812123701@GENIA Treebank@formal@@1@S@Direct exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases infectivity of human erythrocytes to a malarial parasite.@@@@1@17@@oe@16-12-2010 812123702@GENIA Treebank@formal@@1@S@Direct exposure to 10 nM 2,3,7,8-TCDD caused a 75% increase and a 2-fold increase in the infectivity of isolated human erythrocytes to P. falciparum after 48 hours when the parasites were in an unsynchronized or synchronized state of growth, respectively.@@@@1@43@@oe@16-12-2010 812123703@GENIA Treebank@formal@@1@S@Treatment of human erythrocytes with 10 microM sodium orthovanadate (NaOV), an inhibitor of plasma membrane Ca-ATPase and phosphotyrosine phosphatase, decreased parasitemia by 30%.@@@@1@29@@oe@16-12-2010 812123704@GENIA Treebank@formal@@1@S@Co-treatment of RBCs with TCDD and NaOV completely blocked the TCDD-induced increase in parasitemia.@@@@1@15@@oe@16-12-2010 812123705@GENIA Treebank@formal@@1@S@Because erythrocytes are anucleated, these results are discussed as evidence for biochemical changes by TCDD without requiring the activation of gene products.@@@@1@24@@oe@16-12-2010 812236401@GENIA Treebank@formal@@1@S@trans-activation of the HIV promoter by a cDNA and its genomic clones of human herpesvirus-6.@@@@1@16@@oe@16-12-2010 812236402@GENIA Treebank@formal@@1@S@Human herpesvirus 6 (HHV-6) is a lymphotropic herpesvirus, and in vitro, it can productively infect human CD4+ T cells as HIV-1.@@@@1@26@@oe@16-12-2010 812236403@GENIA Treebank@formal@@1@S@Co-infection of T cells by HIV-1 and HHV-6 can lead to both activation of the HIV-1 promoter and acceleration of the cytopathic effects.@@@@1@24@@oe@16-12-2010 812236404@GENIA Treebank@formal@@1@S@An HHV-6 (GS) cDNA clone, pCD41, encoding for a 41-kDa nuclear protein was identified and characterized previously (Chang and Balachandran, J. Virol. 65, 2884-2894 and 7085, 1991).@@@@1@38@@oe@16-12-2010 812236405@GENIA Treebank@formal@@1@S@Sequence analyses show that this protein has significant homology with the human cytomegalovirus UL44 gene coding for the ICP36 family of early-late-class phosphoprotein.@@@@1@24@@oe@16-12-2010 812236406@GENIA Treebank@formal@@1@S@Using this cDNA as the probe, a 3.8-kb EcoRI genomic fragment encoding the HHV-6(GS)P41 was cloned and designated as pGD41.@@@@1@26@@oe@16-12-2010 812236407@GENIA Treebank@formal@@1@S@When cotransfected with the HIV LTR CAT into CV-1 cells, both the pCD41 and pGD41 clones trans-activated the HIV LTR.@@@@1@22@@oe@16-12-2010 812236408@GENIA Treebank@formal@@1@S@Sequence analyses of pCD41 indicate that there are two potential open reading frames (ORFs), A and B, which are homologous to the ORFs found in the genomic clone pGD41.@@@@1@34@@oe@16-12-2010 812236409@GENIA Treebank@formal@@1@S@Deletion constructs of the pCD41 clone demonstrated that ORF-A was critical for the HIV LTR activation.@@@@1@17@@oe@16-12-2010 812236410@GENIA Treebank@formal@@1@S@Deletion analyses of the pCD41 ORF-A and the use of promoter constructs further mapped an internal functional promoter within the pCD41 sequence that can direct the synthesis of the trans-activating protein.@@@@1@32@@oe@16-12-2010 812236411@GENIA Treebank@formal@@1@S@By using HIV LTR deletion mutants, the NF-kappa B binding sites were found to be critical for response to the pCD41 trans-activation.@@@@1@24@@oe@16-12-2010 812385501@GENIA Treebank@formal@@1@S@Isolation and characterization of gelatinase granules from human neutrophils.@@@@1@10@@oe@16-12-2010 812385502@GENIA Treebank@formal@@1@S@We recently confirmed the existence of gelatinase granules as a subpopulation of peroxidase-negative granules by double-labeling immunogold electron microscopy on intact cells and by subcellular fractionation.@@@@1@27@@oe@16-12-2010 812385503@GENIA Treebank@formal@@1@S@Further characterization of gelatinase granules has been hampered by poor separation of specific and gelatinase granules on both two-layer Percoll gradients and sucrose gradients.@@@@1@25@@oe@16-12-2010 812385504@GENIA Treebank@formal@@1@S@We have developed a three-layer Percoll density gradient that allows separation of the different granules and vesicles from human neutrophils; in particular, it allows separation of specific and gelatinase granules.@@@@1@33@@oe@16-12-2010 812385505@GENIA Treebank@formal@@1@S@This allows us to characterize these two granule populations with regard to their content of membrane proteins, which become incorporated into the plasma membrane during exocytosis.@@@@1@28@@oe@16-12-2010 812385506@GENIA Treebank@formal@@1@S@We found that gelatinase granules, defined as peroxidase-negative granules containing gelatinase but lacking lactoferrin, contain 50% of total cell gelatinase, with the remaining residing in specific granules.@@@@1@32@@oe@16-12-2010 812385507@GENIA Treebank@formal@@1@S@Furthermore, we found that 20% to 25% of both the adhesion protein Mac-1 and the NADPH-oxidase component cytochrome b558 is localized in gelatinase granules.@@@@1@28@@oe@16-12-2010 812385508@GENIA Treebank@formal@@1@S@Although no qualitative difference was observed between specific granules and gelatinase granules with respect to cytochrome b558 and Mac-1, stimulation of the neutrophil with FMLP resulted in a selective mobilization of the least dense peroxidase-negative granules, ie, gelatinase granules, which, in concert with secretory vesicles, furnish the plasma membrane with Mac-1 and cytochrome b558.@@@@1@61@@oe@16-12-2010 812385509@GENIA Treebank@formal@@1@S@This shows that gelatinase granules are functionally important relative to specific granules in mediating early inflammatory responses.@@@@1@18@@oe@16-12-2010 812634801@GENIA Treebank@formal@@1@S@Stress response of senescent T lymphocytes: reduced hsp70 is independent of the proliferative block.@@@@1@16@@oe@16-12-2010 812634802@GENIA Treebank@formal@@1@S@Senescent human T lymphocyte cultures are unable to undergo proliferation, but show no difference from early passage cells in cytotoxic function or surface antigenic profile.@@@@1@27@@oe@16-12-2010 812634803@GENIA Treebank@formal@@1@S@A second feature of senescent T cells is the dramatic reduction in hsp70 production in response to heat shock.@@@@1@20@@oe@16-12-2010 812634804@GENIA Treebank@formal@@1@S@This decline is associated with a decrease in binding of nuclear extracts to the consensus heat shock element.@@@@1@19@@oe@16-12-2010 812634805@GENIA Treebank@formal@@1@S@Interestingly, the progressive decline in the heat shock response of cultured T cells correlates with the percent proliferative life span completed rather than with the actual proliferative activity at the time of heat shock.@@@@1@36@@oe@16-12-2010 812634806@GENIA Treebank@formal@@1@S@This suggests that for senescent T cells the reduced ability to respond to heat shock by producing hsp70, although possibly lying at the level of transcriptional control, may nevertheless be unrelated to the reduced DNA synthesis or the diminished proliferative activity also manifested by these cells.@@@@1@49@@oe@16-12-2010 813437801@GENIA Treebank@formal@@1@S@Activation of the interleukin 6 gene by Mycobacterium tuberculosis or lipopolysaccharide is mediated by nuclear factors NF-IL6 and NF-kappa B [published erratum appears in Proc Natl Acad Sci U S A 1995 Apr 11;92(8):3632]@@@@1@43@@oe@16-12-2010 813437802@GENIA Treebank@formal@@1@S@The host response to Mycobacterium tuberculosis includes granuloma formation at sites of infection and systemic symptoms.@@@@1@17@@oe@16-12-2010 813437803@GENIA Treebank@formal@@1@S@Cytokines have been identified by immunohistochemistry in granulomas in animal models of bacillus Calmette-Guerin (BCG) infection and are released by mononuclear phagocytes upon stimulation by mycobacterial proteins.@@@@1@30@@oe@16-12-2010 813437804@GENIA Treebank@formal@@1@S@In this regard, the cytokine interleukin 6 (IL-6) may play a role in the clinical manifestations and pathological events of tuberculosis infection.@@@@1@26@@oe@16-12-2010 813437805@GENIA Treebank@formal@@1@S@We have demonstrated that lipoarabinomannan (LAM) from the mycobacterial cell wall, which was virtually devoid of lipopolysaccharide (LPS), stimulated mononuclear phagocytes to release IL-6 in a dose-response manner.@@@@1@35@@oe@16-12-2010 813437806@GENIA Treebank@formal@@1@S@LAM and LPS were potent inducers of IL-6 gene expression in peripheral blood monocytes.@@@@1@15@@oe@16-12-2010 813437807@GENIA Treebank@formal@@1@S@Both LAM- and LPS-inducible IL-6 promoter activity was localized to a DNA fragment, positions -158 to -49, by deletion analysis and chloramphenicol acetyltransferase assay.@@@@1@27@@oe@16-12-2010 813437808@GENIA Treebank@formal@@1@S@Two nuclear factor NF-IL6 (positions -153 to -145 and -83 to -75) and one nuclear factor NF-kappa B (positions -72 to -63) motifs are present within this fragment.@@@@1@33@@oe@16-12-2010 813437809@GENIA Treebank@formal@@1@S@Site-directed mutagenesis of one or more of these motifs within the IL-6 promoter demonstrated that each has positive regulatory activity and that they could act in a function- and orientation-independent manner.@@@@1@32@@oe@16-12-2010 813437810@GENIA Treebank@formal@@1@S@Deletion of all three elements abolished inducibility of IL-6 promoter activity by both LAM and LPS.@@@@1@17@@oe@16-12-2010 813437811@GENIA Treebank@formal@@1@S@We conclude that the NF-IL6 and NF-kappa B sites mediate IL-6 induction in response to both LPS and LAM, acting as bacterial or mycobacterial response elements.@@@@1@28@@oe@16-12-2010 813578001@GENIA Treebank@formal@@1@S@Calcineurin activates transcription from the GM-CSF promoter in synergy with either protein kinase C or NF-kappa B/AP-1 in T cells.@@@@1@21@@oe@16-12-2010 813578002@GENIA Treebank@formal@@1@S@Two cis-acting elements GM-kappa B/GC-box and CLE0, of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene are required for maximal induction in Jurkat T cells by costimulation with phorbol-12-myristate acetate (PMA) and Ca2+ ionophore (A23187).@@@@1@41@@oe@16-12-2010 813578003@GENIA Treebank@formal@@1@S@The GM-kappa B sequence is recognized by NF-kappa B, which is mainly induced by PMA.@@@@1@17@@oe@16-12-2010 813578004@GENIA Treebank@formal@@1@S@The CLE0 sequence interacts with factors, related to a PMA-induced AP-1 and a PMA/A23187-induced NF-AT.@@@@1@17@@oe@16-12-2010 813578005@GENIA Treebank@formal@@1@S@We examined whether signal transducing components in T cells can activate transcription of the GM-CSF gene.@@@@1@17@@oe@16-12-2010 813578006@GENIA Treebank@formal@@1@S@Cotransfection of NF-kappa B (p50/p65)- or AP-1 (c-Jun/c-Fos)- expression vectors into Jurkat cells with a luciferase reporter containing the GM-CSF promoter did not stimulate transcription from the GM-CSF promoter.@@@@1@36@@oe@16-12-2010 813578007@GENIA Treebank@formal@@1@S@In contrast, cotransfection with a combination of NF-kappa B and AP-1 significantly augmented transcription from the GM-CSF promoter containing the GM-kappa B/GC-box and the CLE0 (AP-1/NF-AT).@@@@1@30@@oe@16-12-2010 813578008@GENIA Treebank@formal@@1@S@Expression of a constitutively active calcineurin (CN), a Ca2+/calmodulin-dependent protein phosphatase, potentiated by two fold the transcriptional activation by NF-kappa B/AP-1.@@@@1@26@@oe@16-12-2010 813578009@GENIA Treebank@formal@@1@S@Both constitutively active forms of CN and protein kinase C (PKC) synergistically activated transcription from the GM-CSF promoter.@@@@1@21@@oe@16-12-2010 813578010@GENIA Treebank@formal@@1@S@These results suggest that cooperation among NF-kappa B-, AP-1- and NF-AT-binding sequences is required for induction of the GM-CSF gene through PKC- and Ca2+- signaling pathways downstream of T cell activation.@@@@1@33@@oe@16-12-2010 813578401@GENIA Treebank@formal@@1@S@Characterization of NF(P), the nuclear factor that interacts with the regulatory P sequence (5'-CGAAAATTTCC-3') of the human interleukin-4 gene: relationship to NF-kappa B and NF-AT.@@@@1@30@@oe@16-12-2010 813578402@GENIA Treebank@formal@@1@S@The P sequence of the human interleukin-4 (IL-4) gene, which was defined as a responsive element for phorbol 12-myristate 13-acetate and calcium ionophore (A23187) in Jurkat T cells, shares sequence similarity with the NF-kappa B and the NF-AT binding sites.@@@@1@47@@oe@16-12-2010 813578403@GENIA Treebank@formal@@1@S@We examined whether NF(P), a nuclear factor specific for the P sequence, is related to NF-kappa B and NF-AT.@@@@1@22@@oe@16-12-2010 813578404@GENIA Treebank@formal@@1@S@NF-kappa B (P65 or P65/P50 heterodimer) bound to the P sequence in electrophoretic mobility shift assays (EMSA) and activated transcription through the P sequence when expression plasmids were cotransfected with P sequence-driven reporter plasmids in Jurkat T cells.@@@@1@43@@oe@16-12-2010 813578405@GENIA Treebank@formal@@1@S@In EMSAs, NF(P) binding was inhibited by the unlabeled NF-AT binding site but not by the unlabeled AP1 binding site and purified NF-AT contained an activity that bound to the P sequence.@@@@1@34@@oe@16-12-2010 813578406@GENIA Treebank@formal@@1@S@Both mobility shift and sequence specificity of NF-AT were similar to those of NF(P) and only a small amount of P65 was detected in NF(P) in crude nuclear extracts.@@@@1@30@@oe@16-12-2010 813578407@GENIA Treebank@formal@@1@S@These results indicate that the component(s) of NF-AT has the potential to reconstitute NF(P) whereas NF-kappa B alone cannot account for NF(P) in crude extracts.@@@@1@30@@oe@16-12-2010 813578408@GENIA Treebank@formal@@1@S@Unlike NF-AT, NF(P) does not contain AP1 as its DNA binding component.@@@@1@14@@oe@16-12-2010 813724301@GENIA Treebank@formal@@1@S@Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues.@@@@1@21@@oe@16-12-2010 813724302@GENIA Treebank@formal@@1@S@The response of mammalian cells to stress is controlled by transcriptional regulatory proteins such as nuclear factor kappa B (NF-kappa B) to induce a wide variety of early response genes.@@@@1@33@@oe@16-12-2010 813724303@GENIA Treebank@formal@@1@S@In this report, we show that exposure of cells to hypoxia (0.02% O2) results in I kappa B alpha degradation, increased NF-kappa B DNA binding activity, and transactivation of a reporter gene construct containing two NF-kappa B DNA binding sites.@@@@1@47@@oe@16-12-2010 813724304@GENIA Treebank@formal@@1@S@Pretreatment of cells with protein tyrosine kinase inhibitors and the dominant negative allele of c-Raf-1 (Raf 301) inhibited I kappa B alpha degradation, NF-kappa B binding, and transactivation of kappa B reporter constructs by hypoxia.@@@@1@40@@oe@16-12-2010 813724305@GENIA Treebank@formal@@1@S@To demonstrate a direct link between changes in the phosphorylation pattern of I kappa B alpha with NF-kappa B activation, we immunoprecipitated I kappa B alpha after varying times of hypoxic exposure and found that its tyrosine phosphorylation status increased during hypoxic exposure.@@@@1@45@@oe@16-12-2010 813724306@GENIA Treebank@formal@@1@S@Inhibition of the transfer of tyrosine phosphoryl groups onto I kappa B alpha prevented I kappa B alpha degradation and NF-kappa B binding.@@@@1@24@@oe@16-12-2010 813724307@GENIA Treebank@formal@@1@S@In comparison to other activators of NF-kappa B such as phorbol myristate acetate or tumor necrosis factor, we did not detect changes in the tyrosine phosphorylation status of I kappa B alpha following treatment with either of these agents.@@@@1@41@@oe@16-12-2010 813724308@GENIA Treebank@formal@@1@S@These results suggest that tyrosine phosphorylation of I kappa B alpha during hypoxia is an important proximal step which precedes its dissociation and degradation from NF-kappa B.@@@@1@28@@oe@16-12-2010 813904101@GENIA Treebank@formal@@1@S@A transcriptional regulatory element is associated with a nuclease-hypersensitive site in the pol gene of human immunodeficiency virus type 1.@@@@1@21@@oe@16-12-2010 813904102@GENIA Treebank@formal@@1@S@Analysis of the chromatin organization of the integrated human immunodeficiency virus type 1 (HIV-1) genome has previously revealed a major constitutive DNase I-hypersensitive site associated with the pol gene (E. Verdin, J. Virol. 65:6790-6799, 1991).@@@@1@47@@oe@16-12-2010 813904103@GENIA Treebank@formal@@1@S@In the present report, high-resolution mapping of this site with DNase I and micrococcal nuclease identified a nucleosome-free region centered around nucleotides (nt) 4490 to 4766.@@@@1@30@@oe@16-12-2010 813904104@GENIA Treebank@formal@@1@S@A 500-bp fragment encompassing this hypersensitive site (nt 4481 to 4982) exhibited transcription-enhancing activity (two- to threefold) when it was cloned in its natural position with respect to the HIV-1 promoter after transient transfection in U937 and CEM cells.@@@@1@44@@oe@16-12-2010 813904105@GENIA Treebank@formal@@1@S@Using in vitro footprinting and gel shift assays, we have identified four distinct binding sites for nuclear proteins within this positive regulatory element.@@@@1@25@@oe@16-12-2010 813904106@GENIA Treebank@formal@@1@S@Site B (nt 4519 to 4545) specifically bound four distinct nuclear protein complexes: a ubiquitous factor, a T-cell-specific factor, a B-cell-specific factor, and the monocyte/macrophage- and B-cell-specific transcription factor PU.1/Spi-1.@@@@1@37@@oe@16-12-2010 813904107@GENIA Treebank@formal@@1@S@In most HIV-1 isolates in which this PU box was not conserved, it was replaced by a binding site for the related factor Ets1.@@@@1@26@@oe@16-12-2010 813904108@GENIA Treebank@formal@@1@S@Factors binding to site C (nt 4681 to 4701) had a DNA-binding specificity similar to that of factors binding to site B, except for PU.1/Spi-1.@@@@1@29@@oe@16-12-2010 813904109@GENIA Treebank@formal@@1@S@A GC box containing a binding site for Sp1 was identified (nt 4623 to 4631).@@@@1@18@@oe@16-12-2010 813904110@GENIA Treebank@formal@@1@S@Site D (nt 4816 to 4851) specifically bound a ubiquitously expressed factor.@@@@1@15@@oe@16-12-2010 813904111@GENIA Treebank@formal@@1@S@These results identify a transcriptional regulatory element associated with a nuclease-hypersensitive site in the pol gene of HIV-1 and suggest that its activity may be controlled by a complex interplay of cis-regulatory elements.@@@@1@34@@oe@16-12-2010 814231801@GENIA Treebank@formal@@1@S@Androgen binding sites in peripheral human mononuclear leukocytes of healthy males and females.@@@@1@14@@oe@16-12-2010 814231802@GENIA Treebank@formal@@1@S@Androgen binding sites have been identified in circulating human mononuclear leukocytes of healthy donors of both sexes.@@@@1@18@@oe@16-12-2010 814231803@GENIA Treebank@formal@@1@S@Cells were separated from blood samples on a Ficoll gradient and incubated with different concentrations of [3H]testosterone in the presence or absence of a 400-fold excess of unlabelled testosterone.@@@@1@30@@oe@16-12-2010 814231804@GENIA Treebank@formal@@1@S@Binding data were derived from Scatchard analysis.@@@@1@8@@oe@16-12-2010 814231805@GENIA Treebank@formal@@1@S@The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the classic androgen receptors from genital skin fibroblast: in fertile adult males (n = 20) the binding sites showed (1) a high affinity for testosterone (1.32 +/- 0.49 nM; mean +/- SD), (2) a saturable capacity (184 +/- 52 binding sites per cell; mean +/- SD), and (3) a characteristic competitive binding profile for other steroid hormones (relative binding affinities: testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone, whereas aldosterone, 17-hydroxy-progesterone and cortisol did not compete appreciably).@@@@1@116@@oe@16-12-2010 814231806@GENIA Treebank@formal@@1@S@Furthermore the number of binding sites determined using [3H]dihydrotestosterone, [3H]RU-1881, or [3H]testosterone were comparable.@@@@1@17@@oe@16-12-2010 814231807@GENIA Treebank@formal@@1@S@This raises the possibility that androgen receptors in peripheral mononuclear leukocytes differ from those in genital skin fibroblasts.@@@@1@19@@oe@16-12-2010 814231808@GENIA Treebank@formal@@1@S@There was no apparent correlation between serum testosterone concentrations and androgen binding sites.@@@@1@14@@oe@16-12-2010 814231809@GENIA Treebank@formal@@1@S@In fertile women remarkable changes in androgen binding sites were seen in the course of the menstrual cycle, with a significant increase in the immediate preovulatory period.@@@@1@29@@oe@16-12-2010 814231810@GENIA Treebank@formal@@1@S@The presence of androgen receptors in peripheral mononuclear leukocytes provides for the first time the experimental basis for an hypothesis of direct, receptor-mediated effects of androgens on mature immunocompetent cells.@@@@1@32@@oe@16-12-2010 814231811@GENIA Treebank@formal@@1@S@The immunological implications of these results are discussed.@@@@1@9@@oe@16-12-2010 814309501@GENIA Treebank@formal@@1@S@Comparative mapping of SRY in the great apes.@@@@1@9@@oe@16-12-2010 814309502@GENIA Treebank@formal@@1@S@Cytogenetic studies of the primate Y chromosomes have suggested that extensive rearrangements have occurred during evolution of the great apes.@@@@1@21@@oe@16-12-2010 814309503@GENIA Treebank@formal@@1@S@We have used in situ hybridization to define these rearrangements at the molecular level.@@@@1@15@@oe@16-12-2010 814309504@GENIA Treebank@formal@@1@S@pHU-14, a probe including sequences from the sex determining gene SRY, hybridizes close to the early replicating pseudoautosomal segment in a telomeric or subtelomeric position of the Y chromosomes of all great apes.@@@@1@36@@oe@16-12-2010 814309505@GENIA Treebank@formal@@1@S@The low copy repeat detected by the probe Fr35-II is obviously included in Y chromosomal rearrangements during hominid evolution.@@@@1@20@@oe@16-12-2010 814309506@GENIA Treebank@formal@@1@S@These results, combined with previous studies, suggest that the Y chromosome in great apes has a conserved region including the pseudoautosomal region and the testis-determining region.@@@@1@29@@oe@16-12-2010 814309507@GENIA Treebank@formal@@1@S@The rest of the Y chromosome has undergone several rearrangements in the different great apes.@@@@1@16@@oe@16-12-2010 814412901@GENIA Treebank@formal@@1@S@Detection of minimal residual disease in a patient with acute promyelocytic leukemia by RT-PCR: necessity of chemotherapy following ATRA therapy.@@@@1@22@@oe@16-12-2010 814412902@GENIA Treebank@formal@@1@S@The PML/RAR alpha fusion gene resulting from the t (15;17) translocation is a specific marker for acute promyelocytic leukemia (APL).@@@@1@22@@oe@16-12-2010 814412903@GENIA Treebank@formal@@1@S@We examined bone marrow cells by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect residual PML/RAR alpha mRNA-containing cells following treatment with all-trans retinoic acid (ATRA) and cytotoxic chemotherapy in a patient with APL.@@@@1@38@@oe@16-12-2010 814412904@GENIA Treebank@formal@@1@S@This RT-PCR assay can detect one leukemic cell in 10(2) normal cells in vitro.@@@@1@15@@oe@16-12-2010 814412905@GENIA Treebank@formal@@1@S@We show that PML/RAR alpha mRNA was still detectable despite clinical remission following ATRA treatment, but undetectable following consolidation with chemotherapy.@@@@1@23@@oe@16-12-2010 814412906@GENIA Treebank@formal@@1@S@These data show that this technique is useful for the identification of minimal residual disease in patients with APL and that cytotoxic chemotherapy following ATRA therapy is required for the elimination of APL cells.@@@@1@35@@oe@16-12-2010 814487801@GENIA Treebank@formal@@1@S@Expression of v-src in T cells correlates with nuclear expression of NF-kappa B.@@@@1@14@@oe@16-12-2010 814487802@GENIA Treebank@formal@@1@S@NF-kappa B is a rapidly inducible transcriptional activator that responds to a variety of signals and influences the expression of many genes involved in the immune response.@@@@1@28@@oe@16-12-2010 814487803@GENIA Treebank@formal@@1@S@Protein tyrosine kinases transmit signals from cytokine and immune receptors.@@@@1@11@@oe@16-12-2010 814487804@GENIA Treebank@formal@@1@S@Very little information exists linking these two important classes of signaling molecules.@@@@1@13@@oe@16-12-2010 814487805@GENIA Treebank@formal@@1@S@We now demonstrate that v-src expression correlates with nuclear expression of a kappa B binding complex similar to that induced by phorbol ester and ionomycin, as detected by electrophoretic mobility shift assay using a variety of kappa B sites.@@@@1@41@@oe@16-12-2010 814487806@GENIA Treebank@formal@@1@S@This complex was blocked by the tyrosine kinase inhibitor, herbimycin A.@@@@1@13@@oe@16-12-2010 814487807@GENIA Treebank@formal@@1@S@The v-src-induced complex comprised the p50 and p65 components of NF-kappa B, as determined by supershift and immunoblot analysis.@@@@1@21@@oe@16-12-2010 814487808@GENIA Treebank@formal@@1@S@As a functional correlate of this finding, transient co-transfection of HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src activated this promoter in a kappa B-dependent manner.@@@@1@33@@oe@16-12-2010 814487809@GENIA Treebank@formal@@1@S@We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal, rather than the distal, kappa B element.@@@@1@28@@oe@16-12-2010 814487810@GENIA Treebank@formal@@1@S@The implications for T cell receptor signaling and HIV-1 gene expression are considered.@@@@1@14@@oe@16-12-2010 815178101@GENIA Treebank@formal@@1@S@Encephalomyocarditis virus internal ribosomal entry site RNA-protein interactions.@@@@1@9@@oe@16-12-2010 815178102@GENIA Treebank@formal@@1@S@Translational initiation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal entry into the 5' nontranslated region of the EMCV mRNA, rather than by ribosomal scanning.@@@@1@29@@oe@16-12-2010 815178103@GENIA Treebank@formal@@1@S@Internal ribosomal binding requires a cis-acting element termed the internal ribosomal entry site (IRES).@@@@1@17@@oe@16-12-2010 815178104@GENIA Treebank@formal@@1@S@IRES elements have been proposed to be involved in the translation of picornavirus mRNAs and some cellular mRNAs.@@@@1@19@@oe@16-12-2010 815178105@GENIA Treebank@formal@@1@S@Internal ribosome binding likely requires the interaction of trans-acting factors that recognize both the mRNA and the ribosomal complex.@@@@1@20@@oe@16-12-2010 815178106@GENIA Treebank@formal@@1@S@Five cellular proteins (p52, p57, p70, p72, and p100) cross-link the EMCV IRES or fragments of the IRES.@@@@1@25@@oe@16-12-2010 815178107@GENIA Treebank@formal@@1@S@For one of these proteins, p57, binding to the IRES correlates with translation.