765048601@GENIA Treebank@formal@@1@S@Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding.@@@@1@28@@oe@16-12-2010 765048602@GENIA Treebank@formal@@1@S@The putative factors that couple the signal transduction from surface receptors to the activation of cytokine synthesis in natural killer (NK) cells have not been elucidated.@@@@1@29@@oe@16-12-2010 765048603@GENIA Treebank@formal@@1@S@We report here that the nuclear factor of activated T cells (NFATp), a cyclosporin A (CsA)-sensitive factor that regulates the transcription of several cytokines, mediates CD16-induced activation of cytokine genes in human NK cells.@@@@1@42@@oe@16-12-2010 765048604@GENIA Treebank@formal@@1@S@CD16 (Fc gamma RIIIA)-induced expression of cytokine mRNA in NK cells occurs via a CsA-sensitive and Ca(2+)-dependent mechanism.@@@@1@22@@oe@16-12-2010 765048605@GENIA Treebank@formal@@1@S@Stimulation of NK cells with CD16 ligands induces NFAT-like DNA binding activity in the nuclear extracts from these cells, as detected in electrophoretic mobility shift assays.@@@@1@28@@oe@16-12-2010 765048606@GENIA Treebank@formal@@1@S@This occurs with fast kinetics after stimulation, via a CsA-sensitive and Ca(2+)-dependent mechanism that does not require de novo protein synthesis.@@@@1@23@@oe@16-12-2010 765048607@GENIA Treebank@formal@@1@S@NK cell NFAT is present in the cytosol of nonstimulated cells, migrates to the nucleus upon stimulation, and can associate with AP-1.@@@@1@25@@oe@16-12-2010 765048608@GENIA Treebank@formal@@1@S@Two distinct molecules, NFATp and NFATc, have been reported to mediate NFAT activity.@@@@1@16@@oe@16-12-2010 765048609@GENIA Treebank@formal@@1@S@The results of supershift assays using NFATp- and NFATc- specific antibodies indicate that NK cell activation early after CD16 ligand binding involves primarily, if not exclusively, NFATp, and Western blot analysis shows that this has the same electrophoretic mobility (approximately 120 kD) as that of T lymphocytes.@@@@1@52@@oe@16-12-2010 765048610@GENIA Treebank@formal@@1@S@NK cells do not express NFATc constitutively, but NFATc mRNA accumulation is induced in these cells within 2 h of stimulation with CD16 ligands.@@@@1@26@@oe@16-12-2010 765048611@GENIA Treebank@formal@@1@S@However, supershift assays using the available mAb recognizing the T cell NFATc revealed no detectable NFATc protein in nuclear and cytoplasmic extracts from CD16- or phorbol ester-stimulated cells at any time tested, up to 4 h.@@@@1@39@@oe@16-12-2010 765048612@GENIA Treebank@formal@@1@S@These results provide the first direct evidence that both CsA-sensitive transcription factors, NFATp and NFATc, are expressed in human NK cells, and that their activation and/or expression can be regulated in primary cells by a single stimulus, that, in the case of CD16 in NK cells, results in early activation of NFATp and subsequently induced expression of NFATc mRNA.@@@@1@66@@oe@16-12-2010 765418401@GENIA Treebank@formal@@1@S@Relationship between Rap1 protein phosphorylation and regulation of Ca2+ transport in platelets: a new approach.@@@@1@17@@oe@16-12-2010 765418402@GENIA Treebank@formal@@1@S@Although the interrelationship between the two messengers Ca2+ and cyclic AMP in platelet function is well documented, its mechanism of action still remains to be established.@@@@1@28@@oe@16-12-2010 765418403@GENIA Treebank@formal@@1@S@We investigated here the question of the regulation of platelet Ca(2+)-ATPases by cyclic AMP through the phosphorylation of the Rap1 protein using a pathological model.@@@@1@26@@oe@16-12-2010 765418404@GENIA Treebank@formal@@1@S@We first found experimental conditions where Ca(2+)-transport by platelet membrane vesicles appeared to be dependent on the phosphorylation of the Rap1 protein.@@@@1@23@@oe@16-12-2010 765418405@GENIA Treebank@formal@@1@S@Then, we studied platelets of patients with congestive heart failure for their expression of the potential 97 kDa Ca(2+)-ATPase target of regulation through the Rap1 protein as well as the phosphorylation of the Rap1 protein using the catalytic subunit of the cyclic AMP-dependent protein kinase (C. Sub.).@@@@1@51@@oe@16-12-2010 765418406@GENIA Treebank@formal@@1@S@In the first patients studied, we found no significant modification in the expression of the 97 kDa Ca(2+)-ATPase by Western blotting using the PL/IM 430 monoclonal antibody which specifically recognized this isoform.@@@@1@34@@oe@16-12-2010 765418407@GENIA Treebank@formal@@1@S@In contrast, the Rap1 protein was differentially phosphorylated when using 15 micrograms/ml of the C. Sub.@@@@1@18@@oe@16-12-2010 765418408@GENIA Treebank@formal@@1@S@These results allowed us to use these pathological platelets to study the relationship between the expression of Rap1 protein and the regulation of Ca2+ transport by selecting a patient with severe heart failure.@@@@1@34@@oe@16-12-2010 765418409@GENIA Treebank@formal@@1@S@We could show a decrease in the expression as well as in the phosphorylation of Rap1 protein and demonstrate a lower effect of C. Sub. on Ca2+ transport.@@@@1@29@@oe@16-12-2010 765418410@GENIA Treebank@formal@@1@S@Finally, by studying a further series of patients, we could confirm that the decrease in Rap1 protein expression in heart failure, whatever its extent, was variable, and could strictly correlate the expression of Rap1 protein with the stimulatory effect of C. Sub. on Ca2+ transport.@@@@1@51@@oe@16-12-2010 765418411@GENIA Treebank@formal@@1@S@Besides the evidence for regulation of the expression of the Rap1 protein in platelets from patients with heart failure, these findings constitute a new approach in favour of the regulation of platelet Ca2+ transport through the phosphorylation of the Rap1 protein.@@@@1@43@@oe@16-12-2010 765716201@GENIA Treebank@formal@@1@S@Activation of the HIV-1 enhancer by the LEF-1 HMG protein on nucleosome-assembled DNA in vitro.@@@@1@16@@oe@16-12-2010 765716202@GENIA Treebank@formal@@1@S@Lymphoid enhancer-binding factor 1 (LEF-1) is a regulatory high mobility group (HMG) protein that activates the T cell receptor alpha (TCR alpha) enhancer in a context-restricted manner in T cells.@@@@1@37@@oe@16-12-2010 765716203@GENIA Treebank@formal@@1@S@In this paper we demonstrate that the distal region of the human immunodeficiency virus-1 (HIV-1) enhancer, which contains DNA-binding sites for LEF-1 and Ets-1, also provides a functional context for activation by LEF-1.@@@@1@38@@oe@16-12-2010 765716204@GENIA Treebank@formal@@1@S@First, we show that mutations in the LEF-1-binding site inhibit the activity of multimerized copies of the HIV-1 enhancer in Jurkat T cells, and that LEF-1/GAL4 can activate a GAL4-substituted HIV-1 enhancer 80- to 100-fold in vivo.@@@@1@40@@oe@16-12-2010 765716205@GENIA Treebank@formal@@1@S@Second, recombinant LEF-1 is shown to activate HIV-1 transcription on chromatin-assembled DNA in vitro.@@@@1@16@@oe@16-12-2010 765716206@GENIA Treebank@formal@@1@S@By using a nucleosome-assembly system derived from Drosophila embryos, we find that the packaging of DNA into chromatin in vitro strongly represses HIV-1 transcription and that repression can be counteracted efficiently by preincubation of the DNA with LEF-1 (or LEF-1 and Ets-1) supplemented with fractions containing the promoter-binding protein, Sp1.@@@@1@55@@oe@16-12-2010 765716207@GENIA Treebank@formal@@1@S@Addition of TFE-3, which binds to an E-box motif upstream of the LEF-1 and Ets-1 sites, further augments transcription in this system.@@@@1@25@@oe@16-12-2010 765716208@GENIA Treebank@formal@@1@S@Individually or collectively, none of the three enhancer-binding proteins (LEF-1, Ets-1, and TFE-3) could activate transcription in the absence of Sp1.@@@@1@27@@oe@16-12-2010 765716209@GENIA Treebank@formal@@1@S@A truncation mutant of LEF-1 (HMG-88), which contains the HMG box but lacks the trans-activation domain, did not activate transcription from nucleosomal DNA, indicating that bending of DNA by the HMG domain is not sufficient to activate transcription in vitro.@@@@1@46@@oe@16-12-2010 765716210@GENIA Treebank@formal@@1@S@We conclude that transcription activation by LEF-1 in vitro is a chromatin-dependent process that requires a functional trans-activation domain in addition to the HMG domain.@@@@1@26@@oe@16-12-2010 765764501@GENIA Treebank@formal@@1@S@Phosphorylation of the transcription factor NFATp inhibits its DNA binding activity in cyclosporin A-treated human B and T cells.@@@@1@20@@oe@16-12-2010 765764502@GENIA Treebank@formal@@1@S@Cyclosporin A (CsA) exerts its immunosuppressive effect by inhibiting the activity of nuclear factor of activated T cells (NFAT), thus preventing transcriptional induction of several cytokine genes.@@@@1@33@@oe@16-12-2010 765764503@GENIA Treebank@formal@@1@S@This effect is thought to be largely mediated through inactivation of the phosphatase calcineurin, which in turn inhibits translocation of an NFAT component to the nucleus.@@@@1@28@@oe@16-12-2010 765764504@GENIA Treebank@formal@@1@S@Here we report that CsA treatment of Raji B and Jurkat T cell lines yields a phosphorylated form of NFATp that is inhibited in DNA-binding and in its ability to form an NFAT complex with Fos and Jun.@@@@1@39@@oe@16-12-2010 765764505@GENIA Treebank@formal@@1@S@Immunoblot analyses and metabolic labeling with [32P]orthophosphate show that CsA alters NFATp migration on SDS-polyacrylamide gel electrophoresis by increasing its phosphorylation level without affecting subcellular distribution.@@@@1@27@@oe@16-12-2010 765764506@GENIA Treebank@formal@@1@S@Dephosphorylation by in vitro treatment with calcineurin or alkaline phosphatase restores NFATp DNA binding activity and its ability to reconstitute an NFAT complex with Fos and Jun proteins.@@@@1@29@@oe@16-12-2010 765764507@GENIA Treebank@formal@@1@S@These data point to a new mechanism for CsA-sensitive regulation of NFATp in which dephosphorylation is critical for DNA binding.@@@@1@21@@oe@16-12-2010 765782501@GENIA Treebank@formal@@1@S@Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells.@@@@1@24@@oe@16-12-2010 765782502@GENIA Treebank@formal@@1@S@HTLV-1 infection causes an adult T cell leukemia in humans.@@@@1@11@@oe@16-12-2010 765782503@GENIA Treebank@formal@@1@S@The viral encoded protein tax, is thought to play an important role in oncogenesis.@@@@1@16@@oe@16-12-2010 765782504@GENIA Treebank@formal@@1@S@Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes, despite comparable levels of tax expression in both tissues.@@@@1@30@@oe@16-12-2010 765782505@GENIA Treebank@formal@@1@S@Constitutive tyrosine phosphorylation of a 130-kD protein(s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines, but not in thymocytes from Thy-tax transgenic mice.@@@@1@36@@oe@16-12-2010 765782506@GENIA Treebank@formal@@1@S@Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines.@@@@1@38@@oe@16-12-2010 765782507@GENIA Treebank@formal@@1@S@Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6.@@@@1@14@@oe@16-12-2010 765782508@GENIA Treebank@formal@@1@S@Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line, which was associated with induction of cell proliferation.@@@@1@29@@oe@16-12-2010 765782509@GENIA Treebank@formal@@1@S@Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies.@@@@1@11@@oe@16-12-2010 765782510@GENIA Treebank@formal@@1@S@Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model.@@@@1@22@@oe@16-12-2010 765952901@GENIA Treebank@formal@@1@S@Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs.@@@@1@18@@oe@16-12-2010 765952902@GENIA Treebank@formal@@1@S@Erythropoietin (Epo), the primary regulator of the production of erythroid cells, acts by binding to a cell surface receptor (EpoR) on erythroid progenitors.@@@@1@30@@oe@16-12-2010 765952903@GENIA Treebank@formal@@1@S@We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5' flanking region of the human EpoR gene.@@@@1@28@@oe@16-12-2010 765952904@GENIA Treebank@formal@@1@S@In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2, Sp1 and the erythroid-specific GATA-1.@@@@1@30@@oe@16-12-2010 765952905@GENIA Treebank@formal@@1@S@The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells, respectively, reflecting the high and low levels of constitutive hEpoR expression.@@@@1@30@@oe@16-12-2010 765952906@GENIA Treebank@formal@@1@S@The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation.@@@@1@23@@oe@16-12-2010 765952907@GENIA Treebank@formal@@1@S@Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif.@@@@1@25@@oe@16-12-2010 765952908@GENIA Treebank@formal@@1@S@By increasing GATA-1 levels via co-transfection, we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells, but not in the highly active OCIM1 cells, although GATA-1 mRNA levels were comparable in OCIM1 and K562.@@@@1@42@@oe@16-12-2010 765952909@GENIA Treebank@formal@@1@S@Interestingly, when we mutated the Sp1 site, resulting in a marked decrease in hEpoR promoter activity, we could restore transactivation by increasing GATA-1 levels in OCIM1 cells.@@@@1@31@@oe@16-12-2010 765952910@GENIA Treebank@formal@@1@S@These data suggest that while GATA-1 can transactivate the EpoR promoter, the level of hEpoR gene expression does not depend on GATA-1 alone.@@@@1@25@@oe@16-12-2010 765952911@GENIA Treebank@formal@@1@S@Rather, hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors, including possibly other Sp1-like binding proteins, to provide high level, tissue-specific expression.@@@@1@32@@oe@16-12-2010 766298201@GENIA Treebank@formal@@1@S@TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia.@@@@1@13@@oe@16-12-2010 766298202@GENIA Treebank@formal@@1@S@The TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1)] and inversions [inv14(q11;q32.1)] with TCR alpha/beta loci in T-cell leukemias, such as T-prolymphocytic (T-PLL).@@@@1@37@@oe@16-12-2010 766298203@GENIA Treebank@formal@@1@S@It is also involved in T- acute and- chronic leukemias arising in cases of ataxia-telangiectasia (AT), an immunodeficiency syndrome.@@@@1@22@@oe@16-12-2010 766298204@GENIA Treebank@formal@@1@S@Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia.@@@@1@22@@oe@16-12-2010 766298205@GENIA Treebank@formal@@1@S@We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes (PBLs) from four AT cases and from healthy controls.@@@@1@26@@oe@16-12-2010 766298206@GENIA Treebank@formal@@1@S@We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases.@@@@1@35@@oe@16-12-2010 766298207@GENIA Treebank@formal@@1@S@Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14.@@@@1@49@@oe@16-12-2010 766298208@GENIA Treebank@formal@@1@S@These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11.@@@@1@26@@oe@16-12-2010 766298209@GENIA Treebank@formal@@1@S@Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation.@@@@1@26@@oe@16-12-2010 766352001@GENIA Treebank@formal@@1@S@Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals.@@@@1@18@@oe@16-12-2010 766352002@GENIA Treebank@formal@@1@S@The mRNA for the Duffy blood group antigen, the erythrocyte receptor for the Plasmodium vivax malaria parasite, has recently been cloned and shown to encode a widely expressed chemokine receptor.@@@@1@33@@oe@16-12-2010 766352003@GENIA Treebank@formal@@1@S@Here, we show that the Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon and that most Duffy-negative blacks carry a silent FY*B allele with a single T to C substitution at nucleotide -46.@@@@1@40@@oe@16-12-2010 766352004@GENIA Treebank@formal@@1@S@This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor.@@@@1@21@@oe@16-12-2010 766352005@GENIA Treebank@formal@@1@S@With the recent characterization of the FY*A and FY*B alleles, these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the DARC gene in Duffy-negative individuals.@@@@1@38@@oe@16-12-2010 766478101@GENIA Treebank@formal@@1@S@Interleukin-2 promoter activity in Epstein-Barr virus-transformed B lymphocytes is controlled by nuclear factor-chi B.@@@@1@15@@oe@16-12-2010 766478102@GENIA Treebank@formal@@1@S@The regulation of interleukin (IL)-2 gene expression has been investigated mainly in T lymphocytes, the predominant producers of IL-2.@@@@1@24@@oe@16-12-2010 766478103@GENIA Treebank@formal@@1@S@However, B cells can also synthesize IL-2.@@@@1@9@@oe@16-12-2010 766478104@GENIA Treebank@formal@@1@S@In the present study we analyzed the control of IL-2 promoter activity in Epstein-Barr virus (EBV)-transformed B cell clones which are capable of secreting IL-2 at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin.@@@@1@44@@oe@16-12-2010 766478105@GENIA Treebank@formal@@1@S@Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL-2 promoter [distal nuclear factor (NF)-AT, proximal NF-AT, AP-1/Octamer (UPS) or NF-chi B (TCEd) sites] were performed.@@@@1@43@@oe@16-12-2010 766478106@GENIA Treebank@formal@@1@S@In EBV-transformed B clones, the chi B site exerted the strongest inducible activity; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells.@@@@1@32@@oe@16-12-2010 766478107@GENIA Treebank@formal@@1@S@An IL-2 promoter bearing a defective NF-chi B site was completely inactive in EBV-transformed B cells, while it still had activity in Jurkat T cells.@@@@1@27@@oe@16-12-2010 766478108@GENIA Treebank@formal@@1@S@In seven EBV-B cell clones or lines differing in their capacity to secrete IL-2, the activity of the IL-2 promoter correlated well with the status of IL-2 secretion.@@@@1@30@@oe@16-12-2010 766478109@GENIA Treebank@formal@@1@S@Similarly, a human immunodeficiency virus promoter, whose activity is controlled through chi B factors, was found to be active in the IL-2 producing EBV-B cells, but inactive in the non-IL-2-producing cells.@@@@1@36@@oe@16-12-2010 766478110@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays using protein extracts from EBV-B cells and the IL-2 NF-chi B probe revealed the constitutive generation of chi B complexes in IL-2-secreting cells consisting mainly of heterodimeric p50/p65 complexes.@@@@1@34@@oe@16-12-2010 766478111@GENIA Treebank@formal@@1@S@A weaker chi B complex formation and faster-migrating complexes were detected in non-IL-2-secreting cells.@@@@1@15@@oe@16-12-2010 766478112@GENIA Treebank@formal@@1@S@These results demonstrate that the IL-2 NF-chi B site is indispensable for the activity of the IL-2 promoter in EBV-transformed B cells, whereas other transcription factors appear to be less important for IL-2 expression in these cells.@@@@1@39@@oe@16-12-2010 766556701@GENIA Treebank@formal@@1@S@Transcriptional regulation of the gene encoding the human C-type lectin leukocyte receptor AIM/CD69 and functional characterization of its tumor necrosis factor-alpha-responsive elements.@@@@1@23@@oe@16-12-2010 766556702@GENIA Treebank@formal@@1@S@The human activation antigen CD69 is a member of the C-type animal lectin superfamily that functions as a signal-transmitting receptor.@@@@1@21@@oe@16-12-2010 766556703@GENIA Treebank@formal@@1@S@Although the expression of CD69 can be induced in vitro on cells of most hematopoietic lineages with a wide variety of stimuli, in vivo it is mainly expressed by T-lymphocytes located in the inflammatory infiltrates of several human diseases.@@@@1@41@@oe@16-12-2010 766556704@GENIA Treebank@formal@@1@S@To elucidate the mechanisms that regulate the constitutive and inducible expression of CD69 by leukocytes, we isolated the promoter region of the CD69 gene and carried out its functional characterization.@@@@1@32@@oe@16-12-2010 766556705@GENIA Treebank@formal@@1@S@Sequence analysis of the 5'-flanking region of the CD69 gene revealed the presence of a potential TATA element 30 base pairs upstream of the major transcription initiation site and several putative binding sequences for inducible transcription factors (NF-kappa B, Egr-1, AP-1), which might mediate the inducible expression of this gene.@@@@1@56@@oe@16-12-2010 766556706@GENIA Treebank@formal@@1@S@Transient expression of CD69 promoter-based reporter gene constructs in K562 cells indicated that the proximal promoter region spanning positions -78 to +16 contained the cis-acting sequences necessary for basal and phorbol 12-myristate 13-acetate-inducible transcription of the CD69 gene.@@@@1@39@@oe@16-12-2010 766556707@GENIA Treebank@formal@@1@S@Removal of the upstream sequences located between positions -78 and -38 resulted in decreased promoter strength and abolished the response to phorbol 12-myristate 13-acetate.@@@@1@25@@oe@16-12-2010 766556708@GENIA Treebank@formal@@1@S@We also found that tumor necrosis factor-alpha (TNF-alpha) is capable of inducing the surface expression of the CD69 molecule as well as the promoter activity of fusion plasmids that contain 5'-flanking sequences of the CD69 gene, suggesting that this cytokine may regulate in vivo the expression of CD69.@@@@1@52@@oe@16-12-2010 766556709@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 766558801@GENIA Treebank@formal@@1@S@Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105.@@@@1@10@@oe@16-12-2010 766558802@GENIA Treebank@formal@@1@S@Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein, E2, and a novel ubiquitin-protein ligase, E3, involved in conjugation.@@@@1@26@@oe@16-12-2010 766558803@GENIA Treebank@formal@@1@S@In most cases, the transcriptional factor NF-kappa B is a heterodimer consisting of two subunits, p50 and p65, which are encoded by two distinct genes of the Rel family.@@@@1@33@@oe@16-12-2010 766558804@GENIA Treebank@formal@@1@S@p50 is translated as a precursor of 105 kDa.@@@@1@10@@oe@16-12-2010 766558805@GENIA Treebank@formal@@1@S@The C-terminal domain of the precursor is rapidly degraded, forming the mature p50 subunit consisted of the N-terminal region of the molecule.@@@@1@24@@oe@16-12-2010 766558806@GENIA Treebank@formal@@1@S@The mechanism of generation of p50 is not known.@@@@1@10@@oe@16-12-2010 766558807@GENIA Treebank@formal@@1@S@It has been suggested that the ubiquitin-proteasome system is involved in the process; however, the specific enzymes involved and the mechanism of limited proteolysis, in which half of the molecule is spared, have been obscure.@@@@1@40@@oe@16-12-2010 766558808@GENIA Treebank@formal@@1@S@Palombella and colleagues (Palombella, V.J., Rando, O.J., Goldberg, A.L., and Maniatis, T.(1994) Cell 78, 773-785) have shown that ubiquitin is required for the processing in a cell-free system of a truncated, artificially constructed, 60-kDa precursor.@@@@1@51@@oe@16-12-2010 766558809@GENIA Treebank@formal@@1@S@They have also shown that proteasome inhibitors block the processing both in vitro and in vivo.@@@@1@17@@oe@16-12-2010 766558810@GENIA Treebank@formal@@1@S@In this study, we demonstrate reconstitution of a cell-free processing system and demonstrate directly that: (a) the ubiquitin-proteasome system is involved in processing of the intact p105 precursor, (b) conjugation of ubiquitin to the precursor is an essential intermediate step in the processing, (c) the recently discovered novel species of the ubiquitin-carrier protein, E2-F1, that is involved in the conjugation and degradation of p53, is also required for the limited processing of the p105 precursor, and (d) a novel, approximately 320-kDa species of ubiquitin-protein ligase, is involved in the process.@@@@1@109@@oe@16-12-2010 766558811@GENIA Treebank@formal@@1@S@This novel enzyme is distinct from E6-AP, the p53-conjugating ligase, and from E3 alpha, the "N-end rule" ligase.@@@@1@24@@oe@16-12-2010 766838501@GENIA Treebank@formal@@1@S@Nonradioactive quantification of glucocorticoid receptor expression during differentiation of human monocytic cells (U937).@@@@1@16@@oe@16-12-2010 766838502@GENIA Treebank@formal@@1@S@We describe a method for relative quantification of specific mRNA using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon (probe) and unlabeled amplicon (target) during hybridization.@@@@1@39@@oe@16-12-2010 766838503@GENIA Treebank@formal@@1@S@As the target quantity increased, that of the double-labeled probe decreased in accordance with the mass action law.@@@@1@20@@oe@16-12-2010 766838504@GENIA Treebank@formal@@1@S@This technique was successfully applied to evaluate differences in glucocorticoid receptor expression in U937 cells before and after the addition of potent differentiation inducers: 12-O-tetradecanoylphorbol 13-acetate (TPA) and a combination of all-trans retinoic acid (RA) and 1,25-dihydroxyvitamin D2 (VD).@@@@1@47@@oe@16-12-2010 766838505@GENIA Treebank@formal@@1@S@We observed that TPA treatment was associated with an increase in specific binding of [3H]dexamethasone and up-regulation of GR mRNA while no enhanced GR expression was perceived with RA/VD treatment.@@@@1@32@@oe@16-12-2010 767011401@GENIA Treebank@formal@@1@S@The hematopoietic transcription factor PU.1 is downregulated in human multiple myeloma cell lines.@@@@1@14@@oe@16-12-2010 767011402@GENIA Treebank@formal@@1@S@PU.1 is a hematopoietic transcription factor belonging to the Ets-family.@@@@1@11@@oe@16-12-2010 767011403@GENIA Treebank@formal@@1@S@It is identical to the Spi-1 oncogene, which is implicated in spleen focus-forming virus-induced murine erythroleukemias.@@@@1@18@@oe@16-12-2010 767011404@GENIA Treebank@formal@@1@S@PU.1 seems to be required for early development of multiple hematopoietic lineages, but its expression in mature cells is preferentially observed in cells of the B-cell-and monocyte/macrophage-differentiation lineage.@@@@1@30@@oe@16-12-2010 767011405@GENIA Treebank@formal@@1@S@It binds the so-called Pu box, an important tissue-specific regulatory DNA element present in a number of genes expressed in these cell lineages.@@@@1@25@@oe@16-12-2010 767011406@GENIA Treebank@formal@@1@S@We have analyzed the expression and activity of PU.1 during human B-cell development using a panel of B-cell lines representing different stages of maturation, from early precursors to differentiated plasma cells.@@@@1@33@@oe@16-12-2010 767011407@GENIA Treebank@formal@@1@S@PU.1 mRNA expression and PU.1 DNA binding activity, as measured by Northern blot analysis and electrophoretic mobility shift assay, respectively, were evident in cell lines representing pro-B, pre-B, and mature B cells.@@@@1@38@@oe@16-12-2010 767011408@GENIA Treebank@formal@@1@S@We could also show Pu box-dependent transactivation of a reporter gene in transient transfections in these cell lines.@@@@1@19@@oe@16-12-2010 767011409@GENIA Treebank@formal@@1@S@In contrast, in a number of multiple myeloma cell lines, representing differentiated, plasma cell-like B cells, PU.1 DNA binding activity, mRNA expression, and Pu box-dependent transactivation were absent or detectable at a very low level.@@@@1@42@@oe@16-12-2010 767011410@GENIA Treebank@formal@@1@S@In lymphoblastoid cell lines, which exemplify an intermediate stage of B-cell differentiation, a reduced expression and activity were observed.@@@@1@22@@oe@16-12-2010 767011411@GENIA Treebank@formal@@1@S@The findings in the human multiple myeloma cell lines represent the first examples of B cells with downregulated PU.1 expression and apparently contradict observations in the murine system in which PU.1 is expressed and active in plasmacytoma cell lines.@@@@1@40@@oe@16-12-2010 767011412@GENIA Treebank@formal@@1@S@At present, it is unclear whether the lack of PU.1 expression and activity in human multiple myeloma cell lines represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in terminally differentiated B cells.@@@@1@39@@oe@16-12-2010 767319401@GENIA Treebank@formal@@1@S@Microtubules mediate cellular 25-hydroxyvitamin D3 trafficking and the genomic response to 1,25-dihydroxyvitamin D3 in normal human monocytes.@@@@1@18@@oe@16-12-2010 767319402@GENIA Treebank@formal@@1@S@The genomic actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the intracellular vitamin D receptor (VDR).@@@@1@21@@oe@16-12-2010 767319403@GENIA Treebank@formal@@1@S@Although immunocytochemistry has shown that disruption of microtubular assembly prevents nuclear access of the sterol-VDR complex, the role of microtubules in the response to 1,25(OH)2D3 has not been studied in viable cells.@@@@1@34@@oe@16-12-2010 767319404@GENIA Treebank@formal@@1@S@Our studies examined this interaction in normal human monocytes.@@@@1@10@@oe@16-12-2010 767319405@GENIA Treebank@formal@@1@S@Monocytes convert 25(OH)D3 to 1,25(OH)2D3 and to 24-hydroxylated metabolites more polar than 1,25(OH)2D3.@@@@1@14@@oe@16-12-2010 767319406@GENIA Treebank@formal@@1@S@Microtubule disruption totally abolished the ability of exogenous 1,25(OH)2D3 to suppress its own synthesis and to induce 24-hydroxylase mRNA and activity, without affecting either total 1,25(OH)2D3 uptake or maximal 1,25(OH)2D3-VDR binding.@@@@1@33@@oe@16-12-2010 767319407@GENIA Treebank@formal@@1@S@Thus, intact microtubules are essential for 1,25(OH)2D3-dependent modulation of gene transcription.@@@@1@13@@oe@16-12-2010 767319408@GENIA Treebank@formal@@1@S@Interestingly, microtubule disruption also decreased monocyte 1,25(OH)2D3 synthesis, not by decreasing the Vmax of monocyte mitochondrial 1 alpha-hydroxylase but through an increase in the Km for 25(OH)2D3.@@@@1@30@@oe@16-12-2010 767319409@GENIA Treebank@formal@@1@S@We examined 25(OH)D3 transport.@@@@1@5@@oe@16-12-2010 767319410@GENIA Treebank@formal@@1@S@Microtubule disruption did not affect total cellular 25(OH)D3 uptake but reduced its intracellular trafficking to the mitochondria.@@@@1@18@@oe@16-12-2010 767319411@GENIA Treebank@formal@@1@S@Thus, microtubules participate in intracellular 25(OH)D3 transport, and their integrity determines normal 1,25(OH)2D3 synthesis.@@@@1@17@@oe@16-12-2010 767324001@GENIA Treebank@formal@@1@S@A regulatory element in the human interleukin 2 gene promoter is a binding site for the zinc finger proteins Sp1 and EGR-1.@@@@1@23@@oe@16-12-2010 767324002@GENIA Treebank@formal@@1@S@Activation of the interleukin 2 (IL-2) gene after antigen recognition is a critical event for T cell proliferation and effector function.@@@@1@24@@oe@16-12-2010 767324003@GENIA Treebank@formal@@1@S@Prior studies have identified several transcription factors that contribute to the activity of the IL-2 promoter in stimulated T lymphocytes.@@@@1@21@@oe@16-12-2010 767324004@GENIA Treebank@formal@@1@S@Here we describe a novel regulatory element within the IL-2 promoter located immediately upstream of the nuclear factor of activated T cell (NFAT) domain.@@@@1@27@@oe@16-12-2010 767324005@GENIA Treebank@formal@@1@S@This region (termed the zinc finger protein binding region (ZIP)) serves as binding site for two differently regulated zinc finger proteins: the constitutively expressed transcription factor Sp1 and the inducible early growth response protein EGR-1.@@@@1@41@@oe@16-12-2010 767324006@GENIA Treebank@formal@@1@S@In unstimulated cells which do not secrete IL-2, only Sp1 binds to this region, while in stimulated IL-2 secreting cells the inducible EGR-1 protein recognizes this element.@@@@1@30@@oe@16-12-2010 767324007@GENIA Treebank@formal@@1@S@In Jurkat T cells, the ZIP site serves as an activator for IL-2 gene expression, and a combination of ZIP and NFAT binding sites is required for maximal IL-2 promoter activity.@@@@1@34@@oe@16-12-2010 767324008@GENIA Treebank@formal@@1@S@These results suggest a critical role of the ZIP site for IL-2 promoter activity.@@@@1@15@@oe@16-12-2010 767877901@GENIA Treebank@formal@@1@S@The zinc finger transcription factor Egr-1 is essential for and restricts differentiation along the macrophage lineage.@@@@1@17@@oe@16-12-2010 767877902@GENIA Treebank@formal@@1@S@We have isolated cDNA clones of myeloid differentiation primary response (MyD) genes, activated in the absence of de novo protein synthesis following induction for differentiation along either the macrophage or granulocyte lineage in human myeloblastic leukemia HL-60 cells.@@@@1@42@@oe@16-12-2010 767877903@GENIA Treebank@formal@@1@S@One cDNA clone of a primary response gene, expressed upon macrophage differentiation, encoded for Egr-1, a zinc finger transcription factor.@@@@1@24@@oe@16-12-2010 767877904@GENIA Treebank@formal@@1@S@The Egr-1 gene was observed to be transcriptionally silent in HL-60 cells, but active in U-937 and M1 cells, the latter two being predetermined for macrophage differentiation.@@@@1@30@@oe@16-12-2010 767877905@GENIA Treebank@formal@@1@S@Egr-1 antisense oligomers in the culture media blocked macrophage differentiation in both myeloid leukemia cell lines and normal myeloblasts.@@@@1@20@@oe@16-12-2010 767877906@GENIA Treebank@formal@@1@S@HL-60 cells constitutively expressing an Egr-1 transgene (HL-60Egr-1) could be induced for macrophage, but not granulocyte, differentiation.@@@@1@22@@oe@16-12-2010 767877907@GENIA Treebank@formal@@1@S@These observations indicate that expression of Egr-1 is essential for and restricts differentiation of myeloblasts along the macrophage lineage.@@@@1@20@@oe@16-12-2010 767899401@GENIA Treebank@formal@@1@S@Expression of tal-1 and GATA-binding proteins during human hematopoiesis.@@@@1@10@@oe@16-12-2010 767899402@GENIA Treebank@formal@@1@S@Tal-1 rearrangements are associated with nearly 30% of human T acute lymphoblastic leukemia.@@@@1@15@@oe@16-12-2010 767899403@GENIA Treebank@formal@@1@S@Tal-1 gene encodes a putative transcription factor with a basic helix-loop-helix domain and is known to be predominantly expressed in hematopoietic cells.@@@@1@23@@oe@16-12-2010 767899404@GENIA Treebank@formal@@1@S@We investigated the pattern of tal-1 expression in purified human hematopoietic cells by in situ hybridization and reverse transcriptase polymerase chain reaction analysis.@@@@1@24@@oe@16-12-2010 767899405@GENIA Treebank@formal@@1@S@Both methods demonstrated that the tal-1 gene is expressed in megakaryocytes and erythroblasts as well as in basophilic granulocytes.@@@@1@20@@oe@16-12-2010 767899406@GENIA Treebank@formal@@1@S@In addition, our results indicate that the tal-1 1A promoter, which contains two consensus GATA-binding sites, is active mainly in these lineages.@@@@1@26@@oe@16-12-2010 767899407@GENIA Treebank@formal@@1@S@Because the GATA-1 gene is known to transactivate several genes specific for the erythroid, megakaryocytic, and mastocytic/basophilic lineages, we studied GATA-1 expression in these purified hematopoietic cells.@@@@1@31@@oe@16-12-2010 767899408@GENIA Treebank@formal@@1@S@We found that GATA-1 and tal-1 genes are coexpressed in these three lineages.@@@@1@14@@oe@16-12-2010 767899409@GENIA Treebank@formal@@1@S@Remarkably, the expression of both genes is downmodulated during erythroid and megakaryocytic terminal maturation.@@@@1@16@@oe@16-12-2010 767899410@GENIA Treebank@formal@@1@S@In immature hematopoietic cells, tal-1 and GATA-1 genes are coexpressed in committed progenitors cells (CD34+/CD38(2+)), whereas they are not detectable in the most primitive cells (CD34(2+)/CD38-).@@@@1@33@@oe@16-12-2010 767899411@GENIA Treebank@formal@@1@S@In contrast, GATA-2 is strongly expressed in both most primitive and committed progenitors cells, whereas GATA-3 is mostly detected in most primitive ones.@@@@1@26@@oe@16-12-2010 767899412@GENIA Treebank@formal@@1@S@Altogether our results strongly suggest that GATA-1 modulates the transcription of tal-1 during the differentiation of the erythroid, megakaryocytic, and basosophilic lineages.@@@@1@25@@oe@16-12-2010 768065301@GENIA Treebank@formal@@1@S@Cell type- and stage-specific expression of the CD20/B1 antigen correlates with the activity of a diverged octamer DNA motif present in its promoter.@@@@1@24@@oe@16-12-2010 768065302@GENIA Treebank@formal@@1@S@The CD20(B1) gene encodes a B cell-specific protein involved in the regulation of human B cell proliferation and differentiation.@@@@1@23@@oe@16-12-2010 768065303@GENIA Treebank@formal@@1@S@Studies with 5' deletion CD20 promoter-CAT constructs have previously revealed two regions of the promoter between bases -186 and -280 and between bases -280 and -454 which contained positive regulatory elements.@@@@1@32@@oe@16-12-2010 768065304@GENIA Treebank@formal@@1@S@In this study we identified a sequence element present in the most proximal region located between bases -214 and -201, TTCTTCTAATTAA, which is important in the high constitutive expression of CD20 in mature B cells and the induction of CD20 in pre-B cells.@@@@1@46@@oe@16-12-2010 768065305@GENIA Treebank@formal@@1@S@This sequence element was referred to as the BAT box and its deletion significantly reduced the activity of a CD20 promoter-CAT construct in B cells.@@@@1@26@@oe@16-12-2010 768065306@GENIA Treebank@formal@@1@S@Mobility shift assays with various mutant probes and B cell nuclear extracts demonstrated that the core sequence TAAT was essential for binding to this site.@@@@1@26@@oe@16-12-2010 768065307@GENIA Treebank@formal@@1@S@Cross competition experiments with an octamer sequence from the Ig heavy chain promoter, the BAT box, and a TA-rich sequence present in the CD21 promoter revealed that all three sequences bound the same nuclear proteins suggesting that the BAT box binding proteins were Oct-1 and Oct-2.@@@@1@49@@oe@16-12-2010 768065308@GENIA Treebank@formal@@1@S@Southwestern blotting and UV cross-linking studies confirmed that the BAT box binding proteins were Oct-1 and Oct-2.@@@@1@18@@oe@16-12-2010 768065309@GENIA Treebank@formal@@1@S@The affinity of the BAT box binding proteins for the BAT box was approximately 25-fold less than for the octamer sequence and the BAT box binding proteins dissociated from the BAT box 10-fold more rapidly than from the octamer sequence.@@@@1@41@@oe@16-12-2010 768065310@GENIA Treebank@formal@@1@S@Despite this lower affinity, a trimer of the BAT box sequence was as efficiently transactivated by an Oct-2 expression vector as was a trimer of the octamer sequence in HeLa cells.@@@@1@33@@oe@16-12-2010 768065311@GENIA Treebank@formal@@1@S@The BAT box and Oct-2 were also implicated in the induction of CD20 in the pre-B cell line, PB-697, via phorbol esters.@@@@1@25@@oe@16-12-2010 768065312@GENIA Treebank@formal@@1@S@The induction of CD20 mRNA was temporally associated with induction of Oct-2 mRNA and a BAT box-deleted CD20-CAT construct, in contrast to the wild type, was poorly induced by phorbol esters.@@@@1@34@@oe@16-12-2010 768065313@GENIA Treebank@formal@@1@S@Together these results suggest that the BAT box binding proteins are important in the B cell specific expression of CD20 and perhaps CD21.@@@@1@24@@oe@16-12-2010 768224301@GENIA Treebank@formal@@1@S@Functional antagonism between vitamin D3 and retinoic acid in the regulation of CD14 and CD23 expression during monocytic differentiation of U-937 cells.@@@@1@23@@oe@16-12-2010 768224302@GENIA Treebank@formal@@1@S@1,25 alpha-Dihydroxicholecalciferol (VitD3) and retinoic acid (RA) are important regulators of the proliferation and differentiation of several cell types.@@@@1@24@@oe@16-12-2010 768224303@GENIA Treebank@formal@@1@S@This paper describes how the expression of the monocyte-macrophage Ag, CD14, and the low affinity Fc receptor for IgE, CD23, were inversely regulated during VitD3- and RA-induced monocytic differentiation of human U-937 monoblasts.@@@@1@38@@oe@16-12-2010 768224304@GENIA Treebank@formal@@1@S@PMA induced the expression of both CD14 and CD23 mRNA and protein.@@@@1@13@@oe@16-12-2010 768224305@GENIA Treebank@formal@@1@S@Exposure to VitD3 rapidly induced the de novo expression of CD14 mRNA and protein.@@@@1@15@@oe@16-12-2010 768224306@GENIA Treebank@formal@@1@S@The addition of cycloheximide completely blocked the VitD3 induction of CD14 mRNA expression, indicating that the induction was dependent on ongoing protein synthesis.@@@@1@25@@oe@16-12-2010 768224307@GENIA Treebank@formal@@1@S@While inducing CD14 expression, VitD3 concomitantly suppressed the basal, PMA-, and RA-inducible CD23 expression in a dose-dependent manner.@@@@1@22@@oe@16-12-2010 768224308@GENIA Treebank@formal@@1@S@In contrast, U-937 cells induced by RA strongly increased their expression of CD23 mRNA and protein, whereas they completely lacked detectable CD14 cell surface or mRNA expression.@@@@1@30@@oe@16-12-2010 768224309@GENIA Treebank@formal@@1@S@Furthermore, the VitD3- and the PMA-induced CD14 expression was inhibited as a temporal consequence of the RA-induced differentiation.@@@@1@20@@oe@16-12-2010 768224310@GENIA Treebank@formal@@1@S@The results suggest that there exists a functional antagonism between VitD3 and RA that may have important implications for the regulation of certain immune and inflammatory responses through their inverse effects on CD14 and CD23 gene expression.@@@@1@38@@oe@16-12-2010 768331601@GENIA Treebank@formal@@1@S@Adenovirus E1A inhibits IFN-induced resistance to cytolysis by natural killer cells.@@@@1@12@@oe@16-12-2010 768331602@GENIA Treebank@formal@@1@S@Infection of target cells with cytopathic viruses inhibits IFN induction of cytolytic resistance to NK cell-mediated cytolysis [IFN-mediated cytoprotection (IFN-MCP)].@@@@1@25@@oe@16-12-2010 768331603@GENIA Treebank@formal@@1@S@It has been thought that the virally induced inhibition of IFN-MCP is secondary to the shutdown of cellular macromolecular synthesis that accompanies cytopathic virus infections.@@@@1@26@@oe@16-12-2010 768331604@GENIA Treebank@formal@@1@S@Group C, adenovirus serotype 5 (Ad5) infection inhibits both IFN-MCP and cellular protein synthesis.@@@@1@18@@oe@16-12-2010 768331605@GENIA Treebank@formal@@1@S@This study determined if the Ad5-induced inhibition of IFN-MCP was independent of adenovirus (Ad) infection and secondary only to the expression of the Ad early region 1A gene (E1A).@@@@1@34@@oe@16-12-2010 768331606@GENIA Treebank@formal@@1@S@To test this hypothesis, 4-h NK cytolysis assays were performed on IFN-gamma-treated human cells infected with an Ad5 E1A deletion mutant, dl343, or transfected with the Ad5 E1A gene.@@@@1@33@@oe@16-12-2010 768331607@GENIA Treebank@formal@@1@S@IFN-MCP was not inhibited by infection with dl343, despite the production of large amounts of both early (E1B, p55) and late (hexon) Ad proteins.@@@@1@31@@oe@16-12-2010 768331608@GENIA Treebank@formal@@1@S@In contrast to E1A-negative, parental cell lines, IFN-MCP was blocked in Ad5 E1A-transfected epithelial and fibroblastic cell lines.@@@@1@21@@oe@16-12-2010 768331609@GENIA Treebank@formal@@1@S@Genetic mapping studies within the E1A gene demonstrated that expression of only the first exon of E1A was sufficient to inhibit IFN-MCP.@@@@1@23@@oe@16-12-2010 768331610@GENIA Treebank@formal@@1@S@DNA sequence homology of E1A genes between different Ad groups (group A, Ad12; group C, Ad5) is limited almost entirely to three conserved regions located within the first exon of E1A.@@@@1@37@@oe@16-12-2010 768331611@GENIA Treebank@formal@@1@S@Because IFN-MCP was also blocked in Ad12 E1A-transfected cell lines, expression of one or more of the E1A-conserved regions may be necessary to inhibit IFN-MCP.@@@@1@27@@oe@16-12-2010 768331612@GENIA Treebank@formal@@1@S@In summary, the expression of E1A gene products inhibited IFN-MCP independently of virus infection.@@@@1@16@@oe@16-12-2010 768331613@GENIA Treebank@formal@@1@S@E1A's inhibition of IFN-MCP has the net effect of promoting the selective NK cell-mediated clearance of Ad-infected or Ad-transformed human cells.@@@@1@23@@oe@16-12-2010 768369201@GENIA Treebank@formal@@1@S@A mutation of the glucocorticoid receptor in primary cortisol resistance.@@@@1@11@@oe@16-12-2010 768369202@GENIA Treebank@formal@@1@S@The precise molecular abnormalities that cause primary cortisol resistance have not been completely described.@@@@1@15@@oe@16-12-2010 768369203@GENIA Treebank@formal@@1@S@In a subject with primary cortisol resistance we have observed glucocorticoid receptors (hGR) with a decreased affinity for dexamethasone.@@@@1@22@@oe@16-12-2010 768369204@GENIA Treebank@formal@@1@S@We hypothesize that a mutation of the hGR glucocorticoid-binding domain is the cause of cortisol resistance.@@@@1@17@@oe@16-12-2010 768369205@GENIA Treebank@formal@@1@S@Total RNA isolated from the index subject's mononuclear leukocytes was used to produce first strand hGR cDNAs, and the entire hGR cDNA was amplified in segments and sequenced.@@@@1@31@@oe@16-12-2010 768369206@GENIA Treebank@formal@@1@S@At nucleotide 2,317 we identified a homozygous A for G point mutation that predicts an isoleucine (ATT) for valine (GTT) substitution at amino acid 729.@@@@1@30@@oe@16-12-2010 768369207@GENIA Treebank@formal@@1@S@When the wild-type hGR and hGR-Ile 729 were expressed in COS-1 cells and assayed for [3H]-Dexamethasone binding, the dissociation constants were 0.799 +/- 0.068 and 1.54 +/- 0.06 nM (mean +/- SEM) (P < 0.01), respectively.@@@@1@43@@oe@16-12-2010 768369208@GENIA Treebank@formal@@1@S@When the wild-type hGR and hGR-Ile 729 were expressed in CV-1 cells that were cotransfected with the mouse mammary tumor virus long terminal repeat fused to the chloramphenicol acetyl transferase (CAT) gene, the hGR-Ile 729 conferred a fourfold decrease in apparent potency on dexamethasone stimulation of CAT activity.@@@@1@52@@oe@16-12-2010 768369209@GENIA Treebank@formal@@1@S@The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject.@@@@1@28@@oe@16-12-2010 768450301@GENIA Treebank@formal@@1@S@Regulation of the interleukin-1 beta (IL-1 beta) gene by mycobacterial components and lipopolysaccharide is mediated by two nuclear factor-IL6 motifs.@@@@1@23@@oe@16-12-2010 768450302@GENIA Treebank@formal@@1@S@The cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) are released by mononuclear phagocytes in vitro after stimulation with mycobacteria and are considered to mediate pathophysiologic events, including granuloma formation and systemic symptoms.@@@@1@42@@oe@16-12-2010 768450303@GENIA Treebank@formal@@1@S@We demonstrated that the Mycobacterium tuberculosis cell wall component lipoarabinomannan (LAM) is a very potent inducer of IL-1 beta gene expression in human monocytes and investigated the mechanism of this effect.@@@@1@34@@oe@16-12-2010 768450304@GENIA Treebank@formal@@1@S@We localized the LAM-, lipopolysaccharide (LPS)-, and TNF-alpha-inducible promoter activity to a -131/+15 (positions -131 to +15) DNA fragment of the IL-1 beta gene by deletion analysis and chloramphenicol acetyltransferase assay.@@@@1@39@@oe@16-12-2010 768450305@GENIA Treebank@formal@@1@S@Within this DNA fragment, there were two novel 9-bp motifs (-90/-82 and -40/-32) with high homology to the nuclear factor-IL6 (NF-IL6) binding site.@@@@1@29@@oe@16-12-2010 768450306@GENIA Treebank@formal@@1@S@Site-directed mutagenesis demonstrated that the two NF-IL-6 motifs could be independently activated by LAM, LPS, or TNF-alpha and that they acted in an orientation-independent manner.@@@@1@28@@oe@16-12-2010 768450307@GENIA Treebank@formal@@1@S@DNA mobility shift assay revealed specific binding of nuclear protein(s) from LAM-, LPS-, or TNF-alpha- stimulated THP-1 cells to the NF-IL6 motifs.@@@@1@27@@oe@16-12-2010 768450308@GENIA Treebank@formal@@1@S@We conclude that the two NF-IL6 sites mediate induction of IL-1 beta in response to the stimuli LAM, LPS, and TNF-alpha.@@@@1@24@@oe@16-12-2010 768859601@GENIA Treebank@formal@@1@S@Cytokine modulation of HIV expression.@@@@1@6@@oe@16-12-2010 768859602@GENIA Treebank@formal@@1@S@Cytokines, the peptide hormones which control the homeostasis of the immune system and also play a fundamental role in inflammatory and immune mediated reactions, have been involved at multiple levels in the pathogenesis of the acquired immune deficiency syndrome (AIDS).@@@@1@45@@oe@16-12-2010 768859603@GENIA Treebank@formal@@1@S@Infection with the human immunodeficiency virus (HIV) has been shown to induce production of several cytokines both in vitro and in vivo.@@@@1@25@@oe@16-12-2010 768859604@GENIA Treebank@formal@@1@S@Conversely, several cytokines modulate the levels of HIV expression in infected cells of both T lymphocytic and mononuclear phagocytic lineage.@@@@1@22@@oe@16-12-2010 768859605@GENIA Treebank@formal@@1@S@Activated mononuclear cells, particularly B cells which are in a state of chronic activation in HIV infected individuals, release HIV-inductive cytokines and thus play a potentially important role in the pathogenesis of HIV infection.@@@@1@37@@oe@16-12-2010 769265201@GENIA Treebank@formal@@1@S@FK506 and ciclosporin: molecular probes for studying intracellular signal transduction.@@@@1@12@@oe@16-12-2010 769265202@GENIA Treebank@formal@@1@S@The immunosuppressants ciclosporin and FK506 block the Ca(2+)-dependent signal-transduction pathway emanating from the T-cell receptor, thereby inhibiting the activation of helper T cells.@@@@1@25@@oe@16-12-2010 769265203@GENIA Treebank@formal@@1@S@Using these drugs as probes, chemists and biologists have uncovered several intracellular signalling molecules bridging the generation of second-messenger Ca2+ ions and the transcriptional activation of IL-2, among which are calmodulin, calcineurin and the nuclear factor of activated T cells (NF-AT).@@@@1@47@@oe@16-12-2010 769265204@GENIA Treebank@formal@@1@S@Hence, Ca2+ binds to calmodulin, leading to the binding of calmodulin to calcineurin; the activated calcineurin, in turn, may dephosphorylate the cytoplasmic subunit of NF-AT, resulting in its translocation from the cytoplasm into the nucleus to form a competent transcriptional activator.@@@@1@48@@oe@16-12-2010 769265205@GENIA Treebank@formal@@1@S@As described by Jun Liu, these drugs manifest their effects in an unprecedented fashion.@@@@1@16@@oe@16-12-2010 769265206@GENIA Treebank@formal@@1@S@They do not directly intercept intracellular signalling molecules.@@@@1@9@@oe@16-12-2010 769265207@GENIA Treebank@formal@@1@S@Instead, they form tight complexes with two different classes of abundant cytosolic receptors called immunophilins upon entering the cell, and consequently inhibit their peptidyl prolyl cis-trans isomerase activities.@@@@1@31@@oe@16-12-2010 769265208@GENIA Treebank@formal@@1@S@The two structurally distinct immunophilin-drug complexes bind to, and inhibit, the phosphatase activity of calcineurin.@@@@1@18@@oe@16-12-2010 769290601@GENIA Treebank@formal@@1@S@Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA.@@@@1@16@@oe@16-12-2010 769290602@GENIA Treebank@formal@@1@S@The initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome.@@@@1@34@@oe@16-12-2010 769290603@GENIA Treebank@formal@@1@S@HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression.@@@@1@21@@oe@16-12-2010 769290604@GENIA Treebank@formal@@1@S@However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1, and interleukin-2).@@@@1@39@@oe@16-12-2010 769290605@GENIA Treebank@formal@@1@S@Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity.@@@@1@35@@oe@16-12-2010 769290606@GENIA Treebank@formal@@1@S@On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS.@@@@1@37@@oe@16-12-2010 769290607@GENIA Treebank@formal@@1@S@So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation.@@@@1@19@@oe@16-12-2010 769290608@GENIA Treebank@formal@@1@S@ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression.@@@@1@27@@oe@16-12-2010 769290609@GENIA Treebank@formal@@1@S@ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), mitogen or cytokines (TNF-alpha), or infection with HSV.@@@@1@30@@oe@16-12-2010 769290610@GENIA Treebank@formal@@1@S@Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation.@@@@1@19@@oe@16-12-2010 769290611@GENIA Treebank@formal@@1@S@Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures.@@@@1@27@@oe@16-12-2010 769290612@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 770623501@GENIA Treebank@formal@@1@S@Nitric oxide-stimulated guanine nucleotide exchange on p21ras.@@@@1@8@@oe@16-12-2010 770623502@GENIA Treebank@formal@@1@S@The protooncogene p21ras, a monomeric G protein family member, plays a critical role in converting extracellular signals into intracellular biochemical events.@@@@1@24@@oe@16-12-2010 770623503@GENIA Treebank@formal@@1@S@Here, we report that nitric oxide (NO) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras.@@@@1@25@@oe@16-12-2010 770623504@GENIA Treebank@formal@@1@S@In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible.@@@@1@16@@oe@16-12-2010 770623505@GENIA Treebank@formal@@1@S@Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange.@@@@1@19@@oe@16-12-2010 770623506@GENIA Treebank@formal@@1@S@The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange.@@@@1@19@@oe@16-12-2010 770623507@GENIA Treebank@formal@@1@S@Furthermore, we demonstrate that p21ras is essential for NO-induced downstream signaling, such as NF-kappa B activation, and that endogenous NO can activate p21ras in the same cell.@@@@1@31@@oe@16-12-2010 770623508@GENIA Treebank@formal@@1@S@These studies identify p21ras as a target of the same cell.@@@@1@12@@oe@16-12-2010 770623509@GENIA Treebank@formal@@1@S@These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors.@@@@1@30@@oe@16-12-2010 770627301@GENIA Treebank@formal@@1@S@Transcriptional regulation of the vacuolar H(+)-ATPase B2 subunit gene in differentiating THP-1 cells.@@@@1@14@@oe@16-12-2010 770627302@GENIA Treebank@formal@@1@S@Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the human vacuolar H(+)-ATPase (V-ATPase).@@@@1@21@@oe@16-12-2010 770627303@GENIA Treebank@formal@@1@S@We examined mRNA levels of various V-ATPase subunits during differentiation of both native monocytes and the cell line THP-1, and found that transcriptional and post-transcriptional mechanisms could account for increases in cell V-ATPase content.@@@@1@36@@oe@16-12-2010 770627304@GENIA Treebank@formal@@1@S@From nuclear runoff experiments, we found that one subunit in particular, the B2 isoform (Mr = 56,000), was amplified primarily by transcriptional means.@@@@1@29@@oe@16-12-2010 770627305@GENIA Treebank@formal@@1@S@We have begun to examine the structure of the B2 subunit promoter region.@@@@1@14@@oe@16-12-2010 770627306@GENIA Treebank@formal@@1@S@Isolation and sequencing of the first exon and 5'-flanking region of this gene reveal a TATA-less promoter with a high G + C content.@@@@1@25@@oe@16-12-2010 770627307@GENIA Treebank@formal@@1@S@Primer extension and ribonuclease protection analyses indicate a single major transcriptional start site.@@@@1@14@@oe@16-12-2010 770627308@GENIA Treebank@formal@@1@S@We transfected promoter-luciferase reporter plasmids into THP-1 cells to define sequences that mediate transcriptional control during monocyte differentiation.@@@@1@19@@oe@16-12-2010 770627309@GENIA Treebank@formal@@1@S@We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during THP-1 differentiation.@@@@1@20@@oe@16-12-2010 770627310@GENIA Treebank@formal@@1@S@DNase I footprinting and sequence analysis revealed the existence of multiple AP2 and Sp1 binding sites in the 5'-untranslated and proximal coding regions.@@@@1@24@@oe@16-12-2010 770671001@GENIA Treebank@formal@@1@S@Functional characterization of novel IL-2 transcriptional inhibitors.@@@@1@8@@oe@16-12-2010 770671002@GENIA Treebank@formal@@1@S@IL-2-mediated T cell proliferation is a critical early event in the inflammatory process.@@@@1@14@@oe@16-12-2010 770671003@GENIA Treebank@formal@@1@S@Formation of the NFAT-1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription.@@@@1@16@@oe@16-12-2010 770671004@GENIA Treebank@formal@@1@S@Using a cell line that is stably transfected with a trimer of the NFAT-1 regulatory element linked to a lac-Z reporter gene, we screened for inhibitors of NFAT-1-mediated beta-galactosidase activity.@@@@1@32@@oe@16-12-2010 770671005@GENIA Treebank@formal@@1@S@WIN 61058 and WIN 53071 were identified as microM inhibitors.@@@@1@11@@oe@16-12-2010 770671006@GENIA Treebank@formal@@1@S@These compounds also inhibited beta-galactosidase mRNA levels.@@@@1@8@@oe@16-12-2010 770671007@GENIA Treebank@formal@@1@S@Similar inhibition of NFAT-1-mediated gene expression was observed in a second cell line, which is stably transfected with NFAT-1 regulatory elements linked to the reporter gene for sCD8.@@@@1@30@@oe@16-12-2010 770671008@GENIA Treebank@formal@@1@S@At 10 microM, both compounds inhibited IL-2 mRNA and protein levels in the NFAT-1-linked lac-Z transfectants, and in human lymphocytes.@@@@1@23@@oe@16-12-2010 770671009@GENIA Treebank@formal@@1@S@Both compounds inhibited the mixed lymphocyte reaction, and this inhibition was reversed by exogenous IL-2.@@@@1@17@@oe@16-12-2010 770671010@GENIA Treebank@formal@@1@S@WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway.@@@@1@14@@oe@16-12-2010 770671011@GENIA Treebank@formal@@1@S@Conversely, calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant.@@@@1@12@@oe@16-12-2010 770671012@GENIA Treebank@formal@@1@S@Both compounds altered the NFAT-1 transcriptional complex, causing its retarded mobility on gels.@@@@1@15@@oe@16-12-2010 770671013@GENIA Treebank@formal@@1@S@By these functional criteria, we believe we have identified two structurally distinct, novel inhibitors of NFAT-1-mediated transcription.@@@@1@20@@oe@16-12-2010 770672701@GENIA Treebank@formal@@1@S@cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line.@@@@1@15@@oe@16-12-2010 770672702@GENIA Treebank@formal@@1@S@A human T lymphoid cell line, PEER, dies by apoptosis in the presence of PMA and calcium ionophore.@@@@1@21@@oe@16-12-2010 770672703@GENIA Treebank@formal@@1@S@A new gene, TINUR, was cloned from apoptotic PEER cells.@@@@1@13@@oe@16-12-2010 770672704@GENIA Treebank@formal@@1@S@The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex.@@@@1@22@@oe@16-12-2010 770672705@GENIA Treebank@formal@@1@S@TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor.@@@@1@17@@oe@16-12-2010 770672706@GENIA Treebank@formal@@1@S@TINUR binds to the same DNA sequence as NGFI-B/nur77.@@@@1@10@@oe@16-12-2010 770672707@GENIA Treebank@formal@@1@S@We also propose that the NGFI-B/nur77 family can be classified into two subtypes.@@@@1@14@@oe@16-12-2010 770698301@GENIA Treebank@formal@@1@S@Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function.@@@@1@12@@oe@16-12-2010 770698302@GENIA Treebank@formal@@1@S@Glucocorticoids are among the most potent antiinflammatory agents that can be used in the treatment of rhinitis.@@@@1@18@@oe@16-12-2010 770698303@GENIA Treebank@formal@@1@S@Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids.@@@@1@22@@oe@16-12-2010 770698304@GENIA Treebank@formal@@1@S@In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids, 14 normal healthy subjects were treated with two doses of either budesonide (BUD) or fluticasone propionate (FP) for 2 weeks.@@@@1@38@@oe@16-12-2010 770698305@GENIA Treebank@formal@@1@S@Before treatment, at regular intervals during the treatment, 1 week and finally 6 weeks after termination of treatment, the effects on glucocorticoid receptor (GR) and methallothionein (MTIIa) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay.@@@@1@48@@oe@16-12-2010 770698306@GENIA Treebank@formal@@1@S@Serum cortisol, osteocalcin and urinary cortisol levels were also determined.@@@@1@12@@oe@16-12-2010 770698307@GENIA Treebank@formal@@1@S@An insulin tolerance test (ITT) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response.@@@@1@36@@oe@16-12-2010 770698308@GENIA Treebank@formal@@1@S@In peripheral lymphocytes, GR mRNA levels were significantly down-regulated.@@@@1@11@@oe@16-12-2010 770698309@GENIA Treebank@formal@@1@S@MTIIa mRNA levels increased significantly.@@@@1@6@@oe@16-12-2010 770698310@GENIA Treebank@formal@@1@S@Serum osteocalcin decreased significantly during treatment with both BUD and FP.@@@@1@12@@oe@16-12-2010 770698311@GENIA Treebank@formal@@1@S@Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment.@@@@1@21@@oe@16-12-2010 770698312@GENIA Treebank@formal@@1@S@In conclusion, intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function, but also have an effect on specific gene expression in peripheral lymphocytes.@@@@1@32@@oe@16-12-2010 770698313@GENIA Treebank@formal@@1@S@These effects are receptor-dependent, reversible, and according to serum and urinary cortisol levels and ITT, leave the hypothalamic-pituitary-adrenal function intact.@@@@1@24@@oe@16-12-2010 770698314@GENIA Treebank@formal@@1@S@Finally, these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids.@@@@1@23@@oe@16-12-2010 770751401@GENIA Treebank@formal@@1@S@Transcriptional activity of core binding factor-alpha (AML1) and beta subunits on murine leukemia virus enhancer cores.@@@@1@19@@oe@16-12-2010 770751402@GENIA Treebank@formal@@1@S@Core binding factor (CBF), also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1, is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses.@@@@1@45@@oe@16-12-2010 770751403@GENIA Treebank@formal@@1@S@The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes.@@@@1@35@@oe@16-12-2010 770751404@GENIA Treebank@formal@@1@S@CBF consists of two subunits, a DNA binding subunit, CBF alpha, and a second subunit, CBF beta, that stimulates the DNA binding activity of CBF alpha.@@@@1@32@@oe@16-12-2010 770751405@GENIA Treebank@formal@@1@S@One of the genes that encodes a CBF alpha subunit is AML1, also called Cbf alpha 2.@@@@1@19@@oe@16-12-2010 770751406@GENIA Treebank@formal@@1@S@This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias.@@@@1@14@@oe@16-12-2010 770751407@GENIA Treebank@formal@@1@S@An exogenously expressed Cbf alpha 2-encoded subunit (CBF alpha 2-451) stimulated transcription from the SL3 enhancer in P19 and HeLa cells.@@@@1@24@@oe@16-12-2010 770751408@GENIA Treebank@formal@@1@S@Activity was mediated through the core elements.@@@@1@8@@oe@16-12-2010 770751409@GENIA Treebank@formal@@1@S@Three different isoforms of CBF beta were also tested for transcriptional activity on the SL3 enhancer.@@@@1@17@@oe@16-12-2010 770751410@GENIA Treebank@formal@@1@S@The longest form, CBF beta-187, increased the transcriptional stimulation by CBF alpha 2-451 twofold in HeLa cells, although it had no effect in P19 cells.@@@@1@29@@oe@16-12-2010 770751411@GENIA Treebank@formal@@1@S@Transcriptional activation by CBF beta required binding to the CBF alpha subunit, as a form of CBF beta that lacked binding ability, CBF beta-148, failed to increase activity.@@@@1@32@@oe@16-12-2010 770751412@GENIA Treebank@formal@@1@S@These results indicated that at least in certain cell types, the maximum activity of CBF required both subunits.@@@@1@20@@oe@16-12-2010 770751413@GENIA Treebank@formal@@1@S@They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores.@@@@1@25@@oe@16-12-2010 770751414@GENIA Treebank@formal@@1@S@We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus, Akv.@@@@1@26@@oe@16-12-2010 770751415@GENIA Treebank@formal@@1@S@This difference strongly affects transcription in T cells and leukemogenicity of SL3.@@@@1@13@@oe@16-12-2010 770751416@GENIA Treebank@formal@@1@S@However, no combination of CBF alpha and CBF beta subunits that we tested was able to distinguish the 1-bp difference in transcription assays.@@@@1@25@@oe@16-12-2010 770751417@GENIA Treebank@formal@@1@S@Thus, a complete understanding of how T cells recognize the SL3 core remains to be elucidated.@@@@1@18@@oe@16-12-2010 771386801@GENIA Treebank@formal@@1@S@Platelet-activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes.@@@@1@15@@oe@16-12-2010 771386802@GENIA Treebank@formal@@1@S@Correlation with an increased kappa B binding activity.@@@@1@9@@oe@16-12-2010 771386803@GENIA Treebank@formal@@1@S@Human peripheral blood monocytes responded to stimulation of platelet-activating factor (PAF) with up-regulation of the transcript for heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells.@@@@1@38@@oe@16-12-2010 771386804@GENIA Treebank@formal@@1@S@This function of PAF was observed at nanomolar concentrations of the ligand, starting at 30 min after stimulation.@@@@1@20@@oe@16-12-2010 771386805@GENIA Treebank@formal@@1@S@The PAF-induced up-regulation of HB-EGF mRNA was accompanied by an increase in kappa B binding activity.@@@@1@17@@oe@16-12-2010 771386806@GENIA Treebank@formal@@1@S@These functions of PAF appeared to be mediated through the cell surface PAF receptors, as two PAF receptor antagonists, WEB 2086 and L-659,989, blocked both the up-regulation of HB-EGF mRNA and kappa B binding activity induced by PAF.@@@@1@44@@oe@16-12-2010 771386807@GENIA Treebank@formal@@1@S@The antagonists, however, had no effect on phorbol ester-induced up-regulation of HB-EGF mRNA and kappa B binding activity.@@@@1@21@@oe@16-12-2010 771386808@GENIA Treebank@formal@@1@S@Pretreatment of monocytes with pertussis toxin inhibited these functions of PAF, whereas cholera toxin had no inhibitory effect.@@@@1@20@@oe@16-12-2010 771386809@GENIA Treebank@formal@@1@S@Pyrrolidine dithiocarbamate, an inhibitor for NF-kappa B activation, markedly reduced PAF-stimulated kappa B binding activity as well as up-regulation of HB-EGF mRNA.@@@@1@25@@oe@16-12-2010 771386810@GENIA Treebank@formal@@1@S@These results suggest a potential role of PAF in HB-EGF expression and provide evidence that this stimulation may occur through increased kappa B binding activity.@@@@1@26@@oe@16-12-2010 771851901@GENIA Treebank@formal@@1@S@IL-1 receptor and TCR signals synergize to activate NF-kappa B-mediated gene transcription.@@@@1@13@@oe@16-12-2010 771851902@GENIA Treebank@formal@@1@S@Previous studies have demonstrated that IL-1 receptor (IL-1R)- and TCR-initiated signals can interact synergistically to increase the rate of transcription of several lymphokine and lymphokine receptor genes during the competence phase of the activation program in T helper lymphocytes.@@@@1@43@@oe@16-12-2010 771851903@GENIA Treebank@formal@@1@S@In this report we describe how signals initiated through the type I IL-1R interact with signals from the antigen receptor to synergistically augment the transactivating properties of NF-kappa B.@@@@1@30@@oe@16-12-2010 771851904@GENIA Treebank@formal@@1@S@The synergistic antigen receptor initiated signals are mediated through protein kinase C because they can be mimicked by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, but not with calcium ionophores; and are staurosporine sensitive but cyclosporine resistant.@@@@1@38@@oe@16-12-2010 771851905@GENIA Treebank@formal@@1@S@Gel shift analyses demonstrate that NF-kappa B nuclear translocation is stimulated primarily by IL-1 rather than by antigen receptor signals.@@@@1@21@@oe@16-12-2010 771851906@GENIA Treebank@formal@@1@S@Western blot and phosphorylation analyses demonstrate that the synergistic effect on NF-kappa B functional activity is independent of I kappa B alpha (MAD3)-NF-kappa B dissociation in the cytosol and is not associated with I kappa B nuclear translocation.@@@@1@42@@oe@16-12-2010 771851907@GENIA Treebank@formal@@1@S@The IL-1-induced NF-kappa B DNA nuclear localization is transient and can be prolonged either by an antigen receptor-initiated signal or by inhibiting protein synthesis.@@@@1@25@@oe@16-12-2010 771851908@GENIA Treebank@formal@@1@S@These results suggest that IL-1 induces both NF-kappa B nuclear translocation and the synthesis of a protein(s) responsible for terminating NF-kappa B-DNA interaction in the nucleus.@@@@1@30@@oe@16-12-2010 771851909@GENIA Treebank@formal@@1@S@Antigen receptor signals prolong NF-kappa B-DNA interaction, probably by functionally antagonizing the IL-1-induced synthesis of a protein(s) responsible for the transient NF-kappa B-DNA interaction and consequently synergistically enhance IL-1-induced NF-kappa B-dependent gene transcription.@@@@1@38@@oe@16-12-2010 771924801@GENIA Treebank@formal@@1@S@A newly established megakaryoblastic/erythroid cell line that differentiates to red cells in the presence of erythropoietin and produces platelet-like particles.@@@@1@21@@oe@16-12-2010 771924802@GENIA Treebank@formal@@1@S@In August, 1992, we established a leukemic cell line (NS-Meg) from a patient in megakaryoblastic transformation of Philadelphia chromosome-positive chronic myeloid leukemia.@@@@1@27@@oe@16-12-2010 771924803@GENIA Treebank@formal@@1@S@The NS-Meg cells were positive for alpha-naphthyl acetate esterase and periodic acid-Schiff (PAS) staining and for surface CD4, CD7, CD13, CD34, CD41a, and glycophorin A antigens.@@@@1@34@@oe@16-12-2010 771924804@GENIA Treebank@formal@@1@S@Ultrastructurally, the cells had alpha-granules, demarcation membranes, and platelet peroxidase activity.@@@@1@15@@oe@16-12-2010 771924805@GENIA Treebank@formal@@1@S@The NS-Meg cells spontaneously produced platelet-like particles which contained alpha-granules, mitochondria and dense bodies, strongly suggesting platelet production.@@@@1@21@@oe@16-12-2010 771924806@GENIA Treebank@formal@@1@S@Erythropoietin (Epo), granulocyte/macrophage colony stimulating factor(GM-CSF), and interleukin 3 (IL-3) promoted the growth of NS-Meg cells.@@@@1@26@@oe@16-12-2010 771924807@GENIA Treebank@formal@@1@S@Phorbol-12-myristate-13-acetate increased the expression of both CD41a and CD61 antigens.@@@@1@11@@oe@16-12-2010 771924808@GENIA Treebank@formal@@1@S@Ten-day exposure to Epo induced mature erythroblasts and red cells.@@@@1@11@@oe@16-12-2010 771924809@GENIA Treebank@formal@@1@S@These benzidine-positive cells were positive for hemoglobin F staining.@@@@1@10@@oe@16-12-2010 771924810@GENIA Treebank@formal@@1@S@Untreated NS-Meg cells expressed mRNA for the Epo receptor (EpoR), for GATA-1, and for alpha 1, alpha 2 and gamma globin genes.@@@@1@28@@oe@16-12-2010 771924811@GENIA Treebank@formal@@1@S@These results indicate that NS-Meg cells undergo terminal differentiation of both megakaryocytic and erythroid lineages.@@@@1@16@@oe@16-12-2010 771924812@GENIA Treebank@formal@@1@S@This cell line should be a very useful tool for the investigation of both megakaryocytic and erythroid maturation.@@@@1@19@@oe@16-12-2010 771993701@GENIA Treebank@formal@@1@S@Identification and purification of human Stat proteins activated in response to interleukin-2.@@@@1@13@@oe@16-12-2010 771993702@GENIA Treebank@formal@@1@S@A key cytokine induced during the immune response is IL-2.@@@@1@11@@oe@16-12-2010 771993703@GENIA Treebank@formal@@1@S@Following T cell activation, the genes encoding IL-2 and the various chains of its receptor are transcriptionally induced.@@@@1@20@@oe@16-12-2010 771993704@GENIA Treebank@formal@@1@S@In turn, secreted IL-2 serves to stimulate the proliferation and differentiation of T lymphocytes.@@@@1@16@@oe@16-12-2010 771993705@GENIA Treebank@formal@@1@S@Several recent studies have implicated Jak kinases in the signaling pathway induced by IL-2.@@@@1@15@@oe@16-12-2010 771993706@GENIA Treebank@formal@@1@S@Following this lead, we set out to identify transcription factors induced in response to IL-2.@@@@1@17@@oe@16-12-2010 771993707@GENIA Treebank@formal@@1@S@Human peripheral blood lymphocytes were observed to contain several IL-2-inducible DNA binding activities.@@@@1@14@@oe@16-12-2010 771993708@GENIA Treebank@formal@@1@S@Similar activities were also observed in a transformed human lymphocyte line, termed YT.@@@@1@15@@oe@16-12-2010 771993709@GENIA Treebank@formal@@1@S@We have purified these activities and found that the principal IL-2-inducible component bears significant relatedness to a prolactin-induced transcription factor first identified in sheep mammary gland tissue.@@@@1@28@@oe@16-12-2010 771993710@GENIA Treebank@formal@@1@S@We hypothesize that activation of this protein, designated hStat5, helps govern the biological effects of IL-2 during the immune response.@@@@1@23@@oe@16-12-2010 771993801@GENIA Treebank@formal@@1@S@The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15.@@@@1@30@@oe@16-12-2010 771993802@GENIA Treebank@formal@@1@S@To understand the molecular bases for cytokine redundancy and pleiotropy, we have compared the Stat proteins activated in peripheral blood lymphocytes (PBLs) by cytokines with shared and distinct actions.@@@@1@33@@oe@16-12-2010 771993803@GENIA Treebank@formal@@1@S@Interleukin-2 (IL-2) rapidly activated Stat5 in fresh PBL, and Stat3 and Stat5 in preactivated PBL.@@@@1@19@@oe@16-12-2010 771993804@GENIA Treebank@formal@@1@S@IL-7 and IL-15 induced the same complexes as IL-2, a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins.@@@@1@39@@oe@16-12-2010 771993805@GENIA Treebank@formal@@1@S@IL-13 Induced the same complexes as IL-4, a finding explained by our studies implicating IL-4R as a shared component of the receptors.@@@@1@24@@oe@16-12-2010 771993806@GENIA Treebank@formal@@1@S@These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions, and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein.@@@@1@35@@oe@16-12-2010 772008501@GENIA Treebank@formal@@1@S@Induction of transcription factors in human T lymphocytes by aspirin-like drugs.@@@@1@12@@oe@16-12-2010 772008502@GENIA Treebank@formal@@1@S@Aspirin-like drugs (ALD) induce calcium mobilization, an essential component of T cell activation, but do not induce the biosynthesis of IL-2.@@@@1@26@@oe@16-12-2010 772008503@GENIA Treebank@formal@@1@S@To understand the extent to which ALD may mimic mitogenic stimulation, we studied cytoplasmic and nuclear signaling steps in ALD-treated T cells.@@@@1@24@@oe@16-12-2010 772008504@GENIA Treebank@formal@@1@S@We found that ALD induce a transient activation of protein kinase (PKC) but have no effect (in comparison to anti-CD3 antibodies) on protein tyrosine phosphorylation nor on PCL gamma 1 tyrosine phosphorylation.@@@@1@37@@oe@16-12-2010 772008505@GENIA Treebank@formal@@1@S@ALD-induced calcium mobilization and PKC activation are independent of tyrosine protein kinase activity as shown by the lack of effect of herbimycin, a tyrosine-protein kinase-specific inhibitor.@@@@1@28@@oe@16-12-2010 772008506@GENIA Treebank@formal@@1@S@Although we detected no IL-2 mRNA in ALD-treated cells, the nuclei of these cells contain proteins capable of binding to three regulatory sequences in the IL-2 promoter region: NFAT, NF kappa B, and AP-1.@@@@1@39@@oe@16-12-2010 772008507@GENIA Treebank@formal@@1@S@These binding activities are expressed only in activated T cells.@@@@1@11@@oe@16-12-2010 772008508@GENIA Treebank@formal@@1@S@The expression of AP-1 depended on calcium mobilization and PKC activation.@@@@1@12@@oe@16-12-2010 772008509@GENIA Treebank@formal@@1@S@These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling, although some events induced by stimulation with anti-CD3 antibodies are not induced by ALD.@@@@1@31@@oe@16-12-2010 772008510@GENIA Treebank@formal@@1@S@The signal is transmitted to the nucleus and induces DNA-binding activity by several transcription factors.@@@@1@16@@oe@16-12-2010 772008511@GENIA Treebank@formal@@1@S@However, the ALD stimulus is not capable of causing complete T cell activation.@@@@1@15@@oe@16-12-2010 772174701@GENIA Treebank@formal@@1@S@Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer.@@@@1@13@@oe@16-12-2010 772174702@GENIA Treebank@formal@@1@S@Erythroid lineage and developmental stage specificities.@@@@1@7@@oe@16-12-2010 772174703@GENIA Treebank@formal@@1@S@Transcriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40.@@@@1@28@@oe@16-12-2010 772174704@GENIA Treebank@formal@@1@S@Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner.@@@@1@29@@oe@16-12-2010 772174705@GENIA Treebank@formal@@1@S@We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures.@@@@1@26@@oe@16-12-2010 772174706@GENIA Treebank@formal@@1@S@Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells.@@@@1@39@@oe@16-12-2010 772174707@GENIA Treebank@formal@@1@S@On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor.@@@@1@50@@oe@16-12-2010 772174708@GENIA Treebank@formal@@1@S@Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells.@@@@1@30@@oe@16-12-2010 772174709@GENIA Treebank@formal@@1@S@These studies have defined the regulatory roles of the different HS-40 motifs.@@@@1@13@@oe@16-12-2010 772174710@GENIA Treebank@formal@@1@S@The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo.@@@@1@39@@oe@16-12-2010 772188501@GENIA Treebank@formal@@1@S@Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes.@@@@1@20@@oe@16-12-2010 772188502@GENIA Treebank@formal@@1@S@IL-10 and IL-4 suppress cytokine synthesis by different mechanisms.@@@@1@10@@oe@16-12-2010 772188503@GENIA Treebank@formal@@1@S@Our previous studies in human monocytes have demonstrated that interleukin (IL)-10 inhibits lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines, IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha by blocking gene transcription.@@@@1@45@@oe@16-12-2010 772188504@GENIA Treebank@formal@@1@S@Using electrophoretic mobility shift assays (EMSA), we now show that, in monocytes stimulated with LPS or TNF alpha, IL-10 inhibits nuclear stimulation of nuclear factor kappa B (NF kappa B), a transcription factor involved in the expression of inflammatory cytokine genes.@@@@1@50@@oe@16-12-2010 772188505@GENIA Treebank@formal@@1@S@Several other transcription factors including NF-IL-6, AP-1, AP-2, GR, CREB, Oct-1, and Sp-1 are not affected by IL-10.@@@@1@25@@oe@16-12-2010 772188506@GENIA Treebank@formal@@1@S@This selective inhibition by IL-10 of NF kappa B activation occurs rapidly and in a dose-dependent manner and correlates well with IL-10's cytokine synthesis inhibitory activity in terms of both kinetics and dose responsiveness.@@@@1@36@@oe@16-12-2010 772188507@GENIA Treebank@formal@@1@S@Furthermore, compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit NF kappa B activation block cytokine gene transcription in LPS-stimulated monocytes.@@@@1@28@@oe@16-12-2010 772188508@GENIA Treebank@formal@@1@S@Taken together, these results suggest that inhibition of NF kappa B activation may be an important mechanism for IL-10 suppression of cytokine gene transcription in human monocytes.@@@@1@29@@oe@16-12-2010 772188509@GENIA Treebank@formal@@1@S@IL-4, another cytokine that inhibits cytokine mRNA accumulation in monocytes, shows little inhibitory effect on LPS-induced NF kappa B activation.@@@@1@23@@oe@16-12-2010 772188510@GENIA Treebank@formal@@1@S@Further examination reveals that, unlike IL-10, IL-4 enhances mRNA degradation and does not suppress cytokine gene transcription.@@@@1@20@@oe@16-12-2010 772188511@GENIA Treebank@formal@@1@S@These data indicate that IL-10 and IL-4 inhibit cytokine production by different mechanisms.@@@@1@14@@oe@16-12-2010 772778701@GENIA Treebank@formal@@1@S@Identification of a major positive regulatory element located 5' to the human zeta-globin gene.@@@@1@15@@oe@16-12-2010 772778702@GENIA Treebank@formal@@1@S@The function of the zeta-globin promoter was studied using a series of zeta-globin promoter deletion constructs to drive luciferase expression in transiently transfected human erythroleukemia cells.@@@@1@27@@oe@16-12-2010 772778703@GENIA Treebank@formal@@1@S@The promoters were used without enhancers, or with enhancers derived from the beta-globin locus control region and the alpha-globin HS-40 enhancer.@@@@1@23@@oe@16-12-2010 772778704@GENIA Treebank@formal@@1@S@When transfected into K562 cells, which express zeta-globin, comparable amounts of activity were obtained from the -557 and -417 zeta-luciferase constructs and the alpha-luciferase constructs when no enhancers or the alpha-globin locus enhancers were used.@@@@1@38@@oe@16-12-2010 772778705@GENIA Treebank@formal@@1@S@When the constructs were transfected into OCIM1 cells, which do not express zeta-globin, the zeta-globin promoters were at best 20% as active as the alpha-globin promoters.@@@@1@30@@oe@16-12-2010 772778706@GENIA Treebank@formal@@1@S@When sequences from -417 to -207 5' to the zeta-globin mRNA cap site were deleted, up to 95% of the zeta-globin promoter activity was lost in K562 cells.@@@@1@31@@oe@16-12-2010 772778707@GENIA Treebank@formal@@1@S@Reinsertion of these sequences into zeta-luciferase constructs missing the -417 to -207 region showed that the sequences lack classical enhancer activity.@@@@1@22@@oe@16-12-2010 772778708@GENIA Treebank@formal@@1@S@Point mutation of a GATA-1 site at -230 reduced promoter activity by 37%.@@@@1@15@@oe@16-12-2010 772778709@GENIA Treebank@formal@@1@S@Point mutation of a CCACC site at -240 had no effect.@@@@1@12@@oe@16-12-2010 772778710@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays indicated that the -230 GATA-1 site has a relatively low affinity for GATA-1.@@@@1@18@@oe@16-12-2010 772778711@GENIA Treebank@formal@@1@S@These experiments show the presence of a strong positive-acting element, located between -417 and -207 bp 5' to the zeta-globin mRNA cap site, is necessary for high-level promoter activity in K562 cells.@@@@1@35@@oe@16-12-2010 772778712@GENIA Treebank@formal@@1@S@This element requires GATA-1 and additional unknown factors for maximal activity.@@@@1@12@@oe@16-12-2010 773036401@GENIA Treebank@formal@@1@S@Analysis of the role of protein kinase C-alpha, -epsilon, and -zeta in T cell activation.@@@@1@18@@oe@16-12-2010 773036402@GENIA Treebank@formal@@1@S@T cells express multiple isotypes of protein kinase C (PKC) and although it is well accepted that PKCs have an important role in T cell activation, little is known about the function of individual PKC isotypes.@@@@1@40@@oe@16-12-2010 773036403@GENIA Treebank@formal@@1@S@To address this issue, mutationally active PKC-alpha, -epsilon, or -zeta have been transfected into T cells and the consequences for T cell activation determined.@@@@1@28@@oe@16-12-2010 773036404@GENIA Treebank@formal@@1@S@p21ras plays an essential role in T cell activation.@@@@1@10@@oe@16-12-2010 773036405@GENIA Treebank@formal@@1@S@Accordingly, the effects of the constitutively active PKCs were compared to the effects of mutationally activated p21ras.@@@@1@19@@oe@16-12-2010 773036406@GENIA Treebank@formal@@1@S@The data indicate that PKC-epsilon and, to a lesser extent PKC-alpha but not -zeta, can regulate the transcription factors AP-1 and nuclear factor of activated T cells (NF-AT-1).@@@@1@33@@oe@16-12-2010 773036407@GENIA Treebank@formal@@1@S@The ability of PKC-epsilon to induce transactivation of NF-AT-1 and AP-1 was similar to the stimulatory effect of a constitutively activated p21ras.@@@@1@23@@oe@16-12-2010 773036408@GENIA Treebank@formal@@1@S@PKC-epsilon, but not PKC-alpha nor activated p21ras, was able to induce NF-KB activity.@@@@1@16@@oe@16-12-2010 773036409@GENIA Treebank@formal@@1@S@Phorbol esters induce expression of CD69 whereas none of the activated PKC isotypes tested were able to have this effect.@@@@1@21@@oe@16-12-2010 773036410@GENIA Treebank@formal@@1@S@Activated Src and p21ras were able to induce CD69 expression.@@@@1@11@@oe@16-12-2010 773036411@GENIA Treebank@formal@@1@S@These results indicate selective functions for different PKC isotypes in T cells.@@@@1@13@@oe@16-12-2010 773036412@GENIA Treebank@formal@@1@S@Moreover, the data comparing the effects of activated Ras and PKC mutants suggest that PKC-alpha, p21ras, and PKC-epsilon are not positioned linearly on a single signal transduction pathway.@@@@1@32@@oe@16-12-2010 773062401@GENIA Treebank@formal@@1@S@Activation of transcription by binding of NF-E1 (YY1) to a newly identified element in the first exon of the human DR alpha gene.@@@@1@26@@oe@16-12-2010 773062402@GENIA Treebank@formal@@1@S@A previously unrecognized element, located downstream of the start site of transcription in the first exon of the DR alpha gene, has been defined that enhances promoter activity up to eightfold in a position-dependent manner.@@@@1@38@@oe@16-12-2010 773062403@GENIA Treebank@formal@@1@S@Mutations in this DNA-binding site abolished binding of a nuclear factor in human B cell nuclear extract and decreased the activity of the DR alpha promoter to a basal level.@@@@1@31@@oe@16-12-2010 773062404@GENIA Treebank@formal@@1@S@Significant sequence homology of this element was found in the DNA of the DR beta, DP alpha and -beta, and DQ alpha genes, always located downstream of the transcriptional start site.@@@@1@35@@oe@16-12-2010 773062405@GENIA Treebank@formal@@1@S@The nuclear factor binds to the DR alpha and DP alpha element but not to the element in the DQ alpha gene.@@@@1@23@@oe@16-12-2010 773062406@GENIA Treebank@formal@@1@S@It was identified as NF-E1 (YY1).@@@@1@9@@oe@16-12-2010 773062407@GENIA Treebank@formal@@1@S@This protein, previously identified by its binding to the Ig kappa 3' enhancer and the Ig heavy chain mu E1 site, thus also appears to be quite important in the regulation of MHC class II gene expression.@@@@1@40@@oe@16-12-2010 773801301@GENIA Treebank@formal@@1@S@Mouse interleukin-2 receptor alpha gene expression.@@@@1@7@@oe@16-12-2010 773801302@GENIA Treebank@formal@@1@S@Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements.@@@@1@10@@oe@16-12-2010 773801303@GENIA Treebank@formal@@1@S@We have shown that interleukin-1 (IL-1) and IL-2 control IL-2 receptor alpha (IL-2R alpha) gene transcription in CD4-CD8- murine T lymphocyte precursors.@@@@1@27@@oe@16-12-2010 773801304@GENIA Treebank@formal@@1@S@Here we map the cis-acting elements that mediate interleukin responsiveness of the mouse IL-2R alpha gene using a thymic lymphoma-derived hybridoma (PC60).@@@@1@25@@oe@16-12-2010 773801305@GENIA Treebank@formal@@1@S@The transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is biphasic.@@@@1@17@@oe@16-12-2010 773801306@GENIA Treebank@formal@@1@S@IL-1 induces a rapid, protein synthesis-independent appearance of IL-2R alpha mRNA that is blocked by inhibitors of NF-kappa B activation.@@@@1@22@@oe@16-12-2010 773801307@GENIA Treebank@formal@@1@S@It also primes cells to become IL-2 responsive and thereby prepares the second phase, in which IL-2 induces a 100-fold further increase in IL-2R alpha transcripts.@@@@1@28@@oe@16-12-2010 773801308@GENIA Treebank@formal@@1@S@Transient transfection experiments show that several elements in the promoter-proximal region of the IL-2R alpha gene contribute to IL-1 responsiveness, most importantly an NF-kappa B site conserved in the human and mouse gene.@@@@1@35@@oe@16-12-2010 773801309@GENIA Treebank@formal@@1@S@IL-2 responsiveness, on the other hand, depends on a 78-nucleotide segment 1.3 kilobases upstream of the major transcription start site.@@@@1@23@@oe@16-12-2010 773801310@GENIA Treebank@formal@@1@S@This segment functions as an IL-2-inducible enhancer and lies within a region that becomes DNase I hypersensitive in normal T cells in which IL-2R alpha expression has been induced.@@@@1@30@@oe@16-12-2010 773801311@GENIA Treebank@formal@@1@S@IL-2 responsiveness requires three distinct elements within the enhancer.@@@@1@10@@oe@16-12-2010 773801312@GENIA Treebank@formal@@1@S@Two of these are potential binding sites for STAT proteins.@@@@1@11@@oe@16-12-2010 773956201@GENIA Treebank@formal@@1@S@Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.@@@@1@19@@oe@16-12-2010 773956202@GENIA Treebank@formal@@1@S@The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth.@@@@1@35@@oe@16-12-2010 773956203@GENIA Treebank@formal@@1@S@The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha.@@@@1@23@@oe@16-12-2010 773956204@GENIA Treebank@formal@@1@S@This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1.@@@@1@42@@oe@16-12-2010 773956205@GENIA Treebank@formal@@1@S@To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes.@@@@1@34@@oe@16-12-2010 773956206@GENIA Treebank@formal@@1@S@Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm.@@@@1@30@@oe@16-12-2010 773956207@GENIA Treebank@formal@@1@S@However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells.@@@@1@28@@oe@16-12-2010 773956208@GENIA Treebank@formal@@1@S@Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors.@@@@1@48@@oe@16-12-2010 773956209@GENIA Treebank@formal@@1@S@In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor.@@@@1@35@@oe@16-12-2010 773956210@GENIA Treebank@formal@@1@S@Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli.@@@@1@39@@oe@16-12-2010 774203701@GENIA Treebank@formal@@1@S@HIV type 1 protease activation of NF-kappa B within T lymphoid cells.@@@@1@13@@oe@16-12-2010 774203702@GENIA Treebank@formal@@1@S@NF-kappa B is a nuclear protein of the rel oncogene family capable of enhancing transcription of several cellular genes, including IL-2 and the IL-2 receptor, and viral genes transcribed from the HIV-1 LTR.@@@@1@36@@oe@16-12-2010 774203703@GENIA Treebank@formal@@1@S@It has been reported that HIV-1 protease may cleave the NF-kappa B precursor to its active form in vitro.@@@@1@20@@oe@16-12-2010 774203704@GENIA Treebank@formal@@1@S@In this study the effects of HIV protease on NF-kappa B precursor activation were examined in Jurkat T cells by introducing a protease expression vector into the cells.@@@@1@29@@oe@16-12-2010 774203705@GENIA Treebank@formal@@1@S@Increased NF-kappa B activity was observed and this increased activity was blocked by a specific inhibitor of the viral protease.@@@@1@21@@oe@16-12-2010 774203706@GENIA Treebank@formal@@1@S@Viral transcription, as measured using LTR-CAT assays, was only slightly enhanced in the HIV-protease expressing cells, while secretion of IL-2 and expression of the IL-2 receptor were not affected.@@@@1@33@@oe@16-12-2010 774203707@GENIA Treebank@formal@@1@S@The limited activation of NF-kappa B by HIV protease appears unlikely to have a significant effect on virus expression or T cell function.@@@@1@24@@oe@16-12-2010 774255201@GENIA Treebank@formal@@1@S@Neutrophils and monocytes express high levels of PU.1 (Spi-1) but not Spi-B.@@@@1@15@@oe@16-12-2010 774255202@GENIA Treebank@formal@@1@S@PU.1 (the Spi-1 oncogene) and Spi-B are closely related members of the ets transcription factor family, sharing similar DNA binding specificities mediated by similar DNA binding domains.@@@@1@31@@oe@16-12-2010 774255203@GENIA Treebank@formal@@1@S@PU.1 and Spi-B have been previously described as being predominantly expressed coordinately in macrophages and B cells, but their expression in early hematopoietic stages and during the course of myeloid differentiation to monocytes and macrophages or to neutrophils has not been extensively investigated.@@@@1@45@@oe@16-12-2010 774255204@GENIA Treebank@formal@@1@S@Here, we report that PU.1 mRNA is upregulated during myeloid differentiation of human purified CD34+ cells and murine multipotential FDCP-mix A4 cells, suggesting that PU.1 is upregulated as an early event during differentiation of multipotential progenitor cells.@@@@1@40@@oe@16-12-2010 774255205@GENIA Treebank@formal@@1@S@PU.1 expression is maintained at stable levels during differentiation of myeloid cell lines U937 and HL-60 to monocytic and neutrophilic cells.@@@@1@22@@oe@16-12-2010 774255206@GENIA Treebank@formal@@1@S@PU.1 is expressed at highest levels in mature human monocytes and human peripheral blood neutrophils.@@@@1@16@@oe@16-12-2010 774255207@GENIA Treebank@formal@@1@S@In contrast to PU.1, significant levels of Spi-B mRNA and protein are found only in some B-cell lines and spleen but are not found in myeloid cell lines, neutrophils, or macrophages.@@@@1@35@@oe@16-12-2010 774255208@GENIA Treebank@formal@@1@S@In vitro translated Spi-B protein can bind to PU.1 binding sites in myeloid promoters and transactivate these promoters in nonmyeloid cells.@@@@1@22@@oe@16-12-2010 774255209@GENIA Treebank@formal@@1@S@Therefore, although PU.1 and Spi-B may bind to similar DNA control elements and have redundancy of transactivation function in vitro, the lack of significant levels of Spi-B in myeloid cells makes it unlikely that Spi-B plays a significant role in myeloid lineage development and gene expression.@@@@1@49@@oe@16-12-2010 774255210@GENIA Treebank@formal@@1@S@In contrast, PU.1 is expressed at high levels not only in monocytes and macrophages but also in neutrophils, indicating that PU.1 can activate gene expression in both major myeloid lineages.@@@@1@33@@oe@16-12-2010 774323001@GENIA Treebank@formal@@1@S@The use of glucocorticoids in acute lymphoblastic leukemia of childhood.@@@@1@11@@oe@16-12-2010 774323002@GENIA Treebank@formal@@1@S@Molecular, cellular, and clinical considerations.@@@@1@8@@oe@16-12-2010 774323003@GENIA Treebank@formal@@1@S@Glucocorticoids have been included in almost all treatment regimens for childhood acute lymphoblastic leukemia for decades.@@@@1@17@@oe@16-12-2010 774323004@GENIA Treebank@formal@@1@S@However, optimal agents, doses, and/or schedules have yet to be defined despite extensive clinical application.@@@@1@19@@oe@16-12-2010 774323005@GENIA Treebank@formal@@1@S@New data on the pharmacokinetics, pharmacodynamics, and molecular mechanisms of action of glucocorticoids have suggested alternative approaches in ALL.@@@@1@22@@oe@16-12-2010 774323006@GENIA Treebank@formal@@1@S@These suggest that prolonged, i.e. 28 day, glucocorticoid therapy may be unnecessary as exposure to glucocorticoid induces down-regulation of glucocorticoid receptors.@@@@1@24@@oe@16-12-2010 774323007@GENIA Treebank@formal@@1@S@Dexamethasone may be superior to prednisone in conventional equi-effective doses.@@@@1@11@@oe@16-12-2010 774323008@GENIA Treebank@formal@@1@S@Blast sensitivity to glucocorticoids correlates closely with sensitivity to other, putatively non-cross-resisting agents and with outcome after multi-agent therapy, suggesting overlapping mechanisms of action, and focusing attention on the determinants of the threshold for apoptosis.@@@@1@39@@oe@16-12-2010 774323009@GENIA Treebank@formal@@1@S@Increasing success in the treatment of childhood acute lymphoblastic leukemia has led to increasing awareness of avascular necrosis of bone as a potentially disabling sequela of glucocorticoid therapy, especially in adolescent and young adult patients.@@@@1@37@@oe@16-12-2010 774462301@GENIA Treebank@formal@@1@S@Differential induction of the NF-AT complex during restimulation and the induction of T-cell anergy.@@@@1@15@@oe@16-12-2010 774462302@GENIA Treebank@formal@@1@S@Stimulation of human CD4+ T-cell clones through the T-cell receptor (TcR) by high doses of specific peptide results in the induction of a long-lived state of nonresponsiveness that has been called anergy.@@@@1@35@@oe@16-12-2010 774462303@GENIA Treebank@formal@@1@S@During the induction of anergy, T cells are phenotypically similar to cells responding to an immunogenic stimulus.@@@@1@19@@oe@16-12-2010 774462304@GENIA Treebank@formal@@1@S@The amount of TcR at the cell surface is downmodulated, whereas the CD2 and CD25 receptors are increased.@@@@1@20@@oe@16-12-2010 774462305@GENIA Treebank@formal@@1@S@When restimulated, however, anergic T cells fail to up-regulate transcription of the IL-2 gene and in consequence do not produce IL-2.@@@@1@24@@oe@16-12-2010 774462306@GENIA Treebank@formal@@1@S@In this study, we have compared the ability of various transcription factors to bind to their appropriate site on DNA.@@@@1@22@@oe@16-12-2010 774462307@GENIA Treebank@formal@@1@S@Factors were isolated from the nuclei of T cells that were in the induction phase of anergy or were undergoing activation.@@@@1@22@@oe@16-12-2010 774462308@GENIA Treebank@formal@@1@S@The pattern of binding activity in restimulated T cells is consistent with the pattern that has previously been shown to regulate T-cell-specific expression of the IL-2 and the beta chain of the TcR genes.@@@@1@35@@oe@16-12-2010 774462309@GENIA Treebank@formal@@1@S@The measured binding to a TCF-1 site is the same in the nuclei of resting, activated, and anergized cells.@@@@1@22@@oe@16-12-2010 774462310@GENIA Treebank@formal@@1@S@The inducible factors NK-kappa B, beta E2, CD28RC, and AP-1 are not expressed in resting cells and are twofold lower in anergized as compared with activated cells.@@@@1@31@@oe@16-12-2010 774462311@GENIA Treebank@formal@@1@S@In contrast, anergic T cells express approximately eightfold lower amounts of NF-AT, a member of the class of inducible factors that regulates IL-2 gene transcription.@@@@1@28@@oe@16-12-2010 774462312@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 774479901@GENIA Treebank@formal@@1@S@Erythropoietin stimulates transcription of the TAL1/SCL gene and phosphorylation of its protein products.@@@@1@14@@oe@16-12-2010 774479902@GENIA Treebank@formal@@1@S@Activation of the TAL1 (or SCL) gene, originally identified through its involvement by a recurrent chromosomal translocation, is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia.@@@@1@34@@oe@16-12-2010 774479903@GENIA Treebank@formal@@1@S@The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers.@@@@1@30@@oe@16-12-2010 774479904@GENIA Treebank@formal@@1@S@TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vivo suggested the gene might regulate aspects of erythroid differentiation.@@@@1@25@@oe@16-12-2010 774479905@GENIA Treebank@formal@@1@S@Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin (Epo), we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus (FVA cells).@@@@1@54@@oe@16-12-2010 774479906@GENIA Treebank@formal@@1@S@Epo elicited a rapid, dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs.@@@@1@23@@oe@16-12-2010 774479907@GENIA Treebank@formal@@1@S@An Epo-inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein.@@@@1@22@@oe@16-12-2010 774479908@GENIA Treebank@formal@@1@S@Induction of DNA binding activity was associated temporally with Epo-induced phosphorylation of nuclear TAL1 protein.@@@@1@16@@oe@16-12-2010 774479909@GENIA Treebank@formal@@1@S@These results indicate that Epo acts at both transcriptional and posttranscriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages.@@@@1@46@@oe@16-12-2010 774741701@GENIA Treebank@formal@@1@S@The retinoblastoma gene product negatively regulates transcriptional activation mediated by the human cytomegalovirus IE2 protein.@@@@1@16@@oe@16-12-2010 774741702@GENIA Treebank@formal@@1@S@The IE2 gene product of human cytomegalovirus (HCMV) is one of a few viral regulatory proteins expressed immediately upon infection of the host cell.@@@@1@27@@oe@16-12-2010 774741703@GENIA Treebank@formal@@1@S@It is a potent transcriptional activator of many viral and cellular promoters.@@@@1@13@@oe@16-12-2010 774741704@GENIA Treebank@formal@@1@S@We found that the retinoblastoma susceptibility gene product (Rb) dramatically suppressed this IE2 transactivation of various promoters.@@@@1@20@@oe@16-12-2010 774741705@GENIA Treebank@formal@@1@S@However, unlike another tumor suppressor protein, p53, Rb did not have any significant effect on basal levels of transcription, suggesting that Rb specifically interacts with IE2 rather than other cellular factors involved in the general transcription machinery.@@@@1@42@@oe@16-12-2010 774741706@GENIA Treebank@formal@@1@S@We found by protein-affinity chromatography that Rb in nuclear extracts or produced by in vitro translation directly bound to IE2.@@@@1@21@@oe@16-12-2010 774741707@GENIA Treebank@formal@@1@S@Our results suggest that Rb may regulate the life cycle of HCMV, which is endemic in the human population.@@@@1@21@@oe@16-12-2010 774741708@GENIA Treebank@formal@@1@S@Furthermore, these data may provide new insights into the slow rate of HCMV DNA replication in cells and the possible involvement of HCMV in tumorigenesis.@@@@1@27@@oe@16-12-2010 774744001@GENIA Treebank@formal@@1@S@Epstein-Barr virus replicative gene transcription during de novo infection of human thymocytes: simultaneous early expression of BZLF-1 and its repressor RAZ.@@@@1@23@@oe@16-12-2010 774744002@GENIA Treebank@formal@@1@S@Epstein-Barr virus (EBV) is known to infect B cells and epithelial cells.@@@@1@15@@oe@16-12-2010 774744003@GENIA Treebank@formal@@1@S@We and others have shown that EBV can also infect a subset of thymocytes.@@@@1@15@@oe@16-12-2010 774744004@GENIA Treebank@formal@@1@S@Infection of thymocytes was accompanied by the appearance of linear EBV genome within 8 hr of infection.@@@@1@18@@oe@16-12-2010 774744005@GENIA Treebank@formal@@1@S@Circularization of the EBV genome was not detected.@@@@1@9@@oe@16-12-2010 774744006@GENIA Treebank@formal@@1@S@This is in contrast to the infection in B cells where the genome can circularize within 24 hr of infection.@@@@1@21@@oe@16-12-2010 774744007@GENIA Treebank@formal@@1@S@The appearance of the BamHI ZLF-1 gene product, ZEBRA, by RT-PCR, was observed within 8 hr of infection.@@@@1@22@@oe@16-12-2010 774744008@GENIA Treebank@formal@@1@S@The appearance of a novel fusion transcript (RAZ), which comprised regions of the BZLF-1 locus and the adjacent BRLF-1 locus, was detected by RT-PCR.@@@@1@29@@oe@16-12-2010 774744009@GENIA Treebank@formal@@1@S@ZEBRA protein was also identified in infected thymocytes by immunoprecipitation.@@@@1@11@@oe@16-12-2010 774744010@GENIA Treebank@formal@@1@S@In addition, we demonstrated that the EBNA-1 gene in infected thymocytes was transcribed from the Fp promoter, rather than from the Cp/Wp promoter which is used in latently infected B cells.@@@@1@34@@oe@16-12-2010 774744011@GENIA Treebank@formal@@1@S@Transcripts encoding gp350/220, the major coat protein of EBV, were identified, but we did not find any evidence of transcription from the LMP-2A or EBER-1 loci in infected thymocytes.@@@@1@33@@oe@16-12-2010 774744012@GENIA Treebank@formal@@1@S@These observations suggest that de novo EBV infection of thymocytes differs from infection of B cells.@@@@1@17@@oe@16-12-2010 774744013@GENIA Treebank@formal@@1@S@The main difference is that with thymocytes, no evidence could be found that the virus ever circularizes.@@@@1@19@@oe@16-12-2010 774744014@GENIA Treebank@formal@@1@S@Rather, EBV remains in a linear configuration from which replicative genes are transcribed.@@@@1@15@@oe@16-12-2010 774744701@GENIA Treebank@formal@@1@S@Induction of Sp1 phosphorylation and NF-kappa B-independent HIV promoter domain activity in T lymphocytes stimulated by okadaic acid.@@@@1@19@@oe@16-12-2010 774744702@GENIA Treebank@formal@@1@S@In contrast to the purely enhancer-dependent effect of cytokines such as TNF on the activity of the HIV regulatory region (LTR), we observed that okadaic acid (OKA) activates HIV transcription through both the enhancer, responding to the factor NF-kappa B, and the promoter domain of the LTR.@@@@1@55@@oe@16-12-2010 774744703@GENIA Treebank@formal@@1@S@The inducibility of HIV LTR-driven luciferase expression constructs in lymphoblastoid cells stimulated by OKA depended on both functional Sp1 binding elements and the ability of the TATA box to bind the protein TBP.@@@@1@34@@oe@16-12-2010 774744704@GENIA Treebank@formal@@1@S@In both transformed and normal lymphocytes, OKA stimulation induced intense phosphorylation of the constitutively expressed Sp1 protein in the nucleus, a property of OKA not shared by TNF, phorbol ester, or PHA and interleukin 2.@@@@1@40@@oe@16-12-2010 774744705@GENIA Treebank@formal@@1@S@Responsiveness of LTR constructs deleted of kappa B elements to HIV Tat expression was increased upon OKA but not TNF stimulation.@@@@1@22@@oe@16-12-2010 774744706@GENIA Treebank@formal@@1@S@Our results suggest that SP1 phosphorylation induced by OKA, a selective inhibitor of the serine-threonine phosphatase PP2A, facilitates the formation of a transcription complex involving general transcription factors, HIV Tat, and Sp1 proteins.@@@@1@38@@oe@16-12-2010 774744707@GENIA Treebank@formal@@1@S@The formation of this complex would increase, independently of an in synergy with NF-kappa B, the low basal activity of the HIV LTR observed in normal T lymphocytes.@@@@1@31@@oe@16-12-2010 774998501@GENIA Treebank@formal@@1@S@Human MHC class II gene transcription directed by the carboxyl terminus of CIITA, one of the defective genes in type II MHC combined immune deficiency.@@@@1@27@@oe@16-12-2010 774998502@GENIA Treebank@formal@@1@S@Type II major histocompatibility complex combined immune deficiency (type II MHC CID or bare lymphocyte syndrome) is a congenital immunodeficiency disease characterized by absent MHC class II expression.@@@@1@31@@oe@16-12-2010 774998503@GENIA Treebank@formal@@1@S@Four distinct complementation groups have been identified.@@@@1@8@@oe@16-12-2010 774998504@GENIA Treebank@formal@@1@S@Recently, the defective gene in group II type II MHC CID has been isolated and termed CIITA.@@@@1@19@@oe@16-12-2010 774998505@GENIA Treebank@formal@@1@S@Here, we demonstrate that CIITA is an MHC class II gene-specific transcription activator.@@@@1@15@@oe@16-12-2010 774998506@GENIA Treebank@formal@@1@S@The transcription activation function is provided by the N-terminal acidic domain (amino acids 26-137), which is experimentally exchangeable with a heterologous viral transcription-activating domain.@@@@1@28@@oe@16-12-2010 774998507@GENIA Treebank@formal@@1@S@The specificity of CIITA for three major MHC class II genes, DR, DQ and DP, is mediated by its remaining C-terminal residues (amino acids 317-1130).@@@@1@31@@oe@16-12-2010 774998508@GENIA Treebank@formal@@1@S@The transactivation of multiple cis elements, especially S and X2, of the DR alpha proximal promoter in group II CID cells is CIITA dependent.@@@@1@27@@oe@16-12-2010 774998509@GENIA Treebank@formal@@1@S@Since CIITA overexpression in normal cells did not increase class II expression, we propose that initiation of CIITA expression serves as the on-off switch, while availability of downstream interactor(s) limits transcription.@@@@1@37@@oe@16-12-2010 775708401@GENIA Treebank@formal@@1@S@CAG repeat length variation in sperm from a patient with Kennedy's disease.@@@@1@14@@oe@16-12-2010 775708402@GENIA Treebank@formal@@1@S@Using a modified sperm typing protocol, the mutation frequency of the CAG repeat region at the androgen receptor locus has been measured using a rare semen sample from an individual with spinal and bulbar muscular atrophy (SBMA).@@@@1@41@@oe@16-12-2010 775708403@GENIA Treebank@formal@@1@S@Among 258 X chromosome-containing sperm, 19% had a repeat number equal to the donor's somatic DNA (47 repeats), 66% were expansions and 15% were contractions.@@@@1@34@@oe@16-12-2010 775708404@GENIA Treebank@formal@@1@S@The average expansion was 2.7 repeats.@@@@1@7@@oe@16-12-2010 775708405@GENIA Treebank@formal@@1@S@More than half of the expansions involved one or two repeats; the largest was 11 repeats.@@@@1@18@@oe@16-12-2010 775708406@GENIA Treebank@formal@@1@S@68% of the contractions were also one or two repeats but six (16%) were very large (12-25 repeats).@@@@1@25@@oe@16-12-2010 775708407@GENIA Treebank@formal@@1@S@One contraction generated an allele in an intermediate size range (33-39 repeats).@@@@1@15@@oe@16-12-2010 775708408@GENIA Treebank@formal@@1@S@Such alleles have not been observed among more than 900 normal and SBMA X-chromosomes that have been examined.@@@@1@19@@oe@16-12-2010 775708409@GENIA Treebank@formal@@1@S@Comparison of the SBMA sperm typing results with mutation frequency data on normal alleles supports the hypothesis that trinucleotide repeat expansions may have a different molecular origin than contractions.@@@@1@30@@oe@16-12-2010 775882001@GENIA Treebank@formal@@1@S@Isolation of differentially expressed sequence tags from steroid-responsive cells using mRNA differential display.@@@@1@14@@oe@16-12-2010 775882002@GENIA Treebank@formal@@1@S@Transcriptional control of steroid-regulated gene networks by nuclear receptor proteins results in the coordinate expression of a limited number of target genes.@@@@1@23@@oe@16-12-2010 775882003@GENIA Treebank@formal@@1@S@Although much is known about the structure and function of steroid receptors, relatively few cell-specific steroid-regulated genes have been isolated and characterized.@@@@1@24@@oe@16-12-2010 775882004@GENIA Treebank@formal@@1@S@In this paper we describe results using mRNA differential display reverse transcriptase PCR (DDPCR) to identify and isolate short cDNA sequence tags from thymocyte and prostate cells under various hormone conditions.@@@@1@34@@oe@16-12-2010 775882005@GENIA Treebank@formal@@1@S@Using this technique we have isolated several differentially expressed sequence tags (DESTs) from the mouse thymocyte cell line WEHI 7.2.@@@@1@23@@oe@16-12-2010 775882006@GENIA Treebank@formal@@1@S@Two of these DESTs, GIG10 and GIG18, are rapidly induced by dexamethasone within 2 h of treatment.@@@@1@20@@oe@16-12-2010 775882007@GENIA Treebank@formal@@1@S@GIG10 is a novel sequence and GIG18 is the mouse homologue of a human expressed sequence tag isolated from activated B lymphocytes.@@@@1@23@@oe@16-12-2010 775882008@GENIA Treebank@formal@@1@S@We also used DDPCR to isolate DESTs from androgen-modulated rat ventral prostate tissue, one of which we characterized and found to correspond to the 3' end of prostatic spermine binding protein mRNA, a known androgen-regulated gene.@@@@1@39@@oe@16-12-2010 775882009@GENIA Treebank@formal@@1@S@Modifications of the original DDPCR protocol, which we found can potentially decrease the frequency of isolating false-positive DESTs, are described and the merits of DDPCR, relative to other differential cDNA cloning strategies, are discussed.@@@@1@39@@oe@16-12-2010 775954801@GENIA Treebank@formal@@1@S@Identification of two novel regulatory elements within the 5'-untranslated region of the human A gamma-globin gene.@@@@1@17@@oe@16-12-2010 775954802@GENIA Treebank@formal@@1@S@Interaction between the stage selector element (SSE) in the proximal gamma-globin promoter and hypersensitivity site 2 in the locus control region partly mediates the competitive silencing of the beta-globin promoter in the fetal developmental stage.@@@@1@38@@oe@16-12-2010 775954803@GENIA Treebank@formal@@1@S@We have now demonstrated that a second SSE-like element in the 5'-untranslated region of the gamma-gene also contributes to this competitive silencing of the beta-gene.@@@@1@26@@oe@16-12-2010 775954804@GENIA Treebank@formal@@1@S@Utilizing transient transfection assays in the fetal erythroid cell line, K562, we have shown that the core enhancer of hypersensitivity site 2 can preferentially interact with the proximal gamma-promoter in the absence of the SSE, completely silencing a linked beta-promoter.@@@@1@44@@oe@16-12-2010 775954805@GENIA Treebank@formal@@1@S@Mutation of a 20-base pair sequence of the gamma-gene 5'-untranslated region (UTR) led to derepression of beta-promoter activity.@@@@1@21@@oe@16-12-2010 775954806@GENIA Treebank@formal@@1@S@A marked activation of gamma-promoter activity was also observed with this mutation, suggesting the presence of a repressor.@@@@1@20@@oe@16-12-2010 775954807@GENIA Treebank@formal@@1@S@Fine mutagenesis dissected these activities to different regions of the 5'-UTR.@@@@1@12@@oe@16-12-2010 775954808@GENIA Treebank@formal@@1@S@The stage selector activity was localized to a region centered on nucleotides +13 to +15.@@@@1@16@@oe@16-12-2010 775954809@GENIA Treebank@formal@@1@S@Electromobility shift assays utilizing this sequence demonstrated binding of a fetal and erythroid-specific protein.@@@@1@15@@oe@16-12-2010 775954810@GENIA Treebank@formal@@1@S@The repressor activity of the 5'-UTR was localized to tandem GATA-like sites, which appear to bind a complex of two proteins, one of which is the erythroid transcription factor GATA-1.@@@@1@33@@oe@16-12-2010 775954811@GENIA Treebank@formal@@1@S@These results indicate that the 5'-UTR of the gamma-gene contains sequences that may be important for its transcriptional and developmental regulation.@@@@1@22@@oe@16-12-2010 775987501@GENIA Treebank@formal@@1@S@Abnormal regulation of the IL-2 promoter in lpr CD4-CD8- T lymphocytes results in constitutive expression of a novel nuclear factor of activated T cells-binding factor.@@@@1@26@@oe@16-12-2010 775987502@GENIA Treebank@formal@@1@S@The inert quality of MRL-Ipr/Ipr (Ipr) peripheral CD4-CD8- (CD4-8-) T cells manifests primarily as an inability to proliferate or produce IL-2 in response to TCR or mitogenic stimulation.@@@@1@33@@oe@16-12-2010 775987503@GENIA Treebank@formal@@1@S@Yet these same cells do initiate early TCR-mediated signaling events, such as generation of inositol phosphates and increased intracellular calcium.@@@@1@22@@oe@16-12-2010 775987504@GENIA Treebank@formal@@1@S@They also display constitutively high levels of p59fyn and CD3 zeta tyrosine phosphorylation.@@@@1@14@@oe@16-12-2010 775987505@GENIA Treebank@formal@@1@S@The generation of second messengers in T cells normally leads to downstream signaling that results in transcriptional activation of the IL-2 gene.@@@@1@23@@oe@16-12-2010 775987506@GENIA Treebank@formal@@1@S@We, therefore, compared the activation state of the IL-2 gene promoter region in freshly isolated and stimulated Ipr CD4-8- T cells with that of normal T lymphocytes.@@@@1@30@@oe@16-12-2010 775987507@GENIA Treebank@formal@@1@S@Levels of the octamer, NF-kappa B (p50-p65 heterodimer), and AP-1 transcriptional factors are constitutively elevated in freshly isolated Ipr CD4-8- T cells, consistent with the activated phenotype of these cells.@@@@1@36@@oe@16-12-2010 775987508@GENIA Treebank@formal@@1@S@Upon stimulation with mitogens, formation of the transactivating complex, nuclear factor of activated T cells (NF-AT), occurs with normal kinetics in Ipr CD4-8- T cells.@@@@1@31@@oe@16-12-2010 775987509@GENIA Treebank@formal@@1@S@Yet, the levels of the activating NF-AT complex never reach those observed in similarly stimulated normal T cells.@@@@1@20@@oe@16-12-2010 775987510@GENIA Treebank@formal@@1@S@Furthermore, nuclear extracts from Ipr CD4-8- T cells display high levels of a novel specific binding activity at the NF-AT site, which is present at much lower levels in freshly isolated normal T lymphocytes.@@@@1@37@@oe@16-12-2010 775987511@GENIA Treebank@formal@@1@S@Upon mitogenic stimulation, the binding activity of the novel NF-AT-binding factor is rapidly down-regulated in normal T cells, but persists at high levels in Ipr CD4-8- T cells.@@@@1@31@@oe@16-12-2010 775987512@GENIA Treebank@formal@@1@S@These two abnormalities at the NF-AT site provide a potential mechanism to account for the defect in IL-2 production from Ipr CD4-8- T cells.@@@@1@25@@oe@16-12-2010 775995601@GENIA Treebank@formal@@1@S@GM-CSF and IL-2 share common control mechanisms in response to costimulatory signals in T cells.@@@@1@16@@oe@16-12-2010 775995602@GENIA Treebank@formal@@1@S@Antigen complexed with major histocompatibility complex class I or II molecules on the surface of antigen presenting cells interacts with the T cell receptor (TCR) on the surface of T cells and initiates an activation cascade.@@@@1@39@@oe@16-12-2010 775995603@GENIA Treebank@formal@@1@S@So called costimulatory signals, mediated by other cell surface interactions or soluble cytokines produced by antigen presenting cells, are also required for complete T cell activation.@@@@1@29@@oe@16-12-2010 775995604@GENIA Treebank@formal@@1@S@High levels of cytokine gene expression in T cells also required both TCR and costimulatory signals.@@@@1@17@@oe@16-12-2010 775995605@GENIA Treebank@formal@@1@S@The granulocyte-macrophage colony-stimulating factor requires sequences in the promoter as well as a powerful enhancer located 3kb upstream to respond to TCR-like signals.@@@@1@24@@oe@16-12-2010 775995606@GENIA Treebank@formal@@1@S@These promoter and enhancer regions are mainly activated by the transcription factor nuclear factor of activated T cells (NFAT).@@@@1@22@@oe@16-12-2010 775995607@GENIA Treebank@formal@@1@S@The activation of NFAT by TCR signals has been well described for interleukin-2 (IL-2) and IL-4 gene transcription in T cells.@@@@1@24@@oe@16-12-2010 775995608@GENIA Treebank@formal@@1@S@Costimulatory signals, such as activation of the CD28 cell surface molecule on T cells, lead to activation through a distinct region of the granulocyte-macrophage colony-stimulating factor (GM-CSF) promoter.@@@@1@33@@oe@16-12-2010 775995609@GENIA Treebank@formal@@1@S@This region is termed the CK-1 or CD28RE and appears to bind specific members of the NF-kappa B family of transcription factors.@@@@1@23@@oe@16-12-2010 775995610@GENIA Treebank@formal@@1@S@Human T leukemia virus type 1 (HTLV-1) infects T cells and can lead to increase GM-CSF expression.@@@@1@20@@oe@16-12-2010 775995611@GENIA Treebank@formal@@1@S@We have found that the HTLV-1 transactivator protein, tax, acts as a costimulatory signal for GM-CSF and IL-2 gene transcription, in that it can cooperate with TCR signals to mediate high level gene expression.@@@@1@38@@oe@16-12-2010 775995612@GENIA Treebank@formal@@1@S@Tax activates the GM-CSF promoter through the CK-1/CD28RE region and also activates nuclear factor-kappa B binding to this region.@@@@1@20@@oe@16-12-2010 775995613@GENIA Treebank@formal@@1@S@However, other transcription factors or coactivators of NF-kappa B are required for tax activation but these remain to be identified.@@@@1@22@@oe@16-12-2010 775995614@GENIA Treebank@formal@@1@S@The CK-1/CD28RE of GM-CSF shows a high degree of similarity to the IL-2 CD28RE and the IL-3 gene also contains a related region.@@@@1@24@@oe@16-12-2010 775995615@GENIA Treebank@formal@@1@S@This observation, together with the fact that both GM-CSF and IL-2 respond to TCR signals via NFAT, implies a high degree of conservation in the regulation of cytokine gene expression in T cells.@@@@1@36@@oe@16-12-2010 776080701@GENIA Treebank@formal@@1@S@MIP1 alpha nuclear protein (MNP), a novel transcription factor expressed in hematopoietic cells that is crucial for transcription of the human MIP-1 alpha gene.@@@@1@28@@oe@16-12-2010 776080702@GENIA Treebank@formal@@1@S@Murine macrophage inflammatory protein 1 alpha (MIP-1 alpha) and its human equivalent (GOS19, LD78, or AT464) are members of the -C-C family of low-molecular-weight chemokines.@@@@1@32@@oe@16-12-2010 776080703@GENIA Treebank@formal@@1@S@Secreted from activated T cells and macrophages, bone marrow-derived MIP-1 alpha/GOS19 inhibits primitive hematopoietic stem cells and appears to be involved in the homeostatic control of stem cell proliferation.@@@@1@31@@oe@16-12-2010 776080704@GENIA Treebank@formal@@1@S@It also induces chemotaxis and inflammatory responses in mature cell types.@@@@1@12@@oe@16-12-2010 776080705@GENIA Treebank@formal@@1@S@Therefore, it is important to understand the mechanisms which control the expression of MIP-1 alpha/GOS19.@@@@1@17@@oe@16-12-2010 776080706@GENIA Treebank@formal@@1@S@Previous work has shown that in Jurkat T cells, a set of widely expressed transcription factors (the ICK-1 family) affect the GOS19 promoter.@@@@1@27@@oe@16-12-2010 776080707@GENIA Treebank@formal@@1@S@One member, ICK-1A, behaves as a strong negative regulator.@@@@1@12@@oe@16-12-2010 776080708@GENIA Treebank@formal@@1@S@In this communication, we provide evidence that the pathway of induction in the macrophage cell line U937 is different from that in Jurkat cells.@@@@1@26@@oe@16-12-2010 776080709@GENIA Treebank@formal@@1@S@Furthermore, we show that the ICK-1 binding site does not confer negative regulation in U937 cells.@@@@1@18@@oe@16-12-2010 776080710@GENIA Treebank@formal@@1@S@We provide evidence for an additional binding site, the MIP-1 alpha nuclear protein (MNP) site, which overlaps the ICK-1 site.@@@@1@25@@oe@16-12-2010 776080711@GENIA Treebank@formal@@1@S@Interaction of nuclear extracts from various cell lines and tissue with the MNP site leads to the formation of fast-migrating protein-DNA complexes with similar but distinct electrophoretic mobilities.@@@@1@29@@oe@16-12-2010 776080712@GENIA Treebank@formal@@1@S@A mutation of the MNP site which does not abrogate ICK-1 binding inactivates the GOS19.1 promoter in U937 cells and reduces its activity by fourfold in Jurkat cells.@@@@1@29@@oe@16-12-2010 776080713@GENIA Treebank@formal@@1@S@We propose that the MNP protein(s) binding at the MNP site constitutes a novel transcription factor(s) expressed in hematopoietic cells.@@@@1@27@@oe@16-12-2010 776081001@GENIA Treebank@formal@@1@S@Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor.@@@@1@13@@oe@16-12-2010 776081002@GENIA Treebank@formal@@1@S@High-dose estrogen administration induces anemia in mammals.@@@@1@8@@oe@16-12-2010 776081003@GENIA Treebank@formal@@1@S@In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation.@@@@1@17@@oe@16-12-2010 776081004@GENIA Treebank@formal@@1@S@This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5.@@@@1@30@@oe@16-12-2010 776081005@GENIA Treebank@formal@@1@S@We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures.@@@@1@20@@oe@16-12-2010 776081006@GENIA Treebank@formal@@1@S@To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes.@@@@1@43@@oe@16-12-2010 776081007@GENIA Treebank@formal@@1@S@We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen.@@@@1@34@@oe@16-12-2010 776081008@GENIA Treebank@formal@@1@S@ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1.@@@@1@33@@oe@16-12-2010 776081009@GENIA Treebank@formal@@1@S@GATA-1 and ER bind to each other in vitro in the absence of DNA.@@@@1@15@@oe@16-12-2010 776081010@GENIA Treebank@formal@@1@S@In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner.@@@@1@17@@oe@16-12-2010 776081011@GENIA Treebank@formal@@1@S@Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1.@@@@1@27@@oe@16-12-2010 776081012@GENIA Treebank@formal@@1@S@We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER.@@@@1@19@@oe@16-12-2010 776081013@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 776081401@GENIA Treebank@formal@@1@S@A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter.@@@@1@19@@oe@16-12-2010 776081402@GENIA Treebank@formal@@1@S@The CD4 promoter plays an important role in the developmental control of CD4 transcription.@@@@1@15@@oe@16-12-2010 776081403@GENIA Treebank@formal@@1@S@In this report, we show that the minimal CD4 promoter has four factor binding sites, each of which is required for full function.@@@@1@26@@oe@16-12-2010 776081404@GENIA Treebank@formal@@1@S@Using biochemical and mutagenesis analyses, we determined that multiple nuclear factors bind to these independent sites.@@@@1@18@@oe@16-12-2010 776081405@GENIA Treebank@formal@@1@S@We determined that an initiator-like sequence present at the cap site and an Ets consensus sequence are required for full promoter function.@@@@1@23@@oe@16-12-2010 776081406@GENIA Treebank@formal@@1@S@We also demonstrate that the Myc-associated zinc finger protein (MAZ) appears to be the predominant factor binding to one of these sites.@@@@1@25@@oe@16-12-2010 776081407@GENIA Treebank@formal@@1@S@This last site closely resembles the ME1a1 G3AG4AG3 motif previously shown to be a critical element in the P2 promoter of the c-myc gene.@@@@1@25@@oe@16-12-2010 776081408@GENIA Treebank@formal@@1@S@We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene.@@@@1@27@@oe@16-12-2010 776894101@GENIA Treebank@formal@@1@S@The transcription factor, Nm23H2, binds to and activates the translocated c-myc allele in Burkitt's lymphoma.@@@@1@19@@oe@16-12-2010 776894102@GENIA Treebank@formal@@1@S@We have identified an in vivo footprint over the PuF site on the translocated c-myc allele in Burkitt's lymphoma cells.@@@@1@22@@oe@16-12-2010 776894103@GENIA Treebank@formal@@1@S@The PuF site on the silent normal c-myc allele was unoccupied.@@@@1@12@@oe@16-12-2010 776894104@GENIA Treebank@formal@@1@S@We demonstrated by electrophoretic mobility shift assay, electrophoretic mobility shift assay with antibody, UV cross-linking followed by SDS-gel electrophoresis, and Western analysis that Nm23H2 in B cell nuclear extracts bound to the c-myc PuF site.@@@@1@39@@oe@16-12-2010 776894105@GENIA Treebank@formal@@1@S@Transfection experiments with c-myc promoter constructs in both DHL-9 and Raji cells revealed that the PuF site functioned as a positive regulatory element in B cells with a drop in activity with mutation of this site.@@@@1@37@@oe@16-12-2010 776894106@GENIA Treebank@formal@@1@S@Access to this site is blocked in the normal silent c-myc allele; these data suggest that the Nm23H2 protein is involved in deregulation of the translocated c-myc allele in Burkitt's lymphoma cells.@@@@1@35@@oe@16-12-2010 776983401@GENIA Treebank@formal@@1@S@Activation of pp90rsk and early growth response-1 gene expression by pokeweed mitogen in human B cells.@@@@1@17@@oe@16-12-2010 776983402@GENIA Treebank@formal@@1@S@The present studies have examined the effects of pokeweed mitogen (PWM) on the induction of early growth response-1 gene (EGR-1) in normal human B cells.@@@@1@30@@oe@16-12-2010 776983403@GENIA Treebank@formal@@1@S@PWM regulates EGR-1 gene expression by both transcriptional and post-transcriptional mechanisms.@@@@1@12@@oe@16-12-2010 776983404@GENIA Treebank@formal@@1@S@Transient transfection assays with EGR-1 promoter fragments linked to the chloramphenicol acetyltransferase (CAT) gene demonstrated that PWM induced EGR-1 transcription is conferred by the CArG motif (C C[AT]6GG) in the EGR-1 promoter.@@@@1@37@@oe@16-12-2010 776983405@GENIA Treebank@formal@@1@S@The results further demonstrated the activation of S6 kinase (pp90rsk), evidenced by phosphorylation of S6 and serum response factor (SRF) peptides, in PWM treated B cells.@@@@1@33@@oe@16-12-2010 776983406@GENIA Treebank@formal@@1@S@Taken together, these findings suggest that PWM is able to initiate an intracytoplasmic signalling cascade and EGR-1 induction in normal human B cells.@@@@1@25@@oe@16-12-2010 777008501@GENIA Treebank@formal@@1@S@Infection with Theileria annulata induces expression of matrix metalloproteinase 9 and transcription factor AP-1 in bovine leucocytes.@@@@1@18@@oe@16-12-2010 777008502@GENIA Treebank@formal@@1@S@Theileria annulata infects bovine leucocytes and results in their reversible transformation such that they become immortalised and metastatic.@@@@1@19@@oe@16-12-2010 777008503@GENIA Treebank@formal@@1@S@The present study describes parasite-induced changes in host cell gene expression which have a direct bearing on this transformation process.@@@@1@21@@oe@16-12-2010 777008504@GENIA Treebank@formal@@1@S@T. annulata-infected leucocytes produce a number of novel metalloproteinase activities.@@@@1@11@@oe@16-12-2010 777008505@GENIA Treebank@formal@@1@S@One of these, previously called B1, is a 97-kDa protein which is secreted in large amounts and has been purified from protein-free, conditioned medium.@@@@1@28@@oe@16-12-2010 777008506@GENIA Treebank@formal@@1@S@An antiserum to this enzyme was used to isolate a cDNA clone.@@@@1@13@@oe@16-12-2010 777008507@GENIA Treebank@formal@@1@S@The predicted protein sequence of B1 is 81% identical to human matrix metalloproteinase 9 (MMP9), demonstrating that it is the bovine homologue of this enzyme.@@@@1@30@@oe@16-12-2010 777008508@GENIA Treebank@formal@@1@S@RNAase protection assays demonstrated that the MMP9 activity, unique to infected cells, is due to increased MMP9 mRNA levels.@@@@1@22@@oe@16-12-2010 777008509@GENIA Treebank@formal@@1@S@We also assayed the levels of transcription factor AP-1 and demonstrated that it was constitutively present in increased amounts in Theileria-infected cells.@@@@1@23@@oe@16-12-2010 777008510@GENIA Treebank@formal@@1@S@In addition we assayed the level of mRNA encoding c-Fos, a common component of AP-1 and observed that it was indeed up-regulated in infected cells.@@@@1@27@@oe@16-12-2010 777008511@GENIA Treebank@formal@@1@S@Since AP-1 is implicated in the control of the cell cycle, and MMP9 can confer metastatic properties, these results are of considerable significance with respect to the transformed phenotype induced by Theileria infection.@@@@1@36@@oe@16-12-2010 777972601@GENIA Treebank@formal@@1@S@Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study.@@@@1@24@@oe@16-12-2010 777972602@GENIA Treebank@formal@@1@S@Immunosuppression has been often associated with the course of malignant diseases.@@@@1@12@@oe@16-12-2010 777972603@GENIA Treebank@formal@@1@S@In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer.@@@@1@37@@oe@16-12-2010 777972604@GENIA Treebank@formal@@1@S@Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case).@@@@1@64@@oe@16-12-2010 777972605@GENIA Treebank@formal@@1@S@PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only.@@@@1@46@@oe@16-12-2010 777972606@GENIA Treebank@formal@@1@S@After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001).@@@@1@58@@oe@16-12-2010 777972607@GENIA Treebank@formal@@1@S@When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery).@@@@1@52@@oe@16-12-2010 777972608@GENIA Treebank@formal@@1@S@In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression.@@@@1@35@@oe@16-12-2010 777972609@GENIA Treebank@formal@@1@S@We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease.@@@@1@33@@oe@16-12-2010 778192701@GENIA Treebank@formal@@1@S@Modulation of transcription factor NF kappa B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply.@@@@1@21@@oe@16-12-2010 778192702@GENIA Treebank@formal@@1@S@HIV-infected individuals and SIV-infected rhesus macaques have, on the average, decreased plasma cysteine and cystine concentrations and decreased intracellular glutathione levels.@@@@1@24@@oe@16-12-2010 778192703@GENIA Treebank@formal@@1@S@We now show that a depletion of intracellular glutathione in a human T cell line (Molt-4) inhibits the activation and nuclear translocation of the transcription factor NF kappa B, whereas incubation with increasing extracellular concentrations of cysteine inhibits the DNA-binding and transactivating activity of NF kappa B.@@@@1@51@@oe@16-12-2010 778192704@GENIA Treebank@formal@@1@S@Because inhibition of DNA-binding activity is associated with increasing intracellular glutathione disulfide levels and GSSG can be shown to inhibit the DNA-binding activity directly in cell-free systems, our studies suggest that GSSG is a physiologically relevant inhibitor in intact cells also.@@@@1@43@@oe@16-12-2010 778192705@GENIA Treebank@formal@@1@S@NF kappa B controls many immunologically important genes, so our studies suggest that the immune system may be sensitive not only against a cysteine and glutathione deficiency but also against an excess of cysteine.@@@@1@36@@oe@16-12-2010 778886101@GENIA Treebank@formal@@1@S@Expression of Ah receptor (TCDD receptor) during human monocytic differentiation.@@@@1@13@@oe@16-12-2010 778886102@GENIA Treebank@formal@@1@S@We have previously found a high expression of human Ah receptor (TCDD receptor) mRNA in peripheral blood cells of individuals.@@@@1@23@@oe@16-12-2010 778886103@GENIA Treebank@formal@@1@S@In this paper, the expression of this gene in blood cells was first investigated in fractions of nucleated cells, revealing predominant expression of the Ah receptor gene in the monocyte fraction.@@@@1@34@@oe@16-12-2010 778886104@GENIA Treebank@formal@@1@S@Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1.@@@@1@22@@oe@16-12-2010 778886105@GENIA Treebank@formal@@1@S@AhR was expressed at high levels in monocytoid U937, THP1, and HEL/S cells, and at moderate levels in promyelocytic HL60 cells and erythroblastic HEL cells.@@@@1@29@@oe@16-12-2010 778886106@GENIA Treebank@formal@@1@S@However, it was not detected in lymphoid cells MOLT4 (T cell) and BALL1 (B cell), nor in K562 erythroblasts.@@@@1@26@@oe@16-12-2010 778886107@GENIA Treebank@formal@@1@S@Furthermore, a specific induction of AhR during monocytic differentiation was investigated in HL60 and HEL cells.@@@@1@18@@oe@16-12-2010 778886108@GENIA Treebank@formal@@1@S@HL60 cells were induced to differentiate toward monocytes-macrophages by incubation with phorbol ester, showing a 5- to 2-fold increase of AhR mRNA.@@@@1@24@@oe@16-12-2010 778886109@GENIA Treebank@formal@@1@S@The incubation with transforming growth factor beta 1 and 1 alpha,25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of AhR mRNA.@@@@1@23@@oe@16-12-2010 778886110@GENIA Treebank@formal@@1@S@The HEL cells also exhibited a similar elevation of AhR mRNA level, when they had differentiated toward monocyte-macrophage cells by these combined inducers, but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types.@@@@1@46@@oe@16-12-2010 778886111@GENIA Treebank@formal@@1@S@Treatment of the differentiated HL60 cells with 3-methylcholanthrene, a ligand of AhR, induced the expression of the P450IA1 gene.@@@@1@22@@oe@16-12-2010 778886112@GENIA Treebank@formal@@1@S@These results indicated that expression of AhR mRNA was significantly induced during monocytic differentiation and that the differentiated cells were responsive to xenobiotics.@@@@1@24@@oe@16-12-2010 778886113@GENIA Treebank@formal@@1@S@Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens.@@@@1@25@@oe@16-12-2010 779151201@GENIA Treebank@formal@@1@S@Physiological concentration of estradiol inhibits polymorphonuclear leukocyte chemotaxis via a receptor mediated system.@@@@1@14@@oe@16-12-2010 779151202@GENIA Treebank@formal@@1@S@Estrogen exhibits a variety of actions, including immuno-modulatory effects, in vivo and in vitro.@@@@1@17@@oe@16-12-2010 779151203@GENIA Treebank@formal@@1@S@The mechanism by which estrogen exerts its anti-inflammatory effect is not yet understood.@@@@1@14@@oe@16-12-2010 779151204@GENIA Treebank@formal@@1@S@We investigated the possible mechanisms of estradiol acting via the polymorphonuclear leukocytes (PMNs), which are important in the immune response.@@@@1@24@@oe@16-12-2010 779151205@GENIA Treebank@formal@@1@S@The agent, 17 beta-estradiol, but not 17 alpha-estradiol, significantly reduced PMNs chemotaxis to FMLP in a dose-dependent manner (control vs estrogen 10(-10)-(-6) M, P < 0.05).@@@@1@33@@oe@16-12-2010 779151206@GENIA Treebank@formal@@1@S@Physiological concentrations of estradiol significantly reduced the chemotaxis of PMNs (10(-10) mol).@@@@1@15@@oe@16-12-2010 779151207@GENIA Treebank@formal@@1@S@Pre-incubation with clomiphene or tamoxifen which are estrogen receptor antagonists, eliminated the inhibitory effect of 17 beta-estradiol on the chemotaxis of PMNs, restoring it to the control level.@@@@1@31@@oe@16-12-2010 779151208@GENIA Treebank@formal@@1@S@These observations suggest that 17 beta-estradiol suppressed the chemotaxis of PMNs by a receptor-dependent mechanism.@@@@1@16@@oe@16-12-2010 779151209@GENIA Treebank@formal@@1@S@In addition, the level of estradiol in human plasma, which PMNs were drawn, showed a close, inverse correlation with the PMNs chemotaxis to FMLP (r = -0.821 p < 0.001).@@@@1@37@@oe@16-12-2010 779151210@GENIA Treebank@formal@@1@S@Estrogen may modify the activity of neutrophils during the normal menstrual cycle, not only during pregnancy, and influence inflammation.@@@@1@22@@oe@16-12-2010 780264201@GENIA Treebank@formal@@1@S@Platelet-activating factor (PAF) positively auto-regulates the expression of human PAF receptor transcript 1 (leukocyte-type) through NF-kappa B.@@@@1@22@@oe@16-12-2010 780264202@GENIA Treebank@formal@@1@S@The human platelet-activating factor receptor (PAFR) gene is transcribed by two distinct promoters (promoter 1 and promoter 2) to generate two transcripts (designated as PAFR transcript 1 and PAFR transcript 2), though their open reading frames are identical.@@@@1@46@@oe@16-12-2010 780264203@GENIA Treebank@formal@@1@S@By primer extension analysis to discriminate two transcripts, we found that the levels of PAFR transcript 1 (leukocyte-type), but not PAFR transcript 2 (tissue-type), are upregulated by PAF as well as by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the human stomach cancer cell line (JR-St cells) which expresses both functional PAFR transcript 1 and PAFR transcript 2 endogenously.@@@@1@67@@oe@16-12-2010 780264204@GENIA Treebank@formal@@1@S@Functional analysis of the promoter 1 with a transient expression assay using chloramphenicol acetyltransferase (CAT) gene as a reporter showed that both PAF and TPA activated the promoter 1 but not the deleted promoter lacking the three consensus binding sites for NF-kappa B located from -571 bp to -459 bp.@@@@1@53@@oe@16-12-2010 780264205@GENIA Treebank@formal@@1@S@These findings suggest a molecular mechanism of positive regulation of PAFR gene expression by PAF through NF-kappa B, possibly by a phosphorylation reaction involving protein kinase C by PAF.@@@@1@31@@oe@16-12-2010 780551801@GENIA Treebank@formal@@1@S@[The changes in glucocorticoid receptors in peripheral leukocytes in asthmatic subjects]@@@@1@13@@oe@16-12-2010 780551802@GENIA Treebank@formal@@1@S@The number of glucocorticoid receptors (GCR) in peripheral leukocytes was determined by radioligand-binding assay in extrinsic and intrinsic asthmatics.@@@@1@22@@oe@16-12-2010 780551803@GENIA Treebank@formal@@1@S@Their corresponding plasma cortisol levels were assessed.@@@@1@8@@oe@16-12-2010 780551804@GENIA Treebank@formal@@1@S@The results showed that the average number of GCR in asthmatics was significantly lower than that in healthy subjects (P < 0.01), and there was a linear correlation between the number of GCR and the course of asthma.@@@@1@42@@oe@16-12-2010 780551805@GENIA Treebank@formal@@1@S@Besides, there was also a linear correlation between the number of GCR and the age of the initial attack of asthma.@@@@1@23@@oe@16-12-2010 780551806@GENIA Treebank@formal@@1@S@No difference in plasma cortisol level was found between asthmatics and healthy subjects.@@@@1@14@@oe@16-12-2010 780551807@GENIA Treebank@formal@@1@S@These findings suggest that there is no primary and general impairment of glucocorticoid metabolism in the asthmatics, but the number of GCR in the asthmatics is lower than that in healthy controls.@@@@1@34@@oe@16-12-2010 780551808@GENIA Treebank@formal@@1@S@The decrease of the number of GCR in asthmatics, we think, is related to heredity and repeated attacks of asthma.@@@@1@23@@oe@16-12-2010 780907201@GENIA Treebank@formal@@1@S@Identification of the TCL1 gene involved in T-cell malignancies.@@@@1@10@@oe@16-12-2010 780907202@GENIA Treebank@formal@@1@S@The TCL1 locus on chromosome 14q32.1 is frequently involved in chromosomal translocations and inversions with one of the T-cell receptor loci in human T-cell leukemias and lymphomas.@@@@1@28@@oe@16-12-2010 780907203@GENIA Treebank@formal@@1@S@The chromosome 14 region translocated or rearranged involves approximately 350 kb of DNA at chromosome band 14q32.1.@@@@1@18@@oe@16-12-2010 780907204@GENIA Treebank@formal@@1@S@Within this region we have identified a gene coding for a 1.3-kb transcript, expressed only in restricted subsets of cells within the lymphoid lineage and expressed at high levels in leukemic cells carrying a t(14;14)(q11;q32) chromosome translocation or a inv(14)(q11;q32) chromosome inversion.@@@@1@45@@oe@16-12-2010 780907205@GENIA Treebank@formal@@1@S@The cognate cDNA sequence reveals an open reading frame of 342 nt encoding a protein of 14 kDa.@@@@1@19@@oe@16-12-2010 780907206@GENIA Treebank@formal@@1@S@The TCL1 gene sequence, which, to our knowledge, shows no sequence homology with other human genes, is preferentially expressed early in T- and B-lymphocyte differentiation.@@@@1@30@@oe@16-12-2010 781123101@GENIA Treebank@formal@@1@S@The transcription factor Sp1 is required for induction of the murine GM-CSF promoter in T cells.@@@@1@17@@oe@16-12-2010 781123102@GENIA Treebank@formal@@1@S@The cis-acting region, GM-kappa B/GC-box (positions -95 and -73), within the murine GM-CSF gene promoter is required for maximal induction by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in T cells.@@@@1@42@@oe@16-12-2010 781123103@GENIA Treebank@formal@@1@S@GM-kappa B defines a binding site for NF-kappa B, and GC-box defines a binding site for three (A1, A2, B) constitutive proteins.@@@@1@28@@oe@16-12-2010 781123104@GENIA Treebank@formal@@1@S@We report here that three copies of the GC-box can functionally compensate for the GM-kappa B/GC-box region, suggesting that the GC-motif can function independently of the GM-kappa B motif.@@@@1@31@@oe@16-12-2010 781123105@GENIA Treebank@formal@@1@S@The major GC-box binding activity A1 was purified and identified as the transcription factor Sp1.@@@@1@16@@oe@16-12-2010 781123106@GENIA Treebank@formal@@1@S@We show that depletion of Sp1 (A1) from nuclear extracts specifically decreases in vitro transcription activity on GM-CSF templates.@@@@1@22@@oe@16-12-2010 781123107@GENIA Treebank@formal@@1@S@Since the human GM-CSF promoter has a base difference within the GC-box, we speculate that this may explain why the human promoter is weak and that an upstream enhancer is required for the induction of the human GM-CSF gene.@@@@1@41@@oe@16-12-2010 781129301@GENIA Treebank@formal@@1@S@The C-terminus of the B cell activator Oct-2 functions as an activation domain in yeast.@@@@1@16@@oe@16-12-2010 781129302@GENIA Treebank@formal@@1@S@Oct-1 and Oct-2 are human transcriptional activators that bind to the same DNA element but activate distinct sets of genes.@@@@1@21@@oe@16-12-2010 781129303@GENIA Treebank@formal@@1@S@We expressed these factors in S. cerevisiae and observed greater than 5-fold stimulation of a lacZ reporter gene only with Oct-2.@@@@1@22@@oe@16-12-2010 781129304@GENIA Treebank@formal@@1@S@Transfer of the Oct-2 C-terminal domain onto either Oct-1 (Oct1.2) or a nonactivating DNA-binding domain from GAL4 created activators capable of greater than 15 and 10-fold stimulation of activity, respectively.@@@@1@34@@oe@16-12-2010 781129305@GENIA Treebank@formal@@1@S@Thus, the C-terminus of Oct-2 is sufficient to confer activation potential to nonactive DNA-binding fragments in yeast.@@@@1@19@@oe@16-12-2010 781555501@GENIA Treebank@formal@@1@S@Characterization of the CD48 gene demonstrates a positive element that is specific to Epstein-Barr virus-immortalized B-cell lines and contains an essential NF-kappa B site.@@@@1@25@@oe@16-12-2010 781555502@GENIA Treebank@formal@@1@S@Epstein-Barr virus (EBV) infection of mature, resting B cells drives them to become lymphoblasts expressing high levels of cell surface molecules, such as CD48, characteristically expressed on normal activated B cells.@@@@1@37@@oe@16-12-2010 781555503@GENIA Treebank@formal@@1@S@Here, we report on the identification of an enhancer element in the CD48 gene which reproducibly confers strong transcriptional activity only in EBV-positive B-lymphoblastoid cell lines.@@@@1@28@@oe@16-12-2010 781555504@GENIA Treebank@formal@@1@S@The element is not activated upon infection of established EBV-negative B-cell lines, indicating that EBV fails to drive these cells to a fully lymphoblastoid phenotype.@@@@1@27@@oe@16-12-2010 781555505@GENIA Treebank@formal@@1@S@An NF-kappa B binding site is an essential component of the element but alone is not sufficient to account for the activity or the specificity of the element.@@@@1@29@@oe@16-12-2010 781555506@GENIA Treebank@formal@@1@S@We have detected a specific nuclear protein complex that binds to the element and show that NF-kappa B1 (p50) is a part of this complex.@@@@1@28@@oe@16-12-2010 781555507@GENIA Treebank@formal@@1@S@The EBV-encoded latent membrane protein 1 is capable of transactivating the isolated CD48 NF-kappa B site but not the intact element, suggesting that the latent membrane protein 1-driven activation of NF-kappa B/Rel must interact with other regulatory pathways to control expression of cellular genes as EBV drives resting B cells into the cell cycle.@@@@1@56@@oe@16-12-2010 781663401@GENIA Treebank@formal@@1@S@An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds inducible factors and contributes to expression.@@@@1@19@@oe@16-12-2010 781663402@GENIA Treebank@formal@@1@S@Expression of the kappa immunoglobulin light chain gene requires developmental- and tissue-specific regulation by trans-acting factors which interact with two distinct enhancer elements.@@@@1@24@@oe@16-12-2010 781663403@GENIA Treebank@formal@@1@S@A new protein-DNA interaction has been identified upstream of the intron enhancer, within the matrix-associated region of the J-C intron.@@@@1@22@@oe@16-12-2010 781663404@GENIA Treebank@formal@@1@S@The binding activity is greatly inducible in pre-B cells by bacterial lipopolysaccharide and interleukin-1 but specific complexes are found at all stages of B cell development tested.@@@@1@28@@oe@16-12-2010 781663405@GENIA Treebank@formal@@1@S@The footprinted binding site is homologous to the consensus AP1 motif.@@@@1@12@@oe@16-12-2010 781663406@GENIA Treebank@formal@@1@S@The protein components of this complex are specifically competed by an AP1 consensus motif and were shown by supershift to include c-Jun and c-Fos, suggesting that this binding site is an AP1 motif and that the Jun and Fos families of transcription factors play a role in the regulation of the kappa light chain gene.@@@@1@57@@oe@16-12-2010 781663407@GENIA Treebank@formal@@1@S@Mutation of the AP1 motif in the context of the intron enhancer was shown to decrease enhancer-mediated activation of the promoter in both pre-B cells induced with LPS and constitutive expression in mature B cells.@@@@1@36@@oe@16-12-2010 782179801@GENIA Treebank@formal@@1@S@Identification of the promoter region of chicken anemia virus (CAV) containing a novel enhancer-like element.@@@@1@18@@oe@16-12-2010 782179802@GENIA Treebank@formal@@1@S@The single promoter region in the cloned genome [Noteborn et al., J. Virol. 65 (1991) 3131-3139] of chicken anemia virus (CAV) in chicken T-cells was analysed via CAT assays.@@@@1@37@@oe@16-12-2010 782179803@GENIA Treebank@formal@@1@S@A unique region containing four or five near-perfect direct repeats (DR) of 21 bp with one 12-bp insert was proven to be the main transcription-activation element, with enhancer-like characteristics.@@@@1@33@@oe@16-12-2010 782179804@GENIA Treebank@formal@@1@S@PCR studies revealed that CAV isolates from across the world all contained this promoter sequence.@@@@1@16@@oe@16-12-2010 782179805@GENIA Treebank@formal@@1@S@Electrophoretic mobility-shift assays (EMSA) showed that individual DR units, as well as the 12-bp insert, can bind to nuclear factors of chicken T-cells.@@@@1@28@@oe@16-12-2010 782179806@GENIA Treebank@formal@@1@S@Competition assays revealed that the DR units bound to factors other than the 12-bp insert.@@@@1@16@@oe@16-12-2010 782179807@GENIA Treebank@formal@@1@S@A synthetic oligodeoxyribonucleotide containing an SP1-box (5'-GGGCGG) could compete with factors binding to the 12-bp insert.@@@@1@19@@oe@16-12-2010 782179808@GENIA Treebank@formal@@1@S@Purified human SP1 was shown to have very strong affinity for the 12-bp insert.@@@@1@15@@oe@16-12-2010 782280901@GENIA Treebank@formal@@1@S@Activation of human thymocytes after infection by EBV.@@@@1@9@@oe@16-12-2010 782280902@GENIA Treebank@formal@@1@S@The discovery of EBV in certain T cell malignancies and the expression of the EBV receptor, CR2/CD21, on a population of immature thymocytes, T lymphoblastoid cell lines, and childhood acute T lymphoblastic leukemia cells suggested that EBV-receptor interactions on T cells may be of importance.@@@@1@50@@oe@16-12-2010 782280903@GENIA Treebank@formal@@1@S@We have shown that, within the thymus, a population of large, immature cells expresses CD21.@@@@1@19@@oe@16-12-2010 782280904@GENIA Treebank@formal@@1@S@EBV altered the activation responses of immature thymocytes in vitro.@@@@1@11@@oe@16-12-2010 782280905@GENIA Treebank@formal@@1@S@Triggering through CD2 is mitogenic for mature, but not immature, T cells.@@@@1@15@@oe@16-12-2010 782280906@GENIA Treebank@formal@@1@S@However, during infection by EBV, ligation of CD2 caused thymocytes to proliferate in the absence of exogenous cytokines.@@@@1@21@@oe@16-12-2010 782280907@GENIA Treebank@formal@@1@S@This function was a result of the interaction of EBV with its receptor, CD21, but was caused by infection rather than surface signaling, because neither specific mAb nor the P3HR-1 strain of virus mimicked the effect of B95-8.@@@@1@42@@oe@16-12-2010 782280908@GENIA Treebank@formal@@1@S@Immature thymocytes were infected by EBV, as determined by the internalization of the viral genome and its transcriptional activity.@@@@1@21@@oe@16-12-2010 782280909@GENIA Treebank@formal@@1@S@Consistent with the activity of B95-8, EBNA-2 transcripts were identified within infected thymocyte populations.@@@@1@16@@oe@16-12-2010 782280910@GENIA Treebank@formal@@1@S@In addition, components of the viral replicative pathway were expressed during infection of thymocytes.@@@@1@16@@oe@16-12-2010 782280911@GENIA Treebank@formal@@1@S@These components included transcription of BZLF-1, an early gene that characterizes EBV-infected B cells after disruption of latency.@@@@1@20@@oe@16-12-2010 782280912@GENIA Treebank@formal@@1@S@A second transcript was identified as encoding the recently characterized RAZ, which also is associated with replicative infection.@@@@1@20@@oe@16-12-2010 782280913@GENIA Treebank@formal@@1@S@The consequences of EBV infection of T cells at an early stage of differentiation may lead to failure of normal T cell repertoire development, autoimmunity, or malignancy.@@@@1@30@@oe@16-12-2010 782394301@GENIA Treebank@formal@@1@S@Distinct roles of the molecular chaperone hsp90 in modulating dioxin receptor function via the basic helix-loop-helix and PAS domains.@@@@1@20@@oe@16-12-2010 782394302@GENIA Treebank@formal@@1@S@The intracellular dioxin receptor mediates signal transduction by dioxin and functions as a ligand-activated transcription factor.@@@@1@17@@oe@16-12-2010 782394303@GENIA Treebank@formal@@1@S@It contains a basic helix-loop-helix (bHLH) motif contiguous with a Per-Arnt-Sim (PAS) homology region.@@@@1@19@@oe@16-12-2010 782394304@GENIA Treebank@formal@@1@S@In extracts from nonstimulated cells the receptor is recovered in an inducible cytoplasmic form associated with the 90-kDa heat shock protein (hsp90), a molecular chaperone.@@@@1@29@@oe@16-12-2010 782394305@GENIA Treebank@formal@@1@S@We have reconstituted ligand-dependent activation of the receptor to a DNA-binding form by using the dioxin receptor and its bHLH-PAS partner factor Arnt expressed by in vitro translation in reticulocyte lysate.@@@@1@32@@oe@16-12-2010 782394306@GENIA Treebank@formal@@1@S@Deletion of the PAS domain of the receptor resulted in constitutive dimerization with Arnt.@@@@1@15@@oe@16-12-2010 782394307@GENIA Treebank@formal@@1@S@In contrast, this receptor mutant showed low levels of xenobiotic response element-binding activity, indicating that the PAS domain may be important for DNA-binding affinity and/or specificity of the receptor.@@@@1@32@@oe@16-12-2010 782394308@GENIA Treebank@formal@@1@S@It was not possible to reconstitute dioxin receptor function with proteins expressed in wheat germ lysate.@@@@1@17@@oe@16-12-2010 782394309@GENIA Treebank@formal@@1@S@In line with these observations, reticulocyte lysate but not wheat germ lysate promoted the association of de novo synthesized dioxin receptor with hsp90.@@@@1@25@@oe@16-12-2010 782394310@GENIA Treebank@formal@@1@S@At least two distinct domains of the receptor mediated interaction with hsp90: the ligand-binding domain located within the PAS region and, surprisingly, the bHLH domain.@@@@1@29@@oe@16-12-2010 782394311@GENIA Treebank@formal@@1@S@Whereas ligand-binding activity correlated with association with hsp90, bHLH-hsp90 interaction appeared to be important for DNA-binding activity but not for dimerization of the receptor.@@@@1@26@@oe@16-12-2010 782394312@GENIA Treebank@formal@@1@S@Several distinct roles for hsp90 in modulating dioxin receptor function are therefore likely: correct folding of the ligand-binding domain, interference with Arnt heterodimerization, and folding of a DNA-binding conformation of the bHLH domain.@@@@1@37@@oe@16-12-2010 782394313@GENIA Treebank@formal@@1@S@Thus, the dioxin receptor system provides a complex and interesting model of the regulation of transcription factors by hsp90.@@@@1@21@@oe@16-12-2010 782662301@GENIA Treebank@formal@@1@S@T-cell functional regions of the human IL-3 proximal promoter.@@@@1@10@@oe@16-12-2010 782662302@GENIA Treebank@formal@@1@S@The human interleukin-3 (IL-3) gene is expressed almost exclusively in activated T cells.@@@@1@16@@oe@16-12-2010 782662303@GENIA Treebank@formal@@1@S@Its expression is regulated at both the transcriptional and post-transcriptional level.@@@@1@12@@oe@16-12-2010 782662304@GENIA Treebank@formal@@1@S@We have previously shown that treatment of Jurkat T cells with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription initiation from the IL-3 gene.@@@@1@30@@oe@16-12-2010 782662305@GENIA Treebank@formal@@1@S@To define the regions of the gene required for transcription activation, we generated a series of reporter constructs containing different regions of the IL-3 gene 5' and 3' flanking sequences.@@@@1@32@@oe@16-12-2010 782662306@GENIA Treebank@formal@@1@S@Both positive and negative regulatory elements were identified in the proximal 5' flanking region of the IL-3 gene.@@@@1@19@@oe@16-12-2010 782662307@GENIA Treebank@formal@@1@S@The promoter region between -173 and -60 contained the strongest activating elements.@@@@1@13@@oe@16-12-2010 782662308@GENIA Treebank@formal@@1@S@The transcription factor AP-1 could bind to this positive activator region of the promoter.@@@@1@15@@oe@16-12-2010 782662309@GENIA Treebank@formal@@1@S@We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA/PHA.@@@@1@43@@oe@16-12-2010 782667001@GENIA Treebank@formal@@1@S@Alternate immune system targets for TCDD: lymphocyte stem cells and extrathymic T-cell development.@@@@1@15@@oe@16-12-2010 782667002@GENIA Treebank@formal@@1@S@We here summarize evidence that thymic atrophy induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can be mediated, at least in part, by damage to extrathymic T-cell precursors in bone marrow and fetal liver.@@@@1@35@@oe@16-12-2010 782667003@GENIA Treebank@formal@@1@S@This atrophy induction does not involve apoptotic mechanisms in thymocytes affected by the bcl-2 proto-oncogene.@@@@1@16@@oe@16-12-2010 782667004@GENIA Treebank@formal@@1@S@TCDD mediates atrophy induction through its specific receptor (the AhR) and not through effects on the estrogen receptor.@@@@1@21@@oe@16-12-2010 782667005@GENIA Treebank@formal@@1@S@Both TCDD and estradiol induce extrathymic T-cell differentiation in the liver.@@@@1@12@@oe@16-12-2010 782667006@GENIA Treebank@formal@@1@S@These extrathymic T-cell populations include cells expressing elevated levels of V beta T-cell receptors that are normally deleted in thymic development.@@@@1@22@@oe@16-12-2010 782859901@GENIA Treebank@formal@@1@S@B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2.@@@@1@16@@oe@16-12-2010 782859902@GENIA Treebank@formal@@1@S@Infection of primary B-lymphocytes by Epstein-Barr virus (EBV) leads to growth transformation of these B-cells in vitro.@@@@1@20@@oe@16-12-2010 782859903@GENIA Treebank@formal@@1@S@EBV nuclear antigen 2 (EBNA2), one of the first genes expressed after EBV infection of B-cells, is a transcriptional activator of viral and cellular genes and is essential for the transforming potential of the virus.@@@@1@40@@oe@16-12-2010 782859904@GENIA Treebank@formal@@1@S@We generated conditional EBV mutants by expressing EBNA2 as chimeric fusion protein with the hormone binding domain of the estrogen receptor on the genetic background of the virus.@@@@1@29@@oe@16-12-2010 782859905@GENIA Treebank@formal@@1@S@Growth transformation of primary normal B-cells by mutant virus resulted in estrogen-dependent lymphoblastoid cell lines expressing the chimeric EBNA2 protein.@@@@1@21@@oe@16-12-2010 782859906@GENIA Treebank@formal@@1@S@In the absence of estrogen about half of the cells enter a quiescent non-proliferative state whereas the others die by apoptosis.@@@@1@22@@oe@16-12-2010 782859907@GENIA Treebank@formal@@1@S@EBNA2 is thus required not only for initiation but also for maintenance of transformation.@@@@1@15@@oe@16-12-2010 782859908@GENIA Treebank@formal@@1@S@Growth arrest occurred at G1 and G2 stages of the cell cycle, indicating that functional EBNA2 is required at different restriction points of the cell cycle.@@@@1@28@@oe@16-12-2010 782859909@GENIA Treebank@formal@@1@S@Growth arrest is reversible for G1/G0 cells as indicated by the sequential accumulation and modification of cell cycle regulating proteins.@@@@1@21@@oe@16-12-2010 782859910@GENIA Treebank@formal@@1@S@EBV induces the same cell cycle regulating proteins as polyclonal stimuli in primary B-cells.@@@@1@15@@oe@16-12-2010 782859911@GENIA Treebank@formal@@1@S@These data suggest that EBV is using a common pathway for B-cell activation bypassing the requirement for antigen, T-cell signals and growth factors.@@@@1@25@@oe@16-12-2010 783337001@GENIA Treebank@formal@@1@S@Evaluation of the respiratory epithelium of normals and individuals with cystic fibrosis for the presence of adenovirus E1a sequences relevant to the use of E1a- adenovirus vectors for gene therapy for the respiratory manifestations of cystic fibrosis.@@@@1@38@@oe@16-12-2010 783337002@GENIA Treebank@formal@@1@S@Lung disease associated with disorders such as cystic fibrosis (CF) may be amenable to somatic gene therapy in which there is delivery of the normal gene directly to the respiratory epithelium using E1a- adenovirus (Ad) type 2- or 5-based vectors.@@@@1@45@@oe@16-12-2010 783337003@GENIA Treebank@formal@@1@S@For safety reasons, the Ad vectors are rendered replication deficient by deletion of the E1a region.@@@@1@18@@oe@16-12-2010 783337004@GENIA Treebank@formal@@1@S@Because there is the theoretical possibility of an E1a- replication-deficient vector replicating as a result of recombination or complementation with Ad 2/5 E1a sequences present in the target cell, this study is directed toward evaluating respiratory epithelium of normals and individuals with CF for the presence of E1a sequences.@@@@1@51@@oe@16-12-2010 783337005@GENIA Treebank@formal@@1@S@Using Ad 2/5 E1a-specific primers and the polymerase chain reaction to evaluate DNA recovered from freshly isolated nasal and bronchial epithelium recovered by brushing, E1a sequences were detected in respiratory epithelium of 19 of 91 normals (21%).@@@@1@42@@oe@16-12-2010 783337006@GENIA Treebank@formal@@1@S@In the E1a-positive samples, the average of E1a copy number was 55 +/- 18/10(3) recovered cells.@@@@1@18@@oe@16-12-2010 783337007@GENIA Treebank@formal@@1@S@In CF individuals, 7 of 52 (13%) had detectable E1a sequences in the respiratory epithelium, with E1a copy number in the positive samples of 80 +/- 21/10(3) recovered cells.@@@@1@35@@oe@16-12-2010 783337008@GENIA Treebank@formal@@1@S@These results demonstrate that there are detectable Ad 2/5 E1a sequences in the respiratory epithelium of a small percentage of normals and individuals with CF.@@@@1@26@@oe@16-12-2010 783337009@GENIA Treebank@formal@@1@S@Because of the theoretical potential of such sequences supporting replication of E1a- Ad vectors, human gene therapy protocols for CF utilizing such vectors should consider evaluating study individuals for the presence of Ad 2/5 E1a sequences in the respiratory epithelium.@@@@1@42@@oe@16-12-2010 783638901@GENIA Treebank@formal@@1@S@Two distinct signalling pathways are involved in the control of the biphasic junB transcription induced by interleukin-6 in the B cell hybridoma 7TD1.@@@@1@24@@oe@16-12-2010 783638902@GENIA Treebank@formal@@1@S@We have measured the level of junB mRNA in the B hybridoma cell line 7TD1, under interleukin-6 (IL-6) stimulation.@@@@1@23@@oe@16-12-2010 783638903@GENIA Treebank@formal@@1@S@IL-6 increases junB mRNA in a biphasic fashion.@@@@1@9@@oe@16-12-2010 783638904@GENIA Treebank@formal@@1@S@The first early-induced peak was transient and likely corresponds to the well documented typical junB mRNA, stimulated in response to numerous growth factors, including IL-6.@@@@1@28@@oe@16-12-2010 783638905@GENIA Treebank@formal@@1@S@At variance, the second peak which has never been reported previously, lasted several hours.@@@@1@17@@oe@16-12-2010 783638906@GENIA Treebank@formal@@1@S@As a consequence of its effect on junB mRNA, IL-6 stimulated, in a biphasic fashion, the nuclear accumulation of the JunB protein.@@@@1@26@@oe@16-12-2010 783638907@GENIA Treebank@formal@@1@S@In this study, we demonstrated that IL-6 regulation occurred exclusively at the transcriptional level and that the bimodal increase of junB mRNA and JunB protein can be accounted for by a biphasic stimulation of junB transcription.@@@@1@38@@oe@16-12-2010 783638908@GENIA Treebank@formal@@1@S@Furthermore, our data point to two major differences between the mechanism of control of the early and the late IL-6-induced junB transcription waves.@@@@1@25@@oe@16-12-2010 783638909@GENIA Treebank@formal@@1@S@First, cycloheximide strongly potentiated the transcription of the second wave, whereas it failed to affect the early-induced burst.@@@@1@21@@oe@16-12-2010 783638910@GENIA Treebank@formal@@1@S@Second, tyrphostin, a tyrosine kinase inhibitor, impaired the expression of the first but not the second junB mRNA peak.@@@@1@23@@oe@16-12-2010 783638911@GENIA Treebank@formal@@1@S@Conversely, genistein, another tyrosine kinase inhibitor, totally abolished the expression of the second peak of junB mRNA whereas it did not affect the expression of the first peak.@@@@1@32@@oe@16-12-2010 783638912@GENIA Treebank@formal@@1@S@Altogether these data indicate that, in 7TD1 cells, IL-6 controls junB transcription in a biphasic fashion by means of two separate transduction pathways.@@@@1@26@@oe@16-12-2010 784323001@GENIA Treebank@formal@@1@S@Biphasic control of nuclear factor-kappa B activation by the T cell receptor complex: role of tumor necrosis factor alpha.@@@@1@21@@oe@16-12-2010 784323002@GENIA Treebank@formal@@1@S@The regulation of nuclear factor (NF)-kappa B activation by the T cell receptor (TcR)/CD3 complex in primary human T cells has been studied at various times after activation.@@@@1@35@@oe@16-12-2010 784323003@GENIA Treebank@formal@@1@S@Only p50 NF-kappa B protein bound the kappa B element of interleukin-2 receptor (IL-2R) alpha chain promoter on resting T cells.@@@@1@24@@oe@16-12-2010 784323004@GENIA Treebank@formal@@1@S@However, immediately after TcR/CD3 cross-linking (after approximately 1 h; immediate) binding of p50.p65 heterodimers was observed.@@@@1@21@@oe@16-12-2010 784323005@GENIA Treebank@formal@@1@S@p50.c-rel heterodimers were also detected bound to this sequence at early time points (7-16 h; early), and both remained active at later time points (40 h; late) after activation.@@@@1@37@@oe@16-12-2010 784323006@GENIA Treebank@formal@@1@S@This regulation takes place mainly at the level of nuclear translocation of p65 and c-rel, at immediate and early time points.@@@@1@23@@oe@16-12-2010 784323007@GENIA Treebank@formal@@1@S@Activation also induced c-rel and p105/p50 mRNA synthesis, but not p65 mRNA whose expression was constitutive.@@@@1@18@@oe@16-12-2010 784323008@GENIA Treebank@formal@@1@S@Interestingly, all those early and late events, but not the immediate ones, were inhibited by a neutralizing anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody.@@@@1@30@@oe@16-12-2010 784323009@GENIA Treebank@formal@@1@S@Similarly, cycloheximide prevented the p65 and c-rel translocation and consequent formation of active binding heterodimers, at early and late times.@@@@1@23@@oe@16-12-2010 784323010@GENIA Treebank@formal@@1@S@Cyclosporin A impaired not only early and late, but also immediate events; however, addition of TNF-alpha prevented all inhibition.@@@@1@23@@oe@16-12-2010 784323011@GENIA Treebank@formal@@1@S@These results indicate that the regulation of NF-kappa B activation during T cell activation by TcR/CD3 signals is biphasic: TcR/CD3 triggers its immediate translocation, which is transient if no TNF-alpha is present.@@@@1@35@@oe@16-12-2010 784323012@GENIA Treebank@formal@@1@S@TNF-alpha, therefore, emerges as the main factor responsible for a second phase of NF-kappa B regulation, controlling both translocation of p65 and c-rel, and new mRNA synthesis for c-rel and p105/p50.@@@@1@36@@oe@16-12-2010 784325101@GENIA Treebank@formal@@1@S@Protein kinase C is not a downstream effector of p21ras in activated T cells.@@@@1@15@@oe@16-12-2010 784325102@GENIA Treebank@formal@@1@S@The aim of this present study was to investigate the role of protein kinase C (PKC), downstream of p21ras, in activating interleukin-2 (IL-2) gene expression.@@@@1@32@@oe@16-12-2010 784325103@GENIA Treebank@formal@@1@S@It has been reported that PKC is an effector of p21ras in T cells.@@@@1@15@@oe@16-12-2010 784325104@GENIA Treebank@formal@@1@S@Data is presented, using the potent and selective PKC inhibitor Ro 31-8425 and transient expression of a constitutively active ras mutant, which clearly shows that PKC is not downstream of p21ras in the induction of NF-AT and AP-1 transcriptional activity and in the expression of IL-2 in human Jurkat T cells.@@@@1@54@@oe@16-12-2010 784325105@GENIA Treebank@formal@@1@S@Reporter gene experiments demonstrated that NF-kappa B transcriptional activity is not affected by expression of activated p21ras.@@@@1@18@@oe@16-12-2010 784325106@GENIA Treebank@formal@@1@S@The signaling pathways involving PKC activation, calcium mobilization and ras activation combine to provide the necessary components for production of IL-2 during T cell activation.@@@@1@27@@oe@16-12-2010 784867901@GENIA Treebank@formal@@1@S@Association of alterations in NF-kappa B moieties with HIV type 1 proviral latency in certain monocytic cells.@@@@1@18@@oe@16-12-2010 784867902@GENIA Treebank@formal@@1@S@Human immunodeficiency virus type 1 (HIV-1) replication is controlled by a complex array of virally encoded and cellular proteins.@@@@1@22@@oe@16-12-2010 784867903@GENIA Treebank@formal@@1@S@A wide spectrum of levels of HIV-1 expression have been demonstrated in various cells, both in cell culture and in vivo.@@@@1@23@@oe@16-12-2010 784867904@GENIA Treebank@formal@@1@S@Molecular mechanisms leading to restricted HIV-1 replication may differ between certain cell types.@@@@1@14@@oe@16-12-2010 784867905@GENIA Treebank@formal@@1@S@It is now demonstrated that HIV-1 proviral latency in the monocytic cell line U1, in which only extremely low levels of HIV-1 expression are detected in the baseline unstimulated state, is associated with alterations in nuclear factor-kappa B (NF-kappa B) moieties demonstrated in these cells by electrophoretic mobility shift assays (EMSAs) and in situ UV cross-linking studies.@@@@1@64@@oe@16-12-2010 784867906@GENIA Treebank@formal@@1@S@A predominance of p50 NF-kappa B moieties and possibly p50 homodimers or closely related species, rather than the p50-p56 heterodimer of NF-kappa B that is the predominant NF-kappa B species in most T lymphocytic and monocytic cells, is demonstrated in the nuclei of U1 cells.@@@@1@48@@oe@16-12-2010 784867907@GENIA Treebank@formal@@1@S@This pattern of NF-kappa B-related moieties differs from the latently infected T lymphocytic cell line ACH-2, and from the U937 monocytic line, the parental cell line of the U1 cellular clone.@@@@1@34@@oe@16-12-2010 784867908@GENIA Treebank@formal@@1@S@As such, these data suggest that different proximal mechanisms may lead to restricted HIV-1 replication in various cell types.@@@@1@21@@oe@16-12-2010 784892101@GENIA Treebank@formal@@1@S@Overexpression of protein kinase C-zeta stimulates leukemic cell differentiation.@@@@1@10@@oe@16-12-2010 784892102@GENIA Treebank@formal@@1@S@A function for protein kinase C-zeta (PKC-zeta), a member of the phorbol ester nonresponsive atypical protein kinase C subfamily, in modulating differentiation was examined in the leukemic U937 cell.@@@@1@34@@oe@16-12-2010 784892103@GENIA Treebank@formal@@1@S@Transfected U937 cells stably overexpressing PKC-zeta displayed a longer doubling time, lower saturation density at confluency, and an increase in adherence to plastic as compared to control cells.@@@@1@31@@oe@16-12-2010 784892104@GENIA Treebank@formal@@1@S@PKC-zeta cells expressed a more differentiated phenotype as assessed by changes in morphology, surface antigen expression, and lysosomal enzyme activities and were distinct from parental U937 cells stimulated to differentiate by exposure to phorbol esters.@@@@1@38@@oe@16-12-2010 784892105@GENIA Treebank@formal@@1@S@In contrast to parental U937 cells, PKC-zeta cells constitutively expressed mRNA transcripts for c-jun and a low mobility AP-1 binding activity.@@@@1@23@@oe@16-12-2010 784892106@GENIA Treebank@formal@@1@S@Thus, PKC-zeta overexpression stimulates a type of phenotypic differentiation that differs significantly from maturation occurring upon activation of other PKC subfamilies induced by phorbol ester treatment.@@@@1@28@@oe@16-12-2010 784892107@GENIA Treebank@formal@@1@S@Increased expression of the c-jun protooncogene and an increase in AP-1 binding activity in PKC-zeta cells provides a potential mechanism for explaining the altered differentiation status of this cell.@@@@1@30@@oe@16-12-2010 784929101@GENIA Treebank@formal@@1@S@Posttranscriptional regulation of macrophage tissue factor expression by antioxidants.@@@@1@10@@oe@16-12-2010 784929102@GENIA Treebank@formal@@1@S@Tissue factor (TF) expression by cells of monocyte/macrophage lineage represents an important mechanism underlying the initiation of fibrin deposition at sites of extravascular inflammation.@@@@1@27@@oe@16-12-2010 784929103@GENIA Treebank@formal@@1@S@Recent evidence suggests a role for oxidant stress in the signalling pathway of various cell types by virtue of its ability to induce DNA binding of various transcription factors, including nuclear factor kappa B and AP-1.@@@@1@38@@oe@16-12-2010 784929104@GENIA Treebank@formal@@1@S@The effect of antioxidant treatment on lipopolysaccharide (LPS)-induced TF expression was examined in murine peritoneal macrophages and human monocytes.@@@@1@23@@oe@16-12-2010 784929105@GENIA Treebank@formal@@1@S@Both pyrrolidine dithiocarbamate, an oxidant scavenger, and N-acetyl-cysteine, a precursor of the endogenous antioxidant glutathione, inhibited stimulation of macrophage procoagulant activity by LPS.@@@@1@28@@oe@16-12-2010 784929106@GENIA Treebank@formal@@1@S@Northern blot analysis showed that neither of these agents reduced LPS-stimulated TF mRNA accumulation, thereby suggesting a posttranscriptional mechanism for the effect.@@@@1@24@@oe@16-12-2010 784929107@GENIA Treebank@formal@@1@S@Immunofluorescence studies of human monocytes using polyclonal anti-TF antibody showed that N-acetyl-cysteine treatment prevented the characteristic plasmalemmal localization of TF antigen that occurs in response to LPS.@@@@1@28@@oe@16-12-2010 784929108@GENIA Treebank@formal@@1@S@Western blot analysis showed that N-acetyl-cysteine reduced the accumulation of the 47-kD mature glycoprotein in LPS-treated cells, a finding consistent with the results of the immunofluorescence studies.@@@@1@29@@oe@16-12-2010 784929109@GENIA Treebank@formal@@1@S@Furthermore, these conditions did not result in an accumulation of the less mature forms of TF.@@@@1@18@@oe@16-12-2010 784929110@GENIA Treebank@formal@@1@S@When considered together, these data suggest that antioxidants exert their effects by impairing translation and/or by causing degradation of newly translated protein.@@@@1@24@@oe@16-12-2010 784929111@GENIA Treebank@formal@@1@S@The effect of antioxidants on tumor necrosis factor appeared to be species specific, with no effect on LPS-induced tumor necrosis factor in murine cells, but with inhibition in human monocytes.@@@@1@33@@oe@16-12-2010 784929112@GENIA Treebank@formal@@1@S@The posttranscriptional effect of antioxidants on TF expression data suggests a novel mechanism whereby these agents might modulate monocyte/macrophage activation.@@@@1@21@@oe@16-12-2010 784954301@GENIA Treebank@formal@@1@S@1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with primary and secondary hyperparathyroidism.@@@@1@16@@oe@16-12-2010 784954302@GENIA Treebank@formal@@1@S@A decreased number of calcitriol (1,25(OH)2D3) receptors has been observed in parathyroid glands of uremic animals.@@@@1@19@@oe@16-12-2010 784954303@GENIA Treebank@formal@@1@S@In humans, studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism.@@@@1@25@@oe@16-12-2010 784954304@GENIA Treebank@formal@@1@S@Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells (PBMC), we have investigated the specific uptake of 3H-labelled 1,25(OH)2D3 in PBMC of 12 women with primary hyperparathyroidism (PHP), 8 women with hyperparathyroidism secondary to chronic renal failure (SH), 9 women with renal transplant (RT), and 23 healthy women.@@@@1@65@@oe@16-12-2010 784954305@GENIA Treebank@formal@@1@S@The median dissociation constant (Kd) was similar in all three groups of patients and in healthy women (mean +/- S.D. (range): PHP, 1.2 +/- 1.0 (0.2-4) x 10(-10) M; SH, 0.6 +/- 0.4 (0.2-1.2) x 10(-10) M; RT, 1.1 +/- 0.5 (0.4-1.9) x 10(-10) M; controls, 1.0 +/- 0.6 (0.3-2.6) x 10(-10) M).@@@@1@76@@oe@16-12-2010 784954306@GENIA Treebank@formal@@1@S@However, the maximal binding capacity (Nmax) was significantly enhanced in PHP (3.9 +/- 1.9 (1.3-7.6) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0006) and decreased in SH (0.8 +/- 0.5 (0.2-1.6) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0001), whereas no changes were seen in RT (2.3 +/- 0.7 (1.2-3.3) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls).@@@@1@98@@oe@16-12-2010 784954307@GENIA Treebank@formal@@1@S@In three patients with PHP who were subjected to parathyroidectomy, the calcitriol number came down to normal.@@@@1@19@@oe@16-12-2010 784954308@GENIA Treebank@formal@@1@S@Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia.@@@@1@36@@oe@16-12-2010 784962801@GENIA Treebank@formal@@1@S@Effects of the antisense myb expression on hemin- and erythropoietin- induced erythroid differentiation of K562 cells.@@@@1@16@@oe@16-12-2010 784962802@GENIA Treebank@formal@@1@S@In order to elucidate the role of c-myb gene in erythroid differentiation of K562 cell induced by hemin (Hm) and erythropoietin (Epo), we constructed recombinant plasmid that could produce antisense myb RNA after induction with dexamethasone.@@@@1@42@@oe@16-12-2010 784962803@GENIA Treebank@formal@@1@S@During treatment with Hm, K562 cells constitutively expressed c-myb mRNA, and 50% of them began to synthesize hemoglobin (Hb).@@@@1@25@@oe@16-12-2010 784962804@GENIA Treebank@formal@@1@S@Expression of antisense myb RNA reduced the amount of c-myb mRNA, and the percentage of Hb-synthesizing cells was decreased to 20%.@@@@1@24@@oe@16-12-2010 784962805@GENIA Treebank@formal@@1@S@In the presence of Epo, c-myb mRNA declined and 20% of K562 cells synthesized Hb regardless of antisense myb RNA expression.@@@@1@24@@oe@16-12-2010 784962806@GENIA Treebank@formal@@1@S@It is suggested that constitutive expression of c-myb mRNA is necessary for Hm-induced differentiation, and that a decrease in the amount of c-myb mRNA induced by antisense myb RNA expression suppresses Hm-induced differentiation.@@@@1@35@@oe@16-12-2010 784962807@GENIA Treebank@formal@@1@S@The amount of c-myb mRNA in K562 cells was reduced during the differentiation induced by Epo.@@@@1@17@@oe@16-12-2010 784962808@GENIA Treebank@formal@@1@S@Expression of GATA-1 mRNA was almost constant during Hm-induced differentiation, but increased during Epo treatment.@@@@1@17@@oe@16-12-2010 784962809@GENIA Treebank@formal@@1@S@It is supposed that the mechanism of Hm-induced differentiation is distinguished from that of Epo-induced differentiation in K562 cells.@@@@1@20@@oe@16-12-2010 785203201@GENIA Treebank@formal@@1@S@Alteration of structural order of human erythrocyte ghost membrane by glucocorticoids and the influence of the glucocorticoid receptor antagonist RU 486.@@@@1@22@@oe@16-12-2010 785203202@GENIA Treebank@formal@@1@S@High-dose pulse glucocorticoid therapy has been used successfully in the clinic in severe pathological conditions for about 20 years.@@@@1@20@@oe@16-12-2010 785203203@GENIA Treebank@formal@@1@S@The mode of glucocorticoid action after administration of such megadoses is inexplicable up to now.@@@@1@16@@oe@16-12-2010 785203204@GENIA Treebank@formal@@1@S@It is supposed that some effects may be due to membrane alterations.@@@@1@13@@oe@16-12-2010 785203205@GENIA Treebank@formal@@1@S@In the present in-vitro experiments the effect of dexamethasone, of further glucocorticoids, and of the glucocorticoid receptor antagonist RU 486, on structural order of human erythrocyte ghost membranes was investigated by determining the steady-state fluorescence anisotropy of diphenylhexatriene (DPH).@@@@1@45@@oe@16-12-2010 785203206@GENIA Treebank@formal@@1@S@Dexamethasone was found to induce a significant decrease in membrane structural order at concentrations of about 10(-6) M in a concentration-dependent manner.@@@@1@23@@oe@16-12-2010 785203207@GENIA Treebank@formal@@1@S@We found a correlation between the uptake of dexamethasone by the ghost membranes and the decrease in the structural order.@@@@1@21@@oe@16-12-2010 785203208@GENIA Treebank@formal@@1@S@The other glucocorticoids tested, methylprednisolone and corticosterone, were also effective at concentrations of 10(-5) M or greater.@@@@1@20@@oe@16-12-2010 785203209@GENIA Treebank@formal@@1@S@We observed no change in membrane structural order with RU 486 up to a concentration of 10(-4) M.@@@@1@19@@oe@16-12-2010 785203210@GENIA Treebank@formal@@1@S@However, simultaneous incubation of RU 486 with dexamethasone caused a distinct interference of RU 486 with dexamethasone.@@@@1@19@@oe@16-12-2010 785203211@GENIA Treebank@formal@@1@S@Thus, the glucocorticoid-induced membrane perturbation, the possibility to inhibit it by RU 486, and the inactivity of the structurally related progesterone, refer to relatively specific binding sites for the glucocorticoids in the membrane of erythrocyte ghosts.@@@@1@41@@oe@16-12-2010 785348301@GENIA Treebank@formal@@1@S@Regulation of I kappa B alpha and p105 in monocytes and macrophages persistently infected with human immunodeficiency virus.@@@@1@19@@oe@16-12-2010 785348302@GENIA Treebank@formal@@1@S@The mechanisms regulating human immunodeficiency virus (HIV) persistence in human monocytes/macrophages are partially understood.@@@@1@17@@oe@16-12-2010 785348303@GENIA Treebank@formal@@1@S@Persistent HIV infection of U937 monocytic cells results in NF-kappa B activation.@@@@1@13@@oe@16-12-2010 785348304@GENIA Treebank@formal@@1@S@Whether virus-induced NF-kappa B activation is a mechanism that favors continuous viral replication in macrophages remains unknown.@@@@1@18@@oe@16-12-2010 785348305@GENIA Treebank@formal@@1@S@To further delineate the molecular mechanisms involved in the activation of NF-kappa B in HIV-infected monocytes and macrophages, we have focused on the regulation of the I kappa B molecules.@@@@1@32@@oe@16-12-2010 785348306@GENIA Treebank@formal@@1@S@First, we show that persistent HIV infection results in the activation of NF-kappa B not only in monocytic cells but also in macrophages.@@@@1@25@@oe@16-12-2010 785348307@GENIA Treebank@formal@@1@S@In HIV-infected cells, I kappa B alpha protein levels are decreased secondary to enhanced protein degradation.@@@@1@18@@oe@16-12-2010 785348308@GENIA Treebank@formal@@1@S@This parallels the increased I kappa B alpha synthesis secondary to increased I kappa B alpha gene transcription, i.e., increased RNA and transcriptional activity of its promoter-enhancer.@@@@1@30@@oe@16-12-2010 785348309@GENIA Treebank@formal@@1@S@Another protein with I kappa B function, p105, is also modified in HIV-infected cells: p105 and p50 steady-state protein levels are increased as a result of increased synthesis and proteolytic processing of p105.@@@@1@37@@oe@16-12-2010 785348310@GENIA Treebank@formal@@1@S@Transcriptional activity of p105 is also increased in infected cells and is also mediated by NF-kappa B through a specific kappa B motif.@@@@1@24@@oe@16-12-2010 785348311@GENIA Treebank@formal@@1@S@These results demonstrate the existence of a triple autoregulatory loop in monocytes and macrophages involving HIV, p105 and p50, and MAD3, with the end result of persistent NF-kappa B activation and viral persistence.@@@@1@37@@oe@16-12-2010 785348312@GENIA Treebank@formal@@1@S@Furthermore, persistent HIV infection of monocytes and macrophages provides a useful model with which to study concomitant modifications of different I kappa B molecules.@@@@1@26@@oe@16-12-2010 785826101@GENIA Treebank@formal@@1@S@Detection of the chromosome 16 CBF beta-MYH11 fusion transcript in myelomonocytic leukemias.@@@@1@13@@oe@16-12-2010 785826102@GENIA Treebank@formal@@1@S@Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult.@@@@1@15@@oe@16-12-2010 785826103@GENIA Treebank@formal@@1@S@Characterization of the two genes involved in the inv(16)(p13q22), CBF beta and MYH11, has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR).@@@@1@31@@oe@16-12-2010 785826104@GENIA Treebank@formal@@1@S@We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias, with or without eosinophilia, to determine whether their presence correlates with morphology.@@@@1@27@@oe@16-12-2010 785826105@GENIA Treebank@formal@@1@S@Fifty-three cases (11 AML M4Eo; 1 AML M4 with atypical abnormal eosinophils (AML M4 "Eo"); 29 AML M4; 8 AML M5; 3 CMML; and 1 AML M2 with eosinophilia) were analyzed.@@@@1@43@@oe@16-12-2010 785826106@GENIA Treebank@formal@@1@S@All 11 typical AML M4Eo were CBF beta-MYH11 positive.@@@@1@10@@oe@16-12-2010 785826107@GENIA Treebank@formal@@1@S@The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype, RT-PCR and fluorescent in situ hybridization (FISH).@@@@1@25@@oe@16-12-2010 785826108@GENIA Treebank@formal@@1@S@Three of 29 (10%) AML M4 without abnormal eosinophils were CBF beta-MYH11 positive, 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis (2 not tested).@@@@1@38@@oe@16-12-2010 785826109@GENIA Treebank@formal@@1@S@Both cases tested also showed MYH11 genomic rearrangement.@@@@1@9@@oe@16-12-2010 785826110@GENIA Treebank@formal@@1@S@None of the other leukemias were RT-PCR positive.@@@@1@9@@oe@16-12-2010 785826111@GENIA Treebank@formal@@1@S@Follow-up of three patient showed residual positivity in apparent complete remission.@@@@1@12@@oe@16-12-2010 785826112@GENIA Treebank@formal@@1@S@These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo, but also in approximately 10% of AML M4 without eosinophilic abnormalities, a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest.@@@@1@51@@oe@16-12-2010 785826113@GENIA Treebank@formal@@1@S@Taken together with the detection of CBF beta-MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques, these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4, regardless of morphologic features, to allow accurate evaluation of the prognostic importance of this fusion transcript.@@@@1@59@@oe@16-12-2010 785849101@GENIA Treebank@formal@@1@S@Expression and genomic configuration of GM-CSF, IL-3, M-CSF receptor (C-FMS), early growth response gene-1 (EGR-1) and M-CSF genes in primary myelodysplastic syndromes.@@@@1@30@@oe@16-12-2010 785849102@GENIA Treebank@formal@@1@S@Peripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes (MDS) in advanced stage were enriched for blasts and tested for (1) karyotype, (2) genomic configuration and (3) expression of IL-3, GM-CSF, FMS and EGR-1 genes which are all located on the long arm of chromosome 5.@@@@1@60@@oe@16-12-2010 785849103@GENIA Treebank@formal@@1@S@The expression of the M-CSF gene, that has been recently reassigned to the short arm of chromosome 1 (lp), was also investigated.@@@@1@27@@oe@16-12-2010 785849104@GENIA Treebank@formal@@1@S@Aims of the study were to (1) assess the potential role of the expression of these genes in the maintenance and expansion of the neoplastic clones and (2) search for constitutional losses or rearrangements of one allele followed by a deletion of the second allele of the same genes in the leukemic cells.@@@@1@58@@oe@16-12-2010 785849105@GENIA Treebank@formal@@1@S@The latter issue was investigated by comparing, in 8 cases, constitutive DNA from skin fibroblasts with leukemic DNA.@@@@1@21@@oe@16-12-2010 785849106@GENIA Treebank@formal@@1@S@Eleven of the 17 patients had abnormal karyotypes.@@@@1@9@@oe@16-12-2010 785849107@GENIA Treebank@formal@@1@S@The M-CSF gene was expressed in 6 cases and the FMS and the EGR-1 genes were expressed in 2 of the latter cases.@@@@1@24@@oe@16-12-2010 785849108@GENIA Treebank@formal@@1@S@An autocrine mechanism of growth could be hypothesized only for the 2 patients whose cells expressed both the M-CSF and FMS genes.@@@@1@23@@oe@16-12-2010 785849109@GENIA Treebank@formal@@1@S@No germline changes or rearrangements were observed in any of the genes studied.@@@@1@14@@oe@16-12-2010 785849110@GENIA Treebank@formal@@1@S@Thus, deregulation of genes encoding for certain hemopoietic growth factors or receptors does not seem to represent a major mechanism of MDS progression.@@@@1@25@@oe@16-12-2010 785929001@GENIA Treebank@formal@@1@S@OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins.@@@@1@18@@oe@16-12-2010 785929002@GENIA Treebank@formal@@1@S@Recent biochemical and genetic studies indicate that in addition to the octamer-binding proteins Oct-1 and Oct-2, other B cell components are required for lymphoid-restricted, octamer site-mediated immunoglobulin gene promoter activity.@@@@1@33@@oe@16-12-2010 785929003@GENIA Treebank@formal@@1@S@Using a genetic screen in yeast, we have isolated B cell-derived cDNAs encoding Oct-binding factor 1 (OBF-1), a novel protein that specifically associates with Oct-1 and Oct-2.@@@@1@32@@oe@16-12-2010 785929004@GENIA Treebank@formal@@1@S@Biochemical studies demonstrate that OBF-1 has no intrinsic DNA-binding activity and recognizes the POU domains of Oct-1 and Oct-2, but not those of Oct-4 and Oct-6.@@@@1@28@@oe@16-12-2010 785929005@GENIA Treebank@formal@@1@S@The OBF-1 mRNA is expressed in a highly cell-specific manner, being most abundant in B cells and essentially absent in most of the other cells or tissues tested.@@@@1@30@@oe@16-12-2010 785929006@GENIA Treebank@formal@@1@S@Furthermore, expression of OBF-1 in HeLa cells selectively stimulates the activity of a natural immunoglobulin promoter in an octamer site-dependent manner.@@@@1@23@@oe@16-12-2010 785929007@GENIA Treebank@formal@@1@S@Thus, OBF-1 has all the properties expected for a B cell-specific transcriptional coactivator protein.@@@@1@16@@oe@16-12-2010 785973501@GENIA Treebank@formal@@1@S@Glucocorticoid-induced apoptosis of human leukemic cells is caused by the repressive function of the glucocorticoid receptor.@@@@1@17@@oe@16-12-2010 785973502@GENIA Treebank@formal@@1@S@Induction of apoptosis in lymphocytes, which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia, depends on the glucocorticoid receptor.@@@@1@27@@oe@16-12-2010 785973503@GENIA Treebank@formal@@1@S@However, the events leading from the activated receptor to cell lysis are not understood.@@@@1@16@@oe@16-12-2010 785973504@GENIA Treebank@formal@@1@S@A prevailing hypothesis postulates induction of so-called 'lysis genes' by the activated receptor.@@@@1@16@@oe@16-12-2010 785973505@GENIA Treebank@formal@@1@S@In this study, we show that an activation-deficient glucocorticoid receptor mutant is as effective as the wild-type receptor in repression of AP-1 activity, inhibition of interleukin-2 production, inhibition of c-myc expression and induction of apoptosis.@@@@1@39@@oe@16-12-2010 785973506@GENIA Treebank@formal@@1@S@Furthermore, we show that retinoic acid can also induce apoptosis in these cells through the retinoic acid receptor, whose repressive functions but not target site specificity, are similar to those of the glucocorticoid receptor.@@@@1@38@@oe@16-12-2010 785973507@GENIA Treebank@formal@@1@S@Therefore, the primary effect of the receptor in glucocorticoid-mediated apoptosis correlates with transcriptional repression rather than activation and could be mediated by interference with other transcription factors required for cell survival.@@@@1@33@@oe@16-12-2010 785974301@GENIA Treebank@formal@@1@S@HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state.@@@@1@16@@oe@16-12-2010 785974302@GENIA Treebank@formal@@1@S@This study demonstrates that human immunodeficiency virus type 1 (HIV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B.@@@@1@37@@oe@16-12-2010 785974303@GENIA Treebank@formal@@1@S@In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity.@@@@1@31@@oe@16-12-2010 785974304@GENIA Treebank@formal@@1@S@A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein.@@@@1@21@@oe@16-12-2010 785974305@GENIA Treebank@formal@@1@S@TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates.@@@@1@16@@oe@16-12-2010 785974306@GENIA Treebank@formal@@1@S@Therefore, Tat-mediated effects on the cellular redox state were analyzed.@@@@1@12@@oe@16-12-2010 785974307@GENIA Treebank@formal@@1@S@In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress.@@@@1@35@@oe@16-12-2010 785974308@GENIA Treebank@formal@@1@S@Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat.@@@@1@17@@oe@16-12-2010 785974309@GENIA Treebank@formal@@1@S@Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione.@@@@1@20@@oe@16-12-2010 785974310@GENIA Treebank@formal@@1@S@A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity.@@@@1@34@@oe@16-12-2010 785974311@GENIA Treebank@formal@@1@S@Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio.@@@@1@44@@oe@16-12-2010 785974312@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010 786215701@GENIA Treebank@formal@@1@S@Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development.@@@@1@15@@oe@16-12-2010 786215702@GENIA Treebank@formal@@1@S@The PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor, PEBP2, which is implicated as a T-cell-specific transcriptional regulator.@@@@1@30@@oe@16-12-2010 786215703@GENIA Treebank@formal@@1@S@These two related genes share the evolutionarily conserved region encoding the Runt domain.@@@@1@14@@oe@16-12-2010 786215704@GENIA Treebank@formal@@1@S@PEBP2 alpha B is the murine counterpart of human AML1, which is located at the breakpoints of the 8;21 and 3;21 chromosome translocations associated with acute myeloid leukemia.@@@@1@30@@oe@16-12-2010 786215705@GENIA Treebank@formal@@1@S@Northern (RNA) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus.@@@@1@26@@oe@16-12-2010 786215706@GENIA Treebank@formal@@1@S@Furthermore, transcripts of PEBP2 alpha A and mouse AML1/PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns, as well as 4-week-old adult mice, by in situ hybridization.@@@@1@39@@oe@16-12-2010 786215707@GENIA Treebank@formal@@1@S@The expression of the genes persisted in peripheral lymph nodes of adult mice.@@@@1@14@@oe@16-12-2010 786215708@GENIA Treebank@formal@@1@S@The transcripts were detected in all the CD4- CD8-, CD4+ CD8+, CD4+ CD8-, and CD4- CD8+ cell populations.@@@@1@22@@oe@16-12-2010 786215709@GENIA Treebank@formal@@1@S@The results indicated that both genes are expressed in T cells throughout their development, supporting the notion that PEBP2 is a T-cell-specific transcription factor.@@@@1@26@@oe@16-12-2010 786215710@GENIA Treebank@formal@@1@S@Transcripts of mouse AML1/PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice.@@@@1@25@@oe@16-12-2010 786215711@GENIA Treebank@formal@@1@S@The implication of mouse AML1/PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis.@@@@1@25@@oe@16-12-2010 786216801@GENIA Treebank@formal@@1@S@Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins.@@@@1@25@@oe@16-12-2010 786216802@GENIA Treebank@formal@@1@S@The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli.@@@@1@24@@oe@16-12-2010 786216803@GENIA Treebank@formal@@1@S@Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified.@@@@1@20@@oe@16-12-2010 786216804@GENIA Treebank@formal@@1@S@We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y).@@@@1@24@@oe@16-12-2010 786216805@GENIA Treebank@formal@@1@S@This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression.@@@@1@18@@oe@16-12-2010 786216806@GENIA Treebank@formal@@1@S@Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated.@@@@1@20@@oe@16-12-2010 786216807@GENIA Treebank@formal@@1@S@Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells.@@@@1@16@@oe@16-12-2010 786216808@GENIA Treebank@formal@@1@S@Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements.@@@@1@33@@oe@16-12-2010 786216809@GENIA Treebank@formal@@1@S@This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins.@@@@1@20@@oe@16-12-2010 786216810@GENIA Treebank@formal@@1@S@These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins.@@@@1@37@@oe@16-12-2010 786407201@GENIA Treebank@formal@@1@S@Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells.@@@@1@14@@oe@16-12-2010 786407202@GENIA Treebank@formal@@1@S@Glucocorticoids have an inhibitory effect on inflammatory and immune responses, and this may be through the modulation of transcription factor binding to DNA.@@@@1@25@@oe@16-12-2010 786407203@GENIA Treebank@formal@@1@S@The interaction of the transcription factors, activator protein-1 (AP-1), nuclear factor kappa B (NF kappa B), and cAMP-responsive element binding protein (CREB) with DNA and glucocorticoid receptors (GR) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays.@@@@1@53@@oe@16-12-2010 786407204@GENIA Treebank@formal@@1@S@TNF-alpha, IL-1 beta and phorbol myristate acetate (PMA) treatment increased AP-1 and NF kappa B DNA binding by up to 200% but decreased CREB binding (38%) over a 60-min time course.@@@@1@39@@oe@16-12-2010 786407205@GENIA Treebank@formal@@1@S@Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50% decrease in AP-1, NF kappa B, and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment.@@@@1@41@@oe@16-12-2010 786407206@GENIA Treebank@formal@@1@S@These latter effects were due to increases in the nuclear localization of GR, not to reduced amounts of the other transcription factors.@@@@1@24@@oe@16-12-2010 786407207@GENIA Treebank@formal@@1@S@This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling.@@@@1@22@@oe@16-12-2010 786407208@GENIA Treebank@formal@@1@S@This may be an important molecular site of steroid action.@@@@1@11@@oe@16-12-2010 786513001@GENIA Treebank@formal@@1@S@Isolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937.@@@@1@20@@oe@16-12-2010 786513002@GENIA Treebank@formal@@1@S@To study the complexity and structural characteristics of zinc finger proteins expressed during human hematopoiesis and to isolate novel regulators of blood cell development, a degenerate oligonucleotide probe specific for a consensus zinc finger peptide domain was used to isolate 63 cDNA clones for Kruppel-related zinc finger genes from the human monoblast cell line U-937.@@@@1@57@@oe@16-12-2010 786513003@GENIA Treebank@formal@@1@S@By extensive nucleotide sequence and Northern blot analysis, these cDNA clones were found to originate from approximately 42 different genes (HZF 1-42) of which only 8 have previously been described.@@@@1@34@@oe@16-12-2010 786513004@GENIA Treebank@formal@@1@S@Northern blot analysis showed that a majority of these genes were expressed at comparable levels in U-937 and HeLa cells.@@@@1@21@@oe@16-12-2010 786513005@GENIA Treebank@formal@@1@S@The large number of individual genes represented among the 63 clones and their apparent non-cell-type-specific expression suggest that the majority of the Kruppel-related zinc finger genes are likely to be expressed in most human tissues.@@@@1@36@@oe@16-12-2010 786513006@GENIA Treebank@formal@@1@S@In contrast, some of the genes displayed a restricted expression pattern, indicating that they represent potential regulators of monocyte differentiation or proliferation.@@@@1@25@@oe@16-12-2010 786513007@GENIA Treebank@formal@@1@S@Detailed structural analysis of the first 12 cDNAs (HZF 1-10) and a partial characterization of HZF 11-42 revealed that a common feature of human Kruppel-related zinc finger proteins is the presence of tandem arrays of zinc fingers ranging in number from 3 to over 20 that are preferentially located in the carboxy-terminal regions of the proteins.@@@@1@59@@oe@16-12-2010 786513008@GENIA Treebank@formal@@1@S@In addition, several novel KRAB-containing zinc finger genes and a novel conserved sequence element were identified.@@@@1@18@@oe@16-12-2010 786903801@GENIA Treebank@formal@@1@S@Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C-mediated pathways for cytokine gene transcription in human T cells.@@@@1@21@@oe@16-12-2010 786903802@GENIA Treebank@formal@@1@S@Engagement of the T cell receptor for antigen activates phospholipase C resulting in an increase in intracellular free calcium concentration ([Ca2+]i) and activation of protein kinase C (PKC).@@@@1@33@@oe@16-12-2010 786903803@GENIA Treebank@formal@@1@S@Increased [Ca2+]i activates Ca2+/calmodulin-dependent kinases including the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaM-K II), as well as calcineurin, a type 2B protein phosphatase.@@@@1@28@@oe@16-12-2010 786903804@GENIA Treebank@formal@@1@S@Recent studies have identified calcineurin as a key enzyme for interleukin (IL)-2 and IL-4 promoter activation.@@@@1@20@@oe@16-12-2010 786903805@GENIA Treebank@formal@@1@S@However, the role of CaM-K II remains unknown.@@@@1@10@@oe@16-12-2010 786903806@GENIA Treebank@formal@@1@S@We have used mutants of these kinases and phosphatases (gamma B*CaM-K and delta CaM-AI, respectively) to explore their relative role in cytokine gene transcription and their interactions with PKC-dependent signaling systems.@@@@1@35@@oe@16-12-2010 786903807@GENIA Treebank@formal@@1@S@gamma B*CaM-K and delta CaM-AI, known to exhibit constitutive Ca(2+)-independent activity, were cotransfected (alone or in combination) in Jurkat T cells with a plasmid containing the intact IL-2 promoter driving the expression of the chloramphenicol acetyltransferase reporter gene.@@@@1@43@@oe@16-12-2010 786903808@GENIA Treebank@formal@@1@S@Cotransfection of gamma B*CaM-K with the IL-2 promoter construct downregulated its transcription in response to stimulation with ionomycin and phorbol myristate acetate (PMA).@@@@1@26@@oe@16-12-2010 786903809@GENIA Treebank@formal@@1@S@The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways.@@@@1@22@@oe@16-12-2010 786903810@GENIA Treebank@formal@@1@S@Under the same conditions, delta CaM-AI superinduced IL-2 promoter activity (approximately twofold increase).@@@@1@17@@oe@16-12-2010 786903811@GENIA Treebank@formal@@1@S@When both mutants were used in combination, gamma B*CaM-K inhibited the induction of the IL-2 promoter by delta CaM-AI.@@@@1@21@@oe@16-12-2010 786903812@GENIA Treebank@formal@@1@S@Similar results were obtained when a construct containing the IL-4 promoter also was used.@@@@1@15@@oe@16-12-2010 786903813@GENIA Treebank@formal@@1@S@gamma B*CaM-K also downregulated the activation of AP-1 in response to transfection with a constitutively active mutant of PKC or stimulation with PMA.@@@@1@24@@oe@16-12-2010 786903814@GENIA Treebank@formal@@1@S@These results suggest that CaM-K II may exert negative influences on cytokine gene transcription in human T cells, and provide preliminary evidence for negative cross-talk with the calcineurin- and PKC- dependent signaling systems.@@@@1@35@@oe@16-12-2010 787387601@GENIA Treebank@formal@@1@S@Deleted chromosome 20 from a patient with Alagille syndrome isolated in a cell hybrid through leucine transport selection: study of three candidate genes.@@@@1@25@@oe@16-12-2010 787387602@GENIA Treebank@formal@@1@S@Alagille syndrome (AGS) is a well-defined genetic entity assigned to the short arm of Chromosome (Chr) 20 by a series of observations of AGS patients associated with microdeletions in this region.@@@@1@36@@oe@16-12-2010 787387603@GENIA Treebank@formal@@1@S@By fusing lymphoblastoid cells of an AGS patient that exhibited a microdeletion in the short arm of Chr 20 encompassing bands p11.23 to p12.3 with rodent thermosensitive mutant cells (CHOtsH1-1) deficient in-leucyl-tRNA synthetase, we isolated a somatic cell hybrid segregating the deleted human Chr 20.@@@@1@49@@oe@16-12-2010 787387604@GENIA Treebank@formal@@1@S@This hybrid clone, designated NR2, was characterized by several methods, including PCR, with eight pairs of oligonucleotides mapped to Chr 20: D20S5, D20S41, D20S42, D20S56, D20S57, D20S58, adenosine deaminase (ADA), and Prion protein (PRIP); Restriction Fragment Length Polymorphism (RFLP) analyses with four genomic anonymous probes (D20S5, cD3H12, D20S17, D20S18); and fluorescent in situ hybridization (FISH) with total human DNA and D20Z1, a sequence specific to the human Chr 20 centromere, as probes.@@@@1@102@@oe@16-12-2010 787387605@GENIA Treebank@formal@@1@S@The NR2 hybrid allowed us to exclude three candidate genes for AGS: hepatic nuclear factor 3 beta (HNF3 beta), paired box 1 (PAX1), and cystatin C (CST3) as shown by their localization outside of the deletion.@@@@1@46@@oe@16-12-2010 787387606@GENIA Treebank@formal@@1@S@The NR2 hybrid is a powerful tool for the mapping of new probes of this region, as well as for obtaining new informative probes specific for the deletion by subtractive cloning of the region.@@@@1@36@@oe@16-12-2010 787387607@GENIA Treebank@formal@@1@S@Such markers will be useful for linkage analysis and screening of cDNA libraries.@@@@1@14@@oe@16-12-2010