"input": "Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein.", "output": {"entities": {"protein": [{"text": "cofactor", "start": 22, "end": 30}, {"text": "mammalian homeodomain protein", "start": 64, "end": 93}]}}, "schema": []} {"input": "Dimerization among transcription factors has become a recurrent theme in the regulation of eukaryotic gene expression.", "output": {"entities": {"protein": [{"text": "transcription factors", "start": 19, "end": 40}]}}, "schema": []} {"input": "Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a homeodomain-containing protein that functions as a dimer.", "output": {"entities": {"protein": [{"text": "Hepatocyte nuclear factor-1 alpha", "start": 0, "end": 33}, {"text": "HNF-1 alpha", "start": 35, "end": 46}, {"text": "homeodomain-containing protein", "start": 53, "end": 83}, {"text": "dimer", "start": 104, "end": 109}]}}, "schema": []} {"input": "A dimerization cofactor of HNF-1 alpha (DCoH) was identified that displayed a restricted tissue distribution and did not bind to DNA, but, rather, selectively stabilized HNF-1 alpha dimers.", "output": {"entities": {"protein": [{"text": "dimerization", "start": 2, "end": 14}, {"text": "cofactor", "start": 15, "end": 23}, {"text": "HNF-1 alpha", "start": 27, "end": 38}, {"text": "DCoH", "start": 40, "end": 44}, {"text": "HNF-1 alpha dimers", "start": 170, "end": 188}]}}, "schema": []} {"input": "The formation of a stable tetrameric DCoH-HNF-1 alpha complex, which required the dimerization domain of HNF-1 alpha, did not change the DNA binding characteristics of HNF-1 alpha, but enhanced its transcriptional activity.", "output": {"entities": {"protein": [{"text": "tetrameric DCoH-HNF-1 alpha complex", "start": 26, "end": 61}, {"text": "dimerization domain", "start": 82, "end": 101}, {"text": "HNF-1 alpha", "start": 105, "end": 116}, {"text": "HNF-1 alpha", "start": 168, "end": 179}]}}, "schema": []} {"input": "However, DCoH did not confer transcriptional activation to the GAL4 DNA binding domain.", "output": {"entities": {"protein": [{"text": "DCoH", "start": 9, "end": 13}, {"text": "GAL4 DNA binding domain", "start": 63, "end": 86}]}}, "schema": []} {"input": "These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex.", "output": {"entities": {"protein": [{"text": "DCoH", "start": 28, "end": 32}, {"text": "tetrameric complexes", "start": 81, "end": 101}, {"text": "developmental specificity", "start": 128, "end": 153}, {"text": "complex", "start": 161, "end": 168}]}}, "schema": []} {"input": "Glucocorticoid resistance in chronic asthma.", "output": {"entities": {}}, "schema": []} {"input": "Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 33, "end": 56}], "cell_type": [{"text": "peripheral blood T cell", "start": 92, "end": 115}]}}, "schema": []} {"input": "A total of 37 chronic, severe, nonsmoking asthmatic patients with documented reversible airways obstruction were classified as glucocorticoid-sensitive or -resistant on the basis of changes in FEV1, FVC, and peak expiratory flow (PEF) after oral prednisolone.", "output": {"entities": {}}, "schema": []} {"input": "The resistant patients showed no significant improvements in airflow limitation.", "output": {"entities": {}}, "schema": []} {"input": "Phytohemagglutinin (PHA )-induced proliferation of peripheral blood T lymphocytes from the sensitive but not the resistant asthmatic patients was significantly (p less than 0.01) inhibited by dexamethasone (10(-7) mol/L), reflecting a shift of the dose-response curve.", "output": {"entities": {"protein": [{"text": "Phytohemagglutinin", "start": 0, "end": 18}, {"text": "PHA", "start": 20, "end": 23}], "cell_type": [{"text": "peripheral blood T lymphocytes", "start": 51, "end": 81}]}}, "schema": []} {"input": "When all the asthmatic patients were analyzed together, there was a significant correlation between the degree of sensitivity of T cells to dexamethasone and the clinical responsiveness to prednisolone (p less than 0.01).", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 129, "end": 136}]}}, "schema": []} {"input": "No differences were observed between six of the sensitive and resistant patients in the clearance of plasma prednisolone derived from orally administered prednisone.", "output": {"entities": {}}, "schema": []} {"input": "Peripheral blood mononuclear cell glucocorticoid receptors were also characterized in five sensitive and seven resistant patients.", "output": {"entities": {"cell_type": [{"text": "Peripheral blood mononuclear cell", "start": 0, "end": 33}], "protein": [{"text": "glucocorticoid receptors", "start": 34, "end": 58}]}}, "schema": []} {"input": "The numbers and binding affinities of these receptors could not account for the observed difference in the susceptibility of these cells to functional inhibition by dexamethasone in vitro.", "output": {"entities": {"protein": [{"text": "receptors", "start": 44, "end": 53}]}}, "schema": []} {"input": "These results suggest that clinical glucocorticoid resistance in chronic asthma does not reflect abnormal glucocorticoid clearance but may be due at least partly to a relative insensitivity of T lymphocytes to glucocorticoids.", "output": {"entities": {"cell_type": [{"text": "T lymphocytes", "start": 193, "end": 206}]}}, "schema": []} {"input": "This lack of sensitivity is unexplained but is not attributable to abnormalities of cellular glucocorticoid receptors.", "output": {"entities": {"protein": [{"text": "cellular glucocorticoid receptors", "start": 84, "end": 117}]}}, "schema": []} {"input": "Inhibition of phorbol ester-induced monocytic differentiation by dexamethasone is associated with down-regulation of c-fos and c-jun (AP-1 ).", "output": {"entities": {"dna": [{"text": "c-fos", "start": 117, "end": 122}, {"text": "c-jun", "start": 127, "end": 132}, {"text": "AP-1", "start": 134, "end": 138}]}}, "schema": []} {"input": "Previous studies have shown that treatment of human myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of monocytic differentiation and expression of the c-jun and c-fos early response genes.", "output": {"entities": {"cell_type": [{"text": "human myeloid leukemia cells", "start": 46, "end": 74}]}}, "schema": []} {"input": "The present work demonstrates that the glucocorticoid dexamethasone inhibits TPA -induced increases in c-jun and c-fos mRNA levels in U-937 leukemia cells.", "output": {"entities": {"cell_line": [{"text": "U-937 leukemia cells", "start": 134, "end": 154}]}}, "schema": []} {"input": "These findings were associated with a block in appearance of the monocytic phenotype, including inhibition of TPA -induced increases in lamin A, lamin C, and vimentin transcripts.", "output": {"entities": {"cell_type": [{"text": "monocytic phenotype", "start": 65, "end": 84}]}}, "schema": []} {"input": "Other studies have demonstrated that TPA -induced monocytic differentiation and expression of the c-jun and c-fos genes in myeloid leukemia cells are regulated by protein kinase C (PKC ).", "output": {"entities": {"dna": [{"text": "c-jun", "start": 98, "end": 103}, {"text": "c-fos genes", "start": 108, "end": 119}], "cell_type": [{"text": "myeloid leukemia cells", "start": 123, "end": 145}], "protein": [{"text": "protein kinase C", "start": 163, "end": 179}, {"text": "PKC", "start": 181, "end": 184}]}}, "schema": []} {"input": "The finding that dexamethasone has no effect on TPA -induced activation of PKC suggests that this glucocorticoid inhibits signals downstream or parallel to this enzyme.", "output": {"entities": {"protein": [{"text": "PKC", "start": 75, "end": 78}, {"text": "enzyme", "start": 161, "end": 167}]}}, "schema": []} {"input": "Nuclear run-on assays demonstrate that: (1) induction of c-jun and c-fos expression by TPA is regulated by transcriptional mechanisms, (2) TPA -induced expression of c-jun and c-fos does not require protein synthesis, and (3) TPA -induced expression of both genes is inhibited at the transcriptional level by dexamethasone.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 166, "end": 171}], "protein": [{"text": "c-fos", "start": 176, "end": 181}]}}, "schema": []} {"input": "To further define the effects of dexamethasone at the molecular level, we prepared a series of deleted c-jun promoter fragments linked to the chloramphenicol acetyltransferase (CAT) gene.", "output": {"entities": {"dna": [{"text": "c-jun promoter fragments", "start": 103, "end": 127}, {"text": "(", "start": 176, "end": 177}, {"text": ") gene", "start": 180, "end": 186}], "protein": [{"text": "chloramphenicol acetyltransferase", "start": 142, "end": 175}, {"text": "CAT", "start": 177, "end": 180}]}}, "schema": []} {"input": "Increases in CAT activity during transient expression of these constructs in TPA -treated U-937 cells could be assigned to the region (-97 to -20) of the promoter that contains the AP-1 binding site.", "output": {"entities": {"protein": [{"text": "CAT", "start": 13, "end": 16}], "cell_line": [{"text": "TPA -treated U-937 cells", "start": 77, "end": 101}], "dna": [{"text": "promoter", "start": 154, "end": 162}, {"text": "AP-1 binding site", "start": 181, "end": 198}]}}, "schema": []} {"input": "This induction of CAT activity was sensitive to dexamethasone.", "output": {"entities": {"protein": [{"text": "CAT", "start": 18, "end": 21}]}}, "schema": []} {"input": "These findings suggest that dexamethasone down-regulates TPA -induced transcription of the c-jun gene during monocytic differentiation by inhibiting activation of the AP-1 site.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 91, "end": 96}, {"text": "AP-1 site", "start": 167, "end": 176}]}}, "schema": []} {"input": "Tumor necrosis factor-alpha mRNA accumulation in human myelomonocytic cell lines.", "output": {"entities": {"rna": [{"text": "Tumor necrosis factor-alpha mRNA", "start": 0, "end": 32}], "cell_line": [{"text": "human myelomonocytic cell lines", "start": 49, "end": 80}]}}, "schema": []} {"input": "Role of transcriptional regulation by DNA sequence motifs and mRNA stabilization.", "output": {"entities": {"dna": [{"text": "DNA sequence motifs", "start": 38, "end": 57}]}}, "schema": []} {"input": "The cytokine TNF mediates many of the pathologic signs of cachexia, inflammation, and sepsis.", "output": {"entities": {"protein": [{"text": "cytokine", "start": 4, "end": 12}, {"text": "TNF", "start": 13, "end": 16}]}}, "schema": []} {"input": "The current work describes the regulation of TNF in human myelomonocytic cell lines after PMA stimulation.", "output": {"entities": {"protein": [{"text": "TNF", "start": 45, "end": 48}], "cell_line": [{"text": "human myelomonocytic cell lines", "start": 52, "end": 83}]}}, "schema": []} {"input": "The cell lines exhibit a low level of constitutive TNF mRNA expression.", "output": {"entities": {"cell_line": [{"text": "cell lines", "start": 4, "end": 14}], "rna": [{"text": "TNF mRNA", "start": 51, "end": 59}]}}, "schema": []} {"input": "Within 2 to 4 h of PMA exposure, steady state levels of TNF mRNA are markedly elevated in all myelomonocytic cell lines studied.", "output": {"entities": {"rna": [{"text": "TNF mRNA", "start": 56, "end": 64}], "cell_line": [{"text": "myelomonocytic cell lines", "start": 94, "end": 119}]}}, "schema": []} {"input": "This rise is due to increased mRNA stability, which increased by almost twofold, and to an overall increase in transcription, which rises by more than sixfold.", "output": {"entities": {}}, "schema": []} {"input": "At the level of the genomic TNF gene, a DNase I hypersensitive site is detected within the TNF promoter between -200 to -100 bp relative to the transcription initiation site.", "output": {"entities": {"dna": [{"text": "genomic TNF gene", "start": 20, "end": 36}, {"text": "DNase I hypersensitive site", "start": 40, "end": 67}, {"text": "TNF promoter", "start": 91, "end": 103}, {"text": "-200 to -100 bp", "start": 112, "end": 127}, {"text": "transcription initiation site", "start": 144, "end": 173}]}}, "schema": []} {"input": "Although absent in nonexpressing erythroleukemia cell lines, the DNase I site is present in uninduced myelomonocytic cell lines and is not changed after PMA induction.", "output": {"entities": {"cell_line": [{"text": "nonexpressing erythroleukemia cell lines", "start": 19, "end": 59}, {"text": "uninduced myelomonocytic cell lines", "start": 92, "end": 127}], "dna": [{"text": "DNase I site", "start": 65, "end": 77}]}}, "schema": []} {"input": "The PMA induction of c-fos mRNA correlated well with TNF gene induction; expression of genes encoding other proteins in the AP-1 complex (junB and junD) were also induced by PMA.", "output": {"entities": {"rna": [{"text": "c-fos mRNA", "start": 21, "end": 31}], "protein": [{"text": "TNF", "start": 53, "end": 56}, {"text": "AP-1 complex", "start": 124, "end": 136}, {"text": "junB", "start": 138, "end": 142}, {"text": "junD", "start": 147, "end": 151}]}}, "schema": []} {"input": "The nuclear extracts from resting and induced ML-1 cells contain proteins binding specifically to the AP-1, AP-2, and NF kappa B sequence located within the TNF promoter.", "output": {"entities": {"cell_line": [{"text": "induced ML-1 cells", "start": 38, "end": 56}], "dna": [{"text": "TNF promoter", "start": 157, "end": 169}]}}, "schema": []} {"input": "PMA induction increases the level of a number of specific binding complexes relative to the resting cells.", "output": {"entities": {"protein": [{"text": "specific binding complexes", "start": 49, "end": 75}], "cell_type": [{"text": "resting cells", "start": 92, "end": 105}]}}, "schema": []} {"input": "The regulatory mechanisms of the human and murine TNF genes are discussed.", "output": {"entities": {}}, "schema": []} {"input": "Enhancement of human immunodeficiency virus 1 replication in monocytes by 1,25-dihydroxycholecalciferol.", "output": {"entities": {"cell_type": [{"text": "monocytes", "start": 61, "end": 70}]}}, "schema": []} {"input": "Human immunodeficiency virus (HIV) expression and replication are under tight regulatory control.", "output": {"entities": {}}, "schema": []} {"input": "We demonstrate that 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] enhances the replication of monocyte- and lymphocyte-tropic strains of HIV-1 up to 10,000-fold in monocyte cell lines, peripheral blood monocytes, and unfractionated peripheral blood mononuclear cells.", "output": {"entities": {"cell_line": [{"text": "monocyte cell lines", "start": 163, "end": 182}], "cell_type": [{"text": "peripheral blood monocytes", "start": 184, "end": 210}, {"text": "unfractionated peripheral blood mononuclear cells", "start": 216, "end": 265}]}}, "schema": []} {"input": "1,25(OH)2D3 is therefore one of the most potent regulators of HIV-1 replication described to date.", "output": {"entities": {}}, "schema": []} {"input": "Precursors of 1,25(OH)2D3 enhance HIV-1 replication in proportion to their affinity for the 1,25(OH)2D3 intracellular receptor, suggesting that 1,25(OH)2D3 influences HIV-1 replication by mechanisms involving this receptor.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 intracellular receptor", "start": 92, "end": 126}]}}, "schema": []} {"input": "These studies may have important implications for the design of effective therapy of HIV-1 infection.", "output": {"entities": {}}, "schema": []} {"input": "Transforming growth factor-beta suppresses human B lymphocyte Ig production by inhibiting synthesis and the switch from the membrane form to the secreted form of Ig mRNA.", "output": {"entities": {"protein": [{"text": "Transforming growth factor-beta", "start": 0, "end": 31}, {"text": "human B lymphocyte Ig", "start": 43, "end": 64}], "rna": [{"text": "membrane form", "start": 124, "end": 137}, {"text": "secreted form", "start": 145, "end": 158}, {"text": "Ig mRNA", "start": 162, "end": 169}]}}, "schema": []} {"input": "Transforming growth factor-beta (TGF-beta) inhibits B cell Ig secretion and reduces B cell membrane Ig expression.", "output": {"entities": {"protein": [{"text": "Transforming growth factor-beta", "start": 0, "end": 31}, {"text": "TGF-beta", "start": 33, "end": 41}, {"text": "Ig", "start": 59, "end": 61}, {"text": "Ig", "start": 100, "end": 102}], "cell_type": [{"text": "B cell", "start": 52, "end": 58}, {"text": "B cell", "start": 84, "end": 90}]}}, "schema": []} {"input": "The addition of TGF-beta to human B lymphocyte cultures stimulated with Staphylococcus aureus Cowan strain I and IL-2 completely inhibited B cell Ig secretion (greater than 90%) and decreased B cell surface IgM, IgD, kappa L chain, and lambda L chain expression.", "output": {"entities": {"protein": [{"text": "TGF-beta", "start": 16, "end": 24}, {"text": "IL-2", "start": 113, "end": 117}, {"text": "Ig", "start": 146, "end": 148}], "cell_line": [{"text": "human B lymphocyte cultures", "start": 28, "end": 55}], "cell_type": [{"text": "B cell", "start": 139, "end": 145}, {"text": "B cell", "start": 192, "end": 198}]}}, "schema": []} {"input": "In contrast, TGF-beta had only minimal effects on two other B cell membrane proteins, HLA-DR and CD20.", "output": {"entities": {"protein": [{"text": "TGF-beta", "start": 13, "end": 21}, {"text": "membrane proteins", "start": 67, "end": 84}, {"text": "HLA-DR", "start": 86, "end": 92}, {"text": "CD20", "start": 97, "end": 101}], "cell_type": [{"text": "B cell", "start": 60, "end": 66}]}}, "schema": []} {"input": "Internal labeling with [35S]methionine and immunoprecipitation with anti-IgM, anti-kappa, and anti-lambda antibodies revealed a striking reduction in kappa L chain in the presence of TGF-beta.", "output": {"entities": {"protein": [{"text": "anti-IgM", "start": 68, "end": 76}, {"text": "anti-kappa", "start": 78, "end": 88}, {"text": "anti-lambda antibodies", "start": 94, "end": 116}, {"text": "kappa L chain", "start": 150, "end": 163}, {"text": "TGF-beta", "start": 183, "end": 191}]}}, "schema": []} {"input": "A less pronounced reduction in lambda L chain and microH chain was also noted.", "output": {"entities": {"protein": [{"text": "lambda L chain", "start": 31, "end": 45}, {"text": "microH chain", "start": 50, "end": 62}]}}, "schema": []} {"input": "Northern blot analysis of RNA purified from B cells treated with TGF-beta for varying time intervals revealed a significant decrease in steady state kappa and lambda L chain mRNA levels.", "output": {"entities": {"cell_type": [{"text": "B cells", "start": 44, "end": 51}], "protein": [{"text": "TGF-beta", "start": 65, "end": 73}]}}, "schema": []} {"input": "Furthermore, a significant decrease in the switch from the membrane forms of mu and gamma to their respective secreted forms was noted in the presence of TGF-beta.", "output": {"entities": {"rna": [{"text": "membrane forms", "start": 59, "end": 73}, {"text": "mu", "start": 77, "end": 79}, {"text": "gamma", "start": 84, "end": 89}, {"text": "secreted forms", "start": 110, "end": 124}], "protein": [{"text": "TGF-beta", "start": 154, "end": 162}]}}, "schema": []} {"input": "Nuclear run-on experiments demonstrated decreased transcription of kappa L chain.", "output": {"entities": {"protein": [{"text": "kappa L chain", "start": 67, "end": 80}]}}, "schema": []} {"input": "The effects of TGF-beta on two transcriptional regulatory factors, Oct-2 and nuclear factor (NF) kappa B, known to be important in Ig gene transcription were examined.", "output": {"entities": {"protein": [{"text": "TGF-beta", "start": 15, "end": 23}, {"text": "transcriptional regulatory factors", "start": 31, "end": 65}, {"text": "Oct-2", "start": 67, "end": 72}, {"text": "nuclear factor (NF) kappa B", "start": 77, "end": 104}, {"text": "Ig", "start": 131, "end": 133}]}}, "schema": []} {"input": "Oct-2 mRNA levels and both Oct-2 and NF-kappa B proteins in nuclear extracts were not altered by treatment with TGF-beta.", "output": {"entities": {"rna": [{"text": "Oct-2 mRNA", "start": 0, "end": 10}], "protein": [{"text": "Oct-2", "start": 27, "end": 32}, {"text": "NF-kappa B proteins", "start": 37, "end": 56}, {"text": "TGF-beta", "start": 112, "end": 120}]}}, "schema": []} {"input": "In contrast, levels of the transcriptional factor AP-1, which is not known to be important in B cell Ig production, were reduced by TGF-beta.", "output": {"entities": {"protein": [{"text": "transcriptional factor AP-1", "start": 27, "end": 54}, {"text": "Ig", "start": 101, "end": 103}, {"text": "TGF-beta", "start": 132, "end": 140}], "cell_type": [{"text": "B cell", "start": 94, "end": 100}]}}, "schema": []} {"input": "These findings demonstrate that TGF-beta decreases B lymphocyte Ig secretion by inhibiting the synthesis of Ig mRNA and inhibiting the switch from the membrane form to the secreted forms of mu and gamma mRNA.", "output": {"entities": {"protein": [{"text": "TGF-beta", "start": 32, "end": 40}, {"text": "Ig", "start": 64, "end": 66}], "rna": [{"text": "Ig mRNA", "start": 108, "end": 115}, {"text": "membrane form", "start": 151, "end": 164}, {"text": "secreted forms", "start": 172, "end": 186}]}}, "schema": []} {"input": "The mechanism by which TGF-beta inhibits Ig chain synthesis is unclear although it does not involve inhibition of the binding of NF-kappa B or Oct-2 to their respective target sequences.", "output": {"entities": {"protein": [{"text": "TGF-beta", "start": 23, "end": 31}, {"text": "NF-kappa B", "start": 129, "end": 139}, {"text": "Oct-2", "start": 143, "end": 148}]}}, "schema": []} {"input": "Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer.", "output": {"entities": {"dna": [{"text": "cis-regulatory element", "start": 77, "end": 99}, {"text": "human T-cell receptor delta gene enhancer", "start": 111, "end": 152}]}}, "schema": []} {"input": "A family of transcriptional activators has recently been identified in chickens; these transcriptional activators recognize a common consensus motif (WGATAR) through a conserved C4 zinc finger DNA-binding domain.", "output": {"entities": {"protein": [{"text": "transcriptional activators", "start": 12, "end": 38}, {"text": "transcriptional activators", "start": 87, "end": 113}, {"text": "C4 zinc finger DNA-binding domain", "start": 178, "end": 211}], "dna": [{"text": "consensus motif", "start": 133, "end": 148}, {"text": "WGATAR", "start": 150, "end": 156}]}}, "schema": []} {"input": "One of the members of this multigene family, cGATA-3, is most abundantly expressed in the T-lymphocyte cell lineage.", "output": {"entities": {"protein": [{"text": "cGATA-3", "start": 45, "end": 52}], "cell_type": [{"text": "T-lymphocyte cell lineage", "start": 90, "end": 115}]}}, "schema": []} {"input": "Analysis of human and murine GATA-3 factors shows a striking degree of amino acid sequence identity and similar patterns of tissue specificity of expression in these three organisms.", "output": {"entities": {"protein": [{"text": "amino acid sequence", "start": 71, "end": 90}]}}, "schema": []} {"input": "The murine and human factors are abundantly expressed in a variety of human and murine T-cell lines and can activate transcription through a tissue-specific GATA-binding site identified within the human T-cell receptor delta gene enhancer.", "output": {"entities": {"cell_line": [{"text": "human and", "start": 70, "end": 79}, {"text": "murine T-cell lines", "start": 80, "end": 99}], "dna": [{"text": "tissue-specific GATA-binding site", "start": 141, "end": 174}, {"text": "human T-cell receptor delta gene enhancer", "start": 197, "end": 238}]}}, "schema": []} {"input": "We infer that the murine and human GATA-3 proteins play a central and highly conserved role in vertebrate T-cell-specific transcriptional regulation.", "output": {"entities": {}}, "schema": []} {"input": "Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 31, "end": 41}, {"text": "HIV-1 protease", "start": 49, "end": 63}]}}, "schema": []} {"input": "Transcription of the human immunodeficiency virus type-1 (HIV-1) genome is regulated in part by cellular factors and is stimulated by activation of latently infected T cells.", "output": {"entities": {"dna": [{"text": "human immunodeficiency virus type-1 (HIV-1) genome", "start": 21, "end": 71}], "protein": [{"text": "cellular factors", "start": 96, "end": 112}], "cell_type": [{"text": "latently infected T cells", "start": 148, "end": 173}]}}, "schema": []} {"input": "T-cell activation also correlates with the induction of the factor NF-kappa B which binds to two adjacent sites in the HIV-1 long terminal repeat.