@@@@1@16@@oe@16-12-2010 815178108@GENIA Treebank@formal@@1@S@Recently, p57 was identified to be very similar, if not identical, to polypyrimidine tract-binding protein.@@@@1@19@@oe@16-12-2010 815178109@GENIA Treebank@formal@@1@S@On the basis of cross-linking results with 21 different EMCV IRES fragments and cytoplasmic HeLa extract or rabbit reticulocyte lysate as the source of polypeptides, consensus binding sites for p52, p57, p70, and p100 are proposed.@@@@1@41@@oe@16-12-2010 815178110@GENIA Treebank@formal@@1@S@It is suggested that each of these proteins recognizes primarily a structural feature of the RNA rather than a specific sequence.@@@@1@22@@oe@16-12-2010 815178601@GENIA Treebank@formal@@1@S@Human immunodeficiency virus type 1 Nef protein down-regulates transcription factors NF-kappa B and AP-1 in human T cells in vitro after T-cell receptor stimulation.@@@@1@25@@oe@16-12-2010 815178602@GENIA Treebank@formal@@1@S@Human immunodeficiency virus type 1 (HIV-1) negative factor (Nef) has been shown to down-regulate the transcription factors NF-kappa B and AP-1 in vitro.@@@@1@28@@oe@16-12-2010 815178603@GENIA Treebank@formal@@1@S@To define the mechanism of action of the Nef protein, the signal transduction pathways which may be affected in T cells by constitutive expression of the nef gene were examined.@@@@1@32@@oe@16-12-2010 815178604@GENIA Treebank@formal@@1@S@Stimulation of T cells with tumor necrosis factor, interleukin-1, or lipopolysaccharide resulted in the recruitment of transcriptional factors to a similar level whether or not the cells expressed the nef gene.@@@@1@34@@oe@16-12-2010 815178605@GENIA Treebank@formal@@1@S@On the other hand, stimulation of T cells by mitogens or antibodies to the T-cell receptor (TCR)-CD3 complex resulted in the down-regulation of transcriptional factors NF-kappa B and AP-1 in cells expressing the nef gene compared with cells not expressing the nef gene.@@@@1@48@@oe@16-12-2010 815178606@GENIA Treebank@formal@@1@S@Because the Nef protein does not affect the surface expression of the CD3-TCR complex, we conclude that the Nef protein down-regulates the transcriptional factors NF-kappa B and AP-1 in T cells in vitro through an effect on the TCR-dependent signal transduction pathway.@@@@1@44@@oe@16-12-2010 815766301@GENIA Treebank@formal@@1@S@Characterization of the human gene encoding LBR, an integral protein of the nuclear envelope inner membrane.@@@@1@18@@oe@16-12-2010 815766302@GENIA Treebank@formal@@1@S@We have characterized the human gene encoding LBR, an integral protein of the nuclear envelope inner membrane.@@@@1@19@@oe@16-12-2010 815766303@GENIA Treebank@formal@@1@S@Restriction mapping shows that the transcription unit spans approximately 35 kilobases.@@@@1@12@@oe@16-12-2010 815766304@GENIA Treebank@formal@@1@S@A transcription start site is located approximately 4 kilobases 5' to the translation initiation codon, and an RNA splice of 3863 bases occurs in the 5'-untranslated region to generate mature HeLa cell mRNA.@@@@1@35@@oe@16-12-2010 815766305@GENIA Treebank@formal@@1@S@5' to the identified transcription start site are two CCAAT sequences and potential recognition sites for several transcription factors including Sp1, AP-1, AP-2, and NF-kB.@@@@1@29@@oe@16-12-2010 815766306@GENIA Treebank@formal@@1@S@There are 13 protein coding exons in the LBR gene.@@@@1@11@@oe@16-12-2010 815766307@GENIA Treebank@formal@@1@S@LBR's nucleoplasmic domain is encoded by exons 1-4, and its hydrophobic domain, with eight putative transmembrane segments, is encoded by exons 5-13.@@@@1@27@@oe@16-12-2010 815766308@GENIA Treebank@formal@@1@S@The hydrophobic domain is homologous to three yeast polypeptides, suggesting that this higher eukaryotic gene could have evolved from recombination between a gene that encoded a soluble nuclear protein and a membrane protein gene similar to those in yeast.@@@@1@41@@oe@16-12-2010 815766309@GENIA Treebank@formal@@1@S@These results are the first to demonstrate the structural organization of a vertebrate gene encoding an integral membrane protein of the nuclear envelope that may be a member of a family of polypeptides conserved in evolution.@@@@1@37@@oe@16-12-2010 815795801@GENIA Treebank@formal@@1@S@Activation of a novel serine/threonine kinase that phosphorylates c-Fos upon stimulation of T and B lymphocytes via antigen and cytokine receptors.@@@@1@22@@oe@16-12-2010 815795802@GENIA Treebank@formal@@1@S@Ligation of Ag receptors in T and B lymphocytes initiates signal transduction cascades which alter the expression of genes that regulate cellular proliferation and differentiation.@@@@1@26@@oe@16-12-2010 815795803@GENIA Treebank@formal@@1@S@The transmission of signals from the membrane to the nucleus is mediated principally through the action of protein tyrosine and serine/threonine kinases.@@@@1@23@@oe@16-12-2010 815795804@GENIA Treebank@formal@@1@S@We have identified and characterized a novel serine/threonine kinase that phosphorylated the proto-oncogene product, c-Fos, and is termed Fos kinase.@@@@1@23@@oe@16-12-2010 815795805@GENIA Treebank@formal@@1@S@Fos kinase was rapidly activated after ligation of the CD3 and CD2 receptors in Jurkat and normal human T lymphocytes and in response to IL-6 and anti-IgM in the human B cell lines AF10 and Ramos, respectively.@@@@1@39@@oe@16-12-2010 815795806@GENIA Treebank@formal@@1@S@The phorbol ester, PMA, was also a potent inducer of Fos kinase activity in all of the above populations, suggesting that PKC plays a role in the regulation of this enzyme.@@@@1@35@@oe@16-12-2010 815795807@GENIA Treebank@formal@@1@S@Fos kinase phosphorylates c-Fos at a site near the C-terminus, as well as a peptide derived from this region (residues 359-370, RKGSSSNEPSSD), and Fos peptide competitively inhibited c-Fos phosphorylation.@@@@1@35@@oe@16-12-2010 815795808@GENIA Treebank@formal@@1@S@Fos kinase was shown to be distinct from other identified serine/threonine kinases, including protein kinase A, protein kinase C, casein kinase II, MAP kinases, p70S6K and p90RSK.@@@@1@33@@oe@16-12-2010 815795809@GENIA Treebank@formal@@1@S@Fos kinase was purified by anion exchange chromatography and exhibited an apparent M(r) = 65,000 and isoelectric point = 6.1.@@@@1@21@@oe@16-12-2010 815795810@GENIA Treebank@formal@@1@S@Fos kinase may play a role in transcriptional regulation through its capacity to phosphorylate c-Fos at a site required for expression of the transcriptional transrepressive activity of this molecule.@@@@1@30@@oe@16-12-2010 815795811@GENIA Treebank@formal@@1@S@Moreover, its rapid activation suggests it may have a wider role within signal transduction cascades in lymphocytes.@@@@1@19@@oe@16-12-2010 815812201@GENIA Treebank@formal@@1@S@Activation of nuclear factor kappa B in human neuroblastoma cell lines.@@@@1@12@@oe@16-12-2010 815812202@GENIA Treebank@formal@@1@S@The nuclear factor kappa B (NF-kappa B) is a eukaryotic transcription factor.@@@@1@15@@oe@16-12-2010 815812203@GENIA Treebank@formal@@1@S@In B cells and macrophages it is constitutively present in cell nuclei, whereas in many other cell types, NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha (TNF alpha), phorbol ester, and other polyclonal signals.@@@@1@50@@oe@16-12-2010 815812204@GENIA Treebank@formal@@1@S@Using neuroblastoma cell lines as models, we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment.@@@@1@33@@oe@16-12-2010 815812205@GENIA Treebank@formal@@1@S@The TNF alpha-activated NF-kappa B was transcriptionally functional.@@@@1@9@@oe@16-12-2010 815812206@GENIA Treebank@formal@@1@S@NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation.@@@@1@15@@oe@16-12-2010 815812207@GENIA Treebank@formal@@1@S@However, reagents such as nerve growth factor (NGF) and the phorbol ester phorbol 12-myristate 13-acetate (PMA), which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line, activated NF-kappa B, but only in that particular cell line.@@@@1@45@@oe@16-12-2010 815812208@GENIA Treebank@formal@@1@S@In a NGF-responsive rat pheochromocytoma cell line, PC12, PMA activated NF-kappa B, whereas NGF did not.@@@@1@20@@oe@16-12-2010 815812209@GENIA Treebank@formal@@1@S@In other neuroblastoma cell lines, such as SK-N-Be(2), the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation.@@@@1@27@@oe@16-12-2010 815812210@GENIA Treebank@formal@@1@S@We found, moreover, that in SK-N-Be(2) cells protein kinase C (PKC) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression.@@@@1@43@@oe@16-12-2010 815812211@GENIA Treebank@formal@@1@S@NF-kappa B was not activated by retinoic acid, which induced morphological differentiation of all the neuroblastoma cell lines used in the present study.@@@@1@25@@oe@16-12-2010 815812212@GENIA Treebank@formal@@1@S@Thus, NF-kappa B activation was not required for neuroblastoma cell differentiation.@@@@1@13@@oe@16-12-2010 815812213@GENIA Treebank@formal@@1@S@Furthermore, the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation.@@@@1@22@@oe@16-12-2010 816205201@GENIA Treebank@formal@@1@S@Genes encoding general initiation factors for RNA polymerase II transcription are dispersed in the human genome.@@@@1@17@@oe@16-12-2010 816205202@GENIA Treebank@formal@@1@S@General transcription factors are required for accurate initiation of transcription by RNA polymerase II.@@@@1@15@@oe@16-12-2010 816205203@GENIA Treebank@formal@@1@S@Human cDNAs encoding subunits of these factors have been cloned and sequenced.@@@@1@13@@oe@16-12-2010 816205204@GENIA Treebank@formal@@1@S@Using fluorescence in situ hybridization (FISH), we show here that the genes encoding the TATA-box binding protein (TBP), TFIIB, TFIIE alpha, TFIIE beta, RAP30, RAP74 and the 62 kDa subunit, of TFIIH are located at the human chromosomal bands 6q26-27, 1p21-22, 3q21-24, 8p12, 13q14, 19p13.3 and 11p14-15.1, respectively.@@@@1@66@@oe@16-12-2010 816205205@GENIA Treebank@formal@@1@S@This dispersed localization of a group of functionally related gene provides insights into the molecular mechanism of human genome evolution and their possible involvement in human diseases.@@@@1@28@@oe@16-12-2010 816346401@GENIA Treebank@formal@@1@S@A novel heterodimerization partner for thyroid hormone receptor.@@@@1@9@@oe@16-12-2010 816346402@GENIA Treebank@formal@@1@S@Peroxisome proliferator-activated receptor.@@@@1@4@@oe@16-12-2010 816346403@GENIA Treebank@formal@@1@S@Retinoid-like receptors play a central role in hormonal responses by forming heterodimers with other nuclear hormone receptors.@@@@1@18@@oe@16-12-2010 816346404@GENIA Treebank@formal@@1@S@In this study we have identified the peroxisome proliferator-activated receptor (PPAR) as a new thyroid hormone receptor (THR) auxiliary nuclear protein, heterodimerizing with THR in solution.@@@@1@32@@oe@16-12-2010 816346405@GENIA Treebank@formal@@1@S@Although these heterodimers do not recognize a classical thyroid hormone response element (TRE) characterized by direct repeat separated by four nucleotides (DR+4), PPAR behaves as a dominant negative regulator of thyroid hormone (TH) action.@@@@1@42@@oe@16-12-2010 816346406@GENIA Treebank@formal@@1@S@However, a TH-dependent positive effect is elicited by selective interaction of the THR beta-PPAR but not the THR alpha-PPAR heterodimer with a novel TRE (DR+2).@@@@1@29@@oe@16-12-2010 816346407@GENIA Treebank@formal@@1@S@The critical region of THR beta was mapped to 3 amino acids in the distal box of the DNA binding domain.@@@@1@22@@oe@16-12-2010 816346408@GENIA Treebank@formal@@1@S@Hence, PPAR can positively or negatively influence TH action depending on TRE structure and THR isotype.@@@@1@18@@oe@16-12-2010 816365801@GENIA Treebank@formal@@1@S@Hypoxic induction of interleukin-8 gene expression in human endothelial cells.@@@@1@11@@oe@16-12-2010 816365802@GENIA Treebank@formal@@1@S@Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue.@@@@1@28@@oe@16-12-2010 816365803@GENIA Treebank@formal@@1@S@Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8.@@@@1@44@@oe@16-12-2010 816365804@GENIA Treebank@formal@@1@S@Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays.@@@@1@34@@oe@16-12-2010 816365805@GENIA Treebank@formal@@1@S@Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines.@@@@1@28@@oe@16-12-2010 816365806@GENIA Treebank@formal@@1@S@IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site.@@@@1@23@@oe@16-12-2010 816365807@GENIA Treebank@formal@@1@S@Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls.@@@@1@21@@oe@16-12-2010 816365808@GENIA Treebank@formal@@1@S@In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates.@@@@1@28@@oe@16-12-2010 816365809@GENIA Treebank@formal@@1@S@In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue.@@@@1@28@@oe@16-12-2010 816365810@GENIA Treebank@formal@@1@S@Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis.@@@@1@18@@oe@16-12-2010 816465201@GENIA Treebank@formal@@1@S@Function of NF-kappa B/Rel binding sites in the major histocompatibility complex class II invariant chain promoter is dependent on cell-specific binding of different NF-kappa B/Rel subunits.@@@@1@27@@oe@16-12-2010 816465202@GENIA Treebank@formal@@1@S@The promoter of the human major histocompatibility complex class II-associated invariant-chain gene (Ii) contains two NF-kappa B/Rel binding sites located at -109 to -118 (Ii kappa B-1) and -163 to -172 (Ii kappa B-2) from the transcription start site.@@@@1@46@@oe@16-12-2010 816465203@GENIA Treebank@formal@@1@S@We report here that the differential function of each of these NF-kappa B/Rel sites in several distinct cell types depends on cell-specific binding of NF-kappa B/Rel transcription factors.@@@@1@29@@oe@16-12-2010 816465204@GENIA Treebank@formal@@1@S@Ii kappa B-1 is a positive regulatory element in B-cell lines and in the Ii-expressing T-cell line, H9, but acts as a negative regulatory element in myelomonocytic and glia cell lines.@@@@1@34@@oe@16-12-2010 816465205@GENIA Treebank@formal@@1@S@In vivo protein-DNA contacts are detectable at Ii kappa B-1 in cell lines in which this site is functional as either a positive or negative regulator.@@@@1@27@@oe@16-12-2010 816465206@GENIA Treebank@formal@@1@S@Electrophoretic mobility supershift assays determine that members of the NF-kappa B/Rel family of transcription factors can bind to this site in vitro and that DNA-binding complexes that contain p50, p52, p65, and cRel correlate with positive regulation whereas the presence of p50 correlates with negative regulation.@@@@1@50@@oe@16-12-2010 816465207@GENIA Treebank@formal@@1@S@Ii kappa B-2 is a site of positive regulation in B-cell lines and a site of negative regulation in H9 T cells, myelomonocytic, and glial cell lines.@@@@1@30@@oe@16-12-2010 816465208@GENIA Treebank@formal@@1@S@In vivo occupancy of this site is observed only in the H9 T-cell line.@@@@1@15@@oe@16-12-2010 816465209@GENIA Treebank@formal@@1@S@Again, in vitro supershift studies indicate that the presence of p50, p52, p65, and cRel correlates with positive function whereas the presence of only p50 and p52 correlates with negative function.@@@@1@36@@oe@16-12-2010 816465210@GENIA Treebank@formal@@1@S@This differential binding of specific NF-kappa B/Rel subunits is likely to mediate the disparate functions of these two NF-kappa B/Rel binding sites.@@@@1@23@@oe@16-12-2010 816466601@GENIA Treebank@formal@@1@S@Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells.@@@@1@13@@oe@16-12-2010 816466602@GENIA Treebank@formal@@1@S@The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages.@@@@1@23@@oe@16-12-2010 816466603@GENIA Treebank@formal@@1@S@GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes.@@@@1@17@@oe@16-12-2010 816466604@GENIA Treebank@formal@@1@S@Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation.@@@@1@25@@oe@16-12-2010 816466605@GENIA Treebank@formal@@1@S@Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development.@@@@1@19@@oe@16-12-2010 816466606@GENIA Treebank@formal@@1@S@Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription.@@@@1@22@@oe@16-12-2010 816466607@GENIA Treebank@formal@@1@S@To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei.@@@@1@41@@oe@16-12-2010 816466608@GENIA Treebank@formal@@1@S@We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells.@@@@1@35@@oe@16-12-2010 816466609@GENIA Treebank@formal@@1@S@Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion.@@@@1@37@@oe@16-12-2010 817047601@GENIA Treebank@formal@@1@S@Patterns of Pan expression and role of Pan proteins in endocrine cell type-specific complex formation.@@@@1@16@@oe@16-12-2010 817047602@GENIA Treebank@formal@@1@S@The Pan gene encodes at least two distinct transcripts, Pan-1 and Pan-2 (also known as E47 and E12, respectively), by the mechanism of alternative RNA splicing.@@@@1@32@@oe@16-12-2010 817047603@GENIA Treebank@formal@@1@S@Northern blot analyses performed on rat and mouse tissues have detected ubiquitously expressed Pan transcripts, but the abundance, distribution, and form of Pan proteins have not been clearly defined.@@@@1@33@@oe@16-12-2010 817047604@GENIA Treebank@formal@@1@S@Studies of cell lines representing endocrine, fibroblast, and lymphoid lineages using polyclonal antisera to detect E2A proteins have suggested that significant E2A protein expression is restricted to B-lymphocytes.@@@@1@31@@oe@16-12-2010 817047605@GENIA Treebank@formal@@1@S@We have developed a monoclonal antibody, Yae, which is specific for Pan/E2A proteins, and have used the Yae antibody to examine a variety of endocrine and nonendocrine cell lineages for differences in Pan/E2A protein expression, subcellular localization, and heteromeric complex formation.@@@@1@47@@oe@16-12-2010 817047606@GENIA Treebank@formal@@1@S@In contrast to previous results obtained using polyclonal antiseras to detect Pan/E2A proteins, we report comparable levels of Pan proteins in GH/PRL- and insulin-producing, B- and T-lymphocyte cells.@@@@1@31@@oe@16-12-2010 817047607@GENIA Treebank@formal@@1@S@IEF-1, a pancreatic beta-cell type-specific complex believed to regulate insulin expression, is demonstrated to consist of at least two distinct species, one of which does not contain Pan molecules.@@@@1@33@@oe@16-12-2010 817047608@GENIA Treebank@formal@@1@S@Although it has been postulated that pituitary endocrine cells and pancreatic endocrine beta-cells share identical Pan/E2A complexes, native-Western analyses of pituitary and endocrine beta-cells detect Pan proteins in distinct cell type-specific complexes.@@@@1@34@@oe@16-12-2010 817577501@GENIA Treebank@formal@@1@S@Functional block for 1 alpha,25-dihydroxyvitamin D3-mediated gene regulation in human B lymphocytes.@@@@1@13@@oe@16-12-2010 817577502@GENIA Treebank@formal@@1@S@Elements necessary for the steroid hormone 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) to induce a biological response include the presence of specific intracellular receptors (vitamin D3 receptors (VDR)) and modulation of gene expression via hormone-activated receptor binding to regulatory regions of target genes.@@@@1@49@@oe@16-12-2010 817577503@GENIA Treebank@formal@@1@S@These parameters were examined in normal and Epstein-Barr virus-immortalized human B cells and compared with 1 alpha,25-(OH)2D3-responsive cells of the T and monocytic lineages.@@@@1@25@@oe@16-12-2010 817577504@GENIA Treebank@formal@@1@S@Although resting tonsillar B cells did not express VDR mRNA, activation of these cells with interleukin-4 induced VDR in the absence of exogenously supplemented 1 alpha,25-(OH)2D3.@@@@1@28@@oe@16-12-2010 817577505@GENIA Treebank@formal@@1@S@As indicators of hormone-mediated gene regulation we analyzed modulation of CD23, a common B cell/monocyte surface antigen, and 24-hydroxylase.@@@@1@22@@oe@16-12-2010 817577506@GENIA Treebank@formal@@1@S@1 alpha,25-(OH)2D3 inhibited CD23 expression in U937 cells, yet failed to modulate CD23 expression in B cells.@@@@1@19@@oe@16-12-2010 817577507@GENIA Treebank@formal@@1@S@Furthermore, 1 alpha,25-(OH)2D3 induced 24-hydroxylase mRNA expression and metabolic activity in both U937 cells and lectin-activated T cells, yet failed to induce 24-hydroxylase mRNA or its metabolic activity in B cells.@@@@1@34@@oe@16-12-2010 817577508@GENIA Treebank@formal@@1@S@These findings suggest that although human B lymphocytes can express VDR mRNA and protein, they exhibit a functional block for vitamin D-dependent gene regulation.@@@@1@26@@oe@16-12-2010 817589401@GENIA Treebank@formal@@1@S@Interferon alpha selectively affects expression of the human myeloid cell nuclear differentiation antigen in late stage cells in the monocytic but not the granulocytic lineage.@@@@1@26@@oe@16-12-2010 817589402@GENIA Treebank@formal@@1@S@The human myeloid cell nuclear differentiation antigen (MNDA) is expressed constitutively in cells of the myeloid lineage, appearing in myeloblast cells in some cases of acute myeloid leukemia and consistently being detected in promyelocyte stage cells as well as in all later stage cells including peripheral blood monocytes and granulocytes.@@@@1@54@@oe@16-12-2010 817589403@GENIA Treebank@formal@@1@S@The human myeloid leukemia cell lines, HL-60, U937, and THP-1, express similar levels of immunochemically detectable MNDA.@@@@1@22@@oe@16-12-2010 817589404@GENIA Treebank@formal@@1@S@Although, the level of MNDA mRNA in primary monocytes is very low it was up-regulated at 6 h following the addition of interferon alpha.@@@@1@26@@oe@16-12-2010 817589405@GENIA Treebank@formal@@1@S@The effect of interferon alpha on the MNDA mRNA is also observed in the cell lines HL-60, U937, and THP-1.@@@@1@23@@oe@16-12-2010 817589406@GENIA Treebank@formal@@1@S@The MNDA mRNA level in primary granulocytes was unaffected by addition of interferon alpha and other agents including interferon gamma, endotoxin, poly (I).poly (C), and FMLP.@@@@1@28@@oe@16-12-2010 817589407@GENIA Treebank@formal@@1@S@The MNDA mRNA level in the myeloid cell lines was also unaffected by the latter four agents.@@@@1@18@@oe@16-12-2010 817589408@GENIA Treebank@formal@@1@S@Induction of differentiation in the myeloid cell lines with phorbol ester induces monocyte differentiation which was accompanied by a decrease in MNDA mRNA level.@@@@1@25@@oe@16-12-2010 817589409@GENIA Treebank@formal@@1@S@This reduced level of mRNA could then be elevated with subsequent interferon alpha treatment.@@@@1@15@@oe@16-12-2010 817589410@GENIA Treebank@formal@@1@S@The effects of phorbol ester on MNDA mRNA appeared to be associated with induced differentiation since inhibiting cell proliferation did not alter the level of MNDA mRNA and cell cycle variation in MNDA mRNA levels were not observed.@@@@1@39@@oe@16-12-2010 817589411@GENIA Treebank@formal@@1@S@The ability of interferon alpha to up-regulate MNDA mRNA in phorbol ester treated myeloid cell lines is consistent with the observations made in primary monocytes.@@@@1@26@@oe@16-12-2010 817589412@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 817959401@GENIA Treebank@formal@@1@S@Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos.@@@@1@13@@oe@16-12-2010 817959402@GENIA Treebank@formal@@1@S@The transcription factor AP-1 is an important human mediator of the cellular response to serum, growth factors, and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate (TPA).@@@@1@30@@oe@16-12-2010 817959403@GENIA Treebank@formal@@1@S@The AP-1 complex consists of distinct protein heterodimers encoded by the proto-oncogene c-fos and c-jun mRNA whose gene expression can be induced by TPA, cyclic AMP and growth factors.@@@@1@31@@oe@16-12-2010 817959404@GENIA Treebank@formal@@1@S@Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and protein kinase C leading to expression of c-fos and c-jun mRNA.@@@@1@27@@oe@16-12-2010 817959405@GENIA Treebank@formal@@1@S@To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid (natural thiol antioxidants) on the expression of c-fos mRNA in human Jurkat T cells.@@@@1@35@@oe@16-12-2010 817959406@GENIA Treebank@formal@@1@S@When cells were preincubated with dihydrolipoic acid (0.2 mM) the expression of c-fos mRNA was suppressed at 30 min after stimulation of TPA (0.5 microM) whereas in the case of preincubation of alpha-lipoic acid (0.2 microM), the expression was enhanced at 30 min.@@@@1@51@@oe@16-12-2010 817959407@GENIA Treebank@formal@@1@S@These studies support the idea that superoxide anion radical plays a role in the expression of c-fos mRNA.@@@@1@19@@oe@16-12-2010 818292201@GENIA Treebank@formal@@1@S@Induction of proto-oncogene and cytokine expression in human peripheral blood monocytes and the monocytic cell line THP-1 after stimulation with mycoplasma-derived material MDHM.@@@@1@24@@oe@16-12-2010 818292202@GENIA Treebank@formal@@1@S@Mycoplasma fermentans-derived high-molecular-weight material (MDHM) was originally described to induce differentiation of murine thymocytes to cytolytic effector T-cells by stimulating IL-6 release from adherent cells.@@@@1@28@@oe@16-12-2010 818292203@GENIA Treebank@formal@@1@S@This study shows that human peripheral blood monocytes (PBMo) also respond to MDHM with increases in IL-1 beta, IL-6 and TNF alpha expression, both at the mRNA and protein level.@@@@1@35@@oe@16-12-2010 818292204@GENIA Treebank@formal@@1@S@The induced expression of IL-1 beta and TNF alpha mRNA in the monocytic THP-1 cell line increased as quickly as in primary cells.@@@@1@24@@oe@16-12-2010 818292205@GENIA Treebank@formal@@1@S@In contrast to PBMo, THP-1 and 14 other monocytic/myeloid leukemia-derived cell lines did not secrete measurable amounts of the cytokines upon treatment with MDHM.@@@@1@26@@oe@16-12-2010 818292206@GENIA Treebank@formal@@1@S@IL-1 beta and IL-6 genes contain AP-1 binding sites as regulatory elements, the AP-1 protein being composed of c-jun and c-fos gene products.@@@@1@25@@oe@16-12-2010 818292207@GENIA Treebank@formal@@1@S@In THP-1 cells c-jun mRNA expression increased after incubation with MDHM while positive c-fos expression remained unaffected.@@@@1@18@@oe@16-12-2010 818292208@GENIA Treebank@formal@@1@S@Although these data suggest AP-1 regulated cytokine mRNA expression, results from PBMo are not in accordance with this notion.@@@@1@21@@oe@16-12-2010 818292209@GENIA Treebank@formal@@1@S@In the primary cells MDHM-induced elevation of cytokine mRNA levels was preceded by a downregulation of c-fos expression while positive c-jun expression was not modulated.@@@@1@26@@oe@16-12-2010 818292210@GENIA Treebank@formal@@1@S@c-myc mRNA expression, constitutively high in THP-1 cells, was induced in MDHM-stimulated PBMo.@@@@1@16@@oe@16-12-2010 818292211@GENIA Treebank@formal@@1@S@In conclusion, MDHM-stimulated induction of cytokine mRNA expression was accompanied by different proto-oncogene responses in PBMo and THP-1 cells.@@@@1@21@@oe@16-12-2010 818292212@GENIA Treebank@formal@@1@S@These differences may represent different regulatory pathways of the two cell systems.@@@@1@13@@oe@16-12-2010 818292213@GENIA Treebank@formal@@1@S@Alternatively, these data support the notion that neither AP-1 nor the c-myc protein are involved in the MDHM-induced increase in IL-1 beta, IL-6 or TNF alpha mRNA levels.@@@@1@31@@oe@16-12-2010 818292214@GENIA Treebank@formal@@1@S@Furthermore, the present results demonstrate clearly that mycoplasma products can have a profound impact on the activation status of eukaryotic cells.@@@@1@23@@oe@16-12-2010 818293801@GENIA Treebank@formal@@1@S@All-trans retinoic acid and 1 alpha,25-dihydroxyvitamin D3 co-operate to promote differentiation of the human promyeloid leukemia cell line HL60 to monocytes.@@@@1@22@@oe@16-12-2010 818293802@GENIA Treebank@formal@@1@S@A basis for differentiation therapy of leukemias is provided by knowledge of agents which induce specific lineage maturation.@@@@1@19@@oe@16-12-2010 818293803@GENIA Treebank@formal@@1@S@All-trans retinoic acid (RA) induces differentiation of HL60 cells to neutrophils and is used to treat acute promyelocytic leukemia.@@@@1@22@@oe@16-12-2010 818293804@GENIA Treebank@formal@@1@S@We observed that RA did not induced neutrophil differentiation in serum-free grown HL60 cells whereas 50 nM 1 alpha,25-dihydroxyvitamin D3 (D3) induced maximal monocyte differentiation.@@@@1@28@@oe@16-12-2010 818293805@GENIA Treebank@formal@@1@S@Increasing RA concentrations reduced the D3 concentration required for monocyte differentiation.@@@@1@12@@oe@16-12-2010 818293806@GENIA Treebank@formal@@1@S@Cells treated with 5 nM D3 showed little response, but differentiated maximally with 5 nM D3 and 10 nM RA.@@@@1@22@@oe@16-12-2010 818293807@GENIA Treebank@formal@@1@S@The D3 analogs MC903, EB1089 and KH1060 were more potent inducers of monocyte differentiation.@@@@1@16@@oe@16-12-2010 818293808@GENIA Treebank@formal@@1@S@The extent to which analog activity was increased after cotreatment with RA was inversely related to potency.@@@@1@18@@oe@16-12-2010 818293809@GENIA Treebank@formal@@1@S@Twenty-four hour treatment with 10 nM RA primed cells for response to 5 nM D3; the reverse sequence being ineffective.@@@@1@22@@oe@16-12-2010 818293810@GENIA Treebank@formal@@1@S@Priming with 10 nM RA, or subsequent treatment with D3 (5 nM), did not alter expression of mRNAs encoding receptors for D3 (VDR), RA (RAR alpha) or 9-CIS RA (RXR alpha, beta, gamma).@@@@1@47@@oe@16-12-2010 818293811@GENIA Treebank@formal@@1@S@That RA promotes both neutrophil and monocyte differentiation has implications for the use of RA and D3 in treatment of leukemias and provides insight into mechanisms whereby RAR, VDR and RXR facilitate monocyte differentiation.@@@@1@36@@oe@16-12-2010 818391501@GENIA Treebank@formal@@1@S@Alternative splicing of RNA transcripts encoded by the murine p105 NF-kappa B gene generates I kappa B gamma isoforms with different inhibitory activities.@@@@1@24@@oe@16-12-2010 818391502@GENIA Treebank@formal@@1@S@The gene encoding the 105-kDa protein (p105) precursor of the p50 subunit of transcription factor NF-kappa B also encodes a p70 I kappa B protein, I kappa B gamma, which is identical to the C-terminal 607 amino acids of p105.@@@@1@45@@oe@16-12-2010 818391503@GENIA Treebank@formal@@1@S@Here we show that alternative RNA splicing generates I kappa B gamma isoforms with properties different from those of p70.@@@@1@21@@oe@16-12-2010 818391504@GENIA Treebank@formal@@1@S@One 63-kDa isoform, termed I kappa B gamma-1, which lacks 59 amino acids C-terminal to ankyrin repeat 7, has a novel 35-amino acid C terminus encoded by an alternative reading frame of the p105 gene.@@@@1@39@@oe@16-12-2010 818391505@GENIA Treebank@formal@@1@S@A 55-kDa isoform, I kappa B gamma-2, lacks the 190 C-terminal amino acids of p70I kappa B gamma.@@@@1@21@@oe@16-12-2010 818391506@GENIA Treebank@formal@@1@S@In contrast to p70I kappa B gamma, which is a cytoplasmic protein, I kappa B gamma-1 is found in both the cytoplasm and nucleus, whereas I kappa B gamma-2 is predominantly nuclear.@@@@1@36@@oe@16-12-2010 818391507@GENIA Treebank@formal@@1@S@The I kappa B gamma isoforms also display differences in specificity and affinity for Rel/NF-kappa B proteins.@@@@1@18@@oe@16-12-2010 818391508@GENIA Treebank@formal@@1@S@While p70I kappa B gamma inhibits p50-, p65-, and c-Rel-mediated transactivation and/or DNA binding, both I kappa B gamma-1 and I kappa B gamma-2 are specific for p50 and have different affinities for this subunit.@@@@1@39@@oe@16-12-2010 818391509@GENIA Treebank@formal@@1@S@The absence in I kappa B gamma-1 and I kappa B gamma-2 of a protein kinase A site whose phosphorylation modulates p70I kappa B gamma inhibitory activity suggests that alternative RNA splicing may be used to generate I kappa B gamma isoforms that respond differently to intracellular signals.@@@@1@49@@oe@16-12-2010 818401101@GENIA Treebank@formal@@1@S@Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation.@@@@1@15@@oe@16-12-2010 818401102@GENIA Treebank@formal@@1@S@Nuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor which is involved in the transcriptional regulation of several specific genes.@@@@1@25@@oe@16-12-2010 818401103@GENIA Treebank@formal@@1@S@Recent reports demonstrated that ionizing radiation in the dose range of 2-50 Gy results in expression of NF-kappa B in human KG-1 myeloid leukemia cells and human B-lymphocyte precursor cells; the precise mechanism involved and the significance are not yet known.@@@@1@43@@oe@16-12-2010 818401104@GENIA Treebank@formal@@1@S@The present report demonstrates that even lower doses of ionizing radiation, 0.25-2.0 Gy, are capable of inducing expression of NF-kappa B in EBV-transformed 244B human lymphoblastoid cells.@@@@1@30@@oe@16-12-2010 818401105@GENIA Treebank@formal@@1@S@These results are in a dose range where the viability of the cells remains very high.@@@@1@17@@oe@16-12-2010 818401106@GENIA Treebank@formal@@1@S@After exposure to 137Cs gamma rays at a dose rate of 1.17 Gy/min, a maximum in expression of NF-kappa B was seen at 8 h after a 0.5-Gy exposure.@@@@1@31@@oe@16-12-2010 818401107@GENIA Treebank@formal@@1@S@Time-course studies revealed a biphasic time-dependent expression after 0.5-, 1- and 2-Gy exposures.@@@@1@15@@oe@16-12-2010 818401108@GENIA Treebank@formal@@1@S@However, for each time examined, the expression of NF-kappa B was maximum after the 0.5-Gy exposure.@@@@1@19@@oe@16-12-2010 818401109@GENIA Treebank@formal@@1@S@The expression of the p50 and p65 NF-kappa B subunits was also shown to be regulated differentially after exposures to 1.0 and 2.0 Gy.@@@@1@25@@oe@16-12-2010 818619201@GENIA Treebank@formal@@1@S@Some antioxidants inhibit, in a co-ordinate fashion, the production of tumor necrosis factor-alpha, IL-beta, and IL-6 by human peripheral blood mononuclear cells.@@@@1@27@@oe@16-12-2010 818619202@GENIA Treebank@formal@@1@S@Some antioxidants, including butylated hydroxyanisole (BHA), tetrahydropapaveroline (THP), nordihydroguiauretic acid, and 10,11-dihydroxyaporphine (DHA), were found to be potent inhibitors of the production of tumor necrosis factor (TNF)-alpha, IL-1 beta, and IL-6 by human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS) (IC50s in the low micromolar range).@@@@1@71@@oe@16-12-2010 818619203@GENIA Treebank@formal@@1@S@Inhibition of cytokine production was gene selective and not due to general effects on protein synthesis.@@@@1@17@@oe@16-12-2010 818619204@GENIA Treebank@formal@@1@S@Inhibition of cytokine production by PBMC was observed also when other inducers were used (staphylococci, silica, zymosan).@@@@1@22@@oe@16-12-2010 818619205@GENIA Treebank@formal@@1@S@Much higher concentrations of other antioxidants--including ascorbic acid, trolox, alpha-tocopherol, butylated hydroxytoluene, and the 5-lipoxygenase inhibitor zileuton--did not affect the production of these cytokines.@@@@1@33@@oe@16-12-2010 818619206@GENIA Treebank@formal@@1@S@The active compounds did not inhibit IL-1-induced production of IL-6 in fibroblasts, showing the cell selectivity of the effect.@@@@1@21@@oe@16-12-2010 818619207@GENIA Treebank@formal@@1@S@Antioxidant-mediated inhibition of cytokine production was correlated with low levels of the corresponding messenger RNAs.@@@@1@16@@oe@16-12-2010 818619208@GENIA Treebank@formal@@1@S@Nuclear run-on experiments showed that THP inhibited transcription of the IL-1 beta gene.@@@@1@14@@oe@16-12-2010 818619209@GENIA Treebank@formal@@1@S@THP decreased the concentration of the transcription factors NF-kappa B and AP-1 detected in nuclear extracts of PBMC cultured in the presence or absence of LPS.@@@@1@27@@oe@16-12-2010 818619210@GENIA Treebank@formal@@1@S@THP and DHA markedly decreased the levels of TNF-alpha and IL-1 beta in the circulation of mice following LPS injection.@@@@1@21@@oe@16-12-2010 818619211@GENIA Treebank@formal@@1@S@Thus antioxidants vary widely in potency as inhibitors of the activation of transcription factors and of the transcription of genes for pro-inflammatory cytokines.@@@@1@24@@oe@16-12-2010 818619212@GENIA Treebank@formal@@1@S@Coordinate inhibition of the transcription of genes for inflammatory cytokines could provide a strategy for therapy of diseases with inflammatory pathogenesis and for septic shock.@@@@1@26@@oe@16-12-2010 818646101@GENIA Treebank@formal@@1@S@Calcineurin potentiates activation of the granulocyte-macrophage colony-stimulating factor gene in T cells: involvement of the conserved lymphokine element 0.@@@@1@21@@oe@16-12-2010 818646102@GENIA Treebank@formal@@1@S@Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) are produced by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in human T cell leukemia Jurkat cells.@@@@1@35@@oe@16-12-2010 818646103@GENIA Treebank@formal@@1@S@The expression of GM-CSF and IL-2 is inhibited by immunosuppressive drugs such as cyclosporin A (CsA) and FK506.@@@@1@21@@oe@16-12-2010 818646104@GENIA Treebank@formal@@1@S@Earlier studies on the IL-2 gene expression showed that overexpression of calcineurin (CN), a Ca2+/calmodulin-dependent protein phosphatase, can stimulate transcription from the IL-2 promoter through the NF-AT-binding site.@@@@1@33@@oe@16-12-2010 818646105@GENIA Treebank@formal@@1@S@In this study, we obtained evidence that transfection of the cDNAs for CN A (catalytic) and CN B (regulatory) subunits also augments transcription from the GM-CSF promoter and recovers the transcription inhibited by CsA.@@@@1@40@@oe@16-12-2010 818646106@GENIA Treebank@formal@@1@S@The constitutively active type of the CN A subunit, which lacks the auto-inhibitory and calmodulin-binding domains, acts in synergy with PMA to activate transcription from the GM-CSF promoter.@@@@1@31@@oe@16-12-2010 818646107@GENIA Treebank@formal@@1@S@We also found that the active CN partially replaces calcium ionophore in synergy with PMA to induce expression of endogenous GM-CSF and IL-2.@@@@1@24@@oe@16-12-2010 818646108@GENIA Treebank@formal@@1@S@By multimerizing the regulatory elements of the GM-CSF promoter, we found that one of the target sites for the CN action is the conserved lymphokine element 0 (CLE0), located at positions between -54 and -40.@@@@1@40@@oe@16-12-2010 818646109@GENIA Treebank@formal@@1@S@Mobility shift assays showed that the CLE0 sequence has an AP1-binding site and is associated with an NF-AT-like factor, termed NF-CLE0 gamma.@@@@1@24@@oe@16-12-2010 818646110@GENIA Treebank@formal@@1@S@NF-CLE0 gamma binding is induced by PMA/A23187 and is inhibited by treatment with CsA.@@@@1@15@@oe@16-12-2010 818646111@GENIA Treebank@formal@@1@S@These results suggest that CN is involved in the coordinated induction of the GM-CSF and IL-2 genes and that the CLE0 sequence of the GM-CSF gene is a functional analogue of the NF-AT-binding site in the IL-2 promoter, which mediates signals downstream of T cell activation.@@@@1@48@@oe@16-12-2010 818953101@GENIA Treebank@formal@@1@S@Central nervous system-derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR-independent transactivation by Tat.@@@@1@26@@oe@16-12-2010 818953102@GENIA Treebank@formal@@1@S@The Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent activator of long terminal repeat-directed transcription.@@@@1@22@@oe@16-12-2010 818953103@GENIA Treebank@formal@@1@S@While in most cell types, activation requires interaction of Tat with the unusual transcription element TAR, astrocytic glial cells support TAR-independent transactivation of HIV-1 transcription by Tat.@@@@1@30@@oe@16-12-2010 818953104@GENIA Treebank@formal@@1@S@This alternative pathway of Tat activation is mediated by the viral enhancer, a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B (NF-kappa B) present in many cell types, including T lymphocytes.@@@@1@45@@oe@16-12-2010 818953105@GENIA Treebank@formal@@1@S@Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR-deleted mutant HIV-1 in astrocytes.@@@@1@20@@oe@16-12-2010 818953106@GENIA Treebank@formal@@1@S@The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B.@@@@1@23@@oe@16-12-2010 818953107@GENIA Treebank@formal@@1@S@The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column, while prototypical NF-kappa B from Jurkat T cells is not.@@@@1@26@@oe@16-12-2010 818953108@GENIA Treebank@formal@@1@S@In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain.@@@@1@30@@oe@16-12-2010 818953109@GENIA Treebank@formal@@1@S@Moreover, TAR-independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity.@@@@1@23@@oe@16-12-2010 818953110@GENIA Treebank@formal@@1@S@The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed.@@@@1@20@@oe@16-12-2010 819154701@GENIA Treebank@formal@@1@S@Novel aldosterone receptors: specificity-conferring mechanism at the level of the cell membrane.@@@@1@14@@oe@16-12-2010 819154702@GENIA Treebank@formal@@1@S@Functional studies in extra-renal, nonepithelial 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.@@@@1@41@@oe@16-12-2010 819154703@GENIA Treebank@formal@@1@S@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 minutes.@@@@1@26@@oe@16-12-2010 819154704@GENIA Treebank@formal@@1@S@A second messenger cascade involved is the inositol-1,4,5-trisphosphate/calcium pathway which responds over the same rapid time course.@@@@1@18@@oe@16-12-2010 819154705@GENIA Treebank@formal@@1@S@Such changes clearly cannot be explained by genomic mechanisms, which are responsible for later effects than the membrane-related rapid responses.@@@@1@23@@oe@16-12-2010 819154706@GENIA Treebank@formal@@1@S@In addition to its rapid time course the unique characteristics of this new pathway for steroid action include a 10000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones, classical mineralocorticoid antagonists, as antagonists of the response.@@@@1@41@@oe@16-12-2010 819154707@GENIA Treebank@formal@@1@S@Subsequently binding sites have been demonstrated in the plasma membrane of human lymphocytes which show pharmacological (aldosterone specificity) and kinetic (high turnover) properties identical with those of the rapid aldosterone effects in the same cells.@@@@1@40@@oe@16-12-2010 819154708@GENIA Treebank@formal@@1@S@SDS-PAGE analysis of the receptor protein has shown a molecular weight of approximately 50 kD.@@@@1@16@@oe@16-12-2010 819154709@GENIA Treebank@formal@@1@S@The present paper reviews the data supporting a new, two-step model for non-genomic and genomic aldosterone effects.@@@@1@19@@oe@16-12-2010 819154710@GENIA Treebank@formal@@1@S@It also suggests a novel specificity-conferring mechanism for mineralocorticoid action at the membrane level.@@@@1@15@@oe@16-12-2010 819521501@GENIA Treebank@formal@@1@S@An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter.@@@@1@23@@oe@16-12-2010 819521502@GENIA Treebank@formal@@1@S@alpha 4 integrins mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle.@@@@1@28@@oe@16-12-2010 819521503@GENIA Treebank@formal@@1@S@Here we examine molecular mechanisms controlling the pattern of alpha 4 expression.@@@@1@13@@oe@16-12-2010 819521504@GENIA Treebank@formal@@1@S@The activity of constructs containing 5' deletion mutants of the alpha 4 gene promoter was compared in transfection assays into cell lines that express alpha 4 and cell lines that do not.@@@@1@33@@oe@16-12-2010 819521505@GENIA Treebank@formal@@1@S@The sequence between position -42 and -76 base pairs (bp) was required for efficient transcription in cells that express alpha 4, but it showed no activity in HeLa cells, which do not express alpha 4.@@@@1@40@@oe@16-12-2010 819521506@GENIA Treebank@formal@@1@S@Three binding sites for the Ets family of transcription factors are found in this region: two adjacent sites at positions -50 and -54 bp and a more 5' site at position -67 bp.@@@@1@35@@oe@16-12-2010 819521507@GENIA Treebank@formal@@1@S@Using a series of constructs containing deletions and mutations in this region, we found that the 3'-most site alone was sufficient for binding GA-binding protein alpha (GABP alpha)/GABP beta and for a low level of transcriptional activation.@@@@1@42@@oe@16-12-2010 819521508@GENIA Treebank@formal@@1@S@When all three sites were present, a second complex "a" was detected, which contains an unknown member of the Ets family.@@@@1@26@@oe@16-12-2010 819521509@GENIA Treebank@formal@@1@S@Formation of complex a was cell-type specific and correlated with a high level of transcription.@@@@1@16@@oe@16-12-2010 819521510@GENIA Treebank@formal@@1@S@Deletion of the 5'-most Ets site had no effect on binding to GABP alpha/GABP beta, but it eliminated a.@@@@1@21@@oe@16-12-2010 819521511@GENIA Treebank@formal@@1@S@Concomitant with this loss of a, a new Ets-1-containing complex "c" appeared.@@@@1@16@@oe@16-12-2010 819521512@GENIA Treebank@formal@@1@S@Complex c substituted efficiently for complex a in transcriptional activation.@@@@1@11@@oe@16-12-2010 819521513@GENIA Treebank@formal@@1@S@We conclude that although neither of the two 5'-most Ets sites alone binds nuclear protein, they appear to act as modulators which control the pattern of Ets proteins that bind the alpha 4 gene promoter.@@@@1@37@@oe@16-12-2010 819521514@GENIA Treebank@formal@@1@S@This arrangement of Ets sites, coupled with the tissue- and developmental-specific expression of Ets members, likely play a key role in defining the pattern of alpha 4 integrin.@@@@1@32@@oe@16-12-2010 819662001@GENIA Treebank@formal@@1@S@Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site.@@@@1@23@@oe@16-12-2010 819662002@GENIA Treebank@formal@@1@S@Exposure of monocytic cells to bacterial lipopolysaccharide (LPS) activates the NF-kappa B/Rel family of proteins and leads to the rapid induction of inflammatory gene products, including tissue factor (TF).@@@@1@35@@oe@16-12-2010 819662003@GENIA Treebank@formal@@1@S@TF is the primary cellular initiator of the coagulation protease cascades.@@@@1@12@@oe@16-12-2010 819662004@GENIA Treebank@formal@@1@S@Here we report the characterization of a nuclear complex from human monocytic cells that bound to a kappa B-like site, 5'-CGGAGTTTCC-3', in the 5'-flanking region of the human TF gene.@@@@1@33@@oe@16-12-2010 819662005@GENIA Treebank@formal@@1@S@This nuclear complex was activated by LPS with kinetics that preceded induction of the TF gene.@@@@1@17@@oe@16-12-2010 819662006@GENIA Treebank@formal@@1@S@In vitro binding studies demonstrated that the TF site bound translated c-Rel and p65 homodimers but not p50/p65 heterodimers or p50 homodimers.@@@@1@23@@oe@16-12-2010 819662007@GENIA Treebank@formal@@1@S@Base-pair substitutions in the TF site indicated that the presence of a cytosine at position 1 precluded binding of NF-kappa B.@@@@1@22@@oe@16-12-2010 819662008@GENIA Treebank@formal@@1@S@In fact, under low-ionic-strength conditions, the TF complex did not migrate with translated p50/p65 dimers but instead comigrated with c-Rel/p65 dimers.@@@@1@24@@oe@16-12-2010 819662009@GENIA Treebank@formal@@1@S@Antibodies against the NF-kappa B and Rel proteins and UV cross-linking studies revealed the presence of c-Rel and p65 and the absence of p50 in the TF complex and further showed that c-Rel/p65 heterodimers selectively bound to the TF kappa B-like site.@@@@1@43@@oe@16-12-2010 819662010@GENIA Treebank@formal@@1@S@Functional studies indicated that the TF site conferred LPS inducibility on a heterologous promoter and was transactivated by c-Rel or p65.@@@@1@22@@oe@16-12-2010 819662011@GENIA Treebank@formal@@1@S@Taken together, our results demonstrated that binding of c-Rel/p65 heterodimers to a novel kappa B-like site mediated LPS induction of TF gene expression in monocytic cells.@@@@1@28@@oe@16-12-2010 820099801@GENIA Treebank@formal@@1@S@Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats.@@@@1@11@@oe@16-12-2010 820099802@GENIA Treebank@formal@@1@S@We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical (HPA) axis functioning when adult.@@@@1@22@@oe@16-12-2010 820099803@GENIA Treebank@formal@@1@S@To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge, 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10(8) human red blood cells (HRBC) or gram-negative bacterial endotoxin (Escherichia coli LPS: 30 micrograms/kg).@@@@1@47@@oe@16-12-2010 820099804@GENIA Treebank@formal@@1@S@The adult male progeny (3 mo old) of both experimental groups showed increased basal plasma corticosterone levels.@@@@1@20@@oe@16-12-2010 820099805@GENIA Treebank@formal@@1@S@In addition, after novelty stress the HRBC group, but not the LPS group, showed increased ACTH and corticosterone levels.@@@@1@23@@oe@16-12-2010 820099806@GENIA Treebank@formal@@1@S@Both groups showed substantial decreases in mineralocorticoid (MR) and glucocorticoid receptor (GR) levels in the hippocampus, a limbic brain structure critical for HPA axis regulation, whereas GR concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased.@@@@1@47@@oe@16-12-2010 820099807@GENIA Treebank@formal@@1@S@HRBC and LPS indeed stimulated the maternal immune system as revealed by specific anti-HRBC antibody production and enhanced IL-1 beta mRNA expression in splenocytes, respectively.@@@@1@27@@oe@16-12-2010 820099808@GENIA Treebank@formal@@1@S@This study demonstrates that a T cell-mediated immune response as well as an endotoxic challenge during pregnancy can induce anomalies in HPA axis function in adulthood.@@@@1@27@@oe@16-12-2010 820099809@GENIA Treebank@formal@@1@S@Clinically, it may be postulated that disturbed fetal brain development due to prenatal immune challenge increases the vulnerability to develop mental illness involving inadequate responses to stress.@@@@1@29@@oe@16-12-2010 820562101@GENIA Treebank@formal@@1@S@JNK is involved in signal integration during costimulation of T lymphocytes.@@@@1@12@@oe@16-12-2010 820562102@GENIA Treebank@formal@@1@S@T lymphocyte activation and interleukin-2 (IL-2) production require at least two signals, generated by phorbol ester (TPA) and Ca2+ ionophore or costimulation of the T cell receptor (TCR) and the CD28 auxiliary receptor.@@@@1@41@@oe@16-12-2010 820562103@GENIA Treebank@formal@@1@S@We investigated how these stimuli affect mitogen activated protein (MAP) kinases.@@@@1@14@@oe@16-12-2010 820562104@GENIA Treebank@formal@@1@S@Full activation of the MAP kinases that phosphorylate the Jun activation domain, JNK1 and JNK2, required costimulation of T cells with either TPA and Ca2+ ionophore or antibodies to TCR and CD28.@@@@1@35@@oe@16-12-2010 820562105@GENIA Treebank@formal@@1@S@Alone, each stimulus resulted in little or no activation.@@@@1@11@@oe@16-12-2010 820562106@GENIA Treebank@formal@@1@S@Similar to its effect on IL-2 induction, cyclosporin A (CsA) inhibited the synergistic activation of JNK, and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation.@@@@1@34@@oe@16-12-2010 820562107@GENIA Treebank@formal@@1@S@By contrast, the MAP kinases ERK1 and ERK2 were fully activated by TPA or TCR stimulation and were not affected by Ca2+, CD28, or CsA.@@@@1@29@@oe@16-12-2010 820562108@GENIA Treebank@formal@@1@S@Hence, integration of signals that lead to T cell activation occurs at the level of JNK activation.@@@@1@19@@oe@16-12-2010 820675301@GENIA Treebank@formal@@1@S@Glucocorticoid-mediated inhibition of interleukin-2 receptor alpha and -beta subunit expression by human T cells.@@@@1@15@@oe@16-12-2010 820675302@GENIA Treebank@formal@@1@S@To determine the mechanism of glucocorticoid (GC)-mediated inhibition of T cell functions, the effect of dexamethasone (DM) on T cell proliferation and interleukin-2 receptor (IL-2R) generation were studied.@@@@1@37@@oe@16-12-2010 820675303@GENIA Treebank@formal@@1@S@Dexamethasone inhibited IL-2-induced T cell proliferation by 30%-88%, relative to its concentration within the cultures.@@@@1@21@@oe@16-12-2010 820675304@GENIA Treebank@formal@@1@S@The effect of DM on expression of IL-2R alpha (Tac, p55, CD25) and beta (p75) genes in activated T cells was examined next.@@@@1@30@@oe@16-12-2010 820675305@GENIA Treebank@formal@@1@S@In T cells stimulated with purified phytohemagglutinin (PHA-p) and 4 beta-phorbol 12-myristate 13-acetate (PMA) addition of DM to the cultures resulted in a 60% reduction in IL-2R alpha and a 30% reduction in IL-2R beta membrane expression compared to T cells cultured in the absence of DM (p < 0.01).@@@@1@59@@oe@16-12-2010 820675306@GENIA Treebank@formal@@1@S@Inhibition of membrane IL-2R alpha and IL-2R beta expression by 10(-6) M DM was partially reversible by recombinant human IL-2 (rhIL-2).@@@@1@24@@oe@16-12-2010 820675307@GENIA Treebank@formal@@1@S@By Northern blot analysis, DM caused a comparable decrease in IL-2R alpha and in IL-2R beta mRNA levels to membrane receptor expression in mitogen-stimulated T cells.@@@@1@28@@oe@16-12-2010 820675308@GENIA Treebank@formal@@1@S@By in vitro transcription assays, DM regulated IL-2R alpha gene expression at a transcriptional level while transcription of IL-2R beta gene was unaffected by DM.@@@@1@27@@oe@16-12-2010 820675309@GENIA Treebank@formal@@1@S@The mechanism of action of DM on IL-2R alpha transcription was examined by determining the mRNA levels of the p50 subunit of nuclear factor kappa B (NF-kappa B), a transcription factor that stimulates IL-2R alpha gene expression.@@@@1@41@@oe@16-12-2010 820675310@GENIA Treebank@formal@@1@S@The data indicate that 10(-6) M DM increased T cell p50 NF-kappa B mRNA levels by four-fold compared to the levels obtained in the absence of DM.@@@@1@28@@oe@16-12-2010 820675311@GENIA Treebank@formal@@1@S@Further, the level of nuclear proteins capable of binding to the NF-kappa B sites in activated T cells increased in response to DM.@@@@1@25@@oe@16-12-2010 820675312@GENIA Treebank@formal@@1@S@In sum, DM regulates T cell membrane expression of IL-2R by more than one molecular mechanism.@@@@1@18@@oe@16-12-2010 820764301@GENIA Treebank@formal@@1@S@Stimulation of HIV replication in mononuclear phagocytes by leukemia inhibitory factor.@@@@1@12@@oe@16-12-2010 820764302@GENIA Treebank@formal@@1@S@This study examined the effects of leukemia inhibitory factor (LIF) on human immunodeficiency virus (HIV) replication in mononuclear phagocytes (MNP).@@@@1@27@@oe@16-12-2010 820764303@GENIA Treebank@formal@@1@S@LIF induced a dose-dependent increase in p24 antigen production in the chronically infected promonocytic cell line U1.@@@@1@18@@oe@16-12-2010 820764304@GENIA Treebank@formal@@1@S@The magnitude and time kinetics of the LIF effects were similar to interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF), other cytokines known to induce HIV replication in this cell line.@@@@1@40@@oe@16-12-2010 820764305@GENIA Treebank@formal@@1@S@To characterize mechanisms responsible for these LIF effects, levels of HIV mRNA, activation of the DNA binding protein nuclear factor (NF)-kB, signal transduction pathways, and potential interactions with other cytokines were analyzed.@@@@1@40@@oe@16-12-2010 820764306@GENIA Treebank@formal@@1@S@LIF increased steady-state levels of HIV mRNA at 2.0, 4.3, and 9.2 kB.@@@@1@16@@oe@16-12-2010 820764307@GENIA Treebank@formal@@1@S@This was detectable by 24 h and persisted until 72 h.@@@@1@12@@oe@16-12-2010 820764308@GENIA Treebank@formal@@1@S@The DNA binding protein NF-kB is a central mediator in cytokine activation of HIV transcription.@@@@1@16@@oe@16-12-2010 820764309@GENIA Treebank@formal@@1@S@NF-kB levels were higher in unstimulated U1 cells as compared to the parent cell line U937.@@@@1@17@@oe@16-12-2010 820764310@GENIA Treebank@formal@@1@S@In both cell lines LIF increased NF-kB activity.@@@@1@9@@oe@16-12-2010 820764311@GENIA Treebank@formal@@1@S@Induction of NF-kB and HIV replication by cytokines are at least in part dependent on reactive oxygen intermediates.@@@@1@19@@oe@16-12-2010 820764312@GENIA Treebank@formal@@1@S@The oxygen radical scavenger N-acetyl-L-cysteine, but not an inhibitor of nitric oxide synthase, inhibited LIF-induced HIV replication.@@@@1@20@@oe@16-12-2010 820764313@GENIA Treebank@formal@@1@S@LIF induces the production of other cytokines in monocytes but its effects on HIV replication were not inhibited by antibodies to IL-1, TNF, or IL-6.@@@@1@28@@oe@16-12-2010 820764314@GENIA Treebank@formal@@1@S@These results identify LIF as a stimulus of HIV replication.@@@@1@11@@oe@16-12-2010 820764315@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 820779301@GENIA Treebank@formal@@1@S@Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells.@@@@1@14@@oe@16-12-2010 820779302@GENIA Treebank@formal@@1@S@Dysregulation of cytokines secreted by T cells may play an important role in the pathogenesis of AIDS.@@@@1@18@@oe@16-12-2010 820779303@GENIA Treebank@formal@@1@S@To investigate the effects of human immunodeficiency virus type 1 (HIV-1) Tat on interleukin-2 (IL-2) expression, we used IL-2 promoter-chloramphenicol acetyltransferase constructs and IL-2-secreting Jurkat T cells as a model system.@@@@1@37@@oe@16-12-2010 820779304@GENIA Treebank@formal@@1@S@Transient expression of HIV-1 Tat induced a five- to eightfold increase in IL-2 promoter activity in Jurkat T cells stimulated with phytohemagglutinin and phorbol myristate acetate.@@@@1@27@@oe@16-12-2010 820779305@GENIA Treebank@formal@@1@S@IL-2 secretion was increased more than twofold in both Jurkat T cells and primary T cells stimulated by extracellular HIV-1 Tat protein.@@@@1@23@@oe@16-12-2010 820779306@GENIA Treebank@formal@@1@S@Analysis of mRNA suggested that Tat exerts its effect on IL-2 primarily at the transcriptional level.@@@@1@17@@oe@16-12-2010 820779307@GENIA Treebank@formal@@1@S@The NF-kappa B site at positions -206 to -195 of the IL-2 promoter was required but not sufficient for the Tat effect.@@@@1@23@@oe@16-12-2010 820779308@GENIA Treebank@formal@@1@S@The Tat-mediated increase in IL-2 promoter activity could selectively be blocked by antisense tat or-unlike the analogous effect of human T-cell lymphotropic virus type 1 Tax-by cyclosporin A.@@@@1@33@@oe@16-12-2010 820779309@GENIA Treebank@formal@@1@S@The observed increase in IL-2 levels might facilitate virus spread from or to T cells.@@@@1@16@@oe@16-12-2010 820779310@GENIA Treebank@formal@@1@S@Furthermore, it might contribute to the hypergammaglobulinemia or, together with other cytokines found to be dysregulated, the T-helper cell dysfunctions observed in AIDS patients.@@@@1@28@@oe@16-12-2010 821296501@GENIA Treebank@formal@@1@S@The impaired transcription factor AP-1 DNA binding activity in lymphocytes derived from subjects with some symptoms of premature aging.@@@@1@20@@oe@16-12-2010 821296502@GENIA Treebank@formal@@1@S@The study of human disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence.@@@@1@20@@oe@16-12-2010 821296503@GENIA Treebank@formal@@1@S@The main feature of cellular senescence in vitro is cessation of cell proliferation.@@@@1@14@@oe@16-12-2010 821296504@GENIA Treebank@formal@@1@S@Down syndrome (DS) and neuronal ceroid-lypofuscinosis (NCL) are clinically characterized by the premature onset of numerous features normally associated with human aging.@@@@1@27@@oe@16-12-2010 821296505@GENIA Treebank@formal@@1@S@Phytohemagglutinin stimulated lymphocytes derived from DS subjects showed a statistically significant diminished proliferation capacity in comparison with lymphocytes derived from NCL and healthy individuals.@@@@1@25@@oe@16-12-2010 821296506@GENIA Treebank@formal@@1@S@We demonstrated, by applying the electrophoretic mobility shift assay, slightly impaired AP-1 DNA binding activity in NCL lymphocytes and strong in DS ones.@@@@1@26@@oe@16-12-2010 821296507@GENIA Treebank@formal@@1@S@Our results showed that the same molecular mechanisms of proliferation cessation could exist in fibroblasts characterized by replicative senescence and in lymphocytes derived from individuals with premature aging syndromes (Down).@@@@1@33@@oe@16-12-2010 825418501@GENIA Treebank@formal@@1@S@Visualization of the endogenous NF-kappa B p50 subunit in the nucleus of follicular dendritic cells in germinal centers.@@@@1@19@@oe@16-12-2010 825418502@GENIA Treebank@formal@@1@S@NF-kappa B, a 50 kDa/65 kDa (p50/p65) heterodimer, is a ubiquitous transcription factor involved in the positive regulation of various immune genes.@@@@1@27@@oe@16-12-2010 825418503@GENIA Treebank@formal@@1@S@The aim of this study was to determine whether NF-kappa B is related to a particular cell type and/or differentiation step during immunopoiesis.@@@@1@24@@oe@16-12-2010 825418504@GENIA Treebank@formal@@1@S@Using in situ hybridization on sections from non HIV hyperplastic lymph nodes, we found that the gene of the 105 kDa precursor of p50 was overexpressed in the light zone of germinal centers, with a network aspect, which suggested the involvement of follicular dendritic cells (FDC).@@@@1@52@@oe@16-12-2010 825418505@GENIA Treebank@formal@@1@S@By immunohistochemistry, p50 protein was detected in the cytoplasm and nucleus of FDC, confirming the involvement of FDC.@@@@1@21@@oe@16-12-2010 825418506@GENIA Treebank@formal@@1@S@Furthermore, p50 protein was detected in the cytoplasm of all lymphocytes.@@@@1@13@@oe@16-12-2010 825418507@GENIA Treebank@formal@@1@S@Thus, we focused our study on isolated FDC clusters from normal tonsils.@@@@1@14@@oe@16-12-2010 825418508@GENIA Treebank@formal@@1@S@As showed on tissue sections, we detected the p50 in both cytoplasm and nucleus of FDC.@@@@1@18@@oe@16-12-2010 825418509@GENIA Treebank@formal@@1@S@Nuclei of lymphocytes from FDC clusters were negative.@@@@1@9@@oe@16-12-2010 825418510@GENIA Treebank@formal@@1@S@We next studied p65 and c-Rel protein expression in FDC clusters.@@@@1@12@@oe@16-12-2010 825418511@GENIA Treebank@formal@@1@S@p65 was detected in the cytoplasm of FDC, whereas nuclei were negative.@@@@1@14@@oe@16-12-2010 825418512@GENIA Treebank@formal@@1@S@Furthermore, p65 was detected in the nuclei of some lymphocytes.@@@@1@12@@oe@16-12-2010 825418513@GENIA Treebank@formal@@1@S@c-Rel protein was detected only in the cytoplasm of lymphocytes and not in the nucleus and cytoplasm of FDC.@@@@1@20@@oe@16-12-2010 825418514@GENIA Treebank@formal@@1@S@Our results indicated that, in the context of T cell-dependent B cell immunopoiesis occurring in FDC clusters, p50 is mainly related to FDC with a massive overexpression in the nuclei, whereas p65 is expressed in a scattered manner in the nuclei of lymphocytes and c-Rel protein exclusively in the cytoplasm of lymphocytes from FDC clusters.@@@@1@59@@oe@16-12-2010 825418515@GENIA Treebank@formal@@1@S@These results suggested that the two subunits of NF-kappa B and the c-Rel protein have different roles in different cell types during B cell immunopoiesis.@@@@1@26@@oe@16-12-2010 825477201@GENIA Treebank@formal@@1@S@Involvement of transcription factor YB-1 in human T-cell lymphotropic virus type I basal gene expression.@@@@1@16@@oe@16-12-2010 825477202@GENIA Treebank@formal@@1@S@Sequences which control basal human T-cell lymphotropic virus type I (HTLV-I) transcription likely play an important role in initiation and maintenance of virus replication.@@@@1@27@@oe@16-12-2010 825477203@GENIA Treebank@formal@@1@S@We previously identified and analyzed a 45-nucleotide sequence (downstream regulatory element 1 [DRE 1]), +195 to +240, at the boundary of the R/U5 region of the long terminal repeat which is required for HTLV-I basal transcription.@@@@1@43@@oe@16-12-2010 825477204@GENIA Treebank@formal@@1@S@We identified a protein, p37, which specifically bound to DRE 1.@@@@1@14@@oe@16-12-2010 825477205@GENIA Treebank@formal@@1@S@An affinity column fraction, containing p37, stimulated HTLV-I transcription approximately 12-fold in vitro.@@@@1@16@@oe@16-12-2010 825477206@GENIA Treebank@formal@@1@S@We now report the identification of a cDNA clone (15B-7), from a Jurkat expression library, that binds specifically to the DRE 1 regulatory sequence.@@@@1@29@@oe@16-12-2010 825477207@GENIA Treebank@formal@@1@S@Binding of the cDNA fusion protein, similarly to the results obtained with purified Jurkat protein, was decreased by introduction of site-specific mutations in the DRE 1 regulatory sequence.@@@@1@31@@oe@16-12-2010 825477208@GENIA Treebank@formal@@1@S@In vitro transcription and translation of 15B-7 cDNA produced a fusion protein which bound specifically to the HTLV-I +195 to +240 oligonucleotide.@@@@1@23@@oe@16-12-2010 825477209@GENIA Treebank@formal@@1@S@The partial cDNA encodes a protein which is homologous to the C-terminal 196 amino acids of the 36-kDa transcription factor, YB-1.@@@@1@23@@oe@16-12-2010 825477210@GENIA Treebank@formal@@1@S@Cotransfection of a YB-1 expression plasmid increases HTLV-I basal transcription approximately 14-fold in Jurkat T lymphocytes.@@@@1@17@@oe@16-12-2010 825477211@GENIA Treebank@formal@@1@S@On the basis of the molecular weight, DNA-binding characteristics, and in vivo transactivation activity, we suggest that the previously identified DRE 1-binding protein, p37, is YB-1.@@@@1@32@@oe@16-12-2010 825516201@GENIA Treebank@formal@@1@S@Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system.@@@@1@10@@oe@16-12-2010 825516202@GENIA Treebank@formal@@1@S@1.Blood cell receptors in volunteers with moderately increased body burdens.@@@@1@13@@oe@16-12-2010 825516203@GENIA Treebank@formal@@1@S@Using monoclonal antibodies (mAbs) and flow cytometry, we studied a variety of surface receptors on lymphocyte subpopulations of workers with moderately increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of other polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), expressed here as International-Toxicity Equivalencies (I-TE).@@@@1@52@@oe@16-12-2010 825516204@GENIA Treebank@formal@@1@S@The hypothesis to be tested was whether or not humans exhibit a similar susceptibility to PCDDs/PCDFs with respect to the surface receptors found previously to respond to small doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Callithrix jacchus.@@@@1@38@@oe@16-12-2010 825516205@GENIA Treebank@formal@@1@S@These are: helper-inducer (memory) T cells (CD4+CD45R0+CD45RA-CD29highCD11a+), CD20+ B cells, and cytotoxic T cells (CD8+CD56+/CD57+).@@@@1@25@@oe@16-12-2010 825516206@GENIA Treebank@formal@@1@S@Furthermore, 68 triple-labellings with mAbs were performed on the cells of each volunteer to possibly generate further hypotheses.@@@@1@20@@oe@16-12-2010 825516207@GENIA Treebank@formal@@1@S@It was evaluated whether any of the variables might be used as a biomarker of effects for this class of compounds.@@@@1@22@@oe@16-12-2010 825516208@GENIA Treebank@formal@@1@S@There were two main goals: (1) to evaluate whether workers with a moderately increased PCDD/PCDF-body burden [25-140 ppt TCDD or 104-522 ppt I-TE in blood fat] exhibit changes in the surface receptors of white blood cells, as observed in previous studies in non-human primates, and (2) to clarify whether persons at the upper range [10-23 ppt TCDD or 30-90 ppt I-TE in blood fat] of the body burden reference values of a not particularly exposed population show detectable deviations in these immunological variables, when compared with persons at the lower and medium range [1-3 ppt TCDD or 9-29 ppt I-TE] of these body burden reference values.@@@@1@121@@oe@16-12-2010 825516209@GENIA Treebank@formal@@1@S@Regression analysis of our data revealed slight trends for some of the biomarkers (e.g. CD45R0+).@@@@1@18@@oe@16-12-2010 825516210@GENIA Treebank@formal@@1@S@With one exception, these were all increases.@@@@1@9@@oe@16-12-2010 825516211@GENIA Treebank@formal@@1@S@None of the alterations observed are of medical relevance.@@@@1@10@@oe@16-12-2010 825516212@GENIA Treebank@formal@@1@S@The slight increase in the percentage of CD4+CD45R0+ cells remained significant even after covariant analysis taking age-related changes into account.@@@@1@21@@oe@16-12-2010 825516213@GENIA Treebank@formal@@1@S@Altogether, the data do not provide any evidence to support an assumption that moderately increased body burdens of PCDDs/PCDFs in adults induce decreases in the cellular components of the human immune system.@@@@1@34@@oe@16-12-2010 825516214@GENIA Treebank@formal@@1@S@Adult humans certainly are less susceptible to this action of PCDDs/PCDFs than adolescent Callithrix jacchus.@@@@1@16@@oe@16-12-2010 826247701@GENIA Treebank@formal@@1@S@Transient pseudohypoaldosteronism in obstructive renal disease with transient reduction of lymphocytic aldosterone receptors.@@@@1@14@@oe@16-12-2010 826247702@GENIA Treebank@formal@@1@S@Results in two affected infants.@@@@1@6@@oe@16-12-2010 826247703@GENIA Treebank@formal@@1@S@We report two patients with transient pseudohypoaldosteronism due to obstructive renal disease.@@@@1@13@@oe@16-12-2010 826247704@GENIA Treebank@formal@@1@S@Both patients presented with a salt-losing episode simulating adrenal insufficiency.@@@@1@11@@oe@16-12-2010 826247705@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010 826247706@GENIA Treebank@formal@@1@S@Aldosterone receptors were normal in both patients when studied after the surgical correction of the obstruction.@@@@1@17@@oe@16-12-2010 826460401@GENIA Treebank@formal@@1@S@The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor.@@@@1@15@@oe@16-12-2010 826460402@GENIA Treebank@formal@@1@S@The macrophage colony-stimulating factor (M-CSF) receptor is expressed in a tissue-specific fashion from two distinct promoters in monocytes/macrophages and the placenta.@@@@1@24@@oe@16-12-2010 826460403@GENIA Treebank@formal@@1@S@In order to further understand the transcription factors which play a role in the commitment of multipotential progenitors to the monocyte/macrophage lineage, we have initiated an investigation of the factors which activate the M-CSF receptor very early during the monocyte differentiation process.@@@@1@44@@oe@16-12-2010 826460404@GENIA Treebank@formal@@1@S@Here we demonstrate that the human monocytic M-CSF receptor promoter directs reporter gene activity in a tissue-specific fashion.@@@@1@19@@oe@16-12-2010 826460405@GENIA Treebank@formal@@1@S@Since one of the few transcription factors which have been implicated in the regulation of monocyte genes is the macrophage- and B-cell-specific PU.1 transcription factor, we investigated whether PU.1 binds and activates the M-CSF receptor promoter.@@@@1@38@@oe@16-12-2010 826460406@GENIA Treebank@formal@@1@S@Here we demonstrate that both in vitro-translated PU.1 and PU.1 from nuclear extracts bind to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site.@@@@1@32@@oe@16-12-2010 826460407@GENIA Treebank@formal@@1@S@Mutations in this site which eliminate PU.1 binding decrease M-CSF receptor promoter activity significantly in macrophage cell lines only.@@@@1@20@@oe@16-12-2010 826460408@GENIA Treebank@formal@@1@S@Furthermore, PU.1 transactivates the M-CSF receptor promoter in nonmacrophage cells.@@@@1@12@@oe@16-12-2010 826460409@GENIA Treebank@formal@@1@S@These results suggest that PU.1 plays a major role in macrophage gene regulation and development by directing the expression of a receptor for a key macrophage growth factor.@@@@1@29@@oe@16-12-2010 828280301@GENIA Treebank@formal@@1@S@Steroid-resistant asthma.@@@@1@3@@oe@16-12-2010 828280302@GENIA Treebank@formal@@1@S@Cellular mechanisms contributing to inadequate response to glucocorticoid therapy.@@@@1@10@@oe@16-12-2010 828280303@GENIA Treebank@formal@@1@S@The current study examined whether alterations in glucocorticoid receptor (GR) binding contribute to poor response to glucocorticoid therapy in asthma.@@@@1@23@@oe@16-12-2010 828280304@GENIA Treebank@formal@@1@S@29 asthma patients with forced expiratory volume in 1 s (FEV1) < 70% predicted were studied.@@@@1@20@@oe@16-12-2010 828280305@GENIA Treebank@formal@@1@S@Patients were classified as steroid sensitive (SS) if their morning FEV1 increased > 30% after a 1-wk course of oral prednisone 20 mg twice daily and steroid resistant (SR) if they failed to increase > 15%.@@@@1@43@@oe@16-12-2010 828280306@GENIA Treebank@formal@@1@S@PBMC obtained from these two groups, 17 SR and 12 SS, as well as 12 normal controls were analyzed.@@@@1@22@@oe@16-12-2010 828280307@GENIA Treebank@formal@@1@S@SR patients had two distinguishable GR binding abnormalities: 15 of the 17 SR patients demonstrated a significantly reduced GR binding affinity, as compared with SS patients (P = 0.0001) and normal controls (P = 0.0001).@@@@1@42@@oe@16-12-2010 828280308@GENIA Treebank@formal@@1@S@This defect was localized to T cells and reverted to normal after 48 h in culture media.@@@@1@18@@oe@16-12-2010 828280309@GENIA Treebank@formal@@1@S@However, incubation with a combination of IL-2 and IL-4 sustained this abnormality.@@@@1@14@@oe@16-12-2010 828280310@GENIA Treebank@formal@@1@S@The other two SR patients had an abnormally low GR number with normal binding affinity that was not limited to T cells.@@@@1@23@@oe@16-12-2010 828280311@GENIA Treebank@formal@@1@S@Furthermore, GR number failed to normalize after incubation in media alone or IL-2 and IL-4.@@@@1@17@@oe@16-12-2010 828280312@GENIA Treebank@formal@@1@S@Therefore, SR asthma may be due to more than one abnormality, the majority related to a reversible cytokine-induced reduction in GR binding affinity and the second related to an irreversible reduction in GR number.@@@@1@37@@oe@16-12-2010 828280313@GENIA Treebank@formal@@1@S@These findings may have important implications for the design of alternative treatment approaches for recalcitrant asthma.@@@@1@17@@oe@16-12-2010 828282001@GENIA Treebank@formal@@1@S@Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic transcription factors.@@@@1@15@@oe@16-12-2010 828282002@GENIA Treebank@formal@@1@S@Skeletal myogenesis is regulated by a group of transcription factors (MyoD, myogenin, myf5, and myf6) that are "basic helix-loop-helix" proteins that bind to the promoters of muscle-specific genes and promote their expression.@@@@1@40@@oe@16-12-2010 828282003@GENIA Treebank@formal@@1@S@We have previously shown that after a mutation of Leu122 to Arg the DNA binding basic domain of MyoD confers c-myc-like functional characteristics to the protein.@@@@1@27@@oe@16-12-2010 828282004@GENIA Treebank@formal@@1@S@In this study we used single-strand conformation polymorphism analysis to determine whether such mutations occur naturally in rhabdomyosarcomas.@@@@1@19@@oe@16-12-2010 828282005@GENIA Treebank@formal@@1@S@We have found that the basic domains of all the myogenic factors remain unaltered in rhabdomyosarcomas.@@@@1@17@@oe@16-12-2010 828282006@GENIA Treebank@formal@@1@S@Selection against such mutations may be the result of functional redundancy of these myogenic transcription factors.@@@@1@17@@oe@16-12-2010 828303201@GENIA Treebank@formal@@1@S@Increased proliferation, cytotoxicity, and gene expression after stimulation of human peripheral blood T lymphocytes through a surface ganglioside (GD3) [published erratum appears in J Immunol 1994 Jul 15;153(2):910]@@@@1@41@@oe@16-12-2010 828303202@GENIA Treebank@formal@@1@S@Previous studies have suggested that gangliosides have an important role in cell signaling and recognition.@@@@1@16@@oe@16-12-2010 828303203@GENIA Treebank@formal@@1@S@However, their specific function in these processes has not been clearly defined.@@@@1@14@@oe@16-12-2010 828303204@GENIA Treebank@formal@@1@S@A mAb, R24, that reacts specifically with a cell surface ganglioside (GD3) has been demonstrated to stimulate proliferation of T cells derived from human peripheral blood.@@@@1@31@@oe@16-12-2010 828303205@GENIA Treebank@formal@@1@S@In this study, we have investigated the mechanisms by which the R24 mAb affects T cell functions.@@@@1@19@@oe@16-12-2010 828303206@GENIA Treebank@formal@@1@S@We have observed that the R24 mAb stimulates GD3+ T cell proliferation, cytotoxicity, and surface marker expression of IL-2R alpha-chain, IL-2R beta-chain, HLA-DR, CD11a, and CD11c.@@@@1@33@@oe@16-12-2010 828303207@GENIA Treebank@formal@@1@S@Additionally, IFN-gamma activity but not IL-1, IL-2, or IL-4 activity was present in culture supernatants 72 h after R24 stimulation.@@@@1@24@@oe@16-12-2010 828303208@GENIA Treebank@formal@@1@S@In some donors, increased IL-6 and TNF-alpha activity also was detected after R24 treatment.@@@@1@16@@oe@16-12-2010 828303209@GENIA Treebank@formal@@1@S@Furthermore, R24 treatment resulted in translocation of c-rel, but little or no NF kappa B p50 or p65, from the cytoplasm to the nucleus and an increase of NF kappa B binding complexes containing c-rel and p50.@@@@1@41@@oe@16-12-2010 828303210@GENIA Treebank@formal@@1@S@This treatment also caused increased tyrosine phosphorylation of specific protein substrates.@@@@1@12@@oe@16-12-2010 828303211@GENIA Treebank@formal@@1@S@R24-stimulated increases in proliferation, cytotoxicity, and cell surface protein expression could be blocked by cyclosporin and staurosporin, indicating that cyclophilin/calcineurin and protein kinase C may be involved in the R24 signaling pathway.@@@@1@36@@oe@16-12-2010 828303212@GENIA Treebank@formal@@1@S@Additionally, herbimycin A, a tyrosine kinase inhibitor, blocked the R24-stimulated increase in proliferation but not cytotoxicity at concentrations consistent with specificity for tyrosine kinases.@@@@1@28@@oe@16-12-2010 828303213@GENIA Treebank@formal@@1@S@These results suggest that multiple biochemical pathways are involved in the activation of human T cells by R24.@@@@1@19@@oe@16-12-2010 828947401@GENIA Treebank@formal@@1@S@The SCL protein displays cell-specific heterogeneity in size.@@@@1@9@@oe@16-12-2010 828947402@GENIA Treebank@formal@@1@S@SCL protein production was examined in a variety of hemopoietic cell lines by immunoblotting using specific polyclonal antisera.@@@@1@19@@oe@16-12-2010 828947403@GENIA Treebank@formal@@1@S@SCL protein was detected in erythroid, megakaryocyte, mast and early myeloid cell lines, as well as in several lymphoid leukemia cell lines which are known to harbor SCL gene rearrangements.@@@@1@34@@oe@16-12-2010 828947404@GENIA Treebank@formal@@1@S@In most cell lines, proteins of molecular weight 49 and 44 kDa were found, however two myeloid cell lines expressed only lower molecular weight species of 24 and 22 kDa.@@@@1@33@@oe@16-12-2010 828947405@GENIA Treebank@formal@@1@S@This size discrepancy appeared to be due to cell-specific translational regulation, since overexpression of a retrovirally transfected SCL gene yielded the higher molecular weight forms in most cell lines (GP+E-86, AT2.5, M1) but only the 22 kDa form in the myeloid cell line, WEHI-3B/D+.@@@@1@51@@oe@16-12-2010 828947406@GENIA Treebank@formal@@1@S@Overexpression of full-length SCL protein in the lymphoid cell lines, SupT1 and Raji, did not alter cell phenotype and there was no evidence for autoregulation of SCL transcription.@@@@1@31@@oe@16-12-2010 828947407@GENIA Treebank@formal@@1@S@The restricted pattern of SCL protein synthesis is consistent with the restricted expression of SCL mRNA documented previously.@@@@1@19@@oe@16-12-2010 828947408@GENIA Treebank@formal@@1@S@In addition, the present results indicate that SCL protein size was determined by regulation of translation in a cell-specific manner.@@@@1@22@@oe@16-12-2010 828979601@GENIA Treebank@formal@@1@S@Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors.@@@@1@20@@oe@16-12-2010 828979602@GENIA Treebank@formal@@1@S@The granulocyte-macrophage colony-stimulating factor (GM-CSF) gene has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation.@@@@1@23@@oe@16-12-2010 828979603@GENIA Treebank@formal@@1@S@The GM-CSF gene is not expressed in resting peripheral blood T cells but is rapidly induced at the transcriptional level following activation through the cell surface T-cell receptor.@@@@1@29@@oe@16-12-2010 828979604@GENIA Treebank@formal@@1@S@A highly conserved 19-bp element located immediately 5' of the human GM-CSF TATA box (bp -34 to -52), herein called purine box 1 (PB1), has been shown to bind a T-cell nuclear protein complex and to be required for transcriptional induction of the GM-CSF gene following T-cell activation.@@@@1@55@@oe@16-12-2010 828979605@GENIA Treebank@formal@@1@S@The PB1 sequence motif is highly conserved in both human and murine GM-CSF genes.@@@@1@15@@oe@16-12-2010 828979606@GENIA Treebank@formal@@1@S@In this report, we demonstrate that the PB1 element alone confers inducibility on a heterologous promoter following transfection into human Jurkat T cells.@@@@1@25@@oe@16-12-2010 828979607@GENIA Treebank@formal@@1@S@In addition, we identify a major PB1 nuclear protein-binding complex that is not present in resting peripheral blood T cells but is rapidly induced following T-cell activation.@@@@1@29@@oe@16-12-2010 828979608@GENIA Treebank@formal@@1@S@Sequence analysis revealed that PB1 is composed of adjacent binding sites for Ets and AP-1 transcription factors.@@@@1@18@@oe@16-12-2010 828979609@GENIA Treebank@formal@@1@S@In vitro mutagenesis experiments demonstrated that both the Ets and AP-1 sites are required for binding of the inducible PB1 nuclear protein complex and for the transcriptional activity of this element and the GM-CSF promoter in activated T cells.@@@@1@40@@oe@16-12-2010 828979610@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 828981301@GENIA Treebank@formal@@1@S@Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product: implications for viral latency.@@@@1@26@@oe@16-12-2010 828981302@GENIA Treebank@formal@@1@S@Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of the adult T-cell leukemia, an aggressive and often fatal malignancy of activated human CD4 T cells.@@@@1@32@@oe@16-12-2010 828981303@GENIA Treebank@formal@@1@S@HTLV-I encodes an essential 40-kDa protein termed Tax that not only transactivates the long terminal repeat of this retrovirus but also induces an array of cellular genes.@@@@1@28@@oe@16-12-2010 828981304@GENIA Treebank@formal@@1@S@Tax-mediated transformation of T cells likely involves the deregulated expression of various cellular genes that normally regulate lymphocyte growth produced by altered activity of various endogenous host transcription factors.@@@@1@30@@oe@16-12-2010 828981305@GENIA Treebank@formal@@1@S@In particular, Tax is capable of modulating the expression or activity of various host transcription factors, including members of the NF-kappa B/Rel and CREB/ATF families, as well as the cellular factors HEB-1 and p67SRF.@@@@1@38@@oe@16-12-2010 828981306@GENIA Treebank@formal@@1@S@An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells.@@@@1@24@@oe@16-12-2010 828981307@GENIA Treebank@formal@@1@S@In this study, we demonstrate that HTLV-I Tax can physically associate with p100, the product of the Rel-related NF-kappa B2 gene, both in transfected cells and in HTLV-I-infected leukemic T-cell lines.@@@@1@35@@oe@16-12-2010 828981308@GENIA Treebank@formal@@1@S@Furthermore, the physical interaction of Tax with p100 leads to the inhibition of Tax-induced activation of the HTLV-I and human immunodeficiency virus type 1 long terminal repeats, reflecting p100-mediated cytoplasmic sequestration of the normally nuclearly expressed Tax protein.@@@@1@41@@oe@16-12-2010 828981309@GENIA Treebank@formal@@1@S@In contrast, a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100.@@@@1@22@@oe@16-12-2010 828981310@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 829122801@GENIA Treebank@formal@@1@S@Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in anti-immunoglobulin-treated B cells.@@@@1@16@@oe@16-12-2010 829122802@GENIA Treebank@formal@@1@S@Initiation of the Epstein-Barr virus (EBV) lytic cycle is dependent on the transcription of the BZLF1 gene.@@@@1@20@@oe@16-12-2010 829122803@GENIA Treebank@formal@@1@S@The BZLF1 gene promoter (Zp) was activated by crosslinking of cell surface immunoglobulin (Ig) with anti-Ig antibody in B cells, even in the absence of other viral genes.@@@@1@34@@oe@16-12-2010 829122804@GENIA Treebank@formal@@1@S@We identified several anti-Ig response elements within Zp, which were originally defined as 12-O-tetradecanoylphorbol-13-acetate (TPA) response elements (ZI repeats and ZII, an AP-1-like domain).@@@@1@31@@oe@16-12-2010 829122805@GENIA Treebank@formal@@1@S@Since anti-Ig crosslinking leads to activation of protein kinase C (PKC) and an increase in intracellular calcium level, Zp was tested for the response to these cellular factors.@@@@1@32@@oe@16-12-2010 829122806@GENIA Treebank@formal@@1@S@Treatment with calcium ionophore A23187 increased Zp activity.@@@@1@9@@oe@16-12-2010 829122807@GENIA Treebank@formal@@1@S@When the calcium ionophore was used in conjunction with TPA, a PKC activator, the Zp induction was synergistically enhanced.@@@@1@22@@oe@16-12-2010 829122808@GENIA Treebank@formal@@1@S@1-(5-Isoquinolinyl sulfonyl)-2-methylpiperazine, an inhibitor of PKC, inhibited the anti-Ig inducibility of Zp.@@@@1@14@@oe@16-12-2010 829122809@GENIA Treebank@formal@@1@S@Calmodulin antagonists, compound R24571 and trifluoperazine, blocked the Zp activation with anti-Ig.@@@@1@15@@oe@16-12-2010 829122810@GENIA Treebank@formal@@1@S@These findings suggest that Zp responds directly to changes in the activity of both PKC and calcium/calmodulin-dependent protein kinase.@@@@1@20@@oe@16-12-2010 829122811@GENIA Treebank@formal@@1@S@Requirement of tyrosine kinase activation for the anti-Ig-mediated Zp activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin.@@@@1@23@@oe@16-12-2010 829122812@GENIA Treebank@formal@@1@S@These cellular gene regulatory molecules induced with anti-Ig may cooperatively play an important part in achieving efficient EBV activation as seen with anti-Ig treatment in B cells.@@@@1@28@@oe@16-12-2010 829812701@GENIA Treebank@formal@@1@S@Retinoic acid downmodulates erythroid differentiation and GATA1 expression in purified adult-progenitor culture.@@@@1@13@@oe@16-12-2010 829812702@GENIA Treebank@formal@@1@S@All-trans retinoic acid (RA) is an important morphogen in vertebrate development, a normal constituent in human adult blood and is also involved in the control of cell growth and differentiation in acute promyelocytic leukemia.@@@@1@38@@oe@16-12-2010 829812703@GENIA Treebank@formal@@1@S@We have examined the effects of RA on normal hematopoiesis by using early hematopoietic progenitor cells (HPC) stringently purified from adult peripheral blood.@@@@1@26@@oe@16-12-2010 829812704@GENIA Treebank@formal@@1@S@In clonogenetic fetal calf serum-supplemented (FCS+) or -nonsupplemented (FCS-) culture treated with saturating levels of interleukin-3 (IL-3) granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Ep) (combined with c-kit ligand in FCS(-)-culture conditions), RA induces a dramatic dose-dependent shift from erythroid to granulomonocytic colony formation, the latter colonies being essentially represented by granulocytic clones.@@@@1@67@@oe@16-12-2010 829812705@GENIA Treebank@formal@@1@S@This shift is apparently not caused by a recruitment phenomenon, because in FCS+ culture, the total number of colonies is not significantly modified by RA addition.@@@@1@29@@oe@16-12-2010 829812706@GENIA Treebank@formal@@1@S@In FCS- liquid-suspension culture supplemented with saturating Ep level and low-dose IL-3/GM-CSF, adult HPC undergo unilineage erythropoietic differentiation: Here again, treatment with high-dose RA induces a shift from the erythroid to granulocytic differentiation pathway.@@@@1@38@@oe@16-12-2010 829812707@GENIA Treebank@formal@@1@S@Studies on RA time-response or pulse treatment in semisolid or liquid culture show that early RA addition is most effective, thus indicating that early but not late HPC are sensitive to its action.@@@@1@35@@oe@16-12-2010 829812708@GENIA Treebank@formal@@1@S@We then analyzed the expression of the master GATA1 gene, which encodes a finger transcription factor required for normal erythroid development; addition of RA to HPC stimulated into unilineage erythropoietic differentiation in liquid culture caused a virtually complete inhibition of GATA1 mRNA induction.@@@@1@46@@oe@16-12-2010 829812709@GENIA Treebank@formal@@1@S@These results indicate that RA directly inhibits the erythroid differentiation program at the level of early adult HPC, and may lead to a shift from the erythroid to granulocytic differentiation pathway.@@@@1@33@@oe@16-12-2010 829812710@GENIA Treebank@formal@@1@S@This phenomenon is correlated with inhibition of GATA1 induction in the early stages of erythropoietic differentiation.@@@@1@17@@oe@16-12-2010 830229601@GENIA Treebank@formal@@1@S@Induction of phosphatidylinositol turnover and EGR-1 mRNA expression by crosslinking of surface IgM and IgD in the human B cell line B104.@@@@1@23@@oe@16-12-2010 830229602@GENIA Treebank@formal@@1@S@We have previously shown that a human B lymphoma cell line, B104, expressed surface IgM (sIgM) and surface IgD (sIgD), and that crosslinking of sIgM and sIgD by anti-IgM antibody (Ab) and anti-IgD Ab, respectively, induced Ca2+ influx to almost the same degree, whereas only sIgM-crosslinking caused B104 cell death.@@@@1@63@@oe@16-12-2010 830229603@GENIA Treebank@formal@@1@S@Here, we investigated the accumulation of cyclic AMP (cAMP), the hydrolysis of inositol phosphates, protein kinase C (PKC) activity and the induction of Egr-1 and c-fos mRNA expression by sIgM- and sIgD-crosslinking to examine differences in the signals mediated through sIgM and sIgD in B104 cells.@@@@1@54@@oe@16-12-2010 830229604@GENIA Treebank@formal@@1@S@Both sIgM- and sIgD-crosslinking with antibodies induced elevation of cAMP levels, phosphatidylinositol turnover, PKC activation and expression of Egr-1 and c-fos mRNA, although sIgM-crosslinking was more effective than sIgD-crosslinking, presumably due to the higher expression of sIgM than of sIgD.@@@@1@45@@oe@16-12-2010 830229605@GENIA Treebank@formal@@1@S@Egr-1 mRNA expression induced by sIgM- and sIgD-crosslinking was inhibited by H7, erbstatin and genistein, but not by HA1004.@@@@1@22@@oe@16-12-2010 830229606@GENIA Treebank@formal@@1@S@Erbstatin and genistein inhibited the sIg-crosslinking-induced Egr-1 mRNA expression in a dose-dependent manner parallel to that observed in the inhibition of sIg-crosslinking-induced protein tyrosine phosphorylation.@@@@1@26@@oe@16-12-2010 830229607@GENIA Treebank@formal@@1@S@Phorbol myristate acetate induced Egr-1 mRNA expression but forskolin and dibutyryl cyclic AMP did not.@@@@1@16@@oe@16-12-2010 830229608@GENIA Treebank@formal@@1@S@These findings suggest that the Egr-1 mRNA activating signals through sIgM and sIgD are protein tyrosine kinase- and PKC-dependent, but protein kinase A-independent.@@@@1@25@@oe@16-12-2010 830229609@GENIA Treebank@formal@@1@S@Cyclosporin A (CsA) and FK506 rescued B104 cells from death induced by anti-IgM Ab, but did not affect the expression of Egr-1 and c-fos mRNA, showing that CsA and FK506 affect signal transducers differently from or downstream to these molecules.@@@@1@45@@oe@16-12-2010 830229610@GENIA Treebank@formal@@1@S@The difference in signals transduced through sIgM and sIgD in B104 cells is discussed.@@@@1@15@@oe@16-12-2010 830798201@GENIA Treebank@formal@@1@S@G(Anh)MTetra, a natural bacterial cell wall breakdown product, induces interleukin-1 beta and interleukin-6 expression in human monocytes.@@@@1@20@@oe@16-12-2010 830798202@GENIA Treebank@formal@@1@S@A study of the molecular mechanisms involved in inflammatory cytokine expression [published erratum appears in J Biol Chem 1994 Jun 17;269(24):16983]@@@@1@30@@oe@16-12-2010 830798203@GENIA Treebank@formal@@1@S@It is believed that induction of cytokine expression by bacterial cell wall components plays a role in the development and course of sepsis.@@@@1@24@@oe@16-12-2010 830798204@GENIA Treebank@formal@@1@S@However, most attention has been focused on lipopolysaccharide (LPS).@@@@1@13@@oe@16-12-2010 830798205@GENIA Treebank@formal@@1@S@We studied the ability of N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D- isoglutamyl-m-diaminopimelyl-D-alanine (G(Anh)MTetra), a naturally occurring breakdown product of peptidoglycan that is produced by soluble lytic transglycosylase of Escherichia coli, to induce cytokine expression in human monocytes.@@@@1@36@@oe@16-12-2010 830798206@GENIA Treebank@formal@@1@S@G(Anh)MTetra was found to strongly induce interleukin (IL)-1 beta and IL-6 mRNA expression after 2 h and IL-1 beta and IL-6 protein secretion after 48 h of activation.@@@@1@32@@oe@16-12-2010 830798207@GENIA Treebank@formal@@1@S@The increase in mRNA accumulation was at least partly due to an increase in the transcription rates of the respective genes and was accompanied by a strong induction of nuclear factor-kappa B and activator protein-1 transcription factor expression.@@@@1@39@@oe@16-12-2010 830798208@GENIA Treebank@formal@@1@S@Experiments using inhibitors of protein kinase C, protein kinase A, and tyrosine kinase-dependent pathways revealed that G(Anh)MTetra-induced IL-1 beta and IL-6 mRNA expression involves activation of an H7-inhibitable pathway.@@@@1@32@@oe@16-12-2010 830798209@GENIA Treebank@formal@@1@S@By using the protein synthesis inhibitor cycloheximide, it was shown that G(Anh)MTetra-induced IL-6 mRNA expression depends on the synthesis of new protein, whereas G(Anh)MTetra-induced IL-1 beta mRNA accumulation does not.@@@@1@33@@oe@16-12-2010 830798210@GENIA Treebank@formal@@1@S@When responses to G(Anh)MTetra were compared with those to LPS and muramyldipeptide (MDP), it was found that the optimal response to G(Anh)MTetra induction was similar to that of LPS but significantly higher than the response to MDP.@@@@1@41@@oe@16-12-2010 830798211@GENIA Treebank@formal@@1@S@Furthermore, maximal G(Anh)MTetra-induced IL-1 beta and IL-6 mRNA expression could be enhanced by co-stimulation with LPS or MDP, suggesting that different receptors and/or transduction pathways were involved.@@@@1@30@@oe@16-12-2010 830798212@GENIA Treebank@formal@@1@S@These results indicate that G(Anh)MTetra induces IL-1 beta and IL-6 expression in human monocytes suggesting a possible role for G(Anh)MTetra in the release of cytokines during sepsis.@@@@1@28@@oe@16-12-2010 831479201@GENIA Treebank@formal@@1@S@Comparative analysis of NFAT (nuclear factor of activated T cells) complex in human T and B lymphocytes.@@@@1@20@@oe@16-12-2010 831479202@GENIA Treebank@formal@@1@S@Nuclear factor of activated T cells (NFAT) is a transcriptional activator that binds to sequences in the interleukin-2 (IL-2) promoter and is thought to be largely responsible for the T cell-specific inducibility of IL-2 expression.@@@@1@40@@oe@16-12-2010 831479203@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays (EMSA) showed that specific NFAT binding activity could also be induced in human B cells.@@@@1@22@@oe@16-12-2010 831479204@GENIA Treebank@formal@@1@S@The B cell NFAT complex, however, was not functional, since it failed to activate transcription from an NFAT-driven chloramphenicol acetyltransferase (CAT) construct.@@@@1@28@@oe@16-12-2010 831479205@GENIA Treebank@formal@@1@S@Competition with an AP-1 motif or with anti-Jun and anti-Fos antibodies abolished binding to the NFAT motif in both T and B cells, indicating that Jun and Fos are critical for NFAT complex formation in both cell types.@@@@1@40@@oe@16-12-2010 831479206@GENIA Treebank@formal@@1@S@Purified recombinant Jun and Fos proteins failed to bind directly to the NFAT motif.@@@@1@15@@oe@16-12-2010 831479207@GENIA Treebank@formal@@1@S@However, when combined with unstimulated B or T cell extracts, full-length, but not truncated, Jun/Fos heterodimers were able to form an NFAT complex, indicating the presence of a constitutively expressed nuclear factor(s) in B and T cells necessary for the formation of the NFAT complex in both cell types.@@@@1@58@@oe@16-12-2010 831479208@GENIA Treebank@formal@@1@S@An NFAT oligonucleotide carrying mutations in the 5' purine-rich part of the NFAT sequence failed to form a complex and to compete with the wild type motif for NFAT complex formation in both T and B cells.@@@@1@38@@oe@16-12-2010 831479209@GENIA Treebank@formal@@1@S@We therefore propose a model whereby a core NFAT complex consisting of Jun, Fos, and a constitutive nuclear factor is formed in both T and B cells, but an additional factor and/or post-translational modification of a factor, missing in B cells, might be required for transactivation by NFAT.@@@@1@54@@oe@16-12-2010 831485701@GENIA Treebank@formal@@1@S@1,25-Dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate synergistically induce monocytic cell differentiation: FOS and RB expression.@@@@1@17@@oe@16-12-2010 831485702@GENIA Treebank@formal@@1@S@1,25-dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate (TPA) interact synergistically to induce monocytic differentiation of U937 histiocytic lymphoma cells.@@@@1@21@@oe@16-12-2010 831485703@GENIA Treebank@formal@@1@S@Addition of TPA causes an otherwise ineffective dose of 1,25-dihydroxy vitamin D3 to induce differentiation.@@@@1@16@@oe@16-12-2010 831485704@GENIA Treebank@formal@@1@S@The induced differentiation depends on the simultaneous (vs. sequential) presence of both agents.@@@@1@16@@oe@16-12-2010 831485705@GENIA Treebank@formal@@1@S@The kinetics of induced differentiation are consistent with a G1 specific cellular response to initiate the metabolic cascade culminating in cell differentiation.@@@@1@23@@oe@16-12-2010 831485706@GENIA Treebank@formal@@1@S@The induced differentiation occurs with down-regulation of c-fos protein and an accompanying up-regulation of RB protein expression, consistent with a possible need for up-regulated RB expression to maintain a given differentiated phenotype and suppress transcriptional activators that might typically be associated with proliferation.@@@@1@45@@oe@16-12-2010 831685901@GENIA Treebank@formal@@1@S@Regulation of lymphoid-specific immunoglobulin mu heavy chain gene enhancer by ETS-domain proteins.@@@@1@13@@oe@16-12-2010 831685902@GENIA Treebank@formal@@1@S@The enhancer for the immunoglobulin mu heavy chain gene (IgH) activates a heterologous gene at the pre-B cell stage of B lymphocyte differentiation.@@@@1@26@@oe@16-12-2010 831685903@GENIA Treebank@formal@@1@S@A lymphoid-specific element, microB, is necessary for enhancer function in pre-B cells.@@@@1@15@@oe@16-12-2010 831685904@GENIA Treebank@formal@@1@S@A microB binding protein is encoded by the PU.1/Spi-1 proto-oncogene.@@@@1@11@@oe@16-12-2010 831685905@GENIA Treebank@formal@@1@S@Another sequence element, microA, was identified in the mu enhancer that binds the product of the ets-1 proto-oncogene.@@@@1@21@@oe@16-12-2010 831685906@GENIA Treebank@formal@@1@S@The microA motif was required for microB-dependent enhancer activity, which suggests that a minimal B cell-specific enhancer is composed of both the PU.1 and Ets-1 binding sites.@@@@1@29@@oe@16-12-2010 831685907@GENIA Treebank@formal@@1@S@Co-expression of both PU.1 and Ets-1 in nonlymphoid cells trans-activated reporter plasmids that contained the minimal mu enhancer.@@@@1@19@@oe@16-12-2010 831685908@GENIA Treebank@formal@@1@S@These results implicate two members of the Ets family in the activation of IgH gene expression.@@@@1@17@@oe@16-12-2010 831957401@GENIA Treebank@formal@@1@S@Differential autoregulation of glucocorticoid receptor expression in human T- and B-cell lines.@@@@1@13@@oe@16-12-2010 831957402@GENIA Treebank@formal@@1@S@Regulation of glucocorticoid receptor (GR) expression by its cognate ligand was examined in the glucocorticoid-sensitive human leukemic T-cell line 6TG1.1 and in the human B-cell line IM-9.@@@@1@30@@oe@16-12-2010 831957403@GENIA Treebank@formal@@1@S@In contrast to the decrease in GR mRNA seen in IM-9 cells after treatment with 1 microM dexamethasone for 16-18 h, treatment of 6TG1.1 cells resulted in an 8-fold increase in GR mRNA, as determined by Northern blot and RNase protection analysis, with a corresponding 3- to 4-fold increase in GR protein.@@@@1@56@@oe@16-12-2010 831957404@GENIA Treebank@formal@@1@S@Half-maximal induction of GR mRNA and protein in 6TG1.1 cells was observed between 10-100 nM dexamethasone, and inclusion of 1 microM RU 38486 completely blocked the effects of 100 nM dexamethasone, demonstrating that positive autoregulation of GR expression in 6TG1.1 cells is a receptor-mediated response.@@@@1@48@@oe@16-12-2010 831957405@GENIA Treebank@formal@@1@S@Positive autoregulation of GR expression was also observed in glucocorticoid-resistant CEM-C1 cells, which contain functional GR, but whose growth is unaffected by glucocorticoids.@@@@1@26@@oe@16-12-2010 831957406@GENIA Treebank@formal@@1@S@Thus, positive autoregulation is neither a consequence nor the sole cause of growth arrest.@@@@1@16@@oe@16-12-2010 831957407@GENIA Treebank@formal@@1@S@The degree of negative autoregulation in IM-9 cells and positive autoregulation in 6TG1.1 cells was unaffected by inhibition of protein synthesis with cycloheximide.@@@@1@24@@oe@16-12-2010 831957408@GENIA Treebank@formal@@1@S@Measurement of GR mRNA turnover in 6TG1.1 cells treated with actinomycin-D revealed a half-life of 2.5 h, which was unaffected by dexamethasone treatment.@@@@1@25@@oe@16-12-2010 831957409@GENIA Treebank@formal@@1@S@A similar half-life was determined in IM-9 cells and was also unaffected by steroid treatment.@@@@1@16@@oe@16-12-2010 831957410@GENIA Treebank@formal@@1@S@These results are consistent with the interpretation that glucocorticoid-mediated autoregulation of GR expression is a tissue-specific primary transcriptional response.@@@@1@20@@oe@16-12-2010 831991201@GENIA Treebank@formal@@1@S@The p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms.@@@@1@15@@oe@16-12-2010 831991202@GENIA Treebank@formal@@1@S@Transcription factor NF-kappa B (p50/p65) is generally localized to the cytoplasm by its inhibitor I kappa B.@@@@1@20@@oe@16-12-2010 831991203@GENIA Treebank@formal@@1@S@Overproduced I kappa B, free from NF-kappa B, is rapidly degraded.@@@@1@14@@oe@16-12-2010 831991204@GENIA Treebank@formal@@1@S@Overexpression of p65 increases endogenous I kappa B protein in both carcinoma and lymphoid cells by two mechanisms: protein stabilization and increased transcription of I kappa B mRNA.@@@@1@30@@oe@16-12-2010 831991205@GENIA Treebank@formal@@1@S@In contrast, p65 delta, a naturally occurring splice variant, fails to markedly augment I kappa B protein levels.@@@@1@22@@oe@16-12-2010 831991206@GENIA Treebank@formal@@1@S@Both overexpressed p65 and coexpressed p50 are cytoplasmic, whereas p65 delta is partly nuclear, indicating that the I kappa B induced by p65 can maintain NF-kappa B in the cytoplasm.@@@@1@33@@oe@16-12-2010 831991207@GENIA Treebank@formal@@1@S@Thus, p65 and I kappa B are linked in an autoregulatory loop, ensuring that NF-kappa B is held in the cytoplasm until cells are specifically induced to translocate it to the nucleus.@@@@1@35@@oe@16-12-2010 832120401@GENIA Treebank@formal@@1@S@Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F.@@@@1@22@@oe@16-12-2010 832120402@GENIA Treebank@formal@@1@S@The transcription factor E2F activates the expression of multiple genes involved in cell proliferation, such as c-myc and the dihydrofolate reductase gene.@@@@1@24@@oe@16-12-2010 832120403@GENIA Treebank@formal@@1@S@Regulation of E2F involves its interactions with other cellular proteins, including the retinoblastoma protein (Rb), the Rb-related protein p107, cyclin A, and cdk2.@@@@1@30@@oe@16-12-2010 832120404@GENIA Treebank@formal@@1@S@We undertook a detailed analysis of E2F DNA-binding activities and their cell cycle behavior in primary human T cells.@@@@1@20@@oe@16-12-2010 832120405@GENIA Treebank@formal@@1@S@Three E2F DNA-binding activities were identified in resting (G0) T cells with mobilities in gel shift assays distinct from those of previously defined E2F complexes.@@@@1@28@@oe@16-12-2010 832120406@GENIA Treebank@formal@@1@S@One of these activities was found to be a novel, less abundant, Rb-E2F complex.@@@@1@17@@oe@16-12-2010 832120407@GENIA Treebank@formal@@1@S@The most prominent E2F activity in resting T cells (termed complex X) was abundant in both G0 and G1 but disappeared as cells entered S phase, suggesting a possible role in negatively regulating E2F function.@@@@1@39@@oe@16-12-2010 832120408@GENIA Treebank@formal@@1@S@Complex X could be dissociated by adenovirus E1A with a requirement for an intact E1A conserved region 2.@@@@1@19@@oe@16-12-2010 832120409@GENIA Treebank@formal@@1@S@However, X failed to react with a variety of antibodies against Rb or p107, implicating the involvement of an E1A-binding protein other than Rb or p107.@@@@1@29@@oe@16-12-2010 832120410@GENIA Treebank@formal@@1@S@In addition to these novel E2F complexes, three distinct forms of unbound (free) E2F were resolved in gel shift experiments.@@@@1@24@@oe@16-12-2010 832120411@GENIA Treebank@formal@@1@S@These species showed different cell cycle kinetics.@@@@1@8@@oe@16-12-2010 832120412@GENIA Treebank@formal@@1@S@UV cross-linking experiments suggested that a distinct E2F DNA-binding protein is uniquely associated with the S-phase p107 complex and is not associated with Rb.@@@@1@25@@oe@16-12-2010 832120413@GENIA Treebank@formal@@1@S@Together, these results suggest that E2F consists of multiple, biochemically distinct DNA-binding proteins which function at different points in the cell cycle.@@@@1@25@@oe@16-12-2010 832532201@GENIA Treebank@formal@@1@S@Occurrence of a silencer of the interleukin-2 gene in naive but not in memory resting T helper lymphocytes.@@@@1@19@@oe@16-12-2010 832532202@GENIA Treebank@formal@@1@S@In the immune system the first activation of a naive T cell by antigen is a key step in the shaping of the peripheral T cell specificity repertoire and maintenance of self-tolerance.@@@@1@33@@oe@16-12-2010 832532203@GENIA Treebank@formal@@1@S@In the present study, analysis of the interleukin-2 (IL-2) gene activation shows that naive human helper T cells (cord blood CD4+ T cells, adult CD4+CD45RO- T cells) regulate IL-2 transcription by a mechanism involving both a silencer and an activator acting on the purine-rich IL-2 promoter elements (NF-AT binding sites).@@@@1@59@@oe@16-12-2010 832532204@GENIA Treebank@formal@@1@S@By contrast, memory cells, either in vitro activated helper T cells reverting to a resting state, or CD4+ T (memory) clones, or CD4+CD45RO+ T cells isolated ex vivo, no longer have a silencer.@@@@1@41@@oe@16-12-2010 832532205@GENIA Treebank@formal@@1@S@Their IL-2 transcription seems to be controlled solely by the transition from inactive to active functional state of a positive transcription factor binding to these promoter elements as well as its cytoplasmic or nuclear location: in resting memory T cells the activator is located in the cytoplasm and is inactive, whereas in stimulated cells it is functional in promoting transcription and now resides in the nucleus.@@@@1@69@@oe@16-12-2010 832532206@GENIA Treebank@formal@@1@S@Thus, the regulation of the gene coding for the main T cell growth factor changes irreversibly after the first encounter of T cells with antigen.@@@@1@27@@oe@16-12-2010 832532207@GENIA Treebank@formal@@1@S@It is most likely that the presence of a silencer contributes to the more stringent activation requirements of naive CD4+ T cells.@@@@1@23@@oe@16-12-2010 832595001@GENIA Treebank@formal@@1@S@Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: application for diagnosis, genetic counseling, and therapy.@@@@1@27@@oe@16-12-2010 832595002@GENIA Treebank@formal@@1@S@Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes, a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males.@@@@1@31@@oe@16-12-2010 832595003@GENIA Treebank@formal@@1@S@In this report, we address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis, genetic counseling, and molecular subclassification of affected patients and their families.@@@@1@34@@oe@16-12-2010 832595004@GENIA Treebank@formal@@1@S@DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied.@@@@1@20@@oe@16-12-2010 832595005@GENIA Treebank@formal@@1@S@Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing.@@@@1@25@@oe@16-12-2010 832595006@GENIA Treebank@formal@@1@S@Female family members were also studied to identify heterozygote carriers.@@@@1@11@@oe@16-12-2010 832595007@GENIA Treebank@formal@@1@S@Point mutations in the AR gene were identified in all six patients, and all mutations caused amino acid substitutions.@@@@1@21@@oe@16-12-2010 832595008@GENIA Treebank@formal@@1@S@One patient with incomplete androgen insensitivity was a mosaic for the mutation.@@@@1@13@@oe@16-12-2010 832595009@GENIA Treebank@formal@@1@S@Four of the five mothers, as well as a young sister of one patient, were carriers of the mutation present in the affected child.@@@@1@27@@oe@16-12-2010 832595010@GENIA Treebank@formal@@1@S@Our data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome.@@@@1@20@@oe@16-12-2010 832595011@GENIA Treebank@formal@@1@S@Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy, and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance.@@@@1@33@@oe@16-12-2010 832595012@GENIA Treebank@formal@@1@S@The identification of carriers is of substantial clinical importance for genetic counseling.@@@@1@13@@oe@16-12-2010 833089801@GENIA Treebank@formal@@1@S@Nuclear factor kappa B, a mediator of lipopolysaccharide effects.@@@@1@11@@oe@16-12-2010 833089802@GENIA Treebank@formal@@1@S@Exposure of certain cell types to bacterial lipopolysaccharide (LPS) leads to activation of nuclear factor kappa B (NF-kappa B), an inducible transcription factor.@@@@1@29@@oe@16-12-2010 833089803@GENIA Treebank@formal@@1@S@One of NF-kappa B's unique properties is its posttranslational activation via release of an inhibitory subunit, called inhibitor of NF-kappa B (I kappa B), from a sequestered cytoplasmic form.@@@@1@35@@oe@16-12-2010 833089804@GENIA Treebank@formal@@1@S@This event is also triggered under various other conditions of biomedical importance.@@@@1@13@@oe@16-12-2010 833089805@GENIA Treebank@formal@@1@S@Other bacterial toxins, tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), T cell mitogens, UV light, gamma rays and oxidative stress were reported to induce NF-kappa B.@@@@1@35@@oe@16-12-2010 833089806@GENIA Treebank@formal@@1@S@The activated form of NF-kappa B, which is rapidly taken up into nuclei, initiates transcription from immediate early genes in a wide variety of cell types.@@@@1@29@@oe@16-12-2010 833089807@GENIA Treebank@formal@@1@S@Most of the target genes for NF-kappa B are of relevance for the immune response and can be grouped into those encoding cytokines, cell surface receptors, acute phase proteins and viral genomes, such as that of human immunodeficiency virus type 1 (HIV-1).@@@@1@48@@oe@16-12-2010 833089808@GENIA Treebank@formal@@1@S@We will discuss recent experimental evidences suggesting that LPS might share a pathway of NF-kappa B activation with other inducers of the factor.@@@@1@24@@oe@16-12-2010 833089809@GENIA Treebank@formal@@1@S@This common pathway may involve reactive oxygen intermediates (ROI) as messenger molecules.@@@@1@15@@oe@16-12-2010 833249201@GENIA Treebank@formal@@1@S@Human T cell transcription factor GATA-3 stimulates HIV-1 expression.@@@@1@10@@oe@16-12-2010 833249202@GENIA Treebank@formal@@1@S@A family of transcriptional activating proteins, the GATA factors, has been shown to bind to a consensus motif through a highly conserved C4 zinc finger DNA binding domain.@@@@1@31@@oe@16-12-2010 833249203@GENIA Treebank@formal@@1@S@One member of this multigene family, GATA-3, is most abundantly expressed in T lymphocytes, a cellular target for human immunodeficiency virus type 1 (HIV-1) infection and replication.@@@@1@33@@oe@16-12-2010 833249204@GENIA Treebank@formal@@1@S@In vitro DNase I footprinting analysis revealed six hGATA-3 binding sites in the U3 region (the transcriptional regulatory domain) of the HIV-1 LTR.@@@@1@26@@oe@16-12-2010 833249205@GENIA Treebank@formal@@1@S@Cotransfection of an hGATA-3 expression plasmid with a reporter plasmid whose transcription is directed by the HIV-1 LTR resulted in 6- to 10-fold stimulation of LTR-mediated transcription, whereas site specific mutation of these GATA sites resulted in virtual abrogation of the activation by hGATA-3.@@@@1@46@@oe@16-12-2010 833249206@GENIA Treebank@formal@@1@S@Further, deletion of the hGATA-3 transcriptional activation domain abolished GATA-dependent HIV-1 trans-activation, showing that the stimulation of viral transcription observed is a direct effect of cotransfected hGATA-3.@@@@1@30@@oe@16-12-2010 833249207@GENIA Treebank@formal@@1@S@Introduction of the HIV-1 plasmids in which the GATA sites have been mutated into human T lymphocytes also caused a significant reduction in LTR-mediated transcription at both the basal level and in (PHA- plus PMA-) stimulated T cells.@@@@1@41@@oe@16-12-2010 833249208@GENIA Treebank@formal@@1@S@These observations suggest that in addition to its normal role in T lymphocyte gene regulation, hGATA-3 may also play a significant role in HIV-1 transcriptional activation.@@@@1@28@@oe@16-12-2010 833591301@GENIA Treebank@formal@@1@S@Analysis of the preexisting and nuclear forms of nuclear factor of activated T cells.@@@@1@15@@oe@16-12-2010 833591302@GENIA Treebank@formal@@1@S@The nuclear factor of activated T cells (NF-AT)3 is an inducible DNA-binding protein that is essential for transcriptional induction of the IL-2 gene during T cell activation.@@@@1@31@@oe@16-12-2010 833591303@GENIA Treebank@formal@@1@S@NF-AT is thought to consist of two components: a ubiquitous, inducible nuclear component that we have identified as Fos and Jun proteins, and a preexisting, T cell-specific component (NF-ATp) which is the target for the immunosuppressive agents cyclosporin A (CsA) and FK506.@@@@1@51@@oe@16-12-2010 833591304@GENIA Treebank@formal@@1@S@We have previously shown that nuclear extracts from activated T cells form two inducible NF-AT complexes with an oligonucleotide corresponding to the distal NF-AT site of the murine IL-2 promoter, although hypotonic extracts of unstimulated T cells form a single complex containing NF-ATp.@@@@1@45@@oe@16-12-2010 833591305@GENIA Treebank@formal@@1@S@We show that the ability to detect NF-ATp in a gel shift assay, which is essential for purification and biochemical studies of this protein, is strikingly dependent on the precise sequence of the NF-AT oligonucleotide used as the labeled probe.@@@@1@43@@oe@16-12-2010 833591306@GENIA Treebank@formal@@1@S@Moreover we present evidence that the component that forms the faster-migrating ("lower") nuclear NF-AT complex is derived by a calcium-dependent, cyclosporin-sensitive, posttranslational modification of NF-ATp, and that Fos and Jun proteins stabilize its interaction with DNA.@@@@1@44@@oe@16-12-2010 833591307@GENIA Treebank@formal@@1@S@The results are discussed in the context of a model relating the two nuclear NF-AT complexes to NF-ATp.@@@@1@19@@oe@16-12-2010 834471401@GENIA Treebank@formal@@1@S@Enhancing effect of 17 beta-estradiol on human NK cell activity.@@@@1@11@@oe@16-12-2010 834471402@GENIA Treebank@formal@@1@S@The in vitro effect of 17 beta-estradiol on NK activity was studied.@@@@1@13@@oe@16-12-2010 834471403@GENIA Treebank@formal@@1@S@The proliferation and NK activity of YT-N17 (a human NK-like cell line) were enhanced by 17 beta-estradiol (E2), and the enhancement was blocked by tamoxifen (Tx), an antagonist of E2.@@@@1@39@@oe@16-12-2010 834471404@GENIA Treebank@formal@@1@S@On the contrary, other steroid hormones such as Tx, progesterone, and testosterone had no effect.@@@@1@19@@oe@16-12-2010 834471405@GENIA Treebank@formal@@1@S@YT-N17 contained 11.8 fmol/mg protein of estrogen receptor (mean of two independent assays), a value which was 5-10-fold higher than that of other hematopoietic cell lines.@@@@1@30@@oe@16-12-2010 834471406@GENIA Treebank@formal@@1@S@An enhancement of NK activity by E2 was also seen in large granular lymphocytes obtained from normal subjects, and it was again suppressed by Tx.@@@@1@27@@oe@16-12-2010 834471407@GENIA Treebank@formal@@1@S@These data suggest that E2 is one of the activating factors for NK/LGL cells.@@@@1@15@@oe@16-12-2010 838134901@GENIA Treebank@formal@@1@S@The Epstein-Barr virus nuclear antigen 2 interacts with an EBNA2 responsive cis-element of the terminal protein 1 gene promoter.@@@@1@20@@oe@16-12-2010 838134902@GENIA Treebank@formal@@1@S@The Epstein-Barr virus protein EBNA2 acts as a transcriptional activator of cellular and viral genes and plays a crucial role in the immortalization of human primary B-cells by EBV.@@@@1@30@@oe@16-12-2010 838134903@GENIA Treebank@formal@@1@S@We have shown previously that EBNA2 transactivates the promoters of the latent membrane antigens LMP, TP1 and TP2.@@@@1@20@@oe@16-12-2010 838134904@GENIA Treebank@formal@@1@S@The promoter of the TP1 gene was chosen as a model system to study the molecular mechanism of EBNA2 mediated transactivation.@@@@1@22@@oe@16-12-2010 838134905@GENIA Treebank@formal@@1@S@To identify an EBNA2 dependent cis-acting element, various TP1 promoter-reporter gene constructs were transfected in the absence and presence of an EBNA2 expression vector into the established B-cell line BL41-P3HR1.@@@@1@32@@oe@16-12-2010 838134906@GENIA Treebank@formal@@1@S@We were able to delineate an 81 bp EBNA2 responsive region between -258 and -177 relative to the TP1 RNA start site.@@@@1@23@@oe@16-12-2010 838134907@GENIA Treebank@formal@@1@S@The element worked in either orientation and could mediate EBNA2 dependent transactivation on a heterologous promoter.@@@@1@17@@oe@16-12-2010 838134908@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays revealed three specific protein-DNA complexes formed with sequences of the EBNA2 responsive element.@@@@1@18@@oe@16-12-2010 838134909@GENIA Treebank@formal@@1@S@Two of these were not cell type specific, but the third was detected only in EBNA2 positive cell extracts.@@@@1@21@@oe@16-12-2010 838134910@GENIA Treebank@formal@@1@S@Gel-shift analysis in the presence of EBNA2 specific monoclonal antibodies revealed that EBNA2 is a component of the third complex.@@@@1@21@@oe@16-12-2010 838134911@GENIA Treebank@formal@@1@S@Thus, these experiments demonstrate that EBNA2 interacts with an EBNA2 responsive cis-element of the TP1 promoter.@@@@1@18@@oe@16-12-2010 838332301@GENIA Treebank@formal@@1@S@The interleukin 2 CD28-responsive complex contains at least three members of the NF kappa B family: c-Rel, p50, and p65.@@@@1@24@@oe@16-12-2010 838332302@GENIA Treebank@formal@@1@S@Optimal activation of T cells requires at least two signals.@@@@1@11@@oe@16-12-2010 838332303@GENIA Treebank@formal@@1@S@One signal can be delivered by the antigen-specific T-cell receptor, and the second signal is provided by the costimulatory molecule(s) delivered by the antigen-presenting cell.@@@@1@30@@oe@16-12-2010 838332304@GENIA Treebank@formal@@1@S@CD28 is a T-cell surface molecule and stimulation through this protein plays an important role in delivering the second activation signal.@@@@1@22@@oe@16-12-2010 838332305@GENIA Treebank@formal@@1@S@In this report, we show that in human peripheral blood T cells, CD28-mediated signal transduction involves the rel family proteins--c-Rel, p50, and p65.@@@@1@30@@oe@16-12-2010 838332306@GENIA Treebank@formal@@1@S@Treatment of peripheral blood T cells with phorbol 12-myristate 13-acetate (PMA) and anti-CD28 monoclonal antibody (mAb) results in augmentation of nuclear c-Rel, p50, and p65, and this augmentation can occur in the presence of the immunosuppressant cyclosporin A.@@@@1@46@@oe@16-12-2010 838332307@GENIA Treebank@formal@@1@S@It is also shown in this report that, in response to PMA/anti-CD28 mAb or anti-CD3/anti-CD28 mAb, c-Rel, p50, and p65 are associated with CD28-responsive element present in the promoter of the human interleukin 2 gene.@@@@1@40@@oe@16-12-2010 838332308@GENIA Treebank@formal@@1@S@The functional significance of c-Rel involvement in the CD28-responsive complex is demonstrated by transient transfection analysis, where cotransfection of c-Rel augments the level of expression of a chloramphenicol acetyltransferase reporter gene linked to the CD28-responsive element.@@@@1@38@@oe@16-12-2010 838367701@GENIA Treebank@formal@@1@S@Stimulation of interleukin-1 alpha and interleukin-1 beta production in human monocytes by protein phosphatase 1 and 2A inhibitors.@@@@1@19@@oe@16-12-2010 838367702@GENIA Treebank@formal@@1@S@Protein phosphatases 1 and 2A are important in regulating cellular functions by controlling the phosphorylation state of their substrates.@@@@1@20@@oe@16-12-2010 838367703@GENIA Treebank@formal@@1@S@In human monocytes, the inhibitors of these phosphatases, okadaic acid and calyculin A, were found to increase the mRNA accumulation and cytokine production of interleukin-1 beta and interleukin-1 alpha.@@@@1@33@@oe@16-12-2010 838367704@GENIA Treebank@formal@@1@S@The increased mRNA accumulation was found to be primarily because of the increase in the transcription rate of the interleukin-1 genes.@@@@1@22@@oe@16-12-2010 838367705@GENIA Treebank@formal@@1@S@Stimulation of interleukin-1 gene transcription may be caused by the stimulation of transcription factor activities, including those of AP-1, by these protein phosphatase inhibitors.@@@@1@27@@oe@16-12-2010 838367706@GENIA Treebank@formal@@1@S@Okadaic acid increased the synthesis of the interleukin-1 beta precursor and mature forms and their secretion.@@@@1@17@@oe@16-12-2010 838367707@GENIA Treebank@formal@@1@S@This increased processing and secretion correlated with the stimulation of IL-1 beta convertase mRNA accumulation.@@@@1@16@@oe@16-12-2010 838367708@GENIA Treebank@formal@@1@S@The stimulation of interleukin-1 alpha production by okadaic acid was more modest than that of interleukin-1 beta.@@@@1@18@@oe@16-12-2010 838367709@GENIA Treebank@formal@@1@S@However, the phosphorylation of the precursor interleukin-1 alpha cytokine was increased.@@@@1@13@@oe@16-12-2010 838367710@GENIA Treebank@formal@@1@S@These results show that protein phosphatase 1 and 2A inhibitors exert multiple effects on cytokine production in human monocytes and suggest that these two phosphatases play important roles in regulating interleukin-1 production.@@@@1@33@@oe@16-12-2010 838591601@GENIA Treebank@formal@@1@S@The lytic transition of Epstein-Barr virus is imitated by recombinant B-cells.@@@@1@12@@oe@16-12-2010 838591602@GENIA Treebank@formal@@1@S@Lytic transition of Epstein-Barr virus (EBV) is initiated by distinct immediate early regulators of the viral cycle, in synchronization to temporary, permissive conditions during host cell differentiation.@@@@1@32@@oe@16-12-2010 838591603@GENIA Treebank@formal@@1@S@We developed eukaryotic vectors suitable to imitate the processes involved in lytic transition in cell culture systems.@@@@1@18@@oe@16-12-2010 838591604@GENIA Treebank@formal@@1@S@Two stable B cell lines were established: R59Z activator cells were used to induce lytic EBV expression in a constitutive manner by the production of the BZLF 1 trans-activator (Zta).@@@@1@34@@oe@16-12-2010 838591605@GENIA Treebank@formal@@1@S@R7-57 reporter cells, on the other hand, signaled induced activity of the lytic origin of EBV replication (ori Lyt).@@@@1@24@@oe@16-12-2010 838591606@GENIA Treebank@formal@@1@S@Different modes, like chemical induction, lytic superinfection with EBV and single gene trans-activation converted the recombinant ori Lyt element in R7-57 reporter cells.@@@@1@26@@oe@16-12-2010 838591607@GENIA Treebank@formal@@1@S@BZLF 1, transiently expressed in R7-57 reporter cells, was the only EBV trans-activator found, sufficient in inducing the viral lytic cycle.@@@@1@25@@oe@16-12-2010 838591608@GENIA Treebank@formal@@1@S@Basing on these experiments, trans-cellular activation of EBV was tested by cocultivation of BZLF 1-expressing R59Z activator cells with the R7-57 reporter line.@@@@1@25@@oe@16-12-2010 838591609@GENIA Treebank@formal@@1@S@No lytic effect on the reporter cells could be measured, neither by cocultivation of activator cells nor by coincubation of BZLF 1-containing cell lysates.@@@@1@26@@oe@16-12-2010 838591610@GENIA Treebank@formal@@1@S@Latency breaking activity, however, was transferred from activator to reporter cells when active, exogenous virus was added.@@@@1@21@@oe@16-12-2010 838591611@GENIA Treebank@formal@@1@S@The cell system described in these experiments provides a tool for the detection of EBV reactivation and demonstrates the potential of the lytic regulatory gene BZLF 1.@@@@1@28@@oe@16-12-2010 838666401@GENIA Treebank@formal@@1@S@Human CD3-CD16+ natural killer cells express the hGATA-3 T cell transcription factor and an unrearranged 2.3-kb TcR delta transcript.@@@@1@20@@oe@16-12-2010 838666402@GENIA Treebank@formal@@1@S@In this study we analyzed the T cell receptor(TcR) delta transcripts expressed by CD3-CD16+ cells and we investigated whether these cells expressed the hGATA-3 T cell transcription factor and the recombination-activating gene (RAG)-1.@@@@1@40@@oe@16-12-2010 838666403@GENIA Treebank@formal@@1@S@Multiple TcR delta transcripts deriving from an unrearranged TcR delta gene were detected in both polyclonal and clonal CD3-CD16+ natural killer(NK) cell lines.@@@@1@27@@oe@16-12-2010 838666404@GENIA Treebank@formal@@1@S@Two unrearranged TcR delta transcripts had a size similar to that of the functional TcR delta mRNA (2.3 and 1.3 kb) found in TcR gamma/delta+ T lymphocytes.@@@@1@30@@oe@16-12-2010 838666405@GENIA Treebank@formal@@1@S@Sequence analysis of nine different 2.3-kb cDNA clones obtained from NK-derived polyA+ RNA confirmed that they corresponded to an unrearranged TcR delta gene.@@@@1@24@@oe@16-12-2010 838666406@GENIA Treebank@formal@@1@S@These cDNA were 2343 bp long and their transcription initiation site was located 814 bp upstream from the J delta 1 segment.@@@@1@23@@oe@16-12-2010 838666407@GENIA Treebank@formal@@1@S@The sequence located upstream of the J delta 1 segment corresponded to the previously reported germ-line sequence.@@@@1@18@@oe@16-12-2010 838666408@GENIA Treebank@formal@@1@S@The J delta 1 segment was correctly spliced to C delta; in addition the four C delta exons were found to be already assembled.@@@@1@26@@oe@16-12-2010 838666409@GENIA Treebank@formal@@1@S@Two polyadenylation sites were present in the fourth C delta exon.@@@@1@12@@oe@16-12-2010 838666410@GENIA Treebank@formal@@1@S@However, only that located at the 3' end appeared to be utilized in the 2.3-kb cDNA.@@@@1@18@@oe@16-12-2010 838666411@GENIA Treebank@formal@@1@S@The expression of hGATA-3, a T cell-specific factor known to be involved in the regulation of the transcription of TcR delta locus, was analyzed by Northern blot, in cultured NK cell population and clones (but not in freshly derived cell populations).@@@@1@47@@oe@16-12-2010 838666412@GENIA Treebank@formal@@1@S@All NK clones and cell lines studied were found to express hGATA-3-specific mRNA, suggesting that hGATA-3 may be involved in the regulation of the unrearranged TcR delta gene expression in NK cells.@@@@1@34@@oe@16-12-2010 838666413@GENIA Treebank@formal@@1@S@Finally, no transcription of the RAG-1 gene could be detected in all NK cell lines or clones analyzed.@@@@1@20@@oe@16-12-2010 838693301@GENIA Treebank@formal@@1@S@Hypertension in pregnancy.@@@@1@4@@oe@16-12-2010 838693302@GENIA Treebank@formal@@1@S@Pregnancy-induced hypertension (PIH) is a frequent cause of maternal and neonatal morbidity and mortality.@@@@1@17@@oe@16-12-2010 838693303@GENIA Treebank@formal@@1@S@In the present study we focused on the pathophysiology of PIH, mainly on the role of mineralocorticoids, reversed blood pressure patterns, and the resulting necessity of continuous monitoring of the preeclamptic mother.@@@@1@36@@oe@16-12-2010 838693304@GENIA Treebank@formal@@1@S@Problems of antihypertensive therapy are discussed and the first results of a pilot study with Urapidil are presented.@@@@1@19@@oe@16-12-2010 838693305@GENIA Treebank@formal@@1@S@To examine the role of mineralocorticoids in the pathophysiology of PIH, we studied plasma aldosterone and 18-hydroxy-corticosterone (18-OH-B) levels in 25 women with PIH and in 25 healthy pregnant women.@@@@1@34@@oe@16-12-2010 838693306@GENIA Treebank@formal@@1@S@Furthermore, we evaluated the mineralocorticoid receptor (MR) count in mononuclear leukocytes in the 2 groups.@@@@1@19@@oe@16-12-2010 838693307@GENIA Treebank@formal@@1@S@The MR-count was significantly decreased in the PIH-group.@@@@1@9@@oe@16-12-2010 838693308@GENIA Treebank@formal@@1@S@The values of plasma aldosterone and 18-OH-B were also low.@@@@1@11@@oe@16-12-2010 838693309@GENIA Treebank@formal@@1@S@These results cannot be explained by receptor down-regulation due to higher level of mineralocorticoids of the zona glomerulosa.@@@@1@20@@oe@16-12-2010 838693310@GENIA Treebank@formal@@1@S@Perhaps deoxycorticosterone or a hitherto unknown mineralocorticoid is responsible for the hypertension and altered MR-status.@@@@1@16@@oe@16-12-2010 838693311@GENIA Treebank@formal@@1@S@The first results of continuous blood pressure measurements with a noninvasive, real-time blood pressure monitor (Finapres) are presented.@@@@1@22@@oe@16-12-2010 838693312@GENIA Treebank@formal@@1@S@The comparison of the obtained values with intraarterial measurements demonstrates a good correlation between the two methods.@@@@1@18@@oe@16-12-2010 838693313@GENIA Treebank@formal@@1@S@We also report on the first experiences with Urapidil in the treatment of hypertension in severe preeclampsia.@@@@1@18@@oe@16-12-2010 838693314@GENIA Treebank@formal@@1@S@The data show that hypertension in preeclamptic women can be treated by Urapidil without side effects or reflex-tachycardia.@@@@1@19@@oe@16-12-2010 838693315@GENIA Treebank@formal@@1@S@Further studies will have to prove if Urapidil is suited for prepartal treatment of PIH as well.@@@@1@18@@oe@16-12-2010 838752101@GENIA Treebank@formal@@1@S@A chimeric type II/type I interleukin-1 receptor can mediate interleukin-1 induction of gene expression in T cells.@@@@1@20@@oe@16-12-2010 838752102@GENIA Treebank@formal@@1@S@The type I interleukin-1 receptor (IL-1R) is capable of transducing a signal resulting in promoter activation in T cells.@@@@1@22@@oe@16-12-2010 838752103@GENIA Treebank@formal@@1@S@This signal transduction is dependent on the cytoplasmic domain, which consists of 213 amino acids.@@@@1@17@@oe@16-12-2010 838752104@GENIA Treebank@formal@@1@S@In contrast to the type I receptor, the type II IL-1R has a small cytoplasmic tail, and it is not clear whether this receptor is a signal-transducing or a regulatory molecule.@@@@1@34@@oe@16-12-2010 838752105@GENIA Treebank@formal@@1@S@Here we report that the type II IL-1R does not mediate gene activation in Jurkat cells.@@@@1@17@@oe@16-12-2010 838752106@GENIA Treebank@formal@@1@S@However, a hybrid receptor composed of the extracellular and transmembrane regions of the human type II interleukin-1 fused to the cytoplasmic domain of the human type I IL-1R was capable of transducing a signal across the membrane resulting in a pattern of gene activation identical to that mediated by the type I IL-1R.@@@@1@55@@oe@16-12-2010 838752107@GENIA Treebank@formal@@1@S@Our results indicated that the extracellular domain of the type II IL-1R was capable of functionally interacting with interleukin-1 and transmitting the resulting signal to a heterologous cytoplasmic domain.@@@@1@30@@oe@16-12-2010 838789301@GENIA Treebank@formal@@1@S@Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection.@@@@1@23@@oe@16-12-2010 838789302@GENIA Treebank@formal@@1@S@The multiple biological activities of tumor necrosis factor (TNF) are mediated by two distinct cell surface receptors of 55 kd (TNFRp55) and 75 kd (TNFRp75).@@@@1@32@@oe@16-12-2010 838789303@GENIA Treebank@formal@@1@S@Using gene targeting, we generated a TNFRp55-deficient mouse strain.@@@@1@11@@oe@16-12-2010 838789304@GENIA Treebank@formal@@1@S@Cells from TNFRp55-/-mutant mice lack expression of TNFRp55 but display normal numbers of high affinity TNFRp75 molecules.@@@@1@18@@oe@16-12-2010 838789305@GENIA Treebank@formal@@1@S@Thymocyte development and lymphocyte populations are unaltered, and clonal deletion of potentially self-reactive T cells is not impaired.@@@@1@20@@oe@16-12-2010 838789306@GENIA Treebank@formal@@1@S@However, TNF signaling is largely abolished, as judged by the failure of TNF to induce NF-kappa B in T lymphocytes from TNFRp55-deficient mice.@@@@1@26@@oe@16-12-2010 838789307@GENIA Treebank@formal@@1@S@The loss of TNFRp55 function renders mice resistant to lethal dosages of either lipopolysaccharides or S. aureus enterotoxin B.@@@@1@20@@oe@16-12-2010 838789308@GENIA Treebank@formal@@1@S@In contrast, TNFRp55-deficient mice are severely impaired to clear L. monocytogenes and readily succumb to infection.@@@@1@18@@oe@16-12-2010 838789309@GENIA Treebank@formal@@1@S@Thus, the 55 kd TNFR plays a decisive role in the host's defense against microorganisms and their pathogenic factors.@@@@1@22@@oe@16-12-2010 838899801@GENIA Treebank@formal@@1@S@Cell-specific bifunctional role of Jun oncogene family members on glucocorticoid receptor-dependent transcription.@@@@1@13@@oe@16-12-2010 838899802@GENIA Treebank@formal@@1@S@Interaction between protein kinase C (PKC)- and glucocorticoid receptor (GR)-mediated signaling is suggested by the ability of the PKC activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to inhibit GR-dependent transcription of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR).@@@@1@52@@oe@16-12-2010 838899803@GENIA Treebank@formal@@1@S@Here we report that this interference is cell specific, as TPA augmented dexamethasone-induced transcriptional activation of the MMTV LTR in several T cell lines but was inhibitory in NIH-3T3 fibroblasts.@@@@1@32@@oe@16-12-2010 838899804@GENIA Treebank@formal@@1@S@TPA-GR synergism was determined to have occurred at the GR-responsive element (GRE) level by functional analysis of deletion mutants or synthetic GRE oligonucleotides driving chloramphenicol acetyl-transferase expression.@@@@1@30@@oe@16-12-2010 838899805@GENIA Treebank@formal@@1@S@Synergism required an intact GR DNA-binding domain, whereas amino- or carboxyl-terminal domains were dispensable.@@@@1@16@@oe@16-12-2010 838899806@GENIA Treebank@formal@@1@S@The effect was abrogated by the PKC inhibitor staurosporine, suggesting a role for PKC.@@@@1@16@@oe@16-12-2010 838899807@GENIA Treebank@formal@@1@S@Increased c-jun, jun-B, and jun-D expression above basal levels and increased transcriptional activity of AP-1/TPA responsive elements fused to chloramphenicol acetyl-transferase vectors were observed in T cells treated with TPA alone or in combination with dexamethasone.@@@@1@39@@oe@16-12-2010 838899808@GENIA Treebank@formal@@1@S@The ability of Jun proteins to cooperate with GR in T cells has been investigated after transfection of c-jun, jun-B, or jun-D expression vectors, which augmented GR-dependent transcription from either MMTV LTR or GRE.@@@@1@38@@oe@16-12-2010 838899809@GENIA Treebank@formal@@1@S@Conversely, c-jun and jun-B transfection blunted GR-dependent transcription in HeLa cells.@@@@1@13@@oe@16-12-2010 838899810@GENIA Treebank@formal@@1@S@The presence of c-fos had a negative influence on GR function and correlated with the cell-specific synergistic or antagonistic activity of Jun with respect to GR; high basal expression of c-fos as well as AP-1 DNA binding and transcriptional activity were observed in HeLa cells, but not in T cells.@@@@1@53@@oe@16-12-2010 838899811@GENIA Treebank@formal@@1@S@Furthermore overexpression of exogenous c-fos has an inhibitory effect on GR-dependent transcription from GRE in T cells.@@@@1@18@@oe@16-12-2010 838899812@GENIA Treebank@formal@@1@S@We propose that Jun plays a bifunctional role on GR-dependent transcriptional activation of GRE, selecting either synergistic or antagonistic activity depending on the cell-specific microenvironment.@@@@1@27@@oe@16-12-2010 838899813@GENIA Treebank@formal@@1@S@In this regard, intracellular levels of c-fos appear to be influential.@@@@1@13@@oe@16-12-2010 838908501@GENIA Treebank@formal@@1@S@A concatenated form of Epstein-Barr viral DNA in lymphoblastoid cell lines induced by transfection with BZLF1.@@@@1@17@@oe@16-12-2010 838908502@GENIA Treebank@formal@@1@S@The replicative form of Epstein-Barr virus (EBV) DNA was studied using two lymphoblastoid cell lines, X50-7 and 6F11, which are latently infected by Epstein-Barr virus.@@@@1@30@@oe@16-12-2010 838908503@GENIA Treebank@formal@@1@S@The lytic cycle of EBV infection was induced by transfection of the cells with the BRLF1/BZLF1 coding region of the P3HR-1 defective genome.@@@@1@24@@oe@16-12-2010 838908504@GENIA Treebank@formal@@1@S@We combined two techniques to identify the productive replicative form of Epstein-Barr viral DNA in the lytic cycle-induced cells.@@@@1@20@@oe@16-12-2010 838908505@GENIA Treebank@formal@@1@S@Restriction enzyme analysis followed by Southern blot hybridization identified a significant increase in the fused fragment encompassing both ends of EBV DNA.@@@@1@23@@oe@16-12-2010 838908506@GENIA Treebank@formal@@1@S@This indicates an increase in either episomal DNA or concatameric linear DNA.@@@@1@13@@oe@16-12-2010 838908507@GENIA Treebank@formal@@1@S@Southern blot analysis of in situ lysing gels revealed that the cellular content of linear EBV DNA was also increased significantly after the initiation of the viral lytic cycle, while the amount of circular DNA remained approximately constant.@@@@1@40@@oe@16-12-2010 838908508@GENIA Treebank@formal@@1@S@We propose from these results that the source of the fused fragment encompassing both ends of EBV DNA is a concatenated linear EBV DNA molecule, and that such a concatenated molecule most likely represents a replicative form of EBV DNA in productively infected cells.@@@@1@46@@oe@16-12-2010 838975701@GENIA Treebank@formal@@1@S@Defective translocation of protein kinase C in multidrug-resistant HL-60 cells confers a reversible loss of phorbol ester-induced monocytic differentiation.@@@@1@20@@oe@16-12-2010 838975702@GENIA Treebank@formal@@1@S@Previous studies have demonstrated that human HL-60 myeloid leukemia cells differentiate in response to phorbol esters.@@@@1@17@@oe@16-12-2010 838975703@GENIA Treebank@formal@@1@S@This event is associated with induction of the c-jun early response gene and appearance of a monocytic phenotype.@@@@1@19@@oe@16-12-2010 838975704@GENIA Treebank@formal@@1@S@The present studies have examined the effects of vincristine-selected, multidrug resistance on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HL-60 cell differentiation.@@@@1@22@@oe@16-12-2010 838975705@GENIA Treebank@formal@@1@S@The results demonstrate that multidrug-resistant HL-60 cells, designated HL-60/vinc, fail to respond to TPA with an increase in c-jun transcripts or other phenotypic characteristics of monocytic differentiation.@@@@1@30@@oe@16-12-2010 838975706@GENIA Treebank@formal@@1@S@By contrast, treatment of HL-60/vinc cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases, induces c-jun transcription, growth arrest, and expression of the c-fms gene.@@@@1@32@@oe@16-12-2010 838975707@GENIA Treebank@formal@@1@S@Studies were also performed with an HL-60/vinc revertant (HL-60/vinc/R) line that has regained partial sensitivity to vincristine.@@@@1@20@@oe@16-12-2010 838975708@GENIA Treebank@formal@@1@S@The finding that HL-60/vinc/R cells respond to TPA with induction of a monocytic phenotype, but not c-jun expression, suggests that c-jun induction is not obligatory for monocytic differentiation.@@@@1@31@@oe@16-12-2010 838975709@GENIA Treebank@formal@@1@S@Other studies further demonstrate that the jun-B and fra-1 genes are induced by TPA in both HL-60/vinc and HL-60/vinc/R cells, whereas c-fos expression is attenuated in the HL-60/vinc line.@@@@1@31@@oe@16-12-2010 838975710@GENIA Treebank@formal@@1@S@Since TPA activates protein kinase C (PKC), we examined translocation of PKC from the cytosol to the membrane fraction.@@@@1@23@@oe@16-12-2010 838975711@GENIA Treebank@formal@@1@S@Although HL-60 and HL-60/vinc/R cells demonstrated translocation of PKC activity, this subcellular redistribution was undetectable in HL-60/vinc cells.@@@@1@20@@oe@16-12-2010 838975712@GENIA Treebank@formal@@1@S@Activity of the mitogen-activated protein kinase family with associated phosphorylation of c-Jun Y-peptide was markedly diminished in TPA-treated HL-60/vinc cells, but not in response to okadaic acid.@@@@1@29@@oe@16-12-2010 838975713@GENIA Treebank@formal@@1@S@Taken together, these findings suggest that vincristine resistance confers insensitivity to TPA-induced differentiation and can include defects in PKC-mediated signaling events and induction of jun/fos early response gene expression.@@@@1@31@@oe@16-12-2010 838994001@GENIA Treebank@formal@@1@S@Differential contribution of herpes simplex virus type 1 gene products and cellular factors to the activation of human immunodeficiency virus type 1 provirus.@@@@1@24@@oe@16-12-2010 838994002@GENIA Treebank@formal@@1@S@We have previously reported that infection with herpes simplex virus type 1 (HSV-1) activates expression of the human immunodeficiency virus type 1 (HIV-1) provirus in T cells.@@@@1@32@@oe@16-12-2010 838994003@GENIA Treebank@formal@@1@S@Activation of the HIV-1 provirus correlated with the activation of binding of 55- and 85-kDa proteins to the kappa B enhancer and binding of the 50-kDa HLP-1 protein to the LBP-1 sequences of the HIV-1 long terminal repeat.@@@@1@39@@oe@16-12-2010 838994004@GENIA Treebank@formal@@1@S@Further examination of this system has shown that the inhibition of HSV-1 replication by the antiviral drug acyclovir does not inhibit HSV-1-mediated induction of HIV-1 provirus.@@@@1@27@@oe@16-12-2010 838994005@GENIA Treebank@formal@@1@S@Surprisingly, the NF-kappa B and HLP-1 binding activities were substantially inhibited in acyclovir-treated cells.@@@@1@16@@oe@16-12-2010 838994006@GENIA Treebank@formal@@1@S@In the transient-transfection assay, ICP0, but not ICP4, activated the HIV-1 long terminal repeat promoter region and the effect of ICP0 was greatly enhanced in the presence of the NF-kappa B binding proteins, suggesting that induction of the HIV-1 provirus involves cooperation between the HSV-1-activated cellular factor, NF-kappa B, and the virus-encoded transactivator, ICP0.@@@@1@62@@oe@16-12-2010 839209201@GENIA Treebank@formal@@1@S@Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate.@@@@1@17@@oe@16-12-2010 839209202@GENIA Treebank@formal@@1@S@We have previously shown that minimally oxidized LDL (MM-LDL) activated endothelial cells to increase their interaction with monocytes but not neutrophils, inducing monocyte but not neutrophil binding and synthesis of monocyte chemotactic protein-1 and monocyte colony-stimulating factor (M-CSF).@@@@1@44@@oe@16-12-2010 839209203@GENIA Treebank@formal@@1@S@In the present studies we have examined the signaling pathways by which this monocyte-specific response is induced.@@@@1@18@@oe@16-12-2010 839209204@GENIA Treebank@formal@@1@S@Both induction of monocyte binding and mRNA levels for M-CSF by MM-LDL were not inhibited in protein kinase C-depleted endothelial cells.@@@@1@22@@oe@16-12-2010 839209205@GENIA Treebank@formal@@1@S@A number of our studies indicate that cAMP is the second messenger for the effects of MM-LDL cited above.@@@@1@20@@oe@16-12-2010 839209206@GENIA Treebank@formal@@1@S@Incubation of endothelial cells with MM-LDL caused a 173% increase in intracellular cAMP levels.@@@@1@16@@oe@16-12-2010 839209207@GENIA Treebank@formal@@1@S@Agents which increased cAMP levels, including cholera toxin, pertussis toxin, dibutyryl cAMP, and isoproterenol mimicked the actions of MM-LDL.@@@@1@24@@oe@16-12-2010 839209208@GENIA Treebank@formal@@1@S@Agents which elevated cAMP were also shown to activate NF kappa B, suggesting a role for this transcription factor in activation of monocyte-endothelial interactions.@@@@1@26@@oe@16-12-2010 839209209@GENIA Treebank@formal@@1@S@Although endothelial leukocyte adhesion molecule (ELAM) mRNA synthesis can be regulated by NF kappa B, ELAM was not expressed and ELAM mRNA was only slightly elevated in response to MM-LDL.@@@@1@34@@oe@16-12-2010 839209210@GENIA Treebank@formal@@1@S@We present evidence that induction of neutrophil binding by LPS is actually suppressed by agents that elevated cAMP levels.@@@@1@20@@oe@16-12-2010 839243701@GENIA Treebank@formal@@1@S@Costimulation of cAMP and protein kinase C pathways inhibits the CD3-dependent T cell activation and leads to a persistent expression of the AP-1 transcription factor.@@@@1@26@@oe@16-12-2010 839243702@GENIA Treebank@formal@@1@S@The effects mediated by a combined stimulation of cAMP- and protein kinase C (PKC)-dependent pathways have been investigated in different cellular systems, and it has been shown that they may complement each other in activating cell proliferation and differentiation.@@@@1@44@@oe@16-12-2010 839243703@GENIA Treebank@formal@@1@S@In this report, we show that upon the stimulation of both pathways T lymphocytes became refractory to activation via the CD3/T cell receptor (TcR) complex.@@@@1@29@@oe@16-12-2010 839243704@GENIA Treebank@formal@@1@S@T cells preincubated with phorbol 12-myristate 13-acetate (PMA) and dibutyryl cAMP (Bt2cAMP) displayed a deficient proliferative ability in response to anti-CD3 mAb stimulation, whereas lymphocytes treated individually with either Bt2cAMP or PMA responded comparably to untreated samples.@@@@1@43@@oe@16-12-2010 839243705@GENIA Treebank@formal@@1@S@We detected an association between the reduced mitogenic response and low expression of both interleukin-2 (IL-2) and the alpha chain (CD25) of the IL-2 receptor (IL-2R).@@@@1@33@@oe@16-12-2010 839243706@GENIA Treebank@formal@@1@S@Analysis of intracellular Ca2+ mobilization suggested that the CD3/TcR-dependent signal transduction was impaired in PMA/Bt2cAMP-treated cells.@@@@1@17@@oe@16-12-2010 839243707@GENIA Treebank@formal@@1@S@Remarkably, we observed that these samples displayed a persistent expression of the c-fos protooncogene, associated to an increased AP-1 DNA-binding activity, whereas no variations of CREB or NF-kB were detected.@@@@1@34@@oe@16-12-2010 839243708@GENIA Treebank@formal@@1@S@Neither Bt2cAMP nor PMA individually mediated these sustained effects, which therefore appear as a consequence of the interplay between both metabolic stimuli.@@@@1@24@@oe@16-12-2010 839243709@GENIA Treebank@formal@@1@S@Altogether, the data provide the evidence that both pathways complement each other in regulating gene expression and, conversely, downregulate the TcR transduction mechanisms.@@@@1@27@@oe@16-12-2010 839518801@GENIA Treebank@formal@@1@S@Tumor necrosis factor receptor expression and signal transduction in HIV-1-infected cells.@@@@1@12@@oe@16-12-2010 839518802@GENIA Treebank@formal@@1@S@OBJECTIVE: To examine the inter-relationship between HIV-1 infection and the cell surface receptors for tumor necrosis factor (TNF)-alpha, an immunoregulatory cytokine that can enhance HIV-1 replication.@@@@1@32@@oe@16-12-2010 839518803@GENIA Treebank@formal@@1@S@DESIGN: Infected promyelocytic and promonocytic cells were examined because they normally express both types of TNF receptors.@@@@1@19@@oe@16-12-2010 839518804@GENIA Treebank@formal@@1@S@METHODS: TNF receptor surface expression was determined by specific monoclonal antibody recognition and flow cytometry, and signal transduction was detected by gel shift analysis.@@@@1@27@@oe@16-12-2010 839518805@GENIA Treebank@formal@@1@S@HIV-1 activation and expression was quantitated by reverse transcriptase assay.@@@@1@11@@oe@16-12-2010 839518806@GENIA Treebank@formal@@1@S@RESULTS: In the OM-10.1 promyelocytic model of chronic infection, TNF-alpha-induced HIV-1 expression also resulted in a substantial increase in 75 kd TNF receptor (TR75) expression although 55 kD TNF receptor (TR55) levels were not dramatically altered.@@@@1@43@@oe@16-12-2010 839518807@GENIA Treebank@formal@@1@S@A series of uninfected parental HL-60 subclones all reduced TR75 surface expression in response to TNF-alpha treatment.@@@@1@18@@oe@16-12-2010 839518808@GENIA Treebank@formal@@1@S@Enhanced TR75 expression on OM-10.1 cells followed the same TNF-alpha-dose dependency as that observed for HIV-1 production.@@@@1@18@@oe@16-12-2010 839518809@GENIA Treebank@formal@@1@S@An increase in TR75 expression was also evident during the peak of an acute HIV-1 infection of HL-60 promyelocytes.@@@@1@20@@oe@16-12-2010 839518810@GENIA Treebank@formal@@1@S@Although TR55 expression was unaltered during TNF-alpha-induced HIV activation, this receptor was still involved in the viral activation process.@@@@1@21@@oe@16-12-2010 839518811@GENIA Treebank@formal@@1@S@Antibody cross-linking of TR55, in the absence of exogenous TNF-alpha, induced maximal HIV-1 expression, an up-modulation of surface TR75, and nuclear NF-kappa B activity in OM-10.1 cultures.@@@@1@32@@oe@16-12-2010 839518812@GENIA Treebank@formal@@1@S@Surprisingly, this was the case even when an antagonistic anti-TR55 antibody was used.@@@@1@15@@oe@16-12-2010 839518813@GENIA Treebank@formal@@1@S@Anti-TR55 antibody cross-linking in chronically infected U1 promonocytic cultures could only partially substitute for TNF-alpha-induced HIV-1 expression.@@@@1@18@@oe@16-12-2010 839518814@GENIA Treebank@formal@@1@S@CONCLUSIONS: Our results demonstrated that HIV-1 infection can selectively influence the surface expression of TNF receptors, potentially influencing its own expression and altering normal immunoregulatory signal transduction.@@@@1@30@@oe@16-12-2010 841933701@GENIA Treebank@formal@@1@S@Involvement of Alu sequences in the cell-specific regulation of transcription of the gamma chain of Fc and T cell receptors.@@@@1@21@@oe@16-12-2010 841933702@GENIA Treebank@formal@@1@S@The Fc epsilon RI-gamma chains are expressed in a variety of hematopoietic cells where they play a critical role in signal transduction.@@@@1@23@@oe@16-12-2010 841933703@GENIA Treebank@formal@@1@S@They are part of the high affinity IgE receptor in mast cells, basophils, Langerhans cells, and possibly other cells; a component of the low affinity receptor for IgG (Fc gamma RIIIA or CD16) in natural killer cells and macrophages; and part of the T cell antigen receptor in subsets of T cells.@@@@1@60@@oe@16-12-2010 841933704@GENIA Treebank@formal@@1@S@Here we have investigated the transcriptional regulation of the gamma chain gene by analyzing the 2.5-kilobase sequence upstream of the transcription start site.@@@@1@24@@oe@16-12-2010 841933705@GENIA Treebank@formal@@1@S@This sequence contains a promoter specific to cells of hematopoietic lineage.@@@@1@12@@oe@16-12-2010 841933706@GENIA Treebank@formal@@1@S@However, the tissue specificity of this promoter is only partial because it is active in all of the hematopoietic cells tested here, regardless of whether they constitutively express Fc epsilon RI- gamma chain transcripts.@@@@1@36@@oe@16-12-2010 841933707@GENIA Treebank@formal@@1@S@We have identified two adjacent cis-acting regulatory elements, both of which are part of an Alu repeat.@@@@1@19@@oe@16-12-2010 841933708@GENIA Treebank@formal@@1@S@The first (-445/-366) is a positive element active in both basophils and T cells.@@@@1@17@@oe@16-12-2010 841933709@GENIA Treebank@formal@@1@S@The second (-365/-264) binds to nuclear factors, which appear to be different in basophils and T cells, and acts as a negative element in basophils and as a positive one in T cells.@@@@1@38@@oe@16-12-2010 841933710@GENIA Treebank@formal@@1@S@Thus, this Alu repeat (90% identical to Alu consensus sequences) has evolved to become both a positive and negative regulator.@@@@1@25@@oe@16-12-2010 841964401@GENIA Treebank@formal@@1@S@Human immunodeficiency viruses containing heterologous enhancer/promoters are replication competent and exhibit different lymphocyte tropisms.@@@@1@15@@oe@16-12-2010 841964402@GENIA Treebank@formal@@1@S@The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) contains binding sites for nuclear factor kappa B (NF-kappa B) and the constitutively expressed transcription factor Sp1, both of which are highly conserved in HIV and simian immunodeficiency virus isolates.@@@@1@49@@oe@16-12-2010 841964403@GENIA Treebank@formal@@1@S@To delineate the effects of these motifs on the replicative capacity of HIV and to explore the possibility of extending the virus host range, known heterologous enhancer/promoters were inserted into the HIV-1 LTR in place of the NF-kappa B and Sp1 binding sites.@@@@1@45@@oe@16-12-2010 841964404@GENIA Treebank@formal@@1@S@The effects of these substitutions on viral replication in transfected HeLa cells and on HIV infection of human peripheral blood lymphocytes or continuous T-leukemia cell lines were evaluated.@@@@1@29@@oe@16-12-2010 841964405@GENIA Treebank@formal@@1@S@HIVs in which the NF-kappa B/Sp1 enhancer plus the downstream TATA element were replaced with heterologous enhancer/promoters were also constructed.@@@@1@22@@oe@16-12-2010 841964406@GENIA Treebank@formal@@1@S@Viruses containing the human cytomegalovirus immediate-early enhancer exhibited infectious kinetics similar to that of wild-type HIV in activated human peripheral blood lymphocytes and AA2 cells but replicated less efficiently in H9 and CEM cells.@@@@1@35@@oe@16-12-2010 841964407@GENIA Treebank@formal@@1@S@These studies indicate that heterologous enhancer elements are capable of restoring Tat responsiveness to the HIV LTR in the context of directing reporter gene expression as well as in the production of infectious progeny virions.@@@@1@36@@oe@16-12-2010 841993101@GENIA Treebank@formal@@1@S@Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors [published erratum appears in Proc Natl Acad Sci U S A 1993 Apr 15;90(8):3775]@@@@1@45@@oe@16-12-2010 841993102@GENIA Treebank@formal@@1@S@Ionizing radiation triggers a signal in human B-lymphocyte precursors that is intimately linked to an active protein-tyrosine kinase regulatory pathway.@@@@1@21@@oe@16-12-2010 841993103@GENIA Treebank@formal@@1@S@We show that in B-lymphocyte precursors, irradiation with gamma-rays leads to (i) stimulation of phosphatidylinositol turnover; (ii) downstream activation by covalent modification of multiple serine-specific protein kinases, including protein kinase C; and (iii) activation of nuclear factor kappa B.@@@@1@50@@oe@16-12-2010 841993104@GENIA Treebank@formal@@1@S@All of the radiation-induced signals were effectively prevented by the protein-tyrosine kinase inhibitors genistein and herbimycin A.@@@@1@18@@oe@16-12-2010 841993105@GENIA Treebank@formal@@1@S@Thus, tyrosine phosphorylation is an important and perhaps mandatory proximal step in the activation of the protein kinase C signaling cascade in human B-lymphocyte precursors.@@@@1@27@@oe@16-12-2010 841993106@GENIA Treebank@formal@@1@S@Our report expands current knowledge of the radiation-induced signaling cascade by clarifying the chronological sequence of biochemical events that follow irradiation.@@@@1@22@@oe@16-12-2010 842227401@GENIA Treebank@formal@@1@S@A human putative lymphocyte G0/G1 switch gene homologous to a rodent gene encoding a zinc-binding potential transcription factor.@@@@1@19@@oe@16-12-2010 842227402@GENIA Treebank@formal@@1@S@G0S24 is a member of a set of genes (putative G0/G1 switch regulatory genes) that are expressed transiently within 1-2 hr of the addition of lectin or cycloheximide to human blood mononuclear cells.@@@@1@36@@oe@16-12-2010 842227403@GENIA Treebank@formal@@1@S@Comparison of a full-length cDNA sequence with the corresponding genomic sequence reveals an open reading frame of 326 amino acids, distributed across two exons.@@@@1@26@@oe@16-12-2010 842227404@GENIA Treebank@formal@@1@S@Potential phosphorylation sites include the sequence PSPTSPT, which resembles an RNA polymerase II repeat reported to be a target of the cell cycle control kinase cdc2.@@@@1@28@@oe@16-12-2010 842227405@GENIA Treebank@formal@@1@S@Comparison of the derived protein sequence with those of rodent homologs allows classification into three groups.@@@@1@17@@oe@16-12-2010 842227406@GENIA Treebank@formal@@1@S@Group 1 contains G0S24 and the rat and mouse TIS11 genes (also known as TTP, Nup475, and Zfp36).@@@@1@23@@oe@16-12-2010 842227407@GENIA Treebank@formal@@1@S@Members of this group have three tetraproline repeats.@@@@1@9@@oe@16-12-2010 842227408@GENIA Treebank@formal@@1@S@Groups 1 and 2 have a serine-rich region and an "arginine element" (RRLPIF) at the carboxyl terminus.@@@@1@22@@oe@16-12-2010 842227409@GENIA Treebank@formal@@1@S@All groups contain cysteine- and histidine-rich putative zinc finger domains and a serine-phenylalanine "SFS" domain similar to part of the large subunit of eukaryotic RNA polymerase II.@@@@1@30@@oe@16-12-2010 842227410@GENIA Treebank@formal@@1@S@Comparison of group 1 human and mouse genomic sequences shows high conservation in the 5' flank and exons.@@@@1@19@@oe@16-12-2010 842227411@GENIA Treebank@formal@@1@S@A CpG island suggests expression in the germ line.@@@@1@10@@oe@16-12-2010 842227412@GENIA Treebank@formal@@1@S@G0S24 has potential sites for transcription factors in the 5' flank and intron; these include a serum response element.@@@@1@21@@oe@16-12-2010 842227413@GENIA Treebank@formal@@1@S@Protein and genomic sequences show similarities with those of a variety of proteins involved in transcription, suggesting that the G0S24 product has a similar role.@@@@1@27@@oe@16-12-2010 842245901@GENIA Treebank@formal@@1@S@Interleukin-4 inhibits the lipopolysaccharide-induced expression of c-jun and c-fos messenger RNA and activator protein-1 binding activity in human monocytes.@@@@1@20@@oe@16-12-2010 842245902@GENIA Treebank@formal@@1@S@We studied the effect of interleukin-4 (IL-4) on the lipopolysaccharide (LPS) induction of two immediate early genes c-fos and c-jun.@@@@1@25@@oe@16-12-2010 842245903@GENIA Treebank@formal@@1@S@These genes encode proteins that form the dimeric complex activator protein-1 (AP-1), which is active as a transcriptional factor.@@@@1@23@@oe@16-12-2010 842245904@GENIA Treebank@formal@@1@S@Maximal accumulation of either c-fos and c-jun messenger RNA (mRNA) occurred 30 minutes after LPS addition.@@@@1@19@@oe@16-12-2010 842245905@GENIA Treebank@formal@@1@S@When cells were treated with IL-4 for 5 hours before LPS activation, both the c-fos and the c-jun mRNA expression was decreased.@@@@1@24@@oe@16-12-2010 842245906@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010 842245907@GENIA Treebank@formal@@1@S@IL-4 did not affect the stability of the c-fos and c-jun transcripts.@@@@1@13@@oe@16-12-2010 842245908@GENIA Treebank@formal@@1@S@Finally, using electrophoretic mobility shift assays, evidence was obtained that IL-4 inhibits LPS-induced expression of AP-1 protein.@@@@1@20@@oe@16-12-2010 842245909@GENIA Treebank@formal@@1@S@These data indicate that IL-4 suppresses the induction of transcription factors in human activated monocytes.@@@@1@16@@oe@16-12-2010 842399301@GENIA Treebank@formal@@1@S@Ras oncogene transformation of human B lymphoblasts is associated with lymphocyte activation and with a block of differentiation.@@@@1@19@@oe@16-12-2010 842399302@GENIA Treebank@formal@@1@S@The p21ras small GTP binding proteins participate in signal transduction from cell surface receptors and affect neoplastic transformation and development in many different cell types.@@@@1@26@@oe@16-12-2010 842399303@GENIA Treebank@formal@@1@S@In the present study, we examined the relationship between ras transformation and differentiation of human B lymphocytes.@@@@1@19@@oe@16-12-2010 842399304@GENIA Treebank@formal@@1@S@We show that the constitutive expression of the T24 Ha-ras oncogene in EBV-immortalized B lymphoblasts was associated with the induction of the interleukin 2 receptor alpha subunit, with an impaired immunoglobulin gene expression, altered adhesion properties and increased survival in serum-free medium.@@@@1@45@@oe@16-12-2010 842399305@GENIA Treebank@formal@@1@S@Since induction of the IL-2 receptor alpha subunit is a hallmark of lymphocyte activation, we suggest that p21ras naturally triggers B cell activation.@@@@1@25@@oe@16-12-2010 842399306@GENIA Treebank@formal@@1@S@The ras-transformed lymphocytes displayed a fully functional IL-2r, as assessed by c-fos induction following treatment with IL-2; nevertheless, they were not growth stimulated by this lymphokine.@@@@1@30@@oe@16-12-2010 842399307@GENIA Treebank@formal@@1@S@The decreased expression of immunoglobulin genes indicates that the ras oncogene blocks terminal differentiation to plasma cells, possibly by inhibiting the activity of lymphocyte-specific transcription factors.@@@@1@28@@oe@16-12-2010 842399308@GENIA Treebank@formal@@1@S@Somewhat unexpectedly, the constitutive p21ras activity did not cause an increased DNA binding of transcription factors PEA1 (AP1), PEA3, Oct-2 or NF-kB.@@@@1@28@@oe@16-12-2010 842410101@GENIA Treebank@formal@@1@S@Transcription factor GATA-1 and erythroid development.@@@@1@7@@oe@16-12-2010 842410102@GENIA Treebank@formal@@1@S@In summary, we derived an experimental system that allows us to dissect the function of GATA-1 in red cell development at a genetic level.@@@@1@26@@oe@16-12-2010 842410103@GENIA Treebank@formal@@1@S@We have established the essential nature of GATA-1 during both primitive and definitive erythropoiesis.@@@@1@15@@oe@16-12-2010 842410104@GENIA Treebank@formal@@1@S@By ablating the expression of the endogenous GATA-1 gene, we are in a position to introduce a variety of constructs that harbor subtle modifications in flanking or protein-coding sequences.@@@@1@31@@oe@16-12-2010 842410105@GENIA Treebank@formal@@1@S@We can now study regulatory regions and functional domains of the protein in the context of a true erythroid environment, experiments that have not been possible heretofore.@@@@1@29@@oe@16-12-2010 842410106@GENIA Treebank@formal@@1@S@Although the assay involves the dramatic loss of red cell production, it should be possible to define important regulatory domains that can then be assayed using less stringent systems, such as cell-free extracts for in vitro transcription.@@@@1@40@@oe@16-12-2010 842410107@GENIA Treebank@formal@@1@S@The ideal situation would be analyses conducted in GATA-1- erythroid cells.@@@@1@12@@oe@16-12-2010 842410108@GENIA Treebank@formal@@1@S@However, these cells have been impossible to generate given the requirement of GATA-1 for Epo receptor expression and red cell viability (C. Simon and S. Orkin, unpublished observations).@@@@1@33@@oe@16-12-2010 842410109@GENIA Treebank@formal@@1@S@It may be possible to produce such cells by first expressing the Epo receptor under the influence of a constitutive promoter and then targeting the GATA-1 gene.@@@@1@28@@oe@16-12-2010 842410110@GENIA Treebank@formal@@1@S@If GATA-1- red cells were available, the analyses would involve the actual transcription of or chromatin structure surrounding the globin genes.@@@@1@23@@oe@16-12-2010 842410111@GENIA Treebank@formal@@1@S@Structure-function studies of the GATA-1 protein could be greatly simplified and a larger number of mutants studied.@@@@1@18@@oe@16-12-2010 842410112@GENIA Treebank@formal@@1@S@However, the ES cell system can be used as an alternative until targeted erythroleukemia cells become available.@@@@1@19@@oe@16-12-2010 842410113@GENIA Treebank@formal@@1@S@Other applications involve the introduction of other GATA-binding protein family members to determine whether they rescue the mutation.@@@@1@19@@oe@16-12-2010 842410114@GENIA Treebank@formal@@1@S@If they cannot, chimeric proteins can be tested to identify which amino acids distinguish the different family members.@@@@1@21@@oe@16-12-2010 842410115@GENIA Treebank@formal@@1@S@We feel that these experiments are vital to understanding the function of GATA-1 during erythroid ontogeny.@@@@1@17@@oe@16-12-2010 842410116@GENIA Treebank@formal@@1@S@How does GATA-1 regulate red cell genes like globin or the Epo receptor?@@@@1@14@@oe@16-12-2010 842410117@GENIA Treebank@formal@@1@S@Once we identify the functional domains of the GATA-binding proteins, we hope to learn what proteins GATA-1 binds to in the basic transcription machinery or in chromatin.@@@@1@29@@oe@16-12-2010 842410118@GENIA Treebank@formal@@1@S@Is GATA-1 necessary for globin gene switching?@@@@1@8@@oe@16-12-2010 842410119@GENIA Treebank@formal@@1@S@GATA-1 may be modified differently during development so that the locus control region can interact with different globin promoters.@@@@1@20@@oe@16-12-2010 842410120@GENIA Treebank@formal@@1@S@We may find that one region of the protein is required for embryonic expression and another for adult globin gene expression.@@@@1@22@@oe@16-12-2010 842798301@GENIA Treebank@formal@@1@S@Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type I (HTLV-I) tax and HTLV-II tax proteins.@@@@1@26@@oe@16-12-2010 842798302@GENIA Treebank@formal@@1@S@The human T-cell leukemia virus type I (HTLV-I) and HTLV-II Tax proteins are potent transactivators of viral and cellular gene expression.@@@@1@24@@oe@16-12-2010 842798303@GENIA Treebank@formal@@1@S@Using deletion mutants, the downstream parathyroid hormone-related protein (PTHrP) promoter is shown to be responsive to both HTLV-I and HTLV-II Tax as well as the AP1/c-jun proto-oncogene.@@@@1@31@@oe@16-12-2010 842798304@GENIA Treebank@formal@@1@S@Transactivation of PTHrP by Tax was seen in T cells but not in B-cell lines or fibroblasts.@@@@1@18@@oe@16-12-2010 842798305@GENIA Treebank@formal@@1@S@A carboxy terminal Tax deletion mutant was deficient in transactivation of both the PTHrP and IL2R alpha promoters but not the HTLV-I long terminal repeat (LTR).@@@@1@29@@oe@16-12-2010 842798306@GENIA Treebank@formal@@1@S@Exogenous provision of NFkB rescued IL2R alpha expression but not the PTHrP promoter.@@@@1@14@@oe@16-12-2010 842798307@GENIA Treebank@formal@@1@S@Thus, HTLV-I Tax, HTLV-II Tax, and c-jun transactivate PTHrP and may contribute to the pathogenesis of hypercalcemia in adult T-cell leukemia.@@@@1@25@@oe@16-12-2010 842800001@GENIA Treebank@formal@@1@S@Interleukin-3 expression by activated T cells involves an inducible, T-cell-specific factor and an octamer binding protein.@@@@1@18@@oe@16-12-2010 842800002@GENIA Treebank@formal@@1@S@Interleukin-3 (IL-3) is exclusively expressed by activated T and natural killer cells, a function that is tightly controlled both in a lineage-specific and in a stimulation-dependent manner.@@@@1@31@@oe@16-12-2010 842800003@GENIA Treebank@formal@@1@S@We have investigated the protein binding characteristics and functional importance of the ACT-1-activating region of the IL-3 promoter.@@@@1@19@@oe@16-12-2010 842800004@GENIA Treebank@formal@@1@S@This region binds an inducible, T-cell-specific factor over its 5' end, a site that is necessary for the expression of IL-3 in the absence of other upstream elements.@@@@1@31@@oe@16-12-2010 842800005@GENIA Treebank@formal@@1@S@Over its 3' end, it binds a factor that is ubiquitously and constitutively expressed.@@@@1@16@@oe@16-12-2010 842800006@GENIA Treebank@formal@@1@S@This factor is Oct-1 or an immunologically related octamer-binding protein, and it plays a role in coordinating the activity of several regulatory elements.@@@@1@25@@oe@16-12-2010 842800007@GENIA Treebank@formal@@1@S@These characteristics make the ACT-1 site analogous to the activating ARRE-1 site in the IL-2 promoter.@@@@1@17@@oe@16-12-2010 842800008@GENIA Treebank@formal@@1@S@Furthermore, and despite a lack of sequence homology, the promoters of IL-3 and IL-2 share an organizational pattern of regulatory elements that is likely to be important for the T-cell-specific expression of these genes.@@@@1@37@@oe@16-12-2010 842894301@GENIA Treebank@formal@@1@S@ras protein activity is essential for T-cell antigen receptor signal transduction.@@@@1@12@@oe@16-12-2010 842894302@GENIA Treebank@formal@@1@S@In a Jurkat cell model of T-cell activation an interleukin-2 promoter/reporter gene construct was activated by antigen receptor agonism in combination with the lymphokine interleukin-1.@@@@1@26@@oe@16-12-2010 842894303@GENIA Treebank@formal@@1@S@Antigen receptor signals could be mimicked by suboptimal activation of protein kinase C (PKC) with phorbol esters in combination with calcium mobilization by an ionophore.@@@@1@28@@oe@16-12-2010 842894304@GENIA Treebank@formal@@1@S@In cotransfection experiments, oncogenic rats obviated the need for PKC stimulation but did not replace either the calcium signal or interleukin-1.@@@@1@23@@oe@16-12-2010 842894305@GENIA Treebank@formal@@1@S@Activated ras expression also replaced the requirement for PKC stimulation in activation of the T-cell transcription factor NF-AT.@@@@1@19@@oe@16-12-2010 842894306@GENIA Treebank@formal@@1@S@A dominant inhibitory ras mutant specifically blocked antigen receptor agonism, indicating that ras activity is required for antigen receptor signaling.@@@@1@22@@oe@16-12-2010 842894307@GENIA Treebank@formal@@1@S@In addition, an inhibitor of PKC blocked both activated ras and phorbol ester stimulation, suggesting a role for ras upstream of PKC.@@@@1@25@@oe@16-12-2010 842896601@GENIA Treebank@formal@@1@S@Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex.@@@@1@21@@oe@16-12-2010 842896602@GENIA Treebank@formal@@1@S@The lymphoid-specific transcription complex, NF-AT, is involved in early gene activation in T cells and is assembled from a pre-existing, T cell restricted cytoplasmic factor and an inducible ubiquitous nuclear component within 30 min after activation through the antigen receptor.@@@@1@44@@oe@16-12-2010 842896603@GENIA Treebank@formal@@1@S@Recent studies have implicated the family of AP1 factors as components of the murine NF-AT complex.@@@@1@17@@oe@16-12-2010 842896604@GENIA Treebank@formal@@1@S@Evidence is provided here that the nuclear component of human NF-AT contains the phorbol ester-inducible transcription factor AP1 (Jun/Fos).@@@@1@22@@oe@16-12-2010 842896605@GENIA Treebank@formal@@1@S@We further characterize which AP1 family members can assume this role.@@@@1@12@@oe@16-12-2010 842896606@GENIA Treebank@formal@@1@S@Antisera to Fos inhibits NF-AT DNA binding as does an oligonucleotide containing a binding site for AP1.@@@@1@18@@oe@16-12-2010 842896607@GENIA Treebank@formal@@1@S@Constitutive expression in vivo of Fos, and to a lesser extent Fra-1, eliminates the requirement for phorbol 12-myristate 13-acetate (PMA) stimulation, leaving NF-AT-directed transcription responsive to calcium ionophore alone.@@@@1@35@@oe@16-12-2010 842896608@GENIA Treebank@formal@@1@S@Overexpression of cJun or JunD, but not JunB, also eliminates the requirement for PMA, indicating that many but not all Jun- and Fos-related proteins functionally activate NF-AT-dependent transcription in the presence of the cytoplasmic component.@@@@1@39@@oe@16-12-2010 842896609@GENIA Treebank@formal@@1@S@NF-AT DNA binding can be reconstituted in vitro using semi-purified AP1 proteins mixed with cytosol from T lymphocytes.@@@@1@19@@oe@16-12-2010 842896610@GENIA Treebank@formal@@1@S@Fos proteins are not needed for this reconstitution, and although JunB is not functional, it can participate in the NF-AT DNA binding complex.@@@@1@26@@oe@16-12-2010 842896611@GENIA Treebank@formal@@1@S@Finally, we have partially purified the cytoplasmic component of NF-AT and show by elution and renaturation from SDS-polyacrylamide gel electrophoresis gels that it has a molecular mass between 94 and 116 kDa and may have multiple differentially modified forms.@@@@1@41@@oe@16-12-2010 843006901@GENIA Treebank@formal@@1@S@The c-rel protooncogene product represses NF-kappa B p65-mediated transcriptional activation of the long terminal repeat of type 1 human immunodeficiency virus.@@@@1@22@@oe@16-12-2010 843006902@GENIA Treebank@formal@@1@S@The long terminal repeat (LTR) of the type 1 human immunodeficiency virus (HIV-1) and the 5' regulatory region of the gene encoding the interleukin 2 receptor alpha subunit (IL-2R alpha) share functional kappa B enhancer elements involved in the regulation of these inducible transcription units during T-cell activation.@@@@1@55@@oe@16-12-2010 843006903@GENIA Treebank@formal@@1@S@These kappa B enhancer elements are recognized by a structurally related family of interactive proteins that includes p50, p65, and the product of the c-rel protooncogene (c-Rel).@@@@1@32@@oe@16-12-2010 843006904@GENIA Treebank@formal@@1@S@Recent biochemical studies have shown that p65 and p50 form the prototypical NF-kappa B complex, which is rapidly translocated from the cytoplasm to the nucleus during T-cell activation.@@@@1@30@@oe@16-12-2010 843006905@GENIA Treebank@formal@@1@S@This intracellular signaling complex potently stimulates kappa B-directed transcription from either the HIV-1 LTR or the IL-2R alpha promoter via the strong transactivation domain present in p65.@@@@1@28@@oe@16-12-2010 843006906@GENIA Treebank@formal@@1@S@We now demonstrate that nuclear expression of human c-Rel, which is induced by either phorbol ester or tumor necrosis factor alpha with delayed kinetics relative to p65, markedly represses p65-mediated activation of these transcription units.@@@@1@38@@oe@16-12-2010 843006907@GENIA Treebank@formal@@1@S@These inhibitory effects of c-Rel correlate with its DNA-binding activity but not with its ability to heterodimerize with p50, suggesting that c-Rel inhibition involves competition with p50/p65 for occupancy of the kappa B enhancer element.@@@@1@37@@oe@16-12-2010 843006908@GENIA Treebank@formal@@1@S@Together, these findings suggest that one function of c-Rel is as a physiologic repressor of the HIV-1 LTR and IL-2R alpha promoters, serving to efficiently counter the strong transcriptional activating effects of p65.@@@@1@36@@oe@16-12-2010 843681601@GENIA Treebank@formal@@1@S@Protease treatment of nuclear extracts distinguishes between class II MHC X1 box DNA-binding proteins in wild-type and class II-deficient B cells.@@@@1@22@@oe@16-12-2010 843681602@GENIA Treebank@formal@@1@S@The X box region is critical for directing the expression of class II major histocompatibility complex genes in B lymphocytes.@@@@1@21@@oe@16-12-2010 843681603@GENIA Treebank@formal@@1@S@Although several class II promoter-specific DNA binding factors have been described, only the X box region factor, RFX, shows a genetic correlation with class II expression, being deficient in some B cell lines derived from patients with class II-deficient congenital immunodeficiency.@@@@1@46@@oe@16-12-2010 843681604@GENIA Treebank@formal@@1@S@To further evaluate the role of X box DNA-binding proteins in class II gene expression, the role of the X box region was examined in both class II-positive and -negative lymphoid cells.@@@@1@34@@oe@16-12-2010 843681605@GENIA Treebank@formal@@1@S@In addition to the wild-type B cell line Raji, two class II transcriptional mutant cell lines, SJO and RJ2.2.5, and Jurkat, a class II negative T cell line, were examined.@@@@1@36@@oe@16-12-2010 843681606@GENIA Treebank@formal@@1@S@In contrast to wild-type B cells, neither of the class II mutant cell lines could use the X box region to direct the expression of a transiently transfected reporter gene, indicating that the X box-dependent transcriptional pathway is defective in these cells.@@@@1@45@@oe@16-12-2010 843681607@GENIA Treebank@formal@@1@S@The binding activity of the X1 box DNA-binding protein RFX was examined and found to be present in wild-type B cells and the mutant RJ2.2.5 but was absent in SJO and Jurkat.@@@@1@33@@oe@16-12-2010 843681608@GENIA Treebank@formal@@1@S@However, other X1 box-specific activities were detected in all these cell lines.@@@@1@14@@oe@16-12-2010 843681609@GENIA Treebank@formal@@1@S@To determine whether these different X1 box activities represented distinct DNA binding proteins or multimeric forms of the same factor(s), protease treatment of the crude nuclear extracts followed by DNA-binding assays were carried out and demonstrated that B cell extracts contain at least two X1-specific factors.@@@@1@51@@oe@16-12-2010 843681610@GENIA Treebank@formal@@1@S@One of these cleaved products (band 1 pk) correlates with RFX activity.@@@@1@15@@oe@16-12-2010 843681611@GENIA Treebank@formal@@1@S@A similar comparison with protease-treated extracts prepared from Jurkat cells demonstrated the presence of the band 1pk activity despite an absence of the native RFX activity.@@@@1@27@@oe@16-12-2010 843681612@GENIA Treebank@formal@@1@S@In contrast, protease treatment and analysis of SJO extracts showed no detectable levels of the band 1pk activity.@@@@1@20@@oe@16-12-2010 843681613@GENIA Treebank@formal@@1@S@These results demonstrate that multiple X1 box-specific DNA-binding activities exist in all lymphoid cells, but the presence of an actively binding RFX species correlates with class II transcription.@@@@1@30@@oe@16-12-2010 843723501@GENIA Treebank@formal@@1@S@Replication of type 1 human immunodeficiency viruses containing linker substitution mutations in the -201 to -130 region of the long terminal repeat.@@@@1@23@@oe@16-12-2010 843723502@GENIA Treebank@formal@@1@S@In previous transfection analyses using the chloramphenicol acetyltransferase reporter gene system, we determined that linker substitution (LS) mutations between -201 and -130 (relative to the transcription start site) of the human immunodeficiency virus type 1 long terminal repeat (LTR) caused moderate decreases in LTR transcriptional activity in a T-cell line (S.L.Zeichner, J.Y.H. Kim, and J.C.Alwine, J.Virol.65:2436-2444, 1991).@@@@1@74@@oe@16-12-2010 843723503@GENIA Treebank@formal@@1@S@In order to confirm the significance of this region in the context of viral replication, we constructed several of these LS mutations (-201 to - 184, -183 to -166, -165 to -148, and -148 to -130) in proviruses and prepared viral stocks by cocultivation of transfected RD cells with CEMx174 cells.@@@@1@57@@oe@16-12-2010 843723504@GENIA Treebank@formal@@1@S@In addition, two mutations between -93 and -76 and between -75 and -58 were utilized, since they affect the nuclear factor kappa B (NF-kappa B)- and Sp1-binding sites and were expected to diminish viral replication.@@@@1@41@@oe@16-12-2010 843723505@GENIA Treebank@formal@@1@S@Our results suggest that while transfection analyses offer an adequate approximation of the effects of the LS mutations, the analysis of viral replication using a mutant viral stock presents a more accurate picture, which is sometimes at variance with the transfection results.@@@@1@45@@oe@16-12-2010 843723506@GENIA Treebank@formal@@1@S@Three mutants (-201/-184 NXS, -165/-148 NXS, and -147/-130 NXS) had effects on viral replication that were much more severe than the effects predicted from their performance in transfection analyses, and the effects of two LS mutations (-201/-184 NXS and -183/-166 NXS) were not predicted by their effects in transfection.@@@@1@57@@oe@16-12-2010 843723507@GENIA Treebank@formal@@1@S@In addition, we observed cell type-specific permissiveness to replication of some mutant viruses.@@@@1@15@@oe@16-12-2010 843723508@GENIA Treebank@formal@@1@S@In the cell types tested, the LS mutations indicated an apparent requirement not only for the intact NF-kappa B and SP1-binding sites but also for several regions between -201 and -130 not previously associated with viral infectivity.@@@@1@39@@oe@16-12-2010 844137701@GENIA Treebank@formal@@1@S@Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3).@@@@1@23@@oe@16-12-2010 844137702@GENIA Treebank@formal@@1@S@Inducible expression of human immunodeficiency virus (HIV) is regulated by a cellular transcription factor, nuclear factor kappa B (NF-kappa B).@@@@1@26@@oe@16-12-2010 844137703@GENIA Treebank@formal@@1@S@NF-kappa B is composed of distinct subunits; five independent genes, NFKB1(p105), NFKB2(p100), RelA(p65), c-rel and relB, that encode related proteins that bind to kappa B DNA elements have been isolated.@@@@1@37@@oe@16-12-2010 844137704@GENIA Treebank@formal@@1@S@We have previously found that NFKB2(p49/p52) acts in concert with RelA(p65) to stimulate the HIV enhancer in Jurkat T-leukemia cells.@@@@1@21@@oe@16-12-2010 844137705@GENIA Treebank@formal@@1@S@Here we examine the biochemical basis for the transcriptional regulation of HIV by NFKB2.@@@@1@15@@oe@16-12-2010 844137706@GENIA Treebank@formal@@1@S@Using Scatchard analysis, we have determined the dissociation constants of homodimeric p49 and heterodimeric p49/p65 for binding to the HIV kappa B site.@@@@1@25@@oe@16-12-2010 844137707@GENIA Treebank@formal@@1@S@p49 has a approximately 18-fold-lower affinity for the HIV kappa B site (KD = 69.1 pM) than does the approximately 50-kDa protein NFKB1(p50) derived from p105 (KD = 3.9 pM).@@@@1@35@@oe@16-12-2010 844137708@GENIA Treebank@formal@@1@S@In contrast, the affinity of heterodimeric NFKB2(p49)/RelA(p65) for this site is approximately 6-fold higher (KD = 11.8 pM) than that of p49 alone.@@@@1@27@@oe@16-12-2010 844137709@GENIA Treebank@formal@@1@S@Consistent with these findings, in vitro transcription was stimulated 18-fold by the addition of preformed, heterodimeric NFKB2(p49)/RelA(p65) protein.@@@@1@21@@oe@16-12-2010 844137710@GENIA Treebank@formal@@1@S@Transcriptional activation of the HIV enhancer was also subject to regulation by recently cloned I kappa B-alpha(MAD-3).@@@@1@21@@oe@16-12-2010 844137711@GENIA Treebank@formal@@1@S@Recombinant I kappa B-alpha(MAD-3) inhibited the DNA binding activity of p65, p49/p65, and p50/p65 but stimulated the binding of NFKB2(p49) or NFKB1(p50).@@@@1@28@@oe@16-12-2010 844137712@GENIA Treebank@formal@@1@S@Functional activation of an HIV reporter plasmid by p49/p65 in transiently transfected Jurkat T-leukemia cells was also inhibited by coexpression of MAD-3.@@@@1@23@@oe@16-12-2010 844137713@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 844137901@GENIA Treebank@formal@@1@S@The human prointerleukin 1 beta gene requires DNA sequences both proximal and distal to the transcription start site for tissue-specific induction.@@@@1@22@@oe@16-12-2010 844137902@GENIA Treebank@formal@@1@S@In these studies, we have identified DNA sequences and specific protein interactions necessary for transcriptional regulation of the human prointerleukin 1 beta (proIL-1 beta) gene.@@@@1@29@@oe@16-12-2010 844137903@GENIA Treebank@formal@@1@S@A cell-type-independent lipopolysaccharide (LPS)-responsive enhancer element located between -3757 and -2729 bp upstream from the transcription start site (cap site) consisted of at least six discrete subregions which were essential to the maximal induction by LPS in transfected monocytes.@@@@1@45@@oe@16-12-2010 844137904@GENIA Treebank@formal@@1@S@The enhancer also appeared to mediate phorbol myristate acetate induction in monocytes and IL-1 responsiveness in fibroblasts.@@@@1@18@@oe@16-12-2010 844137905@GENIA Treebank@formal@@1@S@Deletion and base substitution mutations along with DNA binding studies demonstrated that the enhancer contained a minimum of three functional protein binding sequences, two of which appeared to be important for gene induction.@@@@1@35@@oe@16-12-2010 844137906@GENIA Treebank@formal@@1@S@One of the essential proteins which bound to the enhancer was similar or identical to members of the C/EBP family of transcription factors required for both IL-1- and LPS-specific induction of the IL-6 gene (i.e., the NF-IL6 proteins).@@@@1@42@@oe@16-12-2010 844137907@GENIA Treebank@formal@@1@S@When ligated to the proIL-1 beta cap site-proximal region (located between -131 to +12), both the proIL-1 beta and the simian virus 40 enhancer elements functioned more efficiently in monocytes than in HeLa cells, which are not normally competent for IL-1 beta expression.@@@@1@48@@oe@16-12-2010 844137908@GENIA Treebank@formal@@1@S@When ligated to the murine c-fos promoter, however, the proIL-1 beta enhancer was inducible in phorbol myristate acetate-stimulated HeLa cells, suggesting the existence of a proIL-1 beta promoter-proximal requirement for tissue specificity.@@@@1@36@@oe@16-12-2010 844312201@GENIA Treebank@formal@@1@S@Expression of PILOT, a putative transcription factor, requires two signals and is cyclosporin A sensitive in T cells.@@@@1@21@@oe@16-12-2010 844312202@GENIA Treebank@formal@@1@S@Few known genes (IL-2, members of the IL-8 family, interferon-gamma) are induced in T cells only through the combined effect of phorbol myristic acetate (PMA) and a Ca(2+)-ionophore, and expression of only these genes can be fully suppressed by Cyclosporin A (CyA).@@@@1@52@@oe@16-12-2010 844312203@GENIA Treebank@formal@@1@S@We have identified a putative transcription factor, designated PILOT, with an identical dual signal requirement for expression.@@@@1@20@@oe@16-12-2010 844312204@GENIA Treebank@formal@@1@S@Induction of the PILOT gene is detectable in human T cells 20 min following activation in the presence of cycloheximide and is fully suppressed by CyA.@@@@1@27@@oe@16-12-2010 844312205@GENIA Treebank@formal@@1@S@The PILOT protein has a calculated M(r) of 42.6 kDa and contains three zinc fingers of the C2H2-type at the carboxyl-terminus which are highly homologous to the zinc finger regions of the transcription factors EGR1, EGR2, and pAT 133.@@@@1@42@@oe@16-12-2010 844312206@GENIA Treebank@formal@@1@S@In contrast to T cells, in fibroblasts PILOT gene expression requires only one signal (PMA) and is not affected by CyA.@@@@1@25@@oe@16-12-2010 844312207@GENIA Treebank@formal@@1@S@This observation directly demonstrates the existence of a Ca2+ signal-dependent regulatory element obligatory for expression of some genes in T cells but not in fibroblasts.@@@@1@26@@oe@16-12-2010 844312208@GENIA Treebank@formal@@1@S@This differential expression model will be valuable in the dissection of the dual signal pathway in T cells and the effects of CyA upon it.@@@@1@26@@oe@16-12-2010