820099801@GENIA Treebank@formal@@1@S@Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats.@@@@1@11@@oe@19-12-2010 820099802@GENIA Treebank@formal@@1@S@We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical (HPA) axis functioning when adult.@@@@1@22@@oe@19-12-2010 820099803@GENIA Treebank@formal@@1@S@To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge, 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10(8) human red blood cells (HRBC) or gram-negative bacterial endotoxin (Escherichia coli LPS: 30 micrograms/kg).@@@@1@47@@oe@19-12-2010 820099804@GENIA Treebank@formal@@1@S@The adult male progeny (3 mo old) of both experimental groups showed increased basal plasma corticosterone levels.@@@@1@20@@oe@19-12-2010 820099805@GENIA Treebank@formal@@1@S@In addition, after novelty stress the HRBC group, but not the LPS group, showed increased ACTH and corticosterone levels.@@@@1@23@@oe@19-12-2010 820099806@GENIA Treebank@formal@@1@S@Both groups showed substantial decreases in mineralocorticoid (MR) and glucocorticoid receptor (GR) levels in the hippocampus, a limbic brain structure critical for HPA axis regulation, whereas GR concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased.@@@@1@47@@oe@19-12-2010 820099807@GENIA Treebank@formal@@1@S@HRBC and LPS indeed stimulated the maternal immune system as revealed by specific anti-HRBC antibody production and enhanced IL-1 beta mRNA expression in splenocytes, respectively.@@@@1@27@@oe@19-12-2010 820099808@GENIA Treebank@formal@@1@S@This study demonstrates that a T cell-mediated immune response as well as an endotoxic challenge during pregnancy can induce anomalies in HPA axis function in adulthood.@@@@1@27@@oe@19-12-2010 820099809@GENIA Treebank@formal@@1@S@Clinically, it may be postulated that disturbed fetal brain development due to prenatal immune challenge increases the vulnerability to develop mental illness involving inadequate responses to stress.@@@@1@29@@oe@19-12-2010 820562101@GENIA Treebank@formal@@1@S@JNK is involved in signal integration during costimulation of T lymphocytes.@@@@1@12@@oe@19-12-2010 820562102@GENIA Treebank@formal@@1@S@T lymphocyte activation and interleukin-2 (IL-2) production require at least two signals, generated by phorbol ester (TPA) and Ca2+ ionophore or costimulation of the T cell receptor (TCR) and the CD28 auxiliary receptor.@@@@1@41@@oe@19-12-2010 820562103@GENIA Treebank@formal@@1@S@We investigated how these stimuli affect mitogen activated protein (MAP) kinases.@@@@1@14@@oe@19-12-2010 820562104@GENIA Treebank@formal@@1@S@Full activation of the MAP kinases that phosphorylate the Jun activation domain, JNK1 and JNK2, required costimulation of T cells with either TPA and Ca2+ ionophore or antibodies to TCR and CD28.@@@@1@35@@oe@19-12-2010 820562105@GENIA Treebank@formal@@1@S@Alone, each stimulus resulted in little or no activation.@@@@1@11@@oe@19-12-2010 820562106@GENIA Treebank@formal@@1@S@Similar to its effect on IL-2 induction, cyclosporin A (CsA) inhibited the synergistic activation of JNK, and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation.@@@@1@34@@oe@19-12-2010 820562107@GENIA Treebank@formal@@1@S@By contrast, the MAP kinases ERK1 and ERK2 were fully activated by TPA or TCR stimulation and were not affected by Ca2+, CD28, or CsA.@@@@1@29@@oe@19-12-2010 820562108@GENIA Treebank@formal@@1@S@Hence, integration of signals that lead to T cell activation occurs at the level of JNK activation.@@@@1@19@@oe@19-12-2010 820675301@GENIA Treebank@formal@@1@S@Glucocorticoid-mediated inhibition of interleukin-2 receptor alpha and -beta subunit expression by human T cells.@@@@1@15@@oe@19-12-2010 820675302@GENIA Treebank@formal@@1@S@To determine the mechanism of glucocorticoid (GC)-mediated inhibition of T cell functions, the effect of dexamethasone (DM) on T cell proliferation and interleukin-2 receptor (IL-2R) generation were studied.