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 67, "end": 77}], "dna": [{"text": "HIV-1 long terminal repeat", "start": 119, "end": 145}]}}, "schema": []} {"input": "This factor consists of two DNA-binding subunits of relative molecular mass 50,000 (50K) associated with two 65K subunits.", "output": {"entities": {"protein": [{"text": "DNA-binding subunits", "start": 28, "end": 48}, {"text": "65K subunits", "start": 109, "end": 121}]}}, "schema": []} {"input": "It is located in the nucleus in mature B cells, but is present in other cell types as an inactive cytoplasmic complex.", "output": {"entities": {"cell_type": [{"text": "mature B cells", "start": 32, "end": 46}], "protein": [{"text": "inactive cytoplasmic complex", "start": 89, "end": 117}]}}, "schema": []} {"input": "External stimuli, including those that activate T cells, result in nuclear translocation of active NF-kappa B.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 48, "end": 55}], "protein": [{"text": "NF-kappa B", "start": 99, "end": 109}]}}, "schema": []} {"input": "The cloning of the complementary DNA for the 50K subunit helped to identify an exclusively cytoplasmic 105K precursor (p105) (V.B., P.K. and A.I., manuscript submitted).", "output": {"entities": {"dna": [{"text": "complementary DNA", "start": 19, "end": 36}], "protein": [{"text": "50K subunit", "start": 45, "end": 56}, {"text": "cytoplasmic 105K precursor", "start": 91, "end": 117}, {"text": "p105", "start": 119, "end": 123}]}}, "schema": []} {"input": "The expression of active NF-kappa B might therefore also be regulated by the extent of processing of p105.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 25, "end": 35}, {"text": "p105", "start": 101, "end": 105}]}}, "schema": []} {"input": "Because HIV-1 requires active NF-kappa B for efficient transcription, we tested the effect of HIV-1 infection on the processing of the human 105K precursor.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 30, "end": 40}, {"text": "human 105K precursor", "start": 135, "end": 155}]}}, "schema": []} {"input": "We show here that the HIV-1 protease can process p105 and increases levels of active nuclear NF-kappa B complex.", "output": {"entities": {"protein": [{"text": "p105", "start": 49, "end": 53}, {"text": "nuclear NF-kappa B complex", "start": 85, "end": 111}]}}, "schema": []} {"input": "1,25-Dihydroxyvitamin D3 receptor RNA: expression in hematopoietic cells.", "output": {"entities": {"protein": [{"text": "1,25-Dihydroxyvitamin D3 receptor", "start": 0, "end": 33}], "rna": [{"text": "RNA", "start": 34, "end": 37}], "cell_type": [{"text": "hematopoietic cells", "start": 53, "end": 72}]}}, "schema": []} {"input": "1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] induces differentiation and inhibits proliferation of myeloid leukemic cells from various lines and patients; these effects are probably mediated through the 1,25(OH)2D3 receptor.", "output": {"entities": {"cell_type": [{"text": "myeloid leukemic cells", "start": 93, "end": 115}], "protein": [{"text": "1,25(OH)2D3 receptor", "start": 197, "end": 217}]}}, "schema": []} {"input": "Little is known of expression of 1,25(OH)2D3 receptor RNA in hematopoietic cells.", "output": {"entities": {"rna": [{"text": "1,25(OH)2D3 receptor RNA", "start": 33, "end": 57}], "cell_type": [{"text": "hematopoietic cells", "start": 61, "end": 80}]}}, "schema": []} {"input": "We examined the expression and modulation of expression of 1,25(OH)2D3 receptor RNA in various proliferating and nonproliferating hematopoietic cells.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptor", "start": 59, "end": 79}], "rna": [{"text": "RNA", "start": 80, "end": 83}]}}, "schema": []} {"input": "Constitutive expression of 1,25(OH)2D3 receptor RNA was detected in various kinds of hematopoietic cells, including macrophages and activated T lymphocytes, as well as in cell lines KG-1 (myeloblasts ), HL-60 (promyelocytes ), ML-3 (myelomonoblasts ), U937, THP-1 (monoblasts ), K562 (erythroblasts ), and S-LB1 (HTLV-1-transfected T lymphocytes ).", "output": {"entities": {"rna": [{"text": "1,25(OH)2D3 receptor RNA", "start": 27, "end": 51}], "cell_type": [{"text": "hematopoietic cells", "start": 85, "end": 104}, {"text": "T lymphocytes", "start": 142, "end": 155}, {"text": "T lymphocytes", "start": 332, "end": 345}], "cell_line": [{"text": "KG-1", "start": 182, "end": 186}, {"text": "myeloblasts", "start": 188, "end": 199}, {"text": "HL-60", "start": 203, "end": 208}, {"text": "promyelocytes", "start": 210, "end": 223}, {"text": "ML-3", "start": 227, "end": 231}, {"text": "myelomonoblasts", "start": 233, "end": 248}, {"text": "U937", "start": 252, "end": 256}, {"text": "THP-1", "start": 258, "end": 263}, {"text": "monoblasts", "start": 265, "end": 275}, {"text": "K562", "start": 279, "end": 283}, {"text": "erythroblasts", "start": 285, "end": 298}, {"text": "S-LB1", "start": 306, "end": 311}, {"text": "HTLV-1-transfected", "start": 313, "end": 331}]}}, "schema": []} {"input": "Receptor transcripts were 4.6 kilobases (kb), and no variant sizes were observed.", "output": {"entities": {"rna": [{"text": "Receptor transcripts", "start": 0, "end": 20}, {"text": "4.6 kilobases", "start": 26, "end": 39}]}}, "schema": []} {"input": "All cell lines examined in this group also expressed 1,25(OH)2D3 receptors.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptors", "start": 53, "end": 74}]}}, "schema": []} {"input": "Most B lymphocyte lines expressed negligible levels of 1,25(OH)2D3 receptor RNA and protein; however; analysis of a lymphoid/myeloid somatic hybrid suggested that suppression of expression of 1,25(OH)2D3 receptor RNA in B lymphocytes may be a dominant characteristic.", "output": {"entities": {"cell_line": [{"text": "B lymphocyte lines", "start": 5, "end": 23}, {"text": "lymphoid/myeloid somatic hybrid", "start": 116, "end": 147}], "protein": [{"text": "1,25(OH)2D3 receptor", "start": 55, "end": 75}, {"text": "1,25(OH)2D3 receptor", "start": 192, "end": 212}], "rna": [{"text": "RNA", "start": 76, "end": 79}, {"text": "RNA", "start": 213, "end": 216}], "cell_type": [{"text": "B lymphocytes", "start": 220, "end": 233}]}}, "schema": []} {"input": "HL-60 cells were cultured with 10(-7) mol/L 1,25(OH)2D3 for 24 to 72 hours, and levels of expression of 1,25(OH)2D3 receptor and its RNA were examined.", "output": {"entities": {"cell_line": [{"text": "HL-60 cells", "start": 0, "end": 11}], "protein": [{"text": "1,25(OH)2D3 receptor", "start": 104, "end": 124}], "rna": [{"text": "RNA", "start": 133, "end": 136}]}}, "schema": []} {"input": "Levels of RNA coding for the receptor were not modulated by exposure to high levels of ligand.", "output": {"entities": {"rna": [{"text": "RNA", "start": 10, "end": 13}], "protein": [{"text": "receptor", "start": 29, "end": 37}]}}, "schema": []} {"input": "Levels of occupied 1,25(OH)2D3 receptor protein increased in these HL-60 cells; but the total number of 1,25(OH)2D3 receptors decreased about 50% at 24 hours and returned toward normal at 72 hours.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptor protein", "start": 19, "end": 47}, {"text": "1,25(OH)2D3 receptors", "start": 104, "end": 125}], "cell_line": [{"text": "HL-60 cells", "start": 67, "end": 78}]}}, "schema": []} {"input": "Steady-state levels of 1,25(OH)2D3 receptor RNA were not affected by terminal differentiation of HL-60 toward either granulocytes or macrophages.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptor", "start": 23, "end": 43}], "rna": [{"text": "RNA", "start": 44, "end": 47}], "cell_line": [{"text": "HL-60", "start": 97, "end": 102}], "cell_type": [{"text": "granulocytes", "start": 117, "end": 129}, {"text": "macrophages", "start": 133, "end": 144}]}}, "schema": []} {"input": "Nondividing macrophages from normal individuals also expressed 1,25(OH)2D3 receptor RNA.", "output": {"entities": {"cell_type": [{"text": "macrophages", "start": 12, "end": 23}], "protein": [{"text": "1,25(OH)2D3 receptor", "start": 63, "end": 83}], "rna": [{"text": "RNA", "start": 84, "end": 87}]}}, "schema": []} {"input": "In contrast, nondividing peripheral blood lymphocytes from normal individuals did not express 1,25(OH)2D3 receptor RNA; with stimulation of proliferation of these cells, accumulation of 1,25(OH)2D3 receptor RNA increased markedly.", "output": {"entities": {"cell_type": [{"text": "nondividing peripheral blood lymphocytes", "start": 13, "end": 53}], "rna": [{"text": "1,25(OH)2D3 receptor RNA", "start": 94, "end": 118}, {"text": "RNA", "start": 207, "end": 210}], "protein": [{"text": "1,25(OH)2D3 receptor", "start": 186, "end": 206}]}}, "schema": []} {"input": "Half-life (t1/2) of 1,25(OH)2D3 receptor RNA in T lymphocytes was short (1 hour) as determined by measuring decay of the message after addition of actinomycin D.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptor", "start": 20, "end": 40}], "rna": [{"text": "RNA", "start": 41, "end": 44}], "cell_type": [{"text": "T lymphocytes", "start": 48, "end": 61}]}}, "schema": []} {"input": "Consistent with this short t1/2, accumulation of 1,25(OH)2D3 receptor RNA increased in cells as their protein synthesis was inhibited.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptor", "start": 49, "end": 69}], "rna": [{"text": "RNA", "start": 70, "end": 73}]}}, "schema": []} {"input": "Further studies are required to understand the physiologic role of 1,25(OH)2D3 receptors in myeloid cells and proliferating T lymphocytes.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptors", "start": 67, "end": 88}], "cell_type": [{"text": "myeloid cells", "start": 92, "end": 105}, {"text": "proliferating", "start": 110, "end": 123}, {"text": "T lymphocytes", "start": 124, "end": 137}]}}, "schema": []} {"input": "Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes.", "output": {"entities": {"dna": [{"text": "c-jun,", "start": 14, "end": 20}, {"text": "jun B and", "start": 21, "end": 30}, {"text": "jun D proto-oncogenes", "start": 31, "end": 52}], "cell_type": [{"text": "human peripheral-blood granulocytes", "start": 56, "end": 91}]}}, "schema": []} {"input": "We have found that purified human peripheral-blood granulocytes express constitutively significant levels of proto-oncogenes c-jun, jun B and jun D mRNA.", "output": {"entities": {"cell_type": [{"text": "purified human peripheral-blood granulocytes", "start": 19, "end": 63}], "dna": [{"text": "proto-oncogenes", "start": 109, "end": 124}]}}, "schema": []} {"input": "Upon functional activation of granulocytes by 4 beta-phorbol 12-myristate 13-acetate (PMA ), the levels of c-jun, jun B and jun D transcripts were increased.", "output": {"entities": {"cell_type": [{"text": "granulocytes", "start": 30, "end": 42}]}}, "schema": []} {"input": "The three jun genes showed a similar time course in their induction by PMA, maximal mRNA levels being reached after 60 min of induction.", "output": {"entities": {"dna": [{"text": "jun genes", "start": 10, "end": 19}]}}, "schema": []} {"input": "These results suggest that expression of c-jun, jun B and jun D genes might be involved in terminal granulocyte differentiation or in regulating granulocyte functionality.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 41, "end": 46}, {"text": "jun B", "start": 48, "end": 53}, {"text": "jun D genes", "start": 58, "end": 69}], "cell_type": [{"text": "terminal granulocyte", "start": 91, "end": 111}, {"text": "granulocyte", "start": 145, "end": 156}]}}, "schema": []} {"input": "The 29-kDa proteins phosphorylated in thrombin-activated human platelets are forms of the estrogen receptor -related 27-kDa heat shock protein.", "output": {"entities": {"protein": [{"text": "29-kDa proteins", "start": 4, "end": 19}, {"text": "estrogen receptor -related 27-kDa heat shock protein", "start": 90, "end": 142}], "cell_line": [{"text": "thrombin-activated human platelets", "start": 38, "end": 72}]}}, "schema": []} {"input": "Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis.", "output": {"entities": {"protein": [{"text": "Thrombin", "start": 0, "end": 8}]}}, "schema": []} {"input": "Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified.", "output": {"entities": {"protein": [{"text": "multiple proteins", "start": 64, "end": 81}]}}, "schema": []} {"input": "We have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin.", "output": {"entities": {"protein": [{"text": "29-kDa proteins", "start": 30, "end": 45}, {"text": "thrombin", "start": 126, "end": 134}], "cell_type": [{"text": "intact human platelets", "start": 100, "end": 122}]}}, "schema": []} {"input": "A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein.", "output": {"entities": {"protein": [{"text": "murine monoclonal antibody", "start": 2, "end": 28}, {"text": "unidentified estrogen receptor-related 29-kDa protein", "start": 42, "end": 95}, {"text": "unphosphorylated 27-kDa protein", "start": 159, "end": 190}]}}, "schema": []} {"input": "Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species.", "output": {"entities": {"protein": [{"text": "thrombin", "start": 23, "end": 31}, {"text": "27-kDa unphosphorylated form", "start": 92, "end": 120}, {"text": "29-kDa phosphoprotein species", "start": 128, "end": 157}]}}, "schema": []} {"input": "Using this antibody, we isolated and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27 ), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen.", "output": {"entities": {"dna": [{"text": "cDNA clone", "start": 55, "end": 65}], "protein": [{"text": "mammalian 27-kDa heat shock protein", "start": 111, "end": 146}, {"text": "HSP27", "start": 148, "end": 153}]}}, "schema": []} {"input": "The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies.", "output": {"entities": {"protein": [{"text": "29-kDa proteins", "start": 4, "end": 19}, {"text": "HSP27", "start": 65, "end": 70}]}}, "schema": []} {"input": "Thus, the \" estrogen receptor-related protein\" is HSP27, and the three major 29-kDa proteins phosphorylated in thrombin -activated platelets are forms of HSP27.", "output": {"entities": {"protein": [{"text": "HSP27", "start": 50, "end": 55}, {"text": "29-kDa proteins", "start": 77, "end": 92}, {"text": "thrombin", "start": 111, "end": 119}, {"text": "HSP27", "start": 154, "end": 159}], "cell_type": [{"text": "-activated platelets", "start": 120, "end": 140}]}}, "schema": []} {"input": "These data suggest a role for HSP27 in the signal transduction events of platelet activation.", "output": {"entities": {"protein": [{"text": "HSP27", "start": 30, "end": 35}], "cell_type": [{"text": "platelet", "start": 73, "end": 81}]}}, "schema": []} {"input": "Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta ), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site.", "output": {"entities": {"protein": [{"text": "NF-E1", "start": 46, "end": 51}, {"text": "YY-1", "start": 53, "end": 57}, {"text": "delta", "start": 59, "end": 64}], "dna": [{"text": "immunoglobulin kappa 3' enhancer", "start": 86, "end": 118}, {"text": "immunoglobulin heavy-chain mu E1 site", "start": 127, "end": 164}]}}, "schema": []} {"input": "We have determined that the developmental control of immunoglobulin kappa 3' enhancer (kappa E3') activity is the result of the combined influence of positive- and negative-acting elements.", "output": {"entities": {"dna": [{"text": "immunoglobulin kappa 3' enhancer", "start": 53, "end": 85}, {"text": "kappa E3'", "start": 87, "end": 96}, {"text": "positive- and negative-acting elements", "start": 150, "end": 188}]}}, "schema": []} {"input": "We show that a central core in the kappa E3' enhancer is active at the pre-B-cell stage but is repressed by flanking negative-acting elements.", "output": {"entities": {"dna": [{"text": "kappa E3' enhancer", "start": 35, "end": 53}, {"text": "flanking negative-acting elements", "start": 108, "end": 141}]}}, "schema": []} {"input": "The negative-acting sequences repress enhancer activity in a position- and orientation-independent manner at the pre-B-cell stage.", "output": {"entities": {"dna": [{"text": "negative-acting sequences", "start": 4, "end": 29}]}}, "schema": []} {"input": "We have isolated a human cDNA clone encoding a zinc finger protein (NF-E1) that binds to the negative-acting segment of the kappa E3' enhancer.", "output": {"entities": {"dna": [{"text": "human cDNA clone", "start": 19, "end": 35}, {"text": "negative-acting segment", "start": 93, "end": 116}, {"text": "kappa E3' enhancer", "start": 124, "end": 142}], "protein": [{"text": "zinc finger protein", "start": 47, "end": 66}, {"text": "NF-E1", "start": 68, "end": 73}]}}, "schema": []} {"input": "This protein also binds to the immunoglobulin heavy-chain enhancer mu E1 site.", "output": {"entities": {"dna": [{"text": "immunoglobulin heavy-chain enhancer mu E1 site", "start": 31, "end": 77}]}}, "schema": []} {"input": "NF-E1 is encoded by the same gene as the YY-1 protein, which binds to the adeno-associated virus P5 promoter.", "output": {"entities": {"protein": [{"text": "NF-E1", "start": 0, "end": 5}, {"text": "YY-1 protein", "start": 41, "end": 53}], "dna": [{"text": "adeno-associated virus P5 promoter", "start": 74, "end": 108}]}}, "schema": []} {"input": "NF-E1 is also the human homologue of the mouse delta protein, which binds to ribosomal protein gene promoters.", "output": {"entities": {"protein": [{"text": "NF-E1", "start": 0, "end": 5}, {"text": "human homologue", "start": 18, "end": 33}], "dna": [{"text": "mouse delta protein", "start": 41, "end": 60}, {"text": "ribosomal protein gene promoters", "start": 77, "end": 109}]}}, "schema": []} {"input": "The predicted amino acid sequence of this protein contains features characteristic of transcriptional activators as well as transcriptional repressors.", "output": {"entities": {"protein": [{"text": "amino acid sequence", "start": 14, "end": 33}, {"text": "transcriptional activators", "start": 86, "end": 112}, {"text": "transcriptional repressors", "start": 124, "end": 150}]}}, "schema": []} {"input": "Cotransfection studies with this cDNA indicate that it can repress basal promoter activity.", "output": {"entities": {"dna": [{"text": "cDNA", "start": 33, "end": 37}, {"text": "basal promoter", "start": 67, "end": 81}]}}, "schema": []} {"input": "The apparent dual function of this protein is discussed.", "output": {"entities": {}}, "schema": []} {"input": "A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated.", "output": {"entities": {"dna": [{"text": "human putative lymphocyte G0/G1 switch gene", "start": 2, "end": 45}, {"text": "CpG-rich island", "start": 59, "end": 74}], "protein": [{"text": "small basic protein", "start": 85, "end": 104}]}}, "schema": []} {"input": "Genes actively involved in the G0/G1 switch (G0S genes) may be differentially expressed during the lectin -induced switch of lymphocytes from the G0 to the G1 phases of the cell cycle.", "output": {"entities": {"dna": [{"text": "G0/G1 switch", "start": 31, "end": 43}], "rna": [{"text": "G0S genes", "start": 45, "end": 54}], "protein": [{"text": "lectin", "start": 99, "end": 105}], "cell_type": [{"text": "lymphocytes", "start": 125, "end": 136}]}}, "schema": []} {"input": "This paper presents studies of G0S2, a member of a set of putative G0S genes, for which cDNAs were cloned and selected on the basis of differential cDNA hybridization.", "output": {"entities": {"dna": [{"text": "G0S2", "start": 31, "end": 35}, {"text": "cDNAs", "start": 88, "end": 93}], "rna": [{"text": "G0S genes", "start": 67, "end": 76}]}}, "schema": []} {"input": "G0S2 mRNA increases transiently within 1-2 hr of the addition of lectin or cycloheximide to cultured blood mononuclear cells.", "output": {"entities": {"rna": [{"text": "G0S2 mRNA", "start": 0, "end": 9}], "protein": [{"text": "lectin", "start": 65, "end": 71}], "cell_type": [{"text": "cultured blood mononuclear cells", "start": 92, "end": 124}]}}, "schema": []} {"input": "Comparison of a nearly full-length cDNA sequence with the corresponding genomic sequence reveals one small intron and an open reading frame in the second exon.", "output": {"entities": {"dna": [{"text": "nearly full-length cDNA sequence", "start": 16, "end": 48}, {"text": "genomic sequence", "start": 72, "end": 88}, {"text": "open reading frame", "start": 121, "end": 139}, {"text": "exon", "start": 154, "end": 158}]}}, "schema": []} {"input": "The derived 103-amino-acid basic protein has two potential alpha-helical domains separated by a hydrophobic region with the potential to generate turns and assume a beta-sheet conformation.", "output": {"entities": {"protein": [{"text": "103-amino-acid basic protein", "start": 12, "end": 40}, {"text": "alpha-helical domains", "start": 59, "end": 80}, {"text": "hydrophobic region", "start": 96, "end": 114}]}}, "schema": []} {"input": "Consistent with involvement in the G0/G1 switch, the protein contains potential sites for phosphorylation by protein kinase C and casein kinase II.", "output": {"entities": {"dna": [{"text": "G0/G1 switch", "start": 35, "end": 47}], "protein": [{"text": "protein kinase C", "start": 109, "end": 125}, {"text": "casein kinase II", "start": 130, "end": 146}]}}, "schema": []} {"input": "The gene contains a CpG-rich island suggesting expression in the germ line.", "output": {"entities": {"protein": [{"text": "CpG-rich island", "start": 20, "end": 35}]}}, "schema": []} {"input": "An upstream segment contains tandem dinucleotide repeats (CT)19/(CA)16.", "output": {"entities": {"dna": [{"text": "upstream segment", "start": 3, "end": 19}, {"text": "tandem dinucleotide repeats", "start": 29, "end": 56}, {"text": "(CT)19/(CA)16", "start": 57, "end": 70}]}}, "schema": []} {"input": "There is a suitably located TATA box, but potential sites for CCAAT-box binding factors are far upstream, embedded in a 42-nucleotide repeat element.", "output": {"entities": {"dna": [{"text": "TATA box", "start": 28, "end": 36}, {"text": "CCAAT-box", "start": 62, "end": 71}, {"text": "42-nucleotide repeat element", "start": 120, "end": 148}], "protein": [{"text": "binding factors", "start": 72, "end": 87}]}}, "schema": []} {"input": "Potential sites for transcription factors AP1, AP2, and AP3 are consistent with rapid transcriptional activation in response to inducing agents.", "output": {"entities": {"protein": [{"text": "transcription factors", "start": 20, "end": 41}, {"text": "AP1", "start": 42, "end": 45}, {"text": "AP2", "start": 47, "end": 50}, {"text": "AP3", "start": 56, "end": 59}]}}, "schema": []} {"input": "USF-related transcription factor, HIV-TF1, stimulates transcription of human immunodeficiency virus-1.", "output": {"entities": {"protein": [{"text": "USF-related transcription factor", "start": 0, "end": 32}, {"text": "HIV-TF1", "start": 34, "end": 41}]}}, "schema": []} {"input": "The transcription factor HIV-TF1, which binds to a region about 60 bp upstream from the enhancer of the human immunodeficiency virus-1 (HIV-1 ), was purified from human B cells.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 4, "end": 24}, {"text": "HIV-TF1", "start": 25, "end": 32}], "dna": [{"text": "60 bp upstream", "start": 64, "end": 78}], "cell_type": [{"text": "human B cells", "start": 163, "end": 176}]}}, "schema": []} {"input": "HIV-TF1 had a molecular weight of 39,000.", "output": {"entities": {"protein": [{"text": "HIV-TF1", "start": 0, "end": 7}]}}, "schema": []} {"input": "Binding of HIV-TF1 to the HIV long terminal repeat (LTR) activated transcription from the HIV promoter in vitro.", "output": {"entities": {"protein": [{"text": "HIV-TF1", "start": 11, "end": 18}], "dna": [{"text": "HIV long terminal repeat", "start": 26, "end": 50}, {"text": "LTR", "start": 52, "end": 55}, {"text": "HIV promoter", "start": 90, "end": 102}]}}, "schema": []} {"input": "The HIV-TF1 -binding site in HIV LTR was similar to the site recognized by upstream stimulatory factor (USF) in the adenovirus major late promoter.", "output": {"entities": {"dna": [{"text": "HIV-TF1 -binding site", "start": 4, "end": 25}, {"text": "HIV LTR", "start": 29, "end": 36}, {"text": "adenovirus major late promoter", "start": 116, "end": 146}], "protein": [{"text": "upstream stimulatory factor", "start": 75, "end": 102}, {"text": "USF", "start": 104, "end": 107}]}}, "schema": []} {"input": "DNA-binding properties of HIV-TF1 suggested that HIV-TF1 might be identical or related to USF.", "output": {"entities": {"protein": [{"text": "HIV-TF1", "start": 26, "end": 33}, {"text": "HIV-TF1", "start": 49, "end": 56}, {"text": "USF", "start": 90, "end": 93}]}}, "schema": []} {"input": "Interestingly, treatment of purified HIV-TF1 by phosphatase greatly reduced its DNA-binding activity, suggesting that phosphorylation of HIV-TF1 was essential for DNA binding.", "output": {"entities": {"protein": [{"text": "HIV-TF1", "start": 37, "end": 44}, {"text": "phosphatase", "start": 48, "end": 59}, {"text": "HIV-TF1", "start": 137, "end": 144}]}}, "schema": []} {"input": "The disruption of HIV-TF1 -binding site induced a 60% decrease in the level of transcription from the HIV promoter in vivo.", "output": {"entities": {"dna": [{"text": "HIV-TF1 -binding site", "start": 18, "end": 39}, {"text": "HIV promoter", "start": 102, "end": 114}]}}, "schema": []} {"input": "These results suggest that HIV-TF1 is involved in transcriptional regulation of HIV-1.", "output": {"entities": {"protein": [{"text": "HIV-TF1", "start": 27, "end": 34}]}}, "schema": []} {"input": "Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency.", "output": {"entities": {"protein": [{"text": "dihydropyrimidine dehydrogenase", "start": 44, "end": 75}]}}, "schema": []} {"input": "A potentially more common pharmacogenetic syndrome.", "output": {"entities": {}}, "schema": []} {"input": "This study describes the inheritance of a defect in pyrimidine catabolism and its association with drug-induced toxicity in a patient receiving 5-fluorouracil (FUra) as adjuvant chemotherapy for breast carcinoma.", "output": {"entities": {}}, "schema": []} {"input": "The study population included the affected patient (proband ), nine of her blood relatives, and seven healthy volunteers.", "output": {"entities": {}}, "schema": []} {"input": "The activity of dihydropyrimidine dehydrogenase (DPD ), the initial enzyme of pyrimidine (and FUra) catabolism, in peripheral blood mononuclear cells was measured in each subject by a specific radiometric assay using FUra as the substrate.", "output": {"entities": {"protein": [{"text": "dihydropyrimidine dehydrogenase", "start": 16, "end": 47}, {"text": "DPD", "start": 49, "end": 52}, {"text": "enzyme", "start": 68, "end": 74}], "cell_type": [{"text": "peripheral blood mononuclear cells", "start": 115, "end": 149}]}}, "schema": []} {"input": "The proband had no detectable DPD activity.", "output": {"entities": {"protein": [{"text": "DPD", "start": 30, "end": 33}]}}, "schema": []} {"input": "When enzyme levels in the proband and relatives were compared with that in controls, an autosomal recessive pattern of inheritance was demonstrated.", "output": {"entities": {}}, "schema": []} {"input": "This is the third patient with severe FUra toxicity secondary to an alteration in pyrimidine catabolism and the second from our clinic population suggesting that the frequency of this genetic defect may be greater than previously thought.", "output": {"entities": {}}, "schema": []} {"input": "Monitoring DPD activity may be important in the management of patients experiencing severe toxicity secondary to FUra chemotherapy.", "output": {"entities": {"protein": [{"text": "DPD", "start": 11, "end": 14}]}}, "schema": []} {"input": "Transactivation of the human immunodeficiency virus promoter by human herpesvirus 6 (HHV-6) strains GS and Z-29 in primary human T lymphocytes and identification of transactivating HHV-6 (GS) gene fragments.", "output": {"entities": {"dna": [{"text": "human immunodeficiency virus promoter", "start": 23, "end": 60}, {"text": "transactivating HHV-6 (GS) gene fragments", "start": 165, "end": 206}], "cell_type": [{"text": "primary human T", "start": 115, "end": 130}, {"text": "lymphocytes", "start": 131, "end": 142}]}}, "schema": []} {"input": "Human herpesvirus 6 (HHV-6) can activate the human immunodeficiency virus (HIV) promoter and accelerate cytopathic effects in HIV-infected human T cells.", "output": {"entities": {"dna": [{"text": "human immunodeficiency virus (HIV) promoter", "start": 45, "end": 88}], "cell_type": [{"text": "HIV-infected human T cells", "start": 126, "end": 152}]}}, "schema": []} {"input": "This study examines the regions of the HIV promoter required for HHV-6 transactivation in a heterogeneous population of primary human T lymphocytes with or without antigenic stimulation.", "output": {"entities": {"dna": [{"text": "HIV promoter", "start": 39, "end": 51}], "cell_type": [{"text": "primary human T lymphocytes", "start": 120, "end": 147}]}}, "schema": []} {"input": "Two different strains of HHV-6, GS and Z29, transactivated the HIV promoter.", "output": {"entities": {"dna": [{"text": "HIV promoter", "start": 63, "end": 75}]}}, "schema": []} {"input": "The GS strain transactivated the promoter in both stimulated and resting T cells, while the Z29 strain increased HIV promoter activity only in stimulated T cells.", "output": {"entities": {"dna": [{"text": "promoter", "start": 33, "end": 41}, {"text": "HIV promoter", "start": 113, "end": 125}], "cell_type": [{"text": "T cells", "start": 73, "end": 80}, {"text": "stimulated T cells", "start": 143, "end": 161}]}}, "schema": []} {"input": "Three DNA clones containing HHV-6(GS) genomic fragments transactivated the HIV promoter in cotransfected T cells.", "output": {"entities": {"dna": [{"text": "HHV-6(GS) genomic fragments", "start": 28, "end": 55}, {"text": "HIV promoter", "start": 75, "end": 87}], "cell_line": [{"text": "cotransfected T cells", "start": 91, "end": 112}]}}, "schema": []} {"input": "A 21.4-kb DNA clone, pZVB70, showed the highest transactivating ability, while two other DNA fragments, pZVB10 (6.2 kb) and pZVH14 (8.7 kb), showed lower activity.", "output": {"entities": {"dna": [{"text": "21.4-kb DNA clone", "start": 2, "end": 19}, {"text": "pZVB70", "start": 21, "end": 27}, {"text": "DNA fragments", "start": 89, "end": 102}, {"text": "pZVB10", "start": 104, "end": 110}, {"text": "pZVH14", "start": 124, "end": 130}]}}, "schema": []} {"input": "One of these clones, pZVH14, activated the HIV promoter construct containing a mutation in the NF kappa B site.", "output": {"entities": {"dna": [{"text": "pZVH14", "start": 21, "end": 27}, {"text": "HIV promoter construct", "start": 43, "end": 65}, {"text": "NF kappa B site", "start": 95, "end": 110}]}}, "schema": []} {"input": "However, this mutated NF kappa B promoter was not transactivated during HHV-6(GS) infection or after cotransfection with pZVB70 or pZVB10.", "output": {"entities": {"dna": [{"text": "mutated NF kappa B promoter", "start": 14, "end": 41}, {"text": "pZVB70", "start": 121, "end": 127}, {"text": "pZVB10", "start": 131, "end": 137}]}}, "schema": []} {"input": "These data indicate that the NF kappa B sites of the HIV promoter are essential for its transactivation during HHV-6(GS) infection.", "output": {"entities": {"dna": [{"text": "NF kappa B sites", "start": 29, "end": 45}, {"text": "HIV promoter", "start": 53, "end": 65}]}}, "schema": []} {"input": "By increasing HIV promoter activity in primary T lymphocytes, HHV-6 may consequently increase HIV replication, leading to an increase in the cytopathic effect on coinfected human T cells.", "output": {"entities": {"dna": [{"text": "HIV promoter", "start": 14, "end": 26}], "cell_type": [{"text": "primary T lymphocytes", "start": 39, "end": 60}, {"text": "coinfected human T cells", "start": 162, "end": 186}]}}, "schema": []} {"input": "Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 36, "end": 46}]}}, "schema": []} {"input": "HIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B.", "output": {"entities": {"dna": [{"text": "HIV-1 proviral DNA", "start": 0, "end": 18}, {"text": "binding sites", "start": 32, "end": 45}], "protein": [{"text": "transcription factor", "start": 54, "end": 74}, {"text": "NF-kappa B", "start": 75, "end": 85}]}}, "schema": []} {"input": "HIV-1 -infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels.", "output": {"entities": {"protein": [{"text": "tumour necrosis factor alpha", "start": 72, "end": 100}, {"text": "TNF alpha", "start": 102, "end": 111}]}}, "schema": []} {"input": "We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 94, "end": 104}]}}, "schema": []} {"input": "The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells.", "output": {"entities": {"cell_line": [{"text": "Molt-4", "start": 179, "end": 185}, {"text": "U937 cells", "start": 190, "end": 200}]}}, "schema": []} {"input": "However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels.", "output": {"entities": {}}, "schema": []} {"input": "Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 30, "end": 40}, {"text": "chloramphenicol acetyl-transferase", "start": 109, "end": 143}, {"text": "CAT", "start": 145, "end": 148}, {"text": "NF-kappa B", "start": 183, "end": 193}], "dna": [{"text": "binding sites", "start": 194, "end": 207}], "cell_type": [{"text": "uninfected cells", "start": 211, "end": 227}]}}, "schema": []} {"input": "This suggests that the cysteine deficiency in HIV-1 -infected individuals may cause an over-expression of NF-kappa B -dependent genes and enhance HIV-1 replication.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 106, "end": 116}], "dna": [{"text": "-dependent genes", "start": 117, "end": 133}]}}, "schema": []} {"input": "NAC may be considered for the treatment of HIV-1 -infected individuals.", "output": {"entities": {}}, "schema": []} {"input": "A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer.", "output": {"entities": {"protein": [{"text": "thymus-specific member", "start": 2, "end": 24}, {"text": "HMG protein family", "start": 32, "end": 50}], "dna": [{"text": "human T cell receptor C alpha enhancer", "start": 65, "end": 103}]}}, "schema": []} {"input": "The human T cell-specific transcription factor TCF-1 alpha plays a key role in the tissue-specific activation of the T cell receptor (TCR) C alpha enhancer and binds to pyrimidine -rich elements (5'-PyCTTTG-3') present in a variety of other T cell-specific control regions.", "output": {"entities": {"protein": [{"text": "human T cell-specific transcription factor", "start": 4, "end": 46}, {"text": "TCF-1 alpha", "start": 47, "end": 58}, {"text": "T cell receptor", "start": 117, "end": 132}, {"text": "TCR", "start": 134, "end": 137}], "dna": [{"text": "pyrimidine -rich elements", "start": 169, "end": 194}, {"text": "T cell-specific control regions", "start": 241, "end": 272}]}}, "schema": []} {"input": "Using amino acid sequence information derived from the DNA affinity-purified protein, we have now isolated cDNA clones encoding TCF-1 alpha.", "output": {"entities": {"protein": [{"text": "amino acid sequence", "start": 6, "end": 25}, {"text": "DNA affinity-purified protein", "start": 55, "end": 84}, {"text": "TCF-1 alpha", "start": 128, "end": 139}], "dna": [{"text": "cDNA clones", "start": 107, "end": 118}]}}, "schema": []} {"input": "The TCF-1 alpha cDNA contains a single 68-amino-acid domain that is homologous to a region conserved among high-mobility group (HMG) and nonhistone chromosomal proteins.", "output": {"entities": {"dna": [{"text": "TCF-1 alpha cDNA", "start": 4, "end": 20}], "protein": [{"text": "68-amino-acid domain", "start": 39, "end": 59}, {"text": "high-mobility group", "start": 107, "end": 126}, {"text": "HMG", "start": 128, "end": 131}, {"text": "nonhistone chromosomal proteins", "start": 137, "end": 168}]}}, "schema": []} {"input": "Expression of full-length and mutant cDNA clones in bacteria reveal that the single HMG motif, which is predicted to contain two extended alpha-helical segments, is sufficient to direct the sequence-specific binding of TCF-1 alpha to DNA.", "output": {"entities": {"dna": [{"text": "full-length", "start": 14, "end": 25}, {"text": "mutant cDNA clones", "start": 30, "end": 48}, {"text": "DNA", "start": 234, "end": 237}], "protein": [{"text": "single HMG motif", "start": 77, "end": 93}, {"text": "alpha-helical segments", "start": 138, "end": 160}, {"text": "TCF-1 alpha", "start": 219, "end": 230}]}}, "schema": []} {"input": "Northern blot experiments demonstrate further that TCF-1 alpha mRNA is highly tissue specific, found primarily in the thymus or T cell lines.", "output": {"entities": {"rna": [{"text": "TCF-1 alpha mRNA", "start": 51, "end": 67}]}}, "schema": []} {"input": "The immature CEM T cell line expresses relatively low levels of TCF-1 alpha mRNA, which are increased upon activation of these cells by phorbol esters.", "output": {"entities": {"cell_line": [{"text": "immature CEM T cell line", "start": 4, "end": 28}], "protein": [{"text": "TCF-1 alpha", "start": 64, "end": 75}], "rna": [{"text": "mRNA", "start": 76, "end": 80}]}}, "schema": []} {"input": "Interestingly, the cloned TCF-1 alpha protein is a potent transcriptional activator of the human TCR alpha enhancer in nonlymphoid cell lines, whereas the activity of the endogenous protein in T cell lines is strongly dependent on an additional T cell-specific protein that interacts with the core enhancer.", "output": {"entities": {"protein": [{"text": "TCF-1 alpha protein", "start": 26, "end": 45}, {"text": "transcriptional activator", "start": 58, "end": 83}, {"text": "endogenous protein", "start": 171, "end": 189}], "dna": [{"text": "human TCR alpha enhancer", "start": 91, "end": 115}, {"text": "core enhancer", "start": 293, "end": 306}], "cell_line": [{"text": "nonlymphoid cell lines", "start": 119, "end": 141}, {"text": "T cell lines", "start": 193, "end": 205}, {"text": "T cell-specific protein", "start": 245, "end": 268}]}}, "schema": []} {"input": "TCF-1 alpha is currently unique among the newly emerging family of DNA-binding regulatory proteins that share the HMG motif in that it is a highly tissue-specific RNA polymerase II transcription factor.", "output": {"entities": {"protein": [{"text": "TCF-1 alpha", "start": 0, "end": 11}, {"text": "DNA-binding regulatory proteins", "start": 67, "end": 98}, {"text": "HMG motif", "start": 114, "end": 123}, {"text": "highly tissue-specific RNA polymerase II", "start": 140, "end": 180}, {"text": "transcription factor", "start": 181, "end": 201}]}}, "schema": []} {"input": "A novel HIV-1 isolate containing alterations affecting the NF-kappa B element.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 59, "end": 69}], "dna": [{"text": "element", "start": 70, "end": 77}]}}, "schema": []} {"input": "Three molecular clones of HIV-1, derived from a single isolate (AL1 ), exhibited distinct replicative and cytopathic properties during propagation in a human T cell line.", "output": {"entities": {"cell_line": [{"text": "human T cell line", "start": 152, "end": 169}]}}, "schema": []} {"input": "The phenotypic differences observed were attributable, in large part, to changes affecting the viral LTR.", "output": {"entities": {"dna": [{"text": "viral LTR", "start": 95, "end": 104}]}}, "schema": []} {"input": "Nucleotide sequence and PCR analyses demonstrated the presence of novel duplications or deletions involving the NF-kappa B motif.", "output": {"entities": {"dna": [{"text": "Nucleotide sequence", "start": 0, "end": 19}, {"text": "NF-kappa B motif", "start": 112, "end": 128}]}}, "schema": []} {"input": "These changes in the enhancer element were identified in the original AL1 virus stock.", "output": {"entities": {"dna": [{"text": "enhancer element", "start": 21, "end": 37}]}}, "schema": []} {"input": "Subcloning of the variant NF-kappa B segments into LTR-driven CAT expression vectors confirmed a correlation between promoter activity and replicative/cytopathic capacity.", "output": {"entities": {"dna": [{"text": "variant", "start": 18, "end": 25}, {"text": "segments", "start": 37, "end": 45}, {"text": "LTR-driven CAT expression vectors", "start": 51, "end": 84}], "protein": [{"text": "NF-kappa B", "start": 26, "end": 36}]}}, "schema": []} {"input": "Multiple Oct2 isoforms are generated by alternative splicing.", "output": {"entities": {"protein": [{"text": "Oct2 isoforms", "start": 9, "end": 22}]}}, "schema": []} {"input": "The interaction of the Oct2 transcription factor with the cognate octamer motif ATGCAAAT is a critical determinant of the lymphoid-specific expression of immunoglobulin genes.", "output": {"entities": {"protein": [{"text": "Oct2 transcription factor", "start": 23, "end": 48}], "dna": [{"text": "cognate octamer motif", "start": 58, "end": 79}, {"text": "immunoglobulin genes", "start": 154, "end": 174}]}}, "schema": []} {"input": "Ectopic expression of cloned Oct2 cDNA was shown to be sufficient to reconstitute at least some aspects of this regulation in non-lymphoid cells.", "output": {"entities": {"dna": [{"text": "cloned Oct2 cDNA", "start": 22, "end": 38}], "cell_type": [{"text": "non-lymphoid cells", "start": 126, "end": 144}]}}, "schema": []} {"input": "We describe the isolation and characterization of multiple cDNAs encoding mouse Oct2 from a mature B-cell line and we show that a variety of isoforms of this transcription factor is generated from a single gene by an alternative splicing mechanism.", "output": {"entities": {"dna": [{"text": "multiple cDNAs", "start": 50, "end": 64}], "protein": [{"text": "mouse Oct2", "start": 74, "end": 84}, {"text": "transcription factor", "start": 158, "end": 178}], "cell_line": [{"text": "mature B-cell line", "start": 92, "end": 110}]}}, "schema": []} {"input": "All the isoforms retain the previously characterized POU-domain and are therefore able to bind to the octamer motif.", "output": {"entities": {"protein": [{"text": "isoforms", "start": 8, "end": 16}], "dna": [{"text": "octamer motif", "start": 102, "end": 115}]}}, "schema": []} {"input": "Different amounts of the various isoforms are present within the same B-cell regardless of the developmental stage of B-cell differentiation and at least some of the isoforms are conserved between mouse and humans.", "output": {"entities": {"protein": [{"text": "isoforms", "start": 33, "end": 41}, {"text": "isoforms", "start": 166, "end": 174}], "cell_type": [{"text": "B-cell", "start": 70, "end": 76}, {"text": "B-cell", "start": 118, "end": 124}]}}, "schema": []} {"input": "In cotransfection experiments we show that all the isoforms are able to activate an octamer containing promoter element in fibroblasts revealing an unexpected functional redundancy.", "output": {"entities": {"protein": [{"text": "isoforms", "start": 51, "end": 59}], "dna": [{"text": "octamer", "start": 84, "end": 91}, {"text": "promoter element", "start": 103, "end": 119}]}}, "schema": []} {"input": "Finally, we show that one of the isoforms encodes the previously described lymphoid-specific Oct2B protein which has been suggested to be involved in the function of the octamer motif in the context of the immunoglobulin heavy-chain (IgH) enhancer.", "output": {"entities": {"protein": [{"text": "isoforms", "start": 33, "end": 41}, {"text": "lymphoid-specific Oct2B protein", "start": 75, "end": 106}, {"text": "IgH", "start": 234, "end": 237}], "dna": [{"text": "octamer motif", "start": 170, "end": 183}, {"text": "immunoglobulin heavy-chain (", "start": 206, "end": 234}, {"text": ") enhancer", "start": 237, "end": 247}]}}, "schema": []} {"input": "[Regulation of intracellular cholesterol synthesis in hypercholesterolemia by glucocorticoids]", "output": {"entities": {}}, "schema": []} {"input": "The rate of endogenous cholesterol synthesis in blood lymphocytes and skin fibroblasts from patients with type IIa hyperlipidemia was found to be increased in comparison with healthy donors.", "output": {"entities": {"cell_type": [{"text": "blood lymphocytes", "start": 48, "end": 65}, {"text": "skin fibroblasts", "start": 70, "end": 86}]}}, "schema": []} {"input": "The cells of hyperlipidemic patients had lowered levels of glucocorticoid receptors concomitantly with a partial loss of their sensitivity to glucocorticoids.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 59, "end": 83}]}}, "schema": []} {"input": "In fibroblasts from patients with hereditary hypercholesteremia of homozygous type the number of glucocorticoid receptors did not exceed 10% of their content in normal cells.", "output": {"entities": {"cell_type": [{"text": "fibroblasts", "start": 3, "end": 14}, {"text": "normal cells", "start": 161, "end": 173}], "protein": [{"text": "glucocorticoid receptors", "start": 97, "end": 121}]}}, "schema": []} {"input": "The decrease of the number of glucocorticoid receptors in patients with type IIa hyperlipidemia seems to be a compensatory response of cells culminating in activation of endogenous cholesterol synthesis.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 30, "end": 54}]}}, "schema": []} {"input": "Negative regulation of human immunodeficiency virus type 1 expression in monocytes: role of the 65-kDa plus 50-kDa NF-kappa B dimer.", "output": {"entities": {"protein": [{"text": "65-kDa", "start": 96, "end": 102}, {"text": "50-kDa", "start": 108, "end": 114}, {"text": "NF-kappa B dimer", "start": 115, "end": 131}]}}, "schema": []} {"input": "Although monocytic cells can provide a reservoir for viral production in vivo, their regulation of human immunodeficiency virus type 1 (HIV-1) transcription can be either latent, restricted, or productive.", "output": {"entities": {}}, "schema": []} {"input": "These differences in gene expression have not been molecularly defined.", "output": {"entities": {}}, "schema": []} {"input": "In THP-1 cells with restricted HIV expression, there is an absence of DNA-protein binding complex formation with the HIV-1 promoter-enhancer associated with markedly less viral RNA production.", "output": {"entities": {"cell_line": [{"text": "THP-1 cells", "start": 3, "end": 14}], "protein": [{"text": "DNA-protein binding complex", "start": 70, "end": 97}], "dna": [{"text": "HIV-1 promoter-enhancer", "start": 117, "end": 140}], "rna": [{"text": "viral RNA", "start": 171, "end": 180}]}}, "schema": []} {"input": "This absence of binding was localized to the NF-kappa B region of the HIV-1 enhancer; the 65-kDa plus 50-kDa NF-kappa B heterodimer was preferentially lost.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 45, "end": 55}, {"text": "65-kDa plus 50-kDa", "start": 90, "end": 108}, {"text": "NF-kappa B heterodimer", "start": 109, "end": 131}], "dna": [{"text": "region", "start": 56, "end": 62}, {"text": "HIV-1 enhancer", "start": 70, "end": 84}]}}, "schema": []} {"input": "Adding purified NF-kappa B protein to nuclear extracts from cells with restricted expression overcomes this lack of binding.", "output": {"entities": {"protein": [{"text": "NF-kappa B protein", "start": 16, "end": 34}]}}, "schema": []} {"input": "In addition, treatment of these nuclear extracts with sodium deoxycholate restored their ability to form the heterodimer, suggesting the presence of an inhibitor of NF-kappa B activity.", "output": {"entities": {"protein": [{"text": "heterodimer", "start": 109, "end": 120}, {"text": "NF-kappa B", "start": 165, "end": 175}]}}, "schema": []} {"input": "Furthermore, treatment of nuclear extracts from these cells that had restricted expression with lipopolysaccharide increased viral production and NF-kappa B activity.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 146, "end": 156}]}}, "schema": []} {"input": "Antiserum specific for NF-kappa B binding proteins, but not c-rel-specific antiserum, disrupted heterodimer complex formation.", "output": {"entities": {"protein": [{"text": "NF-kappa B binding proteins", "start": 23, "end": 50}, {"text": "heterodimer complex", "start": 96, "end": 115}]}}, "schema": []} {"input": "Thus, both NF-kappa B -binding complexes are needed for optimal viral transcription.", "output": {"entities": {"protein": [{"text": "NF-kappa B -binding complexes", "start": 11, "end": 40}]}}, "schema": []} {"input": "Binding of the 65-kDa plus 50-kDa heterodimer to the HIV-1 enhancer can be negatively regulated in monocytes, providing one mechanism restricting HIV-1 gene expression.", "output": {"entities": {"protein": [{"text": "65-kDa", "start": 15, "end": 21}, {"text": "50-kDa heterodimer", "start": 27, "end": 45}], "dna": [{"text": "HIV-1 enhancer", "start": 53, "end": 67}, {"text": "HIV-1 gene", "start": 146, "end": 156}], "cell_type": [{"text": "monocytes", "start": 99, "end": 108}]}}, "schema": []} {"input": "Glucocorticoid receptors in normal leukocytes: effects of age, gender, season, and plasma cortisol concentrations.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptors", "start": 0, "end": 24}], "cell_type": [{"text": "normal leukocytes", "start": 28, "end": 45}]}}, "schema": []} {"input": "We measured glucocorticoid receptors (GR) in mononuclear leukocytes (MNL) isolated from peripheral blood of 145 apparently healthy volunteers (86 men and 59 women ).", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 12, "end": 36}, {"text": "GR", "start": 38, "end": 40}], "cell_type": [{"text": "mononuclear leukocytes", "start": 45, "end": 67}, {"text": "MNL", "start": 69, "end": 72}]}}, "schema": []} {"input": "An age-related decrease in the number of GR was suggested between subjects younger than 20 years and elderly subjects; there was no apparent seasonal variation in GR.", "output": {"entities": {"protein": [{"text": "GR", "start": 41, "end": 43}, {"text": "GR", "start": 163, "end": 165}]}}, "schema": []} {"input": "Gender difference in the number of GR was not significant, although women showed slightly fewer GR.", "output": {"entities": {"protein": [{"text": "GR", "start": 35, "end": 37}, {"text": "GR", "start": 96, "end": 98}]}}, "schema": []} {"input": "Eight patients with dermatomyositis/polymyositis were examined to determine whether the number of GR in MNL could be down-regulated by their cognate ligands.", "output": {"entities": {"protein": [{"text": "GR", "start": 98, "end": 100}], "cell_type": [{"text": "MNL", "start": 104, "end": 107}]}}, "schema": []} {"input": "The number of GR in MNL from these patients was significantly decreased one month after the initiation of prednisolone therapy.", "output": {"entities": {"protein": [{"text": "GR", "start": 14, "end": 16}], "cell_type": [{"text": "MNL", "start": 20, "end": 23}]}}, "schema": []} {"input": "However, in normal subjects, the GR in MNL did not demonstrate circadian variation, in contrast to concentrations of plasma cortisol.", "output": {"entities": {"protein": [{"text": "GR", "start": 33, "end": 35}], "cell_type": [{"text": "MNL", "start": 39, "end": 42}]}}, "schema": []} {"input": "Synergism between two distinct elements of the HTLV-I enhancer during activation by the trans-activator of HTLV-I.", "output": {"entities": {"dna": [{"text": "HTLV-I enhancer", "start": 47, "end": 62}], "protein": [{"text": "trans-activator", "start": 88, "end": 103}]}}, "schema": []} {"input": "We have conducted functional studies of the enhancer elements of human T-cell leukemia virus type I (HTLV-I) using the human T-cell lines Jurkat and MOLT 4, which are negative for HTLV-I, and MT-2 and TL-Mor, which carry the proviral genome of HTLV-I.", "output": {"entities": {"dna": [{"text": "enhancer elements", "start": 44, "end": 61}], "cell_line": [{"text": "human T-cell lines", "start": 119, "end": 137}, {"text": "Jurkat", "start": 138, "end": 144}, {"text": "MOLT 4", "start": 149, "end": 155}]}}, "schema": []} {"input": "Two distinct elements have been implicated in function of the HTLV-I enhancer.", "output": {"entities": {"dna": [{"text": "HTLV-I enhancer", "start": 62, "end": 77}]}}, "schema": []} {"input": "One is the 21-base-pair (bp) core element that is responsible for trans-activation by the HTLV-I trans-activator p40tax and that has the ability to bind to cyclic-AMP responsive element binding factor (CREB )-like factor (s).", "output": {"entities": {"dna": [{"text": "21-base-pair (bp) core element", "start": 11, "end": 41}], "protein": [{"text": "trans-activator", "start": 97, "end": 112}, {"text": "p40tax", "start": 113, "end": 119}, {"text": "cyclic-AMP responsive element binding factor (CREB )-like factor", "start": 156, "end": 220}]}}, "schema": []} {"input": "The other is a region interposed between the 21-bp elements.", "output": {"entities": {"dna": [{"text": "21-bp elements", "start": 45, "end": 59}]}}, "schema": []} {"input": "In this study we demonstrate that a subfragment (C26) in the region between the 21-bp elements is involved in trans-activation by p40tax, possibly through binding to an NF-kappa B -like nuclear factor or factors.", "output": {"entities": {"dna": [{"text": "21-bp elements", "start": 80, "end": 94}], "protein": [{"text": "p40tax", "start": 130, "end": 136}, {"text": "NF-kappa B -like nuclear factor", "start": 169, "end": 200}]}}, "schema": []} {"input": "Formation of the protein-DNA complex with the C26 subfragment was positively affected by p40tax.", "output": {"entities": {"protein": [{"text": "protein-DNA complex", "start": 17, "end": 36}, {"text": "C26 subfragment", "start": 46, "end": 61}, {"text": "p40tax", "start": 89, "end": 95}]}}, "schema": []} {"input": "The C26 element conferred partial responsiveness to p40tax when linked to one copy of the 21-bp element that, by itself, showed little activation in response to p40tax.", "output": {"entities": {"dna": [{"text": "C26 element", "start": 4, "end": 15}, {"text": "21-bp element", "start": 90, "end": 103}], "protein": [{"text": "p40tax", "start": 52, "end": 58}, {"text": "p40tax", "start": 161, "end": 167}]}}, "schema": []} {"input": "However, the C26 element alone, even when repeated, could not be activated by p40tax, unlike other NF-kappa B -binding elements.", "output": {"entities": {"dna": [{"text": "C26 element", "start": 13, "end": 24}, {"text": "NF-kappa B -binding elements", "start": 99, "end": 127}], "protein": [{"text": "p40tax", "start": 78, "end": 84}]}}, "schema": []} {"input": "In contrast, the C26 element itself was profoundly activated upon stimulation with 12-O-tetradecanoylphorbol-13-acetate.", "output": {"entities": {"dna": [{"text": "C26 element", "start": 17, "end": 28}]}}, "schema": []} {"input": "These findings therefore suggest that the HTLV-I enhancer contains multiple functional elements, including binding sites for at least CREB- and NF-kappa B- like factors, which synergistically cooperate in activation of the HTLV-I enhancer in response to p40tax.", "output": {"entities": {"dna": [{"text": "HTLV-I enhancer", "start": 42, "end": 57}, {"text": "multiple functional elements", "start": 67, "end": 95}, {"text": "HTLV-I enhancer", "start": 223, "end": 238}], "protein": [{"text": "p40tax", "start": 254, "end": 260}]}}, "schema": []} {"input": "Our results also demonstrate that TPA-dependent activation of the HTLV-I enhancer may be mediated through the C26 element.", "output": {"entities": {"dna": [{"text": "HTLV-I enhancer", "start": 66, "end": 81}, {"text": "C26 element", "start": 110, "end": 121}]}}, "schema": []} {"input": "Human tumor necrosis factor alpha gene regulation in phorbol ester stimulated T and B cell lines.", "output": {"entities": {"protein": [{"text": "tumor necrosis factor alpha", "start": 6, "end": 33}]}}, "schema": []} {"input": "The minimal region of the human tumor necrosis factor alpha (TNF-alpha) gene promoter necessary for its transcriptional induction by phorbol esters (PMA) in human T and B lymphocyte cell lines has been localized between -52 and +89 nucleotides (nt) relative to the gene's transcriptional start site.", "output": {"entities": {"dna": [{"text": "human tumor necrosis factor alpha (", "start": 26, "end": 61}, {"text": ") gene promoter", "start": 70, "end": 85}, {"text": "-52 and +89 nucleotides", "start": 220, "end": 243}, {"text": "transcriptional start site", "start": 272, "end": 298}], "protein": [{"text": "TNF-alpha", "start": 61, "end": 70}], "cell_line": [{"text": "human T and", "start": 157, "end": 168}, {"text": "B lymphocyte cell lines", "start": 169, "end": 192}]}}, "schema": []} {"input": "Comparison of these sequences to those required to mediate virus or lipopolysaccharide (LPS) induction of the gene reveal significant differences, and thus, the sequence requirements for PMA induction are distinct from those that mediate induction by virus or LPS.", "output": {"entities": {}}, "schema": []} {"input": "Although three sites in the TNF-alpha promoter (kappa 1, kappa 2, and kappa 3) specifically bind the transcription factor NF-kappa B in lymphoid nuclear extracts, TNF-alpha mRNA induction by PMA does not correlate with NF-kappa B binding activities displayed by different T and B cell lines.", "output": {"entities": {"dna": [{"text": "TNF-alpha promoter", "start": 28, "end": 46}], "protein": [{"text": "transcription factor", "start": 101, "end": 121}, {"text": "NF-kappa B", "start": 122, "end": 132}, {"text": "NF-kappa B", "start": 219, "end": 229}], "rna": [{"text": "TNF-alpha mRNA", "start": 163, "end": 177}]}}, "schema": []} {"input": "Moreover, kappa 1-kappa 3 can each be deleted from the TNF-alpha promoter with little effect on the gene's inducibility by PMA.", "output": {"entities": {"dna": [{"text": "kappa 1-kappa 3", "start": 10, "end": 25}, {"text": "promoter", "start": 65, "end": 73}], "protein": [{"text": "TNF-alpha", "start": 55, "end": 64}]}}, "schema": []} {"input": "Therefore, TNF-alpha mRNA induction by PMA, like its induction by virus and LPS, is not primarily mediated by NF-kappa B, but rather is mediated through other sequences and protein factors.", "output": {"entities": {"rna": [{"text": "TNF-alpha mRNA", "start": 11, "end": 25}], "protein": [{"text": "NF-kappa B", "start": 110, "end": 120}, {"text": "protein factors", "start": 173, "end": 188}]}}, "schema": []} {"input": "Surprisingly, multimers of kappa 1-kappa 3 can confer PMA inducibility on a heterologous promoter in a B (Raji), but not a T (HUT78) cell line.", "output": {"entities": {"dna": [{"text": "heterologous promoter", "start": 76, "end": 97}], "cell_line": [{"text": "Raji", "start": 106, "end": 110}, {"text": "HUT78", "start": 126, "end": 131}]}}, "schema": []} {"input": "However they are not functional on a truncated TNF-alpha promoter, indicating that promoter context and cell type specificity influence the PMA inducible function of these NF-kappa B binding sites.", "output": {"entities": {"protein": [{"text": "TNF-alpha", "start": 47, "end": 56}, {"text": "NF-kappa B", "start": 172, "end": 182}], "dna": [{"text": "promoter", "start": 57, "end": 65}, {"text": "binding sites", "start": 183, "end": 196}]}}, "schema": []} {"input": "Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia.", "output": {"entities": {"protein": [{"text": "Epstein-Barr virus BZLF1 transactivator protein", "start": 45, "end": 92}]}}, "schema": []} {"input": "The BZLF1 protein of Epstein-Barr virus (EBV) is a key immediate-early protein which has been shown to disrupt virus latency in EBV -infected B cells.", "output": {"entities": {"protein": [{"text": "BZLF1 protein", "start": 4, "end": 17}, {"text": "immediate-early protein", "start": 55, "end": 78}], "cell_type": [{"text": "EBV -infected B cells", "start": 128, "end": 149}]}}, "schema": []} {"input": "We have generated a monoclonal antibody, BZ1, to BZLF1 which reacts in immunohistology, immunoblotting, and immunoprecipitation and which recognizes both the active, dimeric form and the inactive, monomeric form of the protein.", "output": {"entities": {"protein": [{"text": "monoclonal antibody", "start": 20, "end": 39}, {"text": "BZ1", "start": 41, "end": 44}, {"text": "BZLF1", "start": 49, "end": 54}, {"text": "active, dimeric form", "start": 158, "end": 178}, {"text": "inactive, monomeric form", "start": 187, "end": 211}]}}, "schema": []} {"input": "Biopsies of oral hairy leukoplakia, an AIDS-associated lesion characterized by high-level EBV replication, were examined by immunohistochemistry using the BZ1 monoclonal antibody.", "output": {"entities": {"protein": [{"text": "BZ1", "start": 155, "end": 158}, {"text": "monoclonal antibody", "start": 159, "end": 178}]}}, "schema": []} {"input": "A differentiation-associated pattern of BZLF1 expression was observed, BZ1 reacting with nuclei of the upper spinous layer of the lesion.", "output": {"entities": {"protein": [{"text": "BZLF1", "start": 40, "end": 45}, {"text": "BZ1", "start": 71, "end": 74}]}}, "schema": []} {"input": "This finding suggests that the BZLF1 promoter may be regulated by the degree of squamous differentiation.", "output": {"entities": {"protein": [{"text": "BZLF1", "start": 31, "end": 36}], "dna": [{"text": "promoter", "start": 37, "end": 45}]}}, "schema": []} {"input": "A comparison of in situ hybridization to EBV DNA and viral capsid antigen staining with BZ1 reactivity suggested that BZLF1 expression precedes rampant virus replication.", "output": {"entities": {"dna": [{"text": "EBV DNA", "start": 41, "end": 48}], "protein": [{"text": "viral capsid antigen", "start": 53, "end": 73}, {"text": "BZ1", "start": 88, "end": 91}, {"text": "BZLF1", "start": 118, "end": 123}]}}, "schema": []} {"input": "The inability to detect EBV in the lower epithelial layers of oral hairy leukoplakia raises questions concerning the nature of EBV latency and persistence in stratified squamous epithelium.", "output": {"entities": {}}, "schema": []} {"input": "[Changes in levels of leucocytic estrogen receptor in patients with menopausal type II diabetes and its significance]", "output": {"entities": {"protein": [{"text": "leucocytic", "start": 22, "end": 32}, {"text": "estrogen receptor", "start": 33, "end": 50}]}}, "schema": []} {"input": "The number of estrogen receptors (ER) in human peripheral leucocytes in 12 women with menopausal type II diabetes was measured with radio-ligand binding method.", "output": {"entities": {"protein": [{"text": "estrogen receptors", "start": 14, "end": 32}, {"text": "ER", "start": 34, "end": 36}], "cell_type": [{"text": "human peripheral leucocytes", "start": 41, "end": 68}]}}, "schema": []} {"input": "The results were compared with those of 12 menopausal women without diabetes and 12 normal women of childbearing age.", "output": {"entities": {}}, "schema": []} {"input": "It was found that the number of ER in the patients was significantly decreased.", "output": {"entities": {"protein": [{"text": "ER", "start": 32, "end": 34}]}}, "schema": []} {"input": "Our data indicate that decrease of ER level in leukocytes may be related to the pathogenesis of type II diabetes in menopausal period.", "output": {"entities": {"protein": [{"text": "ER", "start": 35, "end": 37}], "cell_type": [{"text": "leukocytes", "start": 47, "end": 57}]}}, "schema": []} {"input": "Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 11, "end": 34}]}}, "schema": []} {"input": "OBJECTIVE: The authors' objective was to investigate the possibility that glucocorticoid receptor changes may be involved in the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in posttraumatic stress disorder (PTSD ).", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 74, "end": 97}]}}, "schema": []} {"input": "METHOD: They measured the number of lymphocyte cytosolic glucocorticoid receptors and plasma cortisol concentrations in 15 consecutively admitted male combat Vietnam veterans with PTSD and in a normal comparison group of 11 subjects.", "output": {"entities": {"protein": [{"text": "lymphocyte cytosolic", "start": 36, "end": 56}, {"text": "glucocorticoid receptors", "start": 57, "end": 81}]}}, "schema": []} {"input": "RESULTS: Both the patients and the normal comparison subjects showed a morning-to-afternoon decline in glucocorticoid receptor concentrations, paralleling the normal diurnal decline in cortisol levels.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 103, "end": 126}]}}, "schema": []} {"input": "The number of glucocorticoid receptors was 63% greater in the morning and 26% greater in the afternoon in the patients with PTSD than in the normal subjects.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 14, "end": 38}]}}, "schema": []} {"input": "No group differences in cortisol levels were observed, nor were glucocorticoid receptor number and cortisol levels correlated.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptor", "start": 64, "end": 87}]}}, "schema": []} {"input": "The number of morning glucocorticoid receptors was positively correlated with symptoms of PTSD and anxiety.", "output": {"entities": {"protein": [{"text": "morning", "start": 14, "end": 21}, {"text": "glucocorticoid receptors", "start": 22, "end": 46}]}}, "schema": []} {"input": "CONCLUSIONS: These results provide further evidence for a dysregulation of the HPA axis in PTSD.", "output": {"entities": {}}, "schema": []} {"input": "The finding that patients with PTSD had a substantially greater number of lymphocyte glucocorticoid receptors than normal comparison subjects is consistent with the authors' previous observations of low 24-hour urinary cortisol excretion in subjects with PTSD.", "output": {"entities": {"protein": [{"text": "lymphocyte", "start": 74, "end": 84}, {"text": "glucocorticoid receptors", "start": 85, "end": 109}]}}, "schema": []} {"input": "Furthermore, the receptor changes observed are opposite of those reported in major depressive disorder.", "output": {"entities": {}}, "schema": []} {"input": "The present data, along with other findings of HPA abnormalities in PTSD, support the possibility of a greater negative feedback sensitivity at one or more levels of the HPA axis.", "output": {"entities": {}}, "schema": []} {"input": "Induction of NF-kappa B during monocyte differentiation is associated with activation of HIV -gene expression.", "output": {"entities": {"protein": [{"text": "NF-kappa B", "start": 13, "end": 23}]}}, "schema": []} {"input": "Cells of the monocyte-macrophage lineage are important targets of HIV infection.", "output": {"entities": {"cell_type": [{"text": "monocyte-macrophage lineage", "start": 13, "end": 40}]}}, "schema": []} {"input": "We report here that the phenotypic differentiation of monocyte cell lines induced by phorbol esters or tumour necrosis factor alpha (TNF alpha) is associated with expression of nuclear factor kappa B (NF-kappa B ).", "output": {"entities": {"cell_line": [{"text": "monocyte cell lines", "start": 54, "end": 73}], "protein": [{"text": "tumour necrosis factor alpha", "start": 103, "end": 131}, {"text": "TNF alpha", "start": 133, "end": 142}, {"text": "nuclear factor kappa B", "start": 177, "end": 199}, {"text": "NF-kappa B", "start": 201, "end": 211}]}}, "schema": []} {"input": "In parallel with such differentiation, HIV transcription, monitored using an HIV long terminal repeat reporter gene construct, is activated in such cells under the influence of enhanced NF-kappa B expression.", "output": {"entities": {"dna": [{"text": "HIV long terminal repeat reporter gene construct", "start": 77, "end": 125}], "protein": [{"text": "NF-kappa B", "start": 186, "end": 196}]}}, "schema": []} {"input": "Also, in a promonocyte cell line chronically infected with HIV, NF-kappa B expression and HIV transcription were enhanced on stimulation with phorbol ester or TNF alpha.", "output": {"entities": {"cell_line": [{"text": "promonocyte cell line", "start": 11, "end": 32}], "protein": [{"text": "NF-kappa B", "start": 64, "end": 74}, {"text": "TNF alpha", "start": 159, "end": 168}]}}, "schema": []} {"input": "Thus, stimulation of monocyte cell lines by phorbol esters or TNF alpha induces cell differentiation and activates HIV transcription.", "output": {"entities": {"cell_line": [{"text": "monocyte cell lines", "start": 21, "end": 40}], "protein": [{"text": "TNF alpha", "start": 62, "end": 71}]}}, "schema": []} {"input": "Such a process may have fundamental implications in AIDS pathogenesis in vivo and may be important in disease progression induced by opportunistic infections directly or indirectly involving macrophages.", "output": {"entities": {"cell_type": [{"text": "macrophages", "start": 191, "end": 202}]}}, "schema": []} {"input": "Demonstration of estrogen and progesterone receptors as well as Ki-67 and p-145 antigens in single tumor cells from blood and pleural effusions using a slide assay.", "output": {"entities": {"cell_type": [{"text": "single tumor cells", "start": 92, "end": 110}]}}, "schema": []} {"input": "We describe a slide assay that allows the demonstration of antigens localized in the nucleus from isolated white blood cells as well as from single tumor cells derived from malignant effusions.", "output": {"entities": {"protein": [{"text": "antigens", "start": 59, "end": 67}], "cell_type": [{"text": "isolated white blood cells", "start": 98, "end": 124}, {"text": "single tumor cells", "start": 141, "end": 159}]}}, "schema": []} {"input": "With the antibodies Ki-67 and anti-p-145 an increased rate of nuclear and nucleolar staining resulted in cells from highly malignant lymphomas.", "output": {"entities": {"protein": [{"text": "Ki-67", "start": 20, "end": 25}, {"text": "anti-p-145", "start": 30, "end": 40}]}}, "schema": []} {"input": "An almost identical reaction was obtained when tumor cells from malignant effusions were tested.", "output": {"entities": {"cell_type": [{"text": "tumor cells", "start": 47, "end": 58}]}}, "schema": []} {"input": "Cells isolated from the blood of patients with leukemic spread of lymphomas of low malignancy yielded a weak staining comparable to that of normal mesothelial cells from non-tumorous cavity fluids.", "output": {"entities": {"cell_type": [{"text": "normal mesothelial cells", "start": 140, "end": 164}]}}, "schema": []} {"input": "The detection of estrogen and progesterone receptors (ER and PR) localized in the cell nucleus can be achieved by the same assay.", "output": {"entities": {"protein": [{"text": "estrogen", "start": 17, "end": 25}, {"text": "progesterone receptors", "start": 30, "end": 52}, {"text": "ER", "start": 54, "end": 56}, {"text": "PR", "start": 61, "end": 63}]}}, "schema": []} {"input": "The reaction is enhanced by incubation of the tumor cells for 30 min at 37 degrees C prior to fixation.", "output": {"entities": {"cell_type": [{"text": "tumor cells", "start": 46, "end": 57}]}}, "schema": []} {"input": "Pleural effusions from 20 patients with breast cancer were tested.", "output": {"entities": {}}, "schema": []} {"input": "ER was positive in 13 and PR was positive in 12 of the 20 samples.", "output": {"entities": {"protein": [{"text": "ER", "start": 0, "end": 2}, {"text": "PR", "start": 26, "end": 28}]}}, "schema": []} {"input": "In 5 cases there was a divergent reaction with ER and PR antibody.", "output": {"entities": {"protein": [{"text": "ER", "start": 47, "end": 49}, {"text": "PR", "start": 54, "end": 56}]}}, "schema": []} {"input": "The hormone receptors of the primary tumor were known in 15 (ER) and 14 (PR) patients, respectively.", "output": {"entities": {"protein": [{"text": "hormone receptors", "start": 4, "end": 21}, {"text": "ER", "start": 61, "end": 63}, {"text": "PR", "start": 73, "end": 75}]}}, "schema": []} {"input": "In each cohort there was only one case with a negative reaction of the primary tumor and a positive reaction with the isolated tumor cells from the pleural effusions.", "output": {"entities": {"cell_type": [{"text": "tumor cells", "start": 127, "end": 138}]}}, "schema": []} {"input": "These results indicate that the demonstration of hormone receptor proteins in cells from malignant effusions is possible and that there is a correlation with the status of the primary site of cancer.", "output": {"entities": {"protein": [{"text": "hormone receptor proteins", "start": 49, "end": 74}]}}, "schema": []} {"input": "Constitutive activation of NF-kB in human thymocytes.", "output": {"entities": {"protein": [{"text": "NF-kB", "start": 27, "end": 32}], "cell_type": [{"text": "human thymocytes", "start": 36, "end": 52}]}}, "schema": []} {"input": "NF-kB is a eukaryotic transcription regulatory factor.", "output": {"entities": {"protein": [{"text": "NF-kB", "start": 0, "end": 5}, {"text": "eukaryotic transcription regulatory factor", "start": 11, "end": 53}]}}, "schema": []} {"input": "In T cells and T cell lines, NF-kB is bound to a cytoplasmic proteic inhibitor, the IkB.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 3, "end": 10}], "cell_line": [{"text": "T cell lines", "start": 15, "end": 27}], "protein": [{"text": "NF-kB", "start": 29, "end": 34}, {"text": "cytoplasmic proteic inhibitor", "start": 49, "end": 78}, {"text": "IkB", "start": 84, "end": 87}]}}, "schema": []} {"input": "Treatment of T cells with mitogens (phorbol esters) or cytokines (TNF alpha) induces NF-kB nuclear translocation and the subsequent expression of NF-kB dependent T cell genes.", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 13, "end": 20}], "protein": [{"text": "cytokines", "start": 55, "end": 64}, {"text": "TNF alpha", "start": 66, "end": 75}, {"text": "NF-kB", "start": 85, "end": 90}, {"text": "NF-kB", "start": 146, "end": 151}], "dna": [{"text": "dependent T cell genes", "start": 152, "end": 174}]}}, "schema": []} {"input": "Here we examined the activation of NF-kB in human T cell thymic progenitors.", "output": {"entities": {"protein": [{"text": "NF-kB", "start": 35, "end": 40}], "cell_type": [{"text": "human T cell thymic progenitors", "start": 44, "end": 75}]}}, "schema": []} {"input": "We report differences in (Ca2+)i requirement for NF-kB activation in thymocytes as compared to mature T cells.", "output": {"entities": {"protein": [{"text": "NF-kB", "start": 49, "end": 54}], "cell_type": [{"text": "thymocytes", "start": 69, "end": 79}, {"text": "T cells", "start": 102, "end": 109}]}}, "schema": []} {"input": "Furthermore, our results indicated that thymocytes have a constitutively active form of NF-kB, suggesting that they are activated in vivo.", "output": {"entities": {"cell_type": [{"text": "thymocytes", "start": 40, "end": 50}], "protein": [{"text": "constitutively active form", "start": 58, "end": 84}, {"text": "NF-kB", "start": 88, "end": 93}]}}, "schema": []} {"input": "TCF-1, a T cell-specific transcription factor of the HMG box family, interacts with sequence motifs in the TCR beta and TCR delta enhancers.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 0, "end": 5}, {"text": "T cell-specific transcription factor", "start": 9, "end": 45}, {"text": "HMG box family", "start": 53, "end": 67}], "dna": [{"text": "sequence motifs", "start": 84, "end": 99}]}}, "schema": []} {"input": "We have recently identified and cloned TCF-1, a T cell-specific transcription factor with specificity for the AACAAAG motif in the CD3 epsilon enhancer and for the TTCAAAG motif in the TCR alpha enhancer.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 39, "end": 44}, {"text": "T cell-specific transcription factor", "start": 48, "end": 84}], "dna": [{"text": "CD3 epsilon enhancer", "start": 131, "end": 151}, {"text": "TTCAAAG motif", "start": 164, "end": 177}, {"text": "TCR alpha enhancer", "start": 185, "end": 203}]}}, "schema": []} {"input": "TCF-1 belongs to the family of transcription-regulating proteins which share a region of homology termed the HMG-box.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 0, "end": 5}, {"text": "transcription-regulating proteins", "start": 31, "end": 64}, {"text": "HMG-box", "start": 109, "end": 116}]}}, "schema": []} {"input": "Here, we show by gel retardation analysis that TCF-1 specifically recognizes the T beta 5 element of the TCR beta enhancer and the T delta 7 element of the TCR delta enhancer.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 47, "end": 52}], "dna": [{"text": "T beta 5 element", "start": 81, "end": 97}, {"text": "TCR beta enhancer", "start": 105, "end": 122}, {"text": "T delta 7 element", "start": 131, "end": 148}, {"text": "TCR delta enhancer", "start": 156, "end": 174}]}}, "schema": []} {"input": "Comparison of the sequences of all elements recognized by TCF-1 defines a consensus motif A/T A/T C A A/G A G.", "output": {"entities": {"dna": [{"text": "elements", "start": 35, "end": 43}, {"text": "consensus motif", "start": 74, "end": 89}, {"text": "A/T A/T C A A/G A G", "start": 90, "end": 109}], "protein": [{"text": "TCF-1", "start": 58, "end": 63}]}}, "schema": []} {"input": "These observations imply that TCF-1 is involved in the control of several T cell-specific genes and might thus play an important role in the establishment and maintenance of the mature T cell phenotype.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 30, "end": 35}], "dna": [{"text": "T cell-specific genes", "start": 74, "end": 95}], "cell_type": [{"text": "mature T cell phenotype", "start": 178, "end": 201}]}}, "schema": []} {"input": "[Regulatory effect of insulin on glucocorticoid receptor in human peripheral leukocytes]", "output": {"entities": {"protein": [{"text": "insulin", "start": 22, "end": 29}, {"text": "glucocorticoid receptor", "start": 33, "end": 56}], "cell_type": [{"text": "human peripheral leukocytes", "start": 60, "end": 87}]}}, "schema": []} {"input": "The regulatory effect of insulin on the specific binding power of glucocorticoid receptor (GR) of human leukocytes was assessed by the unoccupied receptor sites capable of combining with [3H] labelled dexamethasone measured at 3 and 24 h after incubation with various concentrations of insulin added to the medium.", "output": {"entities": {"protein": [{"text": "insulin", "start": 25, "end": 32}, {"text": "glucocorticoid receptor", "start": 66, "end": 89}, {"text": "GR", "start": 91, "end": 93}, {"text": "unoccupied receptor sites", "start": 135, "end": 160}, {"text": "insulin", "start": 286, "end": 293}], "cell_type": [{"text": "human leukocytes", "start": 98, "end": 114}]}}, "schema": []} {"input": "After 3 h incubation the specific binding power with [3H] Dex was decreased by 23.3 +/- 10.0, 32.2 +/- 13.2 and 54.3 +/- 9.2% (P greater than 0.05, P greater than 0.05 and P less than 0.01 as compared with the control value of 100 in the absence of insulin) respectively in the presence of 20 mU/L (physiological testing concentration), 200 mU/L (physiological upper limit) and 2,000 mU/L (pharmacological concentration) insulin in the incubation medium.", "output": {"entities": {"protein": [{"text": "insulin", "start": 249, "end": 256}, {"text": "insulin", "start": 421, "end": 428}]}}, "schema": []} {"input": "After 24 h incubation the decrease of these values increased respectively to 43.5 +/- 19.0, 56.1 +/- 20.7 and 80.2 +/- 15.5 (P less than 0.05, P less than 0.01 and P less than 0.01 compared with control).", "output": {"entities": {}}, "schema": []} {"input": "Thus the inhibitory effect of insulin on the GR binding power is both dose- and time-dependent, which strongly suggests that GR is tonically controlled by insulin concentration change under physiological conditions.", "output": {"entities": {"protein": [{"text": "insulin", "start": 30, "end": 37}, {"text": "GR", "start": 45, "end": 47}, {"text": "GR", "start": 125, "end": 127}, {"text": "insulin", "start": 155, "end": 162}]}}, "schema": []} {"input": "The effect of toremifene therapy on serum immunoglobulin levels in breast cancer.", "output": {"entities": {"protein": [{"text": "serum immunoglobulin", "start": 36, "end": 56}]}}, "schema": []} {"input": "Estrogens and anti-estrogens enhance the number of immunoglobulin (Ig)-secreting cells in pokeweed mitogen (PWM )-stimulated lymphocyte cultures.", "output": {"entities": {"cell_type": [{"text": "immunoglobulin (Ig)-secreting cells", "start": 51, "end": 86}], "protein": [{"text": "pokeweed mitogen", "start": 90, "end": 106}, {"text": "PWM", "start": 108, "end": 111}], "cell_line": [{"text": "(", "start": 107, "end": 108}, {"text": ")-stimulated lymphocyte cultures", "start": 112, "end": 144}]}}, "schema": []} {"input": "Lymphocytes from patients who have received anti-estrogen therapy show similar enhancement of Ig-secreting cells after PWM stimulation.", "output": {"entities": {"cell_type": [{"text": "Lymphocytes", "start": 0, "end": 11}, {"text": "Ig-secreting cells", "start": 94, "end": 112}], "protein": [{"text": "PWM", "start": 119, "end": 122}]}}, "schema": []} {"input": "In this study the effect of anti-estrogen (toremifene) therapy on serum immunoglobulin (IgA, IgM, IgG) levels in breast cancer patients was investigated.", "output": {"entities": {"protein": [{"text": "serum immunoglobulin", "start": 66, "end": 86}, {"text": "IgA", "start": 88, "end": 91}, {"text": "IgM", "start": 93, "end": 96}, {"text": "IgG", "start": 98, "end": 101}]}}, "schema": []} {"input": "Serum Ig levels were followed up to two years after or during the therapy.", "output": {"entities": {}}, "schema": []} {"input": "An unexpected finding was that the Ig levels decreased during the follow-up period.", "output": {"entities": {}}, "schema": []} {"input": "This decrease was seen in patients who responded to the therapy as well as in those who did not.", "output": {"entities": {}}, "schema": []} {"input": "Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA.", "output": {"entities": {"protein": [{"text": "Human erythroid 5-aminolevulinate synthase", "start": 0, "end": 42}], "dna": [{"text": "promoter", "start": 44, "end": 52}, {"text": "iron-responsive element", "start": 87, "end": 110}], "rna": [{"text": "mRNA", "start": 118, "end": 122}]}}, "schema": []} {"input": "5-Aminolevulinate synthase (ALAS) catalyzes the first step of the heme biosynthetic pathway.", "output": {"entities": {"protein": [{"text": "5-Aminolevulinate synthase", "start": 0, "end": 26}, {"text": "ALAS", "start": 28, "end": 32}, {"text": "heme", "start": 66, "end": 70}]}}, "schema": []} {"input": "cDNA clones for the human erythroid ALAS isozyme were isolated from a fetal liver library.", "output": {"entities": {"dna": [{"text": "cDNA clones", "start": 0, "end": 11}, {"text": "fetal liver library", "start": 70, "end": 89}], "protein": [{"text": "human erythroid ALAS isozyme", "start": 20, "end": 48}]}}, "schema": []} {"input": "It can be deduced that the erythroid ALAS precursor protein has a molecular weight of 64.6 kd, and is similar in size to the previously isolated human housekeeping ALAS precursor of molecular weight 70.6 kd.", "output": {"entities": {"protein": [{"text": "erythroid ALAS precursor protein", "start": 27, "end": 59}, {"text": "human housekeeping ALAS precursor", "start": 145, "end": 178}]}}, "schema": []} {"input": "The mature mitochondrial forms of the erythroid and housekeeping ALAS isozymes are predicted to have molecular weights of 59.5 kd and 64.6 kd, respectively.", "output": {"entities": {"protein": [{"text": "housekeeping ALAS isozymes", "start": 52, "end": 78}]}}, "schema": []} {"input": "The two isozymes show little amino acid identity in their N-terminal signal sequences but have considerable sequence identity in the C-terminal two-thirds of their proteins.", "output": {"entities": {"protein": [{"text": "isozymes", "start": 8, "end": 16}, {"text": "N-terminal signal sequences", "start": 58, "end": 85}, {"text": "C-terminal two-thirds", "start": 133, "end": 154}]}}, "schema": []} {"input": "An analysis of the immediate promoter of the human erythroid ALAS gene revealed several putative erythroid-specific cis-acting elements including both a GATA-1 and an NF-E2 binding site.", "output": {"entities": {"dna": [{"text": "immediate promoter", "start": 19, "end": 37}, {"text": "human erythroid ALAS gene", "start": 45, "end": 70}, {"text": "erythroid-specific cis-acting elements", "start": 97, "end": 135}, {"text": "GATA-1", "start": 153, "end": 159}, {"text": "NF-E2 binding site", "start": 167, "end": 185}]}}, "schema": []} {"input": "An iron-responsive element (IRE) motif has been identified in the 5'-untranslated region of the human erythroid ALAS mRNA, but is not present in the housekeeping ALAS mRNA.", "output": {"entities": {"dna": [{"text": "iron-responsive element", "start": 3, "end": 26}], "rna": [{"text": "(IRE) motif", "start": 27, "end": 38}, {"text": "human erythroid ALAS mRNA", "start": 96, "end": 121}, {"text": "housekeeping ALAS mRNA", "start": 149, "end": 171}]}}, "schema": []} {"input": "Gel retardation experiments established that this IRE motif formed a protein - RNA complex with cytosolic extracts from human K562 cells and this binding was strongly competed with IRE transcripts from ferritin or transferrin receptor mRNAs.", "output": {"entities": {"rna": [{"text": "IRE motif", "start": 50, "end": 59}, {"text": "IRE transcripts", "start": 181, "end": 196}], "protein": [{"text": "protein - RNA complex", "start": 69, "end": 90}], "cell_line": [{"text": "human K562 cells", "start": 120, "end": 136}]}}, "schema": []} {"input": "A transcript of the ALAS IRE, mutated in the conserved loop of the IRE, did not readily form this protein - RNA complex.", "output": {"entities": {"dna": [{"text": "ALAS IRE", "start": 20, "end": 28}, {"text": "IRE", "start": 67, "end": 70}], "protein": [{"text": "protein - RNA complex", "start": 98, "end": 119}]}}, "schema": []} {"input": "These results suggest that the IRE motif in the ALAS mRNA is functional and imply that translation of the mRNA is controlled by cellular iron availability during erythropoiesis.", "output": {"entities": {"rna": [{"text": "IRE motif", "start": 31, "end": 40}, {"text": "ALAS mRNA", "start": 48, "end": 57}, {"text": "mRNA", "start": 106, "end": 110}]}}, "schema": []} {"input": "Regulation of jun and fos gene expression in human monocytes by the macrophage colony-stimulating factor.", "output": {"entities": {"cell_type": [{"text": "human monocytes", "start": 45, "end": 60}], "protein": [{"text": "macrophage colony-stimulating factor", "start": 68, "end": 104}]}}, "schema": []} {"input": "The macrophage colony-stimulating factor (M-CSF) is required for the growth and differentiation of mononuclear phagocytes.", "output": {"entities": {"protein": [{"text": "macrophage colony-stimulating factor", "start": 4, "end": 40}, {"text": "M-CSF", "start": 42, "end": 47}], "cell_type": [{"text": "mononuclear phagocytes", "start": 99, "end": 121}]}}, "schema": []} {"input": "However, the signaling events responsible for these effects remain unclear.", "output": {"entities": {}}, "schema": []} {"input": "The present studies have examined the effects of M-CSF on potential signaling pathways involving expression of the jun and fos early response genes.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 49, "end": 54}]}}, "schema": []} {"input": "Low levels of c-jun transcripts were detectable in resting human peripheral blood monocytes.", "output": {"entities": {"protein": [{"text": "c-jun transcripts", "start": 14, "end": 31}], "cell_type": [{"text": "resting human peripheral blood monocytes", "start": 51, "end": 91}]}}, "schema": []} {"input": "Treatment of these cells with 10(3) units/ml human recombinant M-CSF was associated with rapid and transient increases in c-jun mRNA levels.", "output": {"entities": {"protein": [{"text": "human recombinant", "start": 45, "end": 62}, {"text": "M-CSF", "start": 63, "end": 68}], "rna": [{"text": "c-jun mRNA", "start": 122, "end": 132}]}}, "schema": []} {"input": "Nuclear run-on assays and mRNA stability studies demonstrated that M-CSF regulates c-jun expression by both an increase in transcription rate and a prolongation in the half-life of c-jun transcripts.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 67, "end": 72}], "dna": [{"text": "c-jun", "start": 83, "end": 88}], "rna": [{"text": "c-jun transcripts", "start": 181, "end": 198}]}}, "schema": []} {"input": "M-CSF treatment was also associated with a rapid induction of the jun-B gene, although expression of this gene was prolonged compared to that of c-jun.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 0, "end": 5}], "dna": [{"text": "jun-B gene", "start": 66, "end": 76}, {"text": "c-jun", "start": 145, "end": 150}]}}, "schema": []} {"input": "We further demonstrate that M-CSF increases c-fos mRNA levels in human monocytes through control at both the transcriptional and posttranscriptional levels.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 28, "end": 33}], "rna": [{"text": "c-fos mRNA", "start": 44, "end": 54}], "cell_type": [{"text": "human monocytes", "start": 65, "end": 80}]}}, "schema": []} {"input": "Maximal induction of the c-fos gene was followed by that for the fos-B gene.", "output": {"entities": {"dna": [{"text": "c-fos gene", "start": 25, "end": 35}, {"text": "fos-B gene", "start": 65, "end": 75}]}}, "schema": []} {"input": "Moreover, M-CSF -induced expression of the fos-related gene, fra-1, was delayed compared to that for both c-fos and fos-B.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 10, "end": 15}], "dna": [{"text": "fos-related gene", "start": 43, "end": 59}, {"text": "fra-1", "start": 61, "end": 66}, {"text": "c-fos", "start": 106, "end": 111}, {"text": "fos-B", "start": 116, "end": 121}]}}, "schema": []} {"input": "Taken together, the results indicate that M-CSF treatment is associated with differential activation of multiple members of the jun/fos family and that expression of these genes could contribute to nuclear signaling mechanisms that regulate a specific program of monocyte differentiation.", "output": {"entities": {"protein": [{"text": "M-CSF", "start": 42, "end": 47}], "dna": [{"text": "jun/fos family", "start": 128, "end": 142}]}}, "schema": []} {"input": "Glucocorticoid receptors in systemic lupus erythematosus.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptors", "start": 0, "end": 24}]}}, "schema": []} {"input": "Glucocorticosteroids remain the major treatment modality for systemic lupus erythematosus (SLE ), but their mechanism of action is unclear.", "output": {"entities": {}}, "schema": []} {"input": "Over the past decade it has become clear that glucocorticosteroid receptors play a significant role in the mechanism of glucocorticosteroid action.", "output": {"entities": {"protein": [{"text": "glucocorticosteroid receptors", "start": 46, "end": 75}]}}, "schema": []} {"input": "We studied glucocorticosteroid receptor density and affinity on peripheral blood mononuclear cells by the glucocorticosteroid binding assay in 33 patients with SLE who had taken no glucocorticosteroid for the previous 6 months and in 32 healthy controls.", "output": {"entities": {"protein": [{"text": "glucocorticosteroid receptor", "start": 11, "end": 39}], "cell_type": [{"text": "peripheral blood mononuclear cells", "start": 64, "end": 98}]}}, "schema": []} {"input": "Patients' disease activity was measured by the SLE Disease Activity Index (SLEDAI ).", "output": {"entities": {}}, "schema": []} {"input": "Glucocorticosteroid receptors on leukocytes of patients with SLE were significantly higher than in healthy controls (4419 +/- 306 vs 3369 +/- 196, p less than 0.005).", "output": {"entities": {"protein": [{"text": "Glucocorticosteroid receptors", "start": 0, "end": 29}], "cell_type": [{"text": "leukocytes", "start": 33, "end": 43}]}}, "schema": []} {"input": "The binding affinity was not different between patients and controls.", "output": {"entities": {}}, "schema": []} {"input": "There was no correlation between glucocorticosteroid receptor number and SLE disease activity.", "output": {"entities": {"protein": [{"text": "glucocorticosteroid receptor", "start": 33, "end": 61}]}}, "schema": []} {"input": "Kappa B binding proteins are constitutively expressed in an IL-2 autocrine human T cell line.", "output": {"entities": {"protein": [{"text": "Kappa B binding proteins", "start": 0, "end": 24}], "cell_line": [{"text": "IL-2 autocrine human T cell line", "start": 60, "end": 92}]}}, "schema": []} {"input": "The IL-2 and the IL-2-R alpha genes are both expressed transiently in normal T lymphocytes after Ag or mitogen activation.", "output": {"entities": {"cell_type": [{"text": "normal T lymphocytes", "start": 70, "end": 90}]}}, "schema": []} {"input": "In contrast, the human T cell line, IARC 301, expresses these two genes constitutively and we have previously demonstrated that its growth depends on the autocrine production of this T cell growth factor and high affinity IL-2R.", "output": {"entities": {"cell_line": [{"text": "human T cell line", "start": 17, "end": 34}, {"text": "IARC 301", "start": 36, "end": 44}], "protein": [{"text": "T cell growth factor", "start": 183, "end": 203}, {"text": "high affinity IL-2R", "start": 208, "end": 227}]}}, "schema": []} {"input": "To dissect the molecular basis for the unusual persistent expression of the IL-2 and IL-2-R alpha genes in these IARC 301 T cells, we have analyzed the interactions of constitutively expressed nuclear proteins with the 5' flanking regions of the IL-2 and IL-2-R alpha genes using both DNase I footprinting and gel retardation techniques.", "output": {"entities": {"cell_line": [{"text": "IARC 301", "start": 113, "end": 121}], "cell_type": [{"text": "T cells", "start": 122, "end": 129}], "protein": [{"text": "constitutively expressed nuclear proteins", "start": 168, "end": 209}, {"text": "DNase I", "start": 285, "end": 292}], "dna": [{"text": "5' flanking regions", "start": 219, "end": 238}]}}, "schema": []} {"input": "We have found that a region in both genes (-276 to -250 for IL-2-R alpha and -203 to -183 for IL-2 ), which corresponds to a kappa B enhancer element, is specifically protected by nuclear proteins from IARC 301.", "output": {"entities": {"dna": [{"text": "IL-2-R alpha", "start": 60, "end": 72}, {"text": "IL-2", "start": 94, "end": 98}, {"text": "kappa B enhancer element,", "start": 125, "end": 150}], "protein": [{"text": "nuclear proteins", "start": 180, "end": 196}], "cell_line": [{"text": "IARC 301", "start": 202, "end": 210}]}}, "schema": []} {"input": "In agreement with this finding, both the IL-2 and IL-2-R alpha promoters are active in transient transfection assays in IARC 301 cells.", "output": {"entities": {"cell_line": [{"text": "IARC 301 cells", "start": 120, "end": 134}]}}, "schema": []} {"input": "In contrast, mutation of the kappa B enhancer results in markedly attenuated activities of both promoters.", "output": {"entities": {"protein": [{"text": "kappa B enhancer", "start": 29, "end": 45}], "dna": [{"text": "promoters", "start": 96, "end": 105}]}}, "schema": []} {"input": "Two proteins binding the kappa B sequence, NF-kappa B and KBF1, are constitutively expressed in IARC 301 nuclei and induced by PMA and PHA in Jurkat.", "output": {"entities": {"dna": [{"text": "kappa B sequence", "start": 25, "end": 41}], "protein": [{"text": "NF-kappa B", "start": 43, "end": 53}, {"text": "KBF1", "start": 58, "end": 62}, {"text": "PHA", "start": 135, "end": 138}], "cell_line": [{"text": "IARC 301", "start": 96, "end": 104}, {"text": "Jurkat", "start": 142, "end": 148}]}}, "schema": []} {"input": "They bind to the kappa B motifs with different relative affinities that may reflect their different contribution in the expression of various promoters.", "output": {"entities": {"dna": [{"text": "kappa B motifs", "start": 17, "end": 31}, {"text": "promoters", "start": 142, "end": 151}]}}, "schema": []} {"input": "HIV1 infection of human monocytes and macrophages promotes induction or translocation of NF-KB-related factors.", "output": {"entities": {"cell_type": [{"text": "human monocytes", "start": 18, "end": 33}, {"text": "macrophages", "start": 38, "end": 49}], "protein": [{"text": "NF-KB-related factors", "start": 89, "end": 110}]}}, "schema": []} {"input": "In 1991, we demonstrated, using electrophoretic mobility shift assays, that 3 different factors (termed B1, B2 and B3) with affinity for the KB-enhancer target sequence were specifically detected in nuclear extracts from HIV1 -infected monocytes and macrophages.", "output": {"entities": {"protein": [{"text": "B1", "start": 104, "end": 106}, {"text": "B2", "start": 108, "end": 110}, {"text": "B3", "start": 115, "end": 117}], "dna": [{"text": "KB-enhancer target sequence", "start": 141, "end": 168}], "cell_type": [{"text": "HIV1 -infected monocytes", "start": 221, "end": 245}, {"text": "macrophages", "start": 250, "end": 261}]}}, "schema": []} {"input": "The B2 factor was induced in the nuclei of these cells only upon HIV1 infection.", "output": {"entities": {"protein": [{"text": "B2 factor", "start": 4, "end": 13}]}}, "schema": []} {"input": "The B3 factor was only slightly evident in nuclei of uninfected cells but was readily detectable in nuclei of infected monocytes.", "output": {"entities": {"protein": [{"text": "B3 factor", "start": 4, "end": 13}], "cell_type": [{"text": "uninfected cells", "start": 53, "end": 69}, {"text": "infected monocytes", "start": 110, "end": 128}]}}, "schema": []} {"input": "Its expression remained very low in nuclei of HIV1 -infected macrophages.", "output": {"entities": {"cell_type": [{"text": "HIV1 -infected macrophages", "start": 46, "end": 72}]}}, "schema": []} {"input": "In this paper, we demonstrate that the B2 factor is expressed in the cytosol of monocytes and macrophages as a DNA-binding protein, indicating that it is not associated with an inhibitor (IKB ).", "output": {"entities": {"protein": [{"text": "B2 factor", "start": 39, "end": 48}, {"text": "DNA-binding protein", "start": 111, "end": 130}], "cell_type": [{"text": "monocytes", "start": 80, "end": 89}, {"text": "macrophages", "start": 94, "end": 105}]}}, "schema": []} {"input": "This factor remained clustered in the cytosol and was translocated to the nuclei only after HIV1 infection.", "output": {"entities": {}}, "schema": []} {"input": "The B3 factor is detected in the cytosol only when cells are HIV1 -infected.", "output": {"entities": {"protein": [{"text": "B3 factor", "start": 4, "end": 13}]}}, "schema": []} {"input": "The role of HIV1 infection in the expression and the translocation of these factors is discussed.", "output": {"entities": {}}, "schema": []} {"input": "Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 30, "end": 35}, {"text": "T lymphocyte-specific transcription factor", "start": 39, "end": 81}, {"text": "sequence-specific HMG box", "start": 95, "end": 120}]}}, "schema": []} {"input": "CD3 -epsilon expression is controlled by a downstream T lymphocyte-specific enhancer element.", "output": {"entities": {"protein": [{"text": "CD3", "start": 0, "end": 3}], "dna": [{"text": "downstream T lymphocyte-specific enhancer element", "start": 43, "end": 92}]}}, "schema": []} {"input": "We report the identification of a T cell-specific transcription factor, TCF-1, binding to this element.", "output": {"entities": {"protein": [{"text": "T cell-specific transcription factor", "start": 34, "end": 70}, {"text": "TCF-1", "start": 72, "end": 77}]}}, "schema": []} {"input": "The multimerized recognition motif of TCF-1 constituted a T cell-specific enhancer.", "output": {"entities": {"protein": [{"text": "multimerized recognition motif", "start": 4, "end": 34}, {"text": "TCF-1", "start": 38, "end": 43}]}}, "schema": []} {"input": "Subsequent cloning of TCF-1 identified three splice alternatives.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 22, "end": 27}, {"text": "splice alternatives", "start": 45, "end": 64}]}}, "schema": []} {"input": "TCF-1 contained a single DNA-binding HMG box most closely related to similar boxes in the putative mammalian sex-determining gene SRY and in the Schizosaccharomyces pombe Mc mating type gene.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 0, "end": 5}, {"text": "DNA-binding HMG box", "start": 25, "end": 44}], "dna": [{"text": "putative mammalian sex-determining gene", "start": 90, "end": 129}, {"text": "SRY", "start": 130, "end": 133}, {"text": "Schizosaccharomyces pombe Mc mating type gene", "start": 145, "end": 190}]}}, "schema": []} {"input": "TCF-1 mRNA was expressed uniquely in T lymphocytes.", "output": {"entities": {"rna": [{"text": "TCF-1 mRNA", "start": 0, "end": 10}], "cell_type": [{"text": "T lymphocytes", "start": 37, "end": 50}]}}, "schema": []} {"input": "Upon cotransfection into non-T cells, TCF-1 could transactivate through its cognate motif.", "output": {"entities": {"cell_type": [{"text": "non-T cells", "start": 25, "end": 36}], "protein": [{"text": "TCF-1", "start": 38, "end": 43}]}}, "schema": []} {"input": "These results identify TCF-1 as a T cell-specific transcription factor, which might play a role in the establishment of the mature T cell phenotype.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 23, "end": 28}, {"text": "T cell-specific transcription factor", "start": 34, "end": 70}], "cell_type": [{"text": "mature T cell phenotype", "start": 124, "end": 147}]}}, "schema": []} {"input": "Identification of transcriptional suppressor proteins that bind to the negative regulatory element of the human immunodeficiency virus type 1.", "output": {"entities": {"protein": [{"text": "transcriptional suppressor proteins", "start": 18, "end": 53}], "dna": [{"text": "negative regulatory element", "start": 71, "end": 98}]}}, "schema": []} {"input": "Two different proteins which independently bound to neighboring sequences within the negative regulatory element (NRE) of human immunodeficiency virus type 1 (HIV-1) were detected in the nuclear extract of a virus-infected human T cell line.", "output": {"entities": {"dna": [{"text": "negative regulatory element", "start": 85, "end": 112}, {"text": "NRE", "start": 114, "end": 117}], "cell_line": [{"text": "virus-infected human T cell line", "start": 208, "end": 240}]}}, "schema": []} {"input": "One of the factors bound to a novel dyad symmetrical sequence.", "output": {"entities": {"dna": [{"text": "novel dyad symmetrical sequence", "start": 30, "end": 61}]}}, "schema": []} {"input": "This sequence is well conserved in various HIV-1 isolates and partial homology was found with the promoter region of the human retinoblastoma gene.", "output": {"entities": {"dna": [{"text": "promoter region", "start": 98, "end": 113}, {"text": "human retinoblastoma gene", "start": 121, "end": 146}]}}, "schema": []} {"input": "Similar DNA binding activity was detected in a variety of virus-uninfected human T cell lines and HeLa cells by means of a gel mobility shift assay.", "output": {"entities": {"cell_line": [{"text": "virus-uninfected human T cell lines", "start": 58, "end": 93}, {"text": "HeLa cells", "start": 98, "end": 108}]}}, "schema": []} {"input": "The other factor bound to a putative AP-1 recognition sequence predicted for the HIV-1 NRE.", "output": {"entities": {"dna": [{"text": "putative AP-1 recognition sequence", "start": 28, "end": 62}, {"text": "NRE", "start": 87, "end": 90}]}}, "schema": []} {"input": "However, this factor did not bind to a typical AP-1 site.", "output": {"entities": {"dna": [{"text": "AP-1 site", "start": 47, "end": 56}]}}, "schema": []} {"input": "The insertion of multiple copies of the binding site for the former or latter factor into a heterologous promoter reduced the promoter activity to one-tenth or one-third, respectively.", "output": {"entities": {"dna": [{"text": "binding site", "start": 40, "end": 52}, {"text": "heterologous promoter", "start": 92, "end": 113}]}}, "schema": []} {"input": "Thus, each factor may function as a novel negative regulator of transcription.", "output": {"entities": {"protein": [{"text": "novel negative regulator", "start": 36, "end": 60}]}}, "schema": []} {"input": "Protein kinase C activation and protooncogene expression in differentiation/retrodifferentiation of human U-937 leukemia cells.", "output": {"entities": {"protein": [{"text": "Protein kinase C", "start": 0, "end": 16}], "dna": [{"text": "protooncogene", "start": 32, "end": 45}], "cell_line": [{"text": "human U-937 leukemia cells", "start": 100, "end": 126}]}}, "schema": []} {"input": "Human U-937 leukemia cells differentiate along the monocytic lineage following 3-day exposures to 12-O-tetradecanoylphorbol-13-acetate (TPA ).", "output": {"entities": {"cell_line": [{"text": "Human U-937 leukemia cells", "start": 0, "end": 26}], "cell_type": [{"text": "monocytic lineage", "start": 51, "end": 68}]}}, "schema": []} {"input": "This induction of differentiation is accompanied by adherence and loss of proliferation, as well as expression/repression of differentiation-associated genes.", "output": {"entities": {"dna": [{"text": "differentiation-associated genes", "start": 125, "end": 157}]}}, "schema": []} {"input": "Long term culture of TPA -differentiated U-937 cells in the absence of phorbol ester for 32-36 days resulted in a process of retrodifferentiation.", "output": {"entities": {"cell_type": [{"text": "TPA -differentiated U-937 cells", "start": 21, "end": 52}]}}, "schema": []} {"input": "The retrodifferentiated cells detached from the substrate and reinitiated proliferation.", "output": {"entities": {}}, "schema": []} {"input": "Other cellular parameters, such as glycosidase activities, cytokine release, and filament expression, returned to levels similar to that observed in uninduced cells.", "output": {"entities": {"protein": [{"text": "cytokine", "start": 59, "end": 67}], "cell_type": [{"text": "uninduced cells", "start": 149, "end": 164}]}}, "schema": []} {"input": "Treatment of U-937 cells with TPA resulted in a rapid translocation of protein kinase C (PKC) from the cytosol to cell membrane fractions within 2-8 min.", "output": {"entities": {"cell_line": [{"text": "U-937 cells", "start": 13, "end": 24}], "protein": [{"text": "protein kinase C", "start": 71, "end": 87}, {"text": "PKC", "start": 89, "end": 92}]}}, "schema": []} {"input": "Increased levels of membrane-associated PKC activity persisted until 17-29 days.", "output": {"entities": {"protein": [{"text": "PKC", "start": 40, "end": 43}]}}, "schema": []} {"input": "However, longer periods of incubation were associated with a return to the distribution of PKC in control cells.", "output": {"entities": {"protein": [{"text": "PKC", "start": 91, "end": 94}]}}, "schema": []} {"input": "Activation of PKC has been implicated in the regulation of certain immediate early response genes, and in the present studies, TPA rapidly induced c-fos and c-jun gene expression.", "output": {"entities": {"protein": [{"text": "PKC", "start": 14, "end": 17}], "dna": [{"text": "immediate early response genes", "start": 67, "end": 97}, {"text": "c-fos", "start": 147, "end": 152}, {"text": "c-jun gene expression", "start": 157, "end": 178}]}}, "schema": []} {"input": "Levels of c-fos and c-jun transcripts remained elevated during periods of PKC activation and also returned to levels observed in control cells by 30-36 days, when the cells entered retrodifferentiation.", "output": {"entities": {"protein": [{"text": "PKC", "start": 74, "end": 77}]}}, "schema": []} {"input": "Staurosporine, a nonspecific inhibitor of PKC, partially blocked TPA -induced adherence and growth inhibition and concomitantly prevented TPA-induced c-fos and c-jun gene expression.", "output": {"entities": {"protein": [{"text": "PKC", "start": 42, "end": 45}]}}, "schema": []} {"input": "(ABSTRACT TRUNCATED AT 250 WORDS)", "output": {"entities": {}}, "schema": []} {"input": "Kappa B-specific DNA binding proteins are differentially inhibited by enhancer mutations and biological oxidation.", "output": {"entities": {"protein": [{"text": "Kappa B-specific DNA binding proteins", "start": 0, "end": 37}]}}, "schema": []} {"input": "Kappa B (kappa B) enhancer binding proteins isolated from the nuclei of activated human T cells produce two distinct nucleoprotein complexes when incubated with the kappa B element from the interleukin-2 receptor-alpha (IL-2R alpha) gene.", "output": {"entities": {"protein": [{"text": "Kappa B (kappa B) enhancer binding proteins", "start": 0, "end": 43}, {"text": "nucleoprotein complexes", "start": 117, "end": 140}, {"text": "IL-2R alpha", "start": 220, "end": 231}], "cell_type": [{"text": "human T cells", "start": 82, "end": 95}], "dna": [{"text": "kappa B element", "start": 165, "end": 180}, {"text": "interleukin-2 receptor-alpha (", "start": 190, "end": 220}, {"text": ") gene", "start": 231, "end": 237}]}}, "schema": []} {"input": "These two DNA-protein complexes are composed of at least four host proteins (p50, p55, p75, p85 ), each of which shares structural similarity with the v-rel oncogene product.", "output": {"entities": {"protein": [{"text": "DNA-protein complexes", "start": 10, "end": 31}, {"text": "p50", "start": 77, "end": 80}, {"text": "p55", "start": 82, "end": 85}, {"text": "p75", "start": 87, "end": 90}, {"text": "p85", "start": 92, "end": 95}, {"text": "v-rel oncogene product", "start": 151, "end": 173}]}}, "schema": []} {"input": "Nuclear expression of these proteins is induced with distinctly biphasic kinetics following phorbol ester activation of T cells (p55/p75 early and p50/p85 late ).", "output": {"entities": {"cell_type": [{"text": "T cells", "start": 120, "end": 127}], "protein": [{"text": "p55/p75 early", "start": 129, "end": 142}, {"text": "p50/p85 late", "start": 147, "end": 159}]}}, "schema": []} {"input": "DNA-protein crosslinking studies have revealed that the more rapidly migrating B2 complex contains both p50 and p55 while the more slowly migrating B1 complex is composed of p50, p55, p75, and p85.", "output": {"entities": {"protein": [{"text": "B2 complex", "start": 79, "end": 89}, {"text": "p50", "start": 104, "end": 107}, {"text": "p55", "start": 112, "end": 115}, {"text": "B1 complex", "start": 148, "end": 158}, {"text": "p50", "start": 174, "end": 177}, {"text": "p55", "start": 179, "end": 182}, {"text": "p75", "start": 184, "end": 187}, {"text": "p85", "start": 193, "end": 196}]}}, "schema": []} {"input": "Site-directed mutagenesis of the wild-type IL-2R alpha kappa B enhancer (GGGGAATCTCCC) has revealed that the binding of p50 and p55 (B2 complex) is particularly sensitive to alteration of the 5' triplet of deoxyguanosine residues.", "output": {"entities": {"dna": [{"text": "wild-type IL-2R alpha kappa B enhancer", "start": 33, "end": 71}, {"text": "5' triplet", "start": 192, "end": 202}], "protein": [{"text": "p50", "start": 120, "end": 123}, {"text": "p55", "start": 128, "end": 131}, {"text": "B2 complex", "start": 133, "end": 143}]}}, "schema": []} {"input": "In contrast, formation of the B1 complex, reflecting the binding of p75 and p85, critically depends upon the more 3' sequences of this enhancer element.", "output": {"entities": {"protein": [{"text": "B1 complex", "start": 30, "end": 40}, {"text": "p75", "start": 68, "end": 71}, {"text": "p85", "start": 76, "end": 79}], "dna": [{"text": "enhancer element", "start": 135, "end": 151}]}}, "schema": []} {"input": "DNA binding by all four of these Rel-related factors is blocked by selective chemical modification of lysine and arginine residues, suggesting that both of these basic amino acids are required for binding to the kappa B element.", "output": {"entities": {"protein": [{"text": "Rel-related factors", "start": 33, "end": 52}], "dna": [{"text": "kappa B element", "start": 212, "end": 227}]}}, "schema": []} {"input": "Similarly, covalent modification of free sulfhydryl groups with diamide (reversible) or N-ethylmaleimide (irreversible) results in a complete loss of DNA binding activity.", "output": {"entities": {}}, "schema": []} {"input": "In contrast, mild oxidation with glucose oxidase selectively inhibits p75 and p85 binding while not blocking p50 and p55 interactions.", "output": {"entities": {"protein": [{"text": "glucose oxidase", "start": 33, "end": 48}, {"text": "p75", "start": 70, "end": 73}, {"text": "p85", "start": 78, "end": 81}, {"text": "p50", "start": 109, "end": 112}, {"text": "p55", "start": 117, "end": 120}]}}, "schema": []} {"input": "These findings suggest that reduced cysteine thiols play an important role in the DNA binding activity of this family of Rel-related transcription factors.", "output": {"entities": {"protein": [{"text": "Rel-related transcription factors", "start": 121, "end": 154}]}}, "schema": []} {"input": "[Changes in leucocytic estrogen receptor levels in patients with climacteric syndrome and therapeutic effect of liuwei dihuang pills]", "output": {"entities": {"protein": [{"text": "estrogen receptor", "start": 23, "end": 40}]}}, "schema": []} {"input": "The numbers of estrogen receptor (ER) in human peripheral leucocytes in 22 women with climacteric syndrome were measured by radioligand method.", "output": {"entities": {"protein": [{"text": "estrogen receptor", "start": 15, "end": 32}, {"text": "ER", "start": 34, "end": 36}], "cell_type": [{"text": "human peripheral leucocytes", "start": 41, "end": 68}]}}, "schema": []} {"input": "The results were compared with those of 12 normal child-bearing-age women.", "output": {"entities": {}}, "schema": []} {"input": "It wat found that the contents of leucocytic ER in climacteric syndrome patients were significantly lower than normal child-bearing-age women.", "output": {"entities": {"protein": [{"text": "leucocytic", "start": 34, "end": 44}, {"text": "ER", "start": 45, "end": 47}]}}, "schema": []} {"input": "The authors used a Chinese prescription -- Liuwei Dihuang Pills (LDP) to treat the patients for 2 months.", "output": {"entities": {}}, "schema": []} {"input": "The numbers of leucocytic ER were significantly increased after treatment.", "output": {"entities": {"protein": [{"text": "leucocytic", "start": 15, "end": 25}, {"text": "ER", "start": 26, "end": 28}]}}, "schema": []} {"input": "The data indicate that decrease of ER levels in cell may involve in the pathogenesis of climacteric syndrome.", "output": {"entities": {"protein": [{"text": "ER", "start": 35, "end": 37}]}}, "schema": []} {"input": "LDP not only increases plasma estradiol levels, but also increases the leucocytic ER levels.", "output": {"entities": {"protein": [{"text": "ER", "start": 82, "end": 84}]}}, "schema": []} {"input": "This may be the basis of the therapeutic effect on the disease.", "output": {"entities": {}}, "schema": []} {"input": "Evaluation of the role of ligand and thermal activation of specific DNA binding by in vitro synthesized human glucocorticoid receptor.", "output": {"entities": {"protein": [{"text": "in vitro synthesized human glucocorticoid receptor", "start": 83, "end": 133}]}}, "schema": []} {"input": "We have used a DNA-binding/immunoprecipitation assay to analyze the capacity of human glucocorticoid receptor (hGR ), generated in rabbit reticulocyte lysates, to bind DNA.", "output": {"entities": {"protein": [{"text": "human glucocorticoid receptor", "start": 80, "end": 109}, {"text": "hGR", "start": 111, "end": 114}]}}, "schema": []} {"input": "In vitro translated hGR was indistinguishable from native hGR, as determined by migration on sodium dodecyl sulfate-polyacrylamide gels, sedimentation on sucrose density gradients, and reactivity with antipeptide antibodies generated against hGR.", "output": {"entities": {"protein": [{"text": "In vitro translated hGR", "start": 0, "end": 23}, {"text": "native hGR", "start": 51, "end": 61}, {"text": "antipeptide antibodies", "start": 201, "end": 223}, {"text": "hGR", "start": 242, "end": 245}]}}, "schema": []} {"input": "In addition, cell-free synthesized hGR was capable of specific binding to glucocorticoid response element (GRE )-containing DNA fragments.", "output": {"entities": {"protein": [{"text": "cell-free synthesized hGR", "start": 13, "end": 38}], "dna": [{"text": "glucocorticoid response element (", "start": 74, "end": 107}, {"text": "GRE )-containing DNA fragments", "start": 107, "end": 137}]}}, "schema": []} {"input": "Using this assay system, we have evaluated the contributions of ligand binding and heat activation to DNA binding by these glucocorticoid receptors.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 123, "end": 147}]}}, "schema": []} {"input": "In vitro translated hGR was capable of selective DNA binding even in the absence of glucocorticoid.", "output": {"entities": {"protein": [{"text": "In vitro translated hGR", "start": 0, "end": 23}]}}, "schema": []} {"input": "Treatment with dexamethasone or the antiglucocorticoid RU486 had no additional effect on the DNA-binding capacity when receptor preparations were maintained at 0 C (no activation).", "output": {"entities": {}}, "schema": []} {"input": "In contrast, addition of either ligand or antagonist in combination with a heat activation step promoted DNA binding by approximately 3-fold over that of heat-activated unliganded receptors.", "output": {"entities": {"protein": [{"text": "unliganded receptors", "start": 169, "end": 189}]}}, "schema": []} {"input": "Agonist (dexamethasone) was slightly more effective in supporting specific DNA binding than antagonist (RU486 ).", "output": {"entities": {}}, "schema": []} {"input": "DNA binding by in vitro synthesized GR was blocked by the addition of sodium molybdate to the receptor preparations before steroid addition and thermal activation.", "output": {"entities": {"protein": [{"text": "in vitro synthesized GR", "start": 15, "end": 38}]}}, "schema": []} {"input": "Addition of KCl resulted in less DNA binding either due to blockage of DNA- receptor complex formation or disruption of the complexes.", "output": {"entities": {"protein": [{"text": "receptor complex", "start": 76, "end": 92}]}}, "schema": []} {"input": "The specificity of DNA binding by cell-free synthesized hGR was analyzed further by examining the abilities of various DNAs to compete for binding to a naturally occurring GRE found in the mouse mammary tumor virus-long terminal repeat.", "output": {"entities": {"protein": [{"text": "cell-free synthesized hGR", "start": 34, "end": 59}], "dna": [{"text": "various DNAs", "start": 111, "end": 123}, {"text": "GRE", "start": 172, "end": 175}, {"text": "mouse mammary tumor virus-long terminal repeat", "start": 189, "end": 235}]}}, "schema": []} {"input": "Oligonucleotides containing the consensus GRE were the most efficient competitors, and fragments containing regulatory sequences from glucocorticoid -repressible genes were somewhat competitive, whereas single stranded oligonucleotides were unable to compete for mouse mammary tumor virus-long terminal repeat DNA binding, except when competitor was present at extremely high concentrations.", "output": {"entities": {"dna": [{"text": "consensus", "start": 32, "end": 41}, {"text": "GRE", "start": 42, "end": 45}, {"text": "regulatory sequences", "start": 108, "end": 128}, {"text": "glucocorticoid -repressible genes", "start": 134, "end": 167}, {"text": "mouse mammary tumor virus-long terminal repeat", "start": 263, "end": 309}]}}, "schema": []} {"input": "Together these studies indicate that hGR synthesized in rabbit reticulocyte lysates displays many of the same properties, including GRE -specific DNA binding, observed for glucocorticoid receptor present in cytosolic extracts of mammalian cells and tissues.", "output": {"entities": {"protein": [{"text": "hGR", "start": 37, "end": 40}, {"text": "glucocorticoid receptor", "start": 172, "end": 195}], "dna": [{"text": "GRE", "start": 132, "end": 135}], "cell_type": [{"text": "mammalian cells", "start": 229, "end": 244}]}}, "schema": []} {"input": "Similarities between the effects of dexamethasone and RU486 suggest that the antiglucocorticoid properties of RU486 do not occur at the level of specific DNA binding.", "output": {"entities": {}}, "schema": []} {"input": "Expression of 1,25(OH)2D3 receptors on alveolar lymphocytes from patients with pulmonary granulomatous diseases.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptors", "start": 14, "end": 35}], "cell_type": [{"text": "alveolar lymphocytes", "start": 39, "end": 59}]}}, "schema": []} {"input": "1,25(OH)2D3 is known to be produced at sites of granulomatous reactions.", "output": {"entities": {}}, "schema": []} {"input": "In order to characterize the cell types that are targets for this immunoregulatory hormone, we have evaluated the expression of 1,25(OH)2D3 receptors on peripheral blood T-lymphocytes and those recovered from the lung by bronchoalveolar lavage from patients with pulmonary granulomatous diseases (tuberculosis and sarcoidosis) and from normal control subjects using combined autoradiographic and immunohistochemical techniques.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptors", "start": 128, "end": 149}], "cell_type": [{"text": "peripheral blood T-lymphocytes", "start": 153, "end": 183}]}}, "schema": []} {"input": "Lavage T-lymphocytes from patients with tuberculosis or with sarcoidosis, but not those from normal control subjects, expressed 1,25(OH)2D3 receptors as demonstrated by binding of [3H]1,25(OH)2D3, which was inhibited by the presence of excess unlabeled 1,25(OH)2D3, but not by the presence of unlabeled 25(OH)D3 (receptor-positive lymphocytes: sarcoidosis, 20 +/- 12%; tuberculosis, 31 +/- 17%).", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptors", "start": 128, "end": 149}], "cell_type": [{"text": "receptor-positive lymphocytes", "start": 313, "end": 342}]}}, "schema": []} {"input": "In contrast, blood lymphocytes from patients with granulomatous diseases did not express detectable 1,25(OH)2D3 receptors.", "output": {"entities": {"cell_type": [{"text": "blood lymphocytes", "start": 13, "end": 30}], "protein": [{"text": "1,25(OH)2D3 receptors", "start": 100, "end": 121}]}}, "schema": []} {"input": "The percentage of lavage T-lymphocytes expressing 1,25(OH)2D3 receptors was significantly greater for patients with tuberculosis presenting with isolated hilar adenopathy than for patients with pulmonary infiltrates and/or cavities.", "output": {"entities": {"cell_type": [{"text": "lavage T-lymphocytes", "start": 18, "end": 38}], "protein": [{"text": "1,25(OH)2D3 receptors", "start": 50, "end": 71}]}}, "schema": []} {"input": "1,25(OH)2D3 receptors were expressed to a greater extent on CD8+ T-lymphocytes than on CD4+ T-lymphocytes in sarcoidosis, whereas a greater proportion of CD4+ than of CD8+ T-lymphocytes from patients with tuberculosis were receptor-positive.", "output": {"entities": {"protein": [{"text": "1,25(OH)2D3 receptors", "start": 0, "end": 21}], "cell_type": [{"text": "CD8+ T-lymphocytes", "start": 60, "end": 78}, {"text": "CD4+ T-lymphocytes", "start": 87, "end": 105}, {"text": "CD4+", "start": 154, "end": 158}, {"text": "CD8+ T-lymphocytes", "start": 167, "end": 185}]}}, "schema": []} {"input": "These findings support the conclusion that the interaction of 1,25(OH)2D3 with its receptor on T-lymphocytes may play an important role in the regulation of granulomatous reactions, but because these receptors are expressed on different lymphocyte populations, the net effect of this potent immunoregulatory molecule is likely different in sarcoidosis and tuberculosis.", "output": {"entities": {"cell_type": [{"text": "T-lymphocytes", "start": 95, "end": 108}, {"text": "lymphocyte populations", "start": 237, "end": 259}], "protein": [{"text": "immunoregulatory molecule", "start": 291, "end": 316}]}}, "schema": []} {"input": "Role for the Epstein-Barr virus nuclear antigen 2 in viral promoter switching during initial stages of infection.", "output": {"entities": {"protein": [{"text": "Epstein-Barr virus nuclear antigen 2", "start": 13, "end": 49}], "dna": [{"text": "viral promoter", "start": 53, "end": 67}]}}, "schema": []} {"input": "During latent Epstein-Barr virus (EBV) infection of human B lymphocytes, six viral nuclear antigen (EBNAs) are expressed from long primary transcripts by means of alternative splicing and alternative polyadenylylation sites.", "output": {"entities": {"cell_type": [{"text": "human B lymphocytes", "start": 52, "end": 71}], "protein": [{"text": "six viral nuclear antigen", "start": 73, "end": 98}, {"text": "EBNAs", "start": 100, "end": 105}], "rna": [{"text": "long primary transcripts", "start": 126, "end": 150}, {"text": "alternative splicing", "start": 163, "end": 183}, {"text": "alternative polyadenylylation sites", "start": 188, "end": 223}]}}, "schema": []} {"input": "These transcripts initiate from one of two promoters, Cp or Wp, that function in a mutually exclusive fashion.", "output": {"entities": {"dna": [{"text": "promoters", "start": 43, "end": 52}, {"text": "Cp", "start": 54, "end": 56}, {"text": "Wp", "start": 60, "end": 62}]}}, "schema": []} {"input": "Wp is exclusively utilized during the initial stages of infection of primary B lymphocytes, followed by a switch to Cp usage.", "output": {"entities": {"dna": [{"text": "Wp", "start": 0, "end": 2}, {"text": "Cp", "start": 116, "end": 118}], "cell_type": [{"text": "primary B lymphocytes", "start": 69, "end": 90}]}}, "schema": []} {"input": "These studies have been extended to show that (i) a mutant EBV strain lacking the gene encoding EBNA 2 fails to switch from Wp to Cp usage in primary B lymphocytes, although the virus contains a functional Cp; (ii) a region from -429 to -245 base pairs upstream of Cp is essential for Cp activity in B lymphocytes, but only in the context of upstream and downstream sequences; (iii) this region contains an EBNA 2 -dependent enhancer; and (iv) DNase I protection employing nuclear extracts from B and T lymphocytes revealed a B-cell-specific footprint in the region of the EBNA 2 -dependent enhancer.", "output": {"entities": {"protein": [{"text": "EBNA 2", "start": 96, "end": 102}, {"text": "EBNA 2", "start": 407, "end": 413}, {"text": "DNase I", "start": 444, "end": 451}], "dna": [{"text": "Wp", "start": 124, "end": 126}, {"text": "Cp", "start": 130, "end": 132}, {"text": "Cp", "start": 206, "end": 208}, {"text": "-429 to -245 base pairs", "start": 229, "end": 252}, {"text": "Cp", "start": 265, "end": 267}, {"text": "Cp", "start": 285, "end": 287}, {"text": "upstream and downstream sequences", "start": 342, "end": 375}, {"text": "-dependent enhancer", "start": 414, "end": 433}, {"text": "B-cell-specific footprint", "start": 526, "end": 551}, {"text": "EBNA 2 -dependent enhancer", "start": 573, "end": 599}], "cell_type": [{"text": "primary B lymphocytes", "start": 142, "end": 163}, {"text": "B lymphocytes", "start": 300, "end": 313}]}}, "schema": []} {"input": "These results support a model for viral promoter switching during the initial stages of infection in which Wp activity leads to the expression of EBNA 2, followed by activation of Cp through the EBNA 2 -dependent enhancer.", "output": {"entities": {"dna": [{"text": "viral promoter", "start": 34, "end": 48}, {"text": "Wp", "start": 107, "end": 109}, {"text": "Cp", "start": 180, "end": 182}, {"text": "-dependent enhancer", "start": 202, "end": 221}], "protein": [{"text": "EBNA 2", "start": 146, "end": 152}, {"text": "EBNA 2", "start": 195, "end": 201}]}}, "schema": []} {"input": "Immune response of peripheral blood mononuclear cells to HBx-antigen of hepatitis B virus.", "output": {"entities": {"cell_type": [{"text": "peripheral blood mononuclear cells", "start": 19, "end": 53}], "protein": [{"text": "HBx-antigen", "start": 57, "end": 68}]}}, "schema": []} {"input": "The hepatitis B virus genome encodes a transcriptional transactivator protein designated HBxAg.", "output": {"entities": {"dna": [{"text": "hepatitis B virus genome", "start": 4, "end": 28}], "protein": [{"text": "transcriptional transactivator protein", "start": 39, "end": 77}, {"text": "HBxAg", "start": 89, "end": 94}]}}, "schema": []} {"input": "We have investigated whether this antigen is a target structure for human T-lymphocytes.", "output": {"entities": {"cell_type": [{"text": "human T-lymphocytes", "start": 68, "end": 87}]}}, "schema": []} {"input": "Using recombinant HBxAg protein, we found HBxAg -specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis B virus infection (6 of 6) and chronic hepatitis B virus infection (6 of 17) but not in healthy individuals.", "output": {"entities": {"protein": [{"text": "recombinant", "start": 6, "end": 17}, {"text": "HBxAg protein", "start": 18, "end": 31}, {"text": "HBxAg", "start": 42, "end": 47}], "cell_type": [{"text": "peripheral blood mononuclear cells", "start": 73, "end": 107}]}}, "schema": []} {"input": "With HBxAg -specific synthetic polypeptides, several T-cell epitopes were identified.", "output": {"entities": {"protein": [{"text": "HBxAg", "start": 5, "end": 10}, {"text": "T-cell epitopes", "start": 53, "end": 68}]}}, "schema": []} {"input": "Most were located in the carboxyterminal half of the HBxAg protein.", "output": {"entities": {"protein": [{"text": "carboxyterminal half", "start": 25, "end": 45}, {"text": "HBxAg protein", "start": 53, "end": 66}]}}, "schema": []} {"input": "Five T-cell clones specific for a T-cell epitope located at the carboxyterminal region of HBxAg were established and found to belong to the CD2/CD4-positive, CD8-negative subtype.", "output": {"entities": {"cell_line": [{"text": "T-cell clones", "start": 5, "end": 18}, {"text": "CD2/CD4-positive, CD8-negative subtype", "start": 140, "end": 178}], "protein": [{"text": "T-cell epitope", "start": 34, "end": 48}, {"text": "carboxyterminal region", "start": 64, "end": 86}, {"text": "HBxAg", "start": 90, "end": 95}]}}, "schema": []} {"input": "These data establish for the first time HBxAg as an antigen in the cellular immune response.", "output": {"entities": {"protein": [{"text": "HBxAg", "start": 40, "end": 45}]}}, "schema": []} {"input": "[Changes in leucocytic estrogen receptor levels in patients with gynecomastia]", "output": {"entities": {"protein": [{"text": "leucocytic estrogen receptor", "start": 12, "end": 40}]}}, "schema": []} {"input": "The number of estrogen receptor (ER) in human peripheral leucocytes in 13 men with gynecomastia were measured by radioligand binding method. The results were compared with those of 13 sex-and age-matched healthy subjects.", "output": {"entities": {"protein": [{"text": "estrogen receptor", "start": 14, "end": 31}, {"text": "ER", "start": 33, "end": 35}], "cell_type": [{"text": "human peripheral leucocytes", "start": 40, "end": 67}]}}, "schema": []} {"input": "It was found that the number of ER in leucocytes was significantly increased in gynecomastia (Rs of leucocytes were 1054 +/- 254 sites/cell).", "output": {"entities": {"protein": [{"text": "ER", "start": 32, "end": 34}], "cell_type": [{"text": "leucocytes", "start": 38, "end": 48}, {"text": "leucocytes", "start": 100, "end": 110}]}}, "schema": []} {"input": "It suggested that increase of ER levels play an important role in the pathogenesis of gynecomastia.", "output": {"entities": {}}, "schema": []} {"input": "The NF kappa B independent cis-acting sequences in HIV-1 LTR responsive to T-cell activation.", "output": {"entities": {"dna": [{"text": "NF kappa B independent cis-acting sequences", "start": 4, "end": 47}, {"text": "HIV-1 LTR", "start": 51, "end": 60}]}}, "schema": []} {"input": "The rate of transcription initiation directed by the long terminal repeat (LTR) of HIV-1 increases in response to mitogenic stimuli of T cells.", "output": {"entities": {"dna": [{"text": "long terminal repeat", "start": 53, "end": 73}], "cell_type": [{"text": "T cells", "start": 135, "end": 142}]}}, "schema": []} {"input": "Here we show that the response of the HIV-1 LTR may be governed by two independent sequences located 5' to the site of transcription initiation sequences that bind either NFAT-1 or NF kappa B.", "output": {"entities": {"dna": [{"text": "HIV-1 LTR", "start": 38, "end": 47}, {"text": "transcription initiation sequences", "start": 119, "end": 153}], "protein": [{"text": "NFAT-1", "start": 171, "end": 177}, {"text": "NF kappa B", "start": 181, "end": 191}]}}, "schema": []} {"input": "The rate of LTR -directed gene expression increased in response to treatment with either a phorbol ester or tumor necrosis factor alpha if either the NFAT-1 or NF kappa B binding sites were deleted, but failed to respond to these mitogenic stimuli if both sequences were absent.", "output": {"entities": {"dna": [{"text": "LTR", "start": 12, "end": 15}, {"text": "binding sites", "start": 171, "end": 184}], "protein": [{"text": "tumor necrosis factor alpha", "start": 108, "end": 135}, {"text": "NFAT-1", "start": 150, "end": 156}, {"text": "NF kappa B", "start": 160, "end": 170}]}}, "schema": []} {"input": "The HIV-1 mutant virus containing both NF kappa B and NFAT-1 deletion was able to replicate although at a much decreased growth rate, while the deletion of NFAT-1 alone increased the viral growth rate in Jurkat cells.", "output": {"entities": {"protein": [{"text": "NF kappa B", "start": 39, "end": 49}, {"text": "NFAT-1", "start": 156, "end": 162}], "dna": [{"text": "and NFAT-1 deletion", "start": 50, "end": 69}], "cell_line": [{"text": "Jurkat cells", "start": 204, "end": 216}]}}, "schema": []} {"input": "Neither deletion of NF kappa B nor deletion of NFAT-1 decreased activation of viral replication by phorbol ester.", "output": {"entities": {"protein": [{"text": "NF kappa B", "start": 20, "end": 30}, {"text": "NFAT-1", "start": 47, "end": 53}]}}, "schema": []} {"input": "cAMP -dependent regulation of proenkephalin by JunD and JunB: positive and negative effects of AP-1 proteins.", "output": {"entities": {"protein": [{"text": "JunD", "start": 47, "end": 51}, {"text": "JunB", "start": 56, "end": 60}, {"text": "AP-1 proteins", "start": 95, "end": 108}]}}, "schema": []} {"input": "We demonstrate that JunD, a component of the AP-1 transcription factor complex, activates transcription of the human proenkephalin gene in a fashion that is completely dependent upon the cAMP-dependent protein kinase, protein kinase A.", "output": {"entities": {"protein": [{"text": "JunD", "start": 20, "end": 24}, {"text": "AP-1 transcription factor complex", "start": 45, "end": 78}, {"text": "cAMP-dependent protein kinase", "start": 187, "end": 216}, {"text": "protein kinase A", "start": 218, "end": 234}], "dna": [{"text": "human proenkephalin gene", "start": 111, "end": 135}]}}, "schema": []} {"input": "Activation of proenkephalin transcription by JunD is dependent upon a previously characterized cAMP -, phorbol ester -, and Ca(2+) -inducible enhancer, and JunD is shown to bind the enhancer as a homodimer.", "output": {"entities": {"protein": [{"text": "JunD", "start": 45, "end": 49}, {"text": "JunD", "start": 156, "end": 160}, {"text": "homodimer", "start": 196, "end": 205}], "dna": [{"text": "cAMP -, phorbol ester -, and Ca(2+) -inducible enhancer", "start": 95, "end": 150}, {"text": "enhancer", "start": 182, "end": 190}]}}, "schema": []} {"input": "Another component of the AP-1 transcription complex, JunB, is shown to inhibit activation mediated by JunD.", "output": {"entities": {"protein": [{"text": "AP-1 transcription complex", "start": 25, "end": 51}, {"text": "JunB", "start": 53, "end": 57}, {"text": "JunD", "start": 102, "end": 106}]}}, "schema": []} {"input": "As a homodimer JunB is unable to bind the enhancer; however in the presence of c-Fos, high-affinity binding is observed.", "output": {"entities": {"protein": [{"text": "JunB", "start": 15, "end": 19}, {"text": "c-Fos", "start": 79, "end": 84}]}}, "schema": []} {"input": "Furthermore, JunD is shown to activate transcription of genes linked to both cAMP and phorbol ester response elements in a protein kinase A -dependent fashion, further blurring the distinction between these response elements.", "output": {"entities": {"protein": [{"text": "JunD", "start": 13, "end": 17}, {"text": "protein kinase A", "start": 123, "end": 139}], "dna": [{"text": "response elements", "start": 207, "end": 224}]}}, "schema": []} {"input": "These results demonstrate that the transcriptional activity of an AP-1-related protein is regulated by the cAMP -dependent second-messenger pathway and suggest that JunD and other AP-1-related proteins may play an important role in the regulation of gene expression by cAMP -dependent intracellular signaling pathways.", "output": {"entities": {"protein": [{"text": "AP-1-related protein", "start": 66, "end": 86}, {"text": "JunD", "start": 165, "end": 169}, {"text": "AP-1-related proteins", "start": 180, "end": 201}]}}, "schema": []} {"input": "[Plasma cortisol concentration and blood leukocyte content of glucocorticoid receptors in patients with deficiency-cold vs deficiency-heat syndromes]", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 62, "end": 86}]}}, "schema": []} {"input": "Plasma cortisol concentration and blood leukocyte content of glucocorticoid receptors (GCR) were assayed in 20 patients with deficiency syndromes, 10 cold in property (deficiency-cold), the other 10 hot in property (deficiency-heat), and also in 10 healthy individuals as normal control for the purpose of investigating the nature of cold and heat syndromes.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 61, "end": 85}, {"text": "GCR", "start": 87, "end": 90}]}}, "schema": []} {"input": "As a result, the cases of deficiency-cold syndrome (DCS) had a normal concentration of plasma cortisol but a lowered content of GCR in leukocytes when compared with the normal control (P less than 0.05); the cases of deficiency-heat syndrome (DHS) had a higher concentration of plasma cortisol than the normal control (P less than 0.05) and a slightly higher content of GCR in leukocytes.", "output": {"entities": {"protein": [{"text": "GCR", "start": 128, "end": 131}, {"text": "GCR", "start": 370, "end": 373}], "cell_type": [{"text": "leukocytes", "start": 135, "end": 145}, {"text": "leukocytes", "start": 377, "end": 387}]}}, "schema": []} {"input": "It was concluded that the DCS is characterized by diminished biological effects of adrenocortical activity, while the DHS, by augmented biological effects of adrenocortical activity.", "output": {"entities": {}}, "schema": []} {"input": "The role of jun and fos gene family members in 12-O-tetradecanoylphorbol-13-acetate induced hemopoietic differentiation.", "output": {"entities": {}}, "schema": []} {"input": "Terminal differentiation of the leukemic cell lines U-937 and HL-60 by 12-O-tetradecanoylphorbol-13-acetate is accompanied by marked changes in gene expression.", "output": {"entities": {"cell_line": [{"text": "leukemic cell lines", "start": 32, "end": 51}, {"text": "U-937", "start": 52, "end": 57}, {"text": "HL-60", "start": 62, "end": 67}]}}, "schema": []} {"input": "In this study, we demonstrate that the expression of jun and fos gene family members is induced with variable kinetics during 12-O-tetradecanoylphorbol-13-acetate induced differentiation, with c-jun expression best paralleling differentiation.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 193, "end": 198}]}}, "schema": []} {"input": "The generation of AP-1 complexes, as measured by DNA binding activity, closely parallels morphological differentiation.", "output": {"entities": {"protein": [{"text": "AP-1 complexes", "start": 18, "end": 32}]}}, "schema": []} {"input": "Furthermore, the ability of these complexes to regulate gene expression is demonstrated by increased transcription from an AP-1 driven reporter construct and marked increases in the expression of endogenous AP-1 regulated genes.", "output": {"entities": {"dna": [{"text": "AP-1 driven reporter construct", "start": 123, "end": 153}, {"text": "endogenous AP-1 regulated genes", "start": 196, "end": 227}]}}, "schema": []} {"input": "Differentiation assays using water soluble phorbol esters reveal that differentiation becomes irreversible soon after AP-1 appears.", "output": {"entities": {"protein": [{"text": "AP-1", "start": 118, "end": 122}]}}, "schema": []} {"input": "This tight correlation between c-jun expression, the generation of AP-1 activity, and differentiation suggests a critical role for this gene and transcriptional complex during this process.", "output": {"entities": {"dna": [{"text": "c-jun", "start": 31, "end": 36}], "protein": [{"text": "AP-1", "start": 67, "end": 71}, {"text": "transcriptional complex", "start": 145, "end": 168}]}}, "schema": []} {"input": "Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A [see comments]", "output": {"entities": {"protein": [{"text": "T-cell transcription factor", "start": 25, "end": 52}]}}, "schema": []} {"input": "Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response.", "output": {"entities": {}}, "schema": []} {"input": "In T lymphocytes these drugs disrupt an unknown step in the transmission of signals from the T-cell antigen receptor to cytokine genes that coordinate the immune response.", "output": {"entities": {"cell_type": [{"text": "T lymphocytes", "start": 3, "end": 16}], "protein": [{"text": "T-cell antigen receptor", "start": 93, "end": 116}], "dna": [{"text": "cytokine genes", "start": 120, "end": 134}]}}, "schema": []} {"input": "The putative intracellular receptors for FK506 and cyclosporin are cis-trans prolyl isomerases.", "output": {"entities": {"protein": [{"text": "putative intracellular receptors", "start": 4, "end": 36}]}}, "schema": []} {"input": "Binding of the drug inhibits isomerase activity, but studies with other prolyl isomerase inhibitors and analysis of cyclosporin -resistant mutants in yeast suggest that the effects of the drug result from the formation of an inhibitory complex between the drug and isomerase, and not from inhibition of isomerase activity.", "output": {"entities": {"protein": [{"text": "isomerase", "start": 29, "end": 38}, {"text": "isomerase", "start": 79, "end": 88}, {"text": "inhibitory complex", "start": 225, "end": 243}, {"text": "isomerase", "start": 265, "end": 274}, {"text": "isomerase", "start": 303, "end": 312}], "cell_line": [{"text": "cyclosporin -resistant mutants", "start": 116, "end": 146}]}}, "schema": []} {"input": "A transcription factor, NF-AT, which is essential for early T-cell gene activation, seems to be a specific target of cyclosporin A and FK506 action because transcription directed by this protein is blocked in T cells treated with these drugs, with little or no effect on other transcription factors such as AP-1 and NF-kappa B.", "output": {"entities": {"protein": [{"text": "transcription factor", "start": 2, "end": 22}, {"text": "NF-AT", "start": 24, "end": 29}, {"text": "transcription factors", "start": 277, "end": 298}, {"text": "AP-1", "start": 307, "end": 311}, {"text": "NF-kappa B", "start": 316, "end": 326}], "cell_type": [{"text": "T cells", "start": 209, "end": 216}]}}, "schema": []} {"input": "Here we demonstrate that NF-AT is formed when a signal from the antigen receptor induces a pre-existing cytoplasmic subunit to translocate to the nucleus and combine with a newly synthesized nuclear subunit of NF-AT.", "output": {"entities": {"protein": [{"text": "NF-AT", "start": 25, "end": 30}, {"text": "antigen receptor", "start": 64, "end": 80}, {"text": "NF-AT", "start": 210, "end": 215}]}}, "schema": []} {"input": "FK506 and cyclosporin A block translocation of the cytoplasmic component without affecting synthesis of the nuclear subunit.", "output": {"entities": {"protein": [{"text": "cytoplasmic component", "start": 51, "end": 72}, {"text": "nuclear subunit", "start": 108, "end": 123}]}}, "schema": []} {"input": "Glucocorticoid receptors in lymphocytes in anorexia nervosa.", "output": {"entities": {"protein": [{"text": "Glucocorticoid receptors", "start": 0, "end": 24}], "cell_type": [{"text": "lymphocytes", "start": 28, "end": 39}]}}, "schema": []} {"input": "OBJECTIVE: The aim was to explore the down-regulation of the glucocorticoid receptors during hypercortisolaemia in anorexia nervosa.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 61, "end": 85}]}}, "schema": []} {"input": "DESIGN: Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were isolated for receptor binding studies.", "output": {"entities": {"cell_type": [{"text": "blood lymphocytes", "start": 78, "end": 95}]}}, "schema": []} {"input": "PATIENTS: Sixteen anorexic patients, aged 16-27 years, with a mean +/- SEM body mass index of 14.2 +/- 2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied.", "output": {"entities": {}}, "schema": []} {"input": "Six patients were reinvestigated after a significant weight gain.", "output": {"entities": {}}, "schema": []} {"input": "MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured with dexamethasone as ligand on lymphocytes.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 55, "end": 79}], "cell_type": [{"text": "lymphocytes", "start": 126, "end": 137}]}}, "schema": []} {"input": "RESULTS: In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of glucocorticoid receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687 +/- 1750 vs 7347 +/- 1285 sites/cell; Kd: 7.7 +/- 2.4 vs 7.4 +/- 1.7 nM at 24 degrees C).", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 161, "end": 185}]}}, "schema": []} {"input": "After weight gain (14 +/- 2 to 16 +/- 2 kg/m2), receptor numbers were 8421 +/- 2126 (pre) and 9011 +/- 500 (post) sites/cell, which are not significantly different (P greater than 0.2); the Kd was unchanged (9.3 +/- 2.6 vs 9.2 +/- 2.4 nM).", "output": {"entities": {}}, "schema": []} {"input": "CONCLUSIONS Hypercortisolaemia does not down-regulate the lymphocyte glucocorticoid receptors in anorexia nervosa and a post-receptor defect might be involved in peripheral tissue resistance to the effects of glucocorticoid hormones in undernutrition.", "output": {"entities": {"protein": [{"text": "glucocorticoid receptors", "start": 69, "end": 93}]}}, "schema": []} {"input": "Inhibition of protein phosphatases by okadaic acid induces AP1 in human T cells.", "output": {"entities": {"protein": [{"text": "protein phosphatases", "start": 14, "end": 34}, {"text": "AP1", "start": 59, "end": 62}], "cell_type": [{"text": "human", "start": 66, "end": 71}, {"text": "T cells", "start": 72, "end": 79}]}}, "schema": []} {"input": "To examine the role of protein phosphatases in T cell activation, Jurkat cells were treated with okadaic acid, an inhibitor of type 1 and 2A phosphatases, and nuclear extracts were examined for the presence of AP1 as a measure of early T cell activation.", "output": {"entities": {"protein": [{"text": "protein phosphatases", "start": 23, "end": 43}, {"text": "AP1", "start": 210, "end": 213}], "cell_line": [{"text": "Jurkat cells", "start": 66, "end": 78}]}}, "schema": []} {"input": "Okadaic acid was found to be a potent inducer of AP1.", "output": {"entities": {"protein": [{"text": "AP1", "start": 49, "end": 52}]}}, "schema": []} {"input": "In contrast to phorbol esters such as phorbol myristate acetate (PMA ), the induction of AP1 by okadaic acid occurs predominantly by transcriptional activation of the jun and fos family of proto-oncogenes.", "output": {"entities": {"protein": [{"text": "AP1", "start": 89, "end": 92}], "dna": [{"text": "proto-oncogenes", "start": 189, "end": 204}]}}, "schema": []} {"input": "Surprisingly, while the addition of phytohemagglutinin further enhanced the induction of AP1, the addition of PMA inhibited it.", "output": {"entities": {"protein": [{"text": "phytohemagglutinin", "start": 36, "end": 54}, {"text": "AP1", "start": 89, "end": 92}]}}, "schema": []} {"input": "Okadaic acid treatment was found to dramatically increase mRNA transcripts of the jun family of proto-oncogenes including c-jun, junD, and junB and to a lesser extent the fos family including c-fos and fra-1.", "output": {"entities": {"rna": [{"text": "mRNA transcripts", "start": 58, "end": 74}], "dna": [{"text": "jun family of proto-oncogenes", "start": 82, "end": 111}, {"text": "c-jun", "start": 122, "end": 127}, {"text": "junD", "start": 129, "end": 133}, {"text": "junB", "start": 139, "end": 143}, {"text": "fos family", "start": 171, "end": 181}, {"text": "c-fos", "start": 192, "end": 197}, {"text": "fra-1", "start": 202, "end": 207}]}}, "schema": []} {"input": "By comparison, PMA is a very inefficient inducer of the jun gene family in Jurkat cells.", "output": {"entities": {"dna": [{"text": "jun gene family", "start": 56, "end": 71}], "cell_line": [{"text": "Jurkat cells", "start": 75, "end": 87}]}}, "schema": []} {"input": "Similar to its effect on the induction of AP1 by okadaic acid, PMA inhibits the induction of c-jun mRNA by okadaic acid.", "output": {"entities": {"protein": [{"text": "AP1", "start": 42, "end": 45}], "rna": [{"text": "c-jun mRNA", "start": 93, "end": 103}]}}, "schema": []} {"input": "Transfection of c-jun promoter constructs confirmed the marked difference between PMA and okadaic acid in inducing c-jun transcription.", "output": {"entities": {"dna": [{"text": "c-jun promoter constructs", "start": 16, "end": 41}, {"text": "c-jun", "start": 115, "end": 120}]}}, "schema": []} {"input": "The induction of AP1 by okadaic acid suggests that protein phosphatases 1 and 2A (PP1 and PP2A) may be involved in T cell activation as important negative regulators of the transcription factor AP1.", "output": {"entities": {"protein": [{"text": "AP1", "start": 17, "end": 20}, {"text": "PP1", "start": 82, "end": 85}, {"text": "PP2A", "start": 90, "end": 94}, {"text": "transcription factor", "start": 173, "end": 193}, {"text": "AP1", "start": 194, "end": 197}]}}, "schema": []} {"input": "Cloning of murine TCF-1, a T cell-specific transcription factor interacting with functional motifs in the CD3-epsilon and T cell receptor alpha enhancers.", "output": {"entities": {"protein": [{"text": "murine TCF-1", "start": 11, "end": 23}, {"text": "transcription factor", "start": 43, "end": 63}], "dna": [{"text": "functional motifs", "start": 81, "end": 98}]}}, "schema": []} {"input": "CD3 -epsilon gene expression is confined to the T cell lineage.", "output": {"entities": {"protein": [{"text": "CD3", "start": 0, "end": 3}], "cell_line": [{"text": "T cell lineage", "start": 48, "end": 62}]}}, "schema": []} {"input": "We have recently identified and cloned a human transcription factor, TCF-1, that binds to a functional element in the T lymphocyte-specific enhancer of CD3-epsilon.", "output": {"entities": {"protein": [{"text": "human transcription factor", "start": 41, "end": 67}, {"text": "TCF-1", "start": 69, "end": 74}]}}, "schema": []} {"input": "In a panel of human cell lines, TCF-1 expression was restricted to T lineage cells.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 32, "end": 37}], "cell_type": [{"text": "T lineage cells", "start": 67, "end": 82}]}}, "schema": []} {"input": "TCF-1 belonged to a novel family of genes that contain the so-called high mobility group 1 (HMG) box.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 0, "end": 5}], "dna": [{"text": "mobility group 1 (HMG) box", "start": 74, "end": 100}]}}, "schema": []} {"input": "Here we report the cloning of murine TCF-1.", "output": {"entities": {"protein": [{"text": "murine", "start": 30, "end": 36}, {"text": "TCF-1", "start": 37, "end": 42}]}}, "schema": []} {"input": "Two splice alternatives were identified that were not previously observed in human TCF-1.", "output": {"entities": {"protein": [{"text": "human TCF-1", "start": 77, "end": 88}]}}, "schema": []} {"input": "Murine and human TCF-1 displayed a 95.5% overall amino acid homology.", "output": {"entities": {}}, "schema": []} {"input": "Recombinant murine and human TCF-1 recognized the same sequence motif in the CD3-epsilon enhancer as judged by gel retardation and methylation interference assays.", "output": {"entities": {"dna": [{"text": "CD3-epsilon enhancer", "start": 77, "end": 97}]}}, "schema": []} {"input": "With the murine cDNA clones several aspects of TCF-1 were analyzed.", "output": {"entities": {"dna": [{"text": "murine cDNA clones", "start": 9, "end": 27}], "protein": [{"text": "TCF-1", "start": 47, "end": 52}]}}, "schema": []} {"input": "First, deletion analysis revealed that a region of TCF-1 containing the HMG box was sufficient for sequence-specific binding.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 51, "end": 56}], "dna": [{"text": "HMG box", "start": 72, "end": 79}]}}, "schema": []} {"input": "Second, by high stringency Northern blotting and in situ hybridization, TCF-1 expression was shown to be confined to the thymus and to the T cell areas of the spleen.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 72, "end": 77}]}}, "schema": []} {"input": "Third, TCF-1 bound specifically to a functional T cell-specific element in the T cell receptor alpha (TCR-alpha) enhancer.", "output": {"entities": {"protein": [{"text": "TCF-1", "start": 7, "end": 12}], "dna": [{"text": "T cell-specific element", "start": 48, "end": 71}, {"text": "T cell receptor alpha (TCR-alpha) enhancer", "start": 79, "end": 121}]}}, "schema": []} {"input": "The T lineage-specific expression and the affinity for functional motifs in the TCR-alpha and CD3-epsilon enhancers imply an important role for TCF-1 in the establishment of the mature T cell phenotype.", "output": {"entities": {"dna": [{"text": "functional motifs", "start": 55, "end": 72}], "protein": [{"text": "TCF-1", "start": 144, "end": 149}], "cell_type": [{"text": "mature T cell phenotype", "start": 178, "end": 201}]}}, "schema": []} {"input": "Cloning of a human homeobox gene that resembles a diverged Drosophila homeobox gene and is expressed in activated lymphocytes.", "output": {"entities": {"dna": [{"text": "human homeobox gene", "start": 13, "end": 32}, {"text": "diverged Drosophila homeobox gene", "start": 50, "end": 83}], "cell_type": [{"text": "lymphocytes", "start": 114, "end": 125}]}}, "schema": []} {"input": "A new homeobox gene, HB24, has been isolated from a human B-lymphocyte cDNA library.", "output": {"entities": {"dna": [{"text": "homeobox gene", "start": 6, "end": 19}, {"text": "HB24", "start": 21, "end": 25}, {"text": "human B-lymphocyte cDNA library", "start": 52, "end": 83}]}}, "schema": []} {"input": "Northern blot analysis of polyadenylated RNA purified from activated human B cells revealed a single mRNA transcript of approximately 2.3 kb.", "output": {"entities": {"rna": [{"text": "polyadenylated RNA", "start": 26, "end": 44}, {"text": "single mRNA transcript", "start": 94, "end": 116}], "cell_type": [{"text": "activated human B cells", "start": 59, "end": 82}]}}, "schema": []} {"input": "Two cDNA clones were sequenced and provided 2,250 nucleotides (nt) of DNA sequence information.", "output": {"entities": {"dna": [{"text": "cDNA clones", "start": 4, "end": 15}, {"text": "DNA sequence", "start": 70, "end": 82}]}}, "schema": []}