@@@@1@37@@oe@19-12-2010 820675303@GENIA Treebank@formal@@1@S@Dexamethasone inhibited IL-2-induced T cell proliferation by 30%-88%, relative to its concentration within the cultures.@@@@1@21@@oe@19-12-2010 820675304@GENIA Treebank@formal@@1@S@The effect of DM on expression of IL-2R alpha (Tac, p55, CD25) and beta (p75) genes in activated T cells was examined next.@@@@1@30@@oe@19-12-2010 820675305@GENIA Treebank@formal@@1@S@In T cells stimulated with purified phytohemagglutinin (PHA-p) and 4 beta-phorbol 12-myristate 13-acetate (PMA) addition of DM to the cultures resulted in a 60% reduction in IL-2R alpha and a 30% reduction in IL-2R beta membrane expression compared to T cells cultured in the absence of DM (p < 0.01).@@@@1@59@@oe@19-12-2010 820675306@GENIA Treebank@formal@@1@S@Inhibition of membrane IL-2R alpha and IL-2R beta expression by 10(-6) M DM was partially reversible by recombinant human IL-2 (rhIL-2).@@@@1@24@@oe@19-12-2010 820675307@GENIA Treebank@formal@@1@S@By Northern blot analysis, DM caused a comparable decrease in IL-2R alpha and in IL-2R beta mRNA levels to membrane receptor expression in mitogen-stimulated T cells.@@@@1@28@@oe@19-12-2010 820675308@GENIA Treebank@formal@@1@S@By in vitro transcription assays, DM regulated IL-2R alpha gene expression at a transcriptional level while transcription of IL-2R beta gene was unaffected by DM.@@@@1@27@@oe@19-12-2010 820675309@GENIA Treebank@formal@@1@S@The mechanism of action of DM on IL-2R alpha transcription was examined by determining the mRNA levels of the p50 subunit of nuclear factor kappa B (NF-kappa B), a transcription factor that stimulates IL-2R alpha gene expression.@@@@1@41@@oe@19-12-2010 820675310@GENIA Treebank@formal@@1@S@The data indicate that 10(-6) M DM increased T cell p50 NF-kappa B mRNA levels by four-fold compared to the levels obtained in the absence of DM.@@@@1@28@@oe@19-12-2010 820675311@GENIA Treebank@formal@@1@S@Further, the level of nuclear proteins capable of binding to the NF-kappa B sites in activated T cells increased in response to DM.@@@@1@25@@oe@19-12-2010 820675312@GENIA Treebank@formal@@1@S@In sum, DM regulates T cell membrane expression of IL-2R by more than one molecular mechanism.@@@@1@18@@oe@19-12-2010 821296501@GENIA Treebank@formal@@1@S@The impaired transcription factor AP-1 DNA binding activity in lymphocytes derived from subjects with some symptoms of premature aging.@@@@1@20@@oe@19-12-2010 821296502@GENIA Treebank@formal@@1@S@The study of human disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence.@@@@1@20@@oe@19-12-2010 821296503@GENIA Treebank@formal@@1@S@The main feature of cellular senescence in vitro is cessation of cell proliferation.@@@@1@14@@oe@19-12-2010 821296504@GENIA Treebank@formal@@1@S@Down syndrome (DS) and neuronal ceroid-lypofuscinosis (NCL) are clinically characterized by the premature onset of numerous features normally associated with human aging.@@@@1@27@@oe@19-12-2010 821296505@GENIA Treebank@formal@@1@S@Phytohemagglutinin stimulated lymphocytes derived from DS subjects showed a statistically significant diminished proliferation capacity in comparison with lymphocytes derived from NCL and healthy individuals.@@@@1@25@@oe@19-12-2010 821296506@GENIA Treebank@formal@@1@S@We demonstrated, by applying the electrophoretic mobility shift assay, slightly impaired AP-1 DNA binding activity in NCL lymphocytes and strong in DS ones.@@@@1@26@@oe@19-12-2010 821296507@GENIA Treebank@formal@@1@S@Our results showed that the same molecular mechanisms of proliferation cessation could exist in fibroblasts characterized by replicative senescence and in lymphocytes derived from individuals with premature aging syndromes (Down).@@@@1@33@@oe@19-12-2010 825418501@GENIA Treebank@formal@@1@S@Visualization of the endogenous NF-kappa B p50 subunit in the nucleus of follicular dendritic cells in germinal centers.@@@@1@19@@oe@19-12-2010 825418502@GENIA Treebank@formal@@1@S@NF-kappa B, a 50 kDa/65 kDa (p50/p65) heterodimer, is a ubiquitous transcription factor involved in the positive regulation of various immune genes.@@@@1@27@@oe@19-12-2010 825418503@GENIA Treebank@formal@@1@S@The aim of this study was to determine whether NF-kappa B is related to a particular cell type and/or differentiation step during immunopoiesis.@@@@1@24@@oe@19-12-2010 825418504@GENIA Treebank@formal@@1@S@Using in situ hybridization on sections from non HIV hyperplastic lymph nodes, we found that the gene of the 105 kDa precursor of p50 was overexpressed in the light zone of germinal centers, with a network aspect, which suggested the involvement of follicular dendritic cells (FDC).@@@@1@52@@oe@19-12-2010 825418505@GENIA Treebank@formal@@1@S@By immunohistochemistry, p50 protein was detected in the cytoplasm and nucleus of FDC, confirming the involvement of FDC.@@@@1@21@@oe@19-12-2010 825418506@GENIA Treebank@formal@@1@S@Furthermore, p50 protein was detected in the cytoplasm of all lymphocytes.@@@@1@13@@oe@19-12-2010 825418507@GENIA Treebank@formal@@1@S@Thus, we focused our study on isolated FDC clusters from normal tonsils.@@@@1@14@@oe@19-12-2010 825418508@GENIA Treebank@formal@@1@S@As showed on tissue sections, we detected the p50 in both cytoplasm and nucleus of FDC.@@@@1@18@@oe@19-12-2010 825418509@GENIA Treebank@formal@@1@S@Nuclei of lymphocytes from FDC clusters were negative.@@@@1@9@@oe@19-12-2010 825418510@GENIA Treebank@formal@@1@S@We next studied p65 and c-Rel protein expression in FDC clusters.@@@@1@12@@oe@19-12-2010 825418511@GENIA Treebank@formal@@1@S@p65 was detected in the cytoplasm of FDC, whereas nuclei were negative.@@@@1@14@@oe@19-12-2010 825418512@GENIA Treebank@formal@@1@S@Furthermore, p65 was detected in the nuclei of some lymphocytes.@@@@1@12@@oe@19-12-2010 825418513@GENIA Treebank@formal@@1@S@c-Rel protein was detected only in the cytoplasm of lymphocytes and not in the nucleus and cytoplasm of FDC.@@@@1@20@@oe@19-12-2010 825418514@GENIA Treebank@formal@@1@S@Our results indicated that, in the context of T cell-dependent B cell immunopoiesis occurring in FDC clusters, p50 is mainly related to FDC with a massive overexpression in the nuclei, whereas p65 is expressed in a scattered manner in the nuclei of lymphocytes and c-Rel protein exclusively in the cytoplasm of lymphocytes from FDC clusters.@@@@1@59@@oe@19-12-2010 825418515@GENIA Treebank@formal@@1@S@These results suggested that the two subunits of NF-kappa B and the c-Rel protein have different roles in different cell types during B cell immunopoiesis.@@@@1@26@@oe@19-12-2010 825477201@GENIA Treebank@formal@@1@S@Involvement of transcription factor YB-1 in human T-cell lymphotropic virus type I basal gene expression.@@@@1@16@@oe@19-12-2010 825477202@GENIA Treebank@formal@@1@S@Sequences which control basal human T-cell lymphotropic virus type I (HTLV-I) transcription likely play an important role in initiation and maintenance of virus replication.@@@@1@27@@oe@19-12-2010 825477203@GENIA Treebank@formal@@1@S@We previously identified and analyzed a 45-nucleotide sequence (downstream regulatory element 1 [DRE 1]), +195 to +240, at the boundary of the R/U5 region of the long terminal repeat which is required for HTLV-I basal transcription.@@@@1@43@@oe@19-12-2010 825477204@GENIA Treebank@formal@@1@S@We identified a protein, p37, which specifically bound to DRE 1.@@@@1@14@@oe@19-12-2010 825477205@GENIA Treebank@formal@@1@S@An affinity column fraction, containing p37, stimulated HTLV-I transcription approximately 12-fold in vitro.@@@@1@16@@oe@19-12-2010 825477206@GENIA Treebank@formal@@1@S@We now report the identification of a cDNA clone (15B-7), from a Jurkat expression library, that binds specifically to the DRE 1 regulatory sequence.@@@@1@29@@oe@19-12-2010 825477207@GENIA Treebank@formal@@1@S@Binding of the cDNA fusion protein, similarly to the results obtained with purified Jurkat protein, was decreased by introduction of site-specific mutations in the DRE 1 regulatory sequence.@@@@1@31@@oe@19-12-2010 825477208@GENIA Treebank@formal@@1@S@In vitro transcription and translation of 15B-7 cDNA produced a fusion protein which bound specifically to the HTLV-I +195 to +240 oligonucleotide.@@@@1@23@@oe@19-12-2010 825477209@GENIA Treebank@formal@@1@S@The partial cDNA encodes a protein which is homologous to the C-terminal 196 amino acids of the 36-kDa transcription factor, YB-1.@@@@1@23@@oe@19-12-2010 825477210@GENIA Treebank@formal@@1@S@Cotransfection of a YB-1 expression plasmid increases HTLV-I basal transcription approximately 14-fold in Jurkat T lymphocytes.@@@@1@17@@oe@19-12-2010 825477211@GENIA Treebank@formal@@1@S@On the basis of the molecular weight, DNA-binding characteristics, and in vivo transactivation activity, we suggest that the previously identified DRE 1-binding protein, p37, is YB-1.@@@@1@32@@oe@19-12-2010 825516201@GENIA Treebank@formal@@1@S@Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system.@@@@1@10@@oe@19-12-2010 825516202@GENIA Treebank@formal@@1@S@1.Blood cell receptors in volunteers with moderately increased body burdens.@@@@1@13@@oe@19-12-2010 825516203@GENIA Treebank@formal@@1@S@Using monoclonal antibodies (mAbs) and flow cytometry, we studied a variety of surface receptors on lymphocyte subpopulations of workers with moderately increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of other polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), expressed here as International-Toxicity Equivalencies (I-TE).@@@@1@52@@oe@19-12-2010 825516204@GENIA Treebank@formal@@1@S@The hypothesis to be tested was whether or not humans exhibit a similar susceptibility to PCDDs/PCDFs with respect to the surface receptors found previously to respond to small doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Callithrix jacchus.@@@@1@38@@oe@19-12-2010 825516205@GENIA Treebank@formal@@1@S@These are: helper-inducer (memory) T cells (CD4+CD45R0+CD45RA-CD29highCD11a+), CD20+ B cells, and cytotoxic T cells (CD8+CD56+/CD57+).@@@@1@25@@oe@19-12-2010 825516206@GENIA Treebank@formal@@1@S@Furthermore, 68 triple-labellings with mAbs were performed on the cells of each volunteer to possibly generate further hypotheses.@@@@1@20@@oe@19-12-2010 825516207@GENIA Treebank@formal@@1@S@It was evaluated whether any of the variables might be used as a biomarker of effects for this class of compounds.@@@@1@22@@oe@19-12-2010 825516208@GENIA Treebank@formal@@1@S@There were two main goals: (1) to evaluate whether workers with a moderately increased PCDD/PCDF-body burden [25-140 ppt TCDD or 104-522 ppt I-TE in blood fat] exhibit changes in the surface receptors of white blood cells, as observed in previous studies in non-human primates, and (2) to clarify whether persons at the upper range [10-23 ppt TCDD or 30-90 ppt I-TE in blood fat] of the body burden reference values of a not particularly exposed population show detectable deviations in these immunological variables, when compared with persons at the lower and medium range [1-3 ppt TCDD or 9-29 ppt I-TE] of these body burden reference values.@@@@1@121@@oe@19-12-2010 825516209@GENIA Treebank@formal@@1@S@Regression analysis of our data revealed slight trends for some of the biomarkers (e.g. CD45R0+).@@@@1@18@@oe@19-12-2010 825516210@GENIA Treebank@formal@@1@S@With one exception, these were all increases.@@@@1@9@@oe@19-12-2010 825516211@GENIA Treebank@formal@@1@S@None of the alterations observed are of medical relevance.@@@@1@10@@oe@19-12-2010 825516212@GENIA Treebank@formal@@1@S@The slight increase in the percentage of CD4+CD45R0+ cells remained significant even after covariant analysis taking age-related changes into account.@@@@1@21@@oe@19-12-2010 825516213@GENIA Treebank@formal@@1@S@Altogether, the data do not provide any evidence to support an assumption that moderately increased body burdens of PCDDs/PCDFs in adults induce decreases in the cellular components of the human immune system.@@@@1@34@@oe@19-12-2010 825516214@GENIA Treebank@formal@@1@S@Adult humans certainly are less susceptible to this action of PCDDs/PCDFs than adolescent Callithrix jacchus.@@@@1@16@@oe@19-12-2010 826247701@GENIA Treebank@formal@@1@S@Transient pseudohypoaldosteronism in obstructive renal disease with transient reduction of lymphocytic aldosterone receptors.@@@@1@14@@oe@19-12-2010 826247702@GENIA Treebank@formal@@1@S@Results in two affected infants.@@@@1@6@@oe@19-12-2010 826247703@GENIA Treebank@formal@@1@S@We report two patients with transient pseudohypoaldosteronism due to obstructive renal disease.@@@@1@13@@oe@19-12-2010 826247704@GENIA Treebank@formal@@1@S@Both patients presented with a salt-losing episode simulating adrenal insufficiency.@@@@1@11@@oe@19-12-2010 826247705@GENIA Treebank@formal@@1@S@In one patient, transient reduction of aldosterone receptors could be documented, while in the second patient the clinical and biochemical parameters were consistent with transient pseudohypoaldosteronism.@@@@1@29@@oe@19-12-2010 826247706@GENIA Treebank@formal@@1@S@Aldosterone receptors were normal in both patients when studied after the surgical correction of the obstruction.@@@@1@17@@oe@19-12-2010 828280301@GENIA Treebank@formal@@1@S@Steroid-resistant asthma.@@@@1@3@@oe@19-12-2010 828280302@GENIA Treebank@formal@@1@S@Cellular mechanisms contributing to inadequate response to glucocorticoid therapy.@@@@1@10@@oe@19-12-2010 828280303@GENIA Treebank@formal@@1@S@The current study examined whether alterations in glucocorticoid receptor (GR) binding contribute to poor response to glucocorticoid therapy in asthma.@@@@1@23@@oe@19-12-2010 828280304@GENIA Treebank@formal@@1@S@29 asthma patients with forced expiratory volume in 1 s (FEV1) < 70% predicted were studied.@@@@1@20@@oe@19-12-2010 828280305@GENIA Treebank@formal@@1@S@Patients were classified as steroid sensitive (SS) if their morning FEV1 increased > 30% after a 1-wk course of oral prednisone 20 mg twice daily and steroid resistant (SR) if they failed to increase > 15%.@@@@1@43@@oe@19-12-2010 828280306@GENIA Treebank@formal@@1@S@PBMC obtained from these two groups, 17 SR and 12 SS, as well as 12 normal controls were analyzed.@@@@1@22@@oe@19-12-2010 828280307@GENIA Treebank@formal@@1@S@SR patients had two distinguishable GR binding abnormalities: 15 of the 17 SR patients demonstrated a significantly reduced GR binding affinity, as compared with SS patients (P = 0.0001) and normal controls (P = 0.0001).@@@@1@42@@oe@19-12-2010 828280308@GENIA Treebank@formal@@1@S@This defect was localized to T cells and reverted to normal after 48 h in culture media.@@@@1@18@@oe@19-12-2010 828280309@GENIA Treebank@formal@@1@S@However, incubation with a combination of IL-2 and IL-4 sustained this abnormality.@@@@1@14@@oe@19-12-2010 828280310@GENIA Treebank@formal@@1@S@The other two SR patients had an abnormally low GR number with normal binding affinity that was not limited to T cells.@@@@1@23@@oe@19-12-2010 828280311@GENIA Treebank@formal@@1@S@Furthermore, GR number failed to normalize after incubation in media alone or IL-2 and IL-4.@@@@1@17@@oe@19-12-2010 828280312@GENIA Treebank@formal@@1@S@Therefore, SR asthma may be due to more than one abnormality, the majority related to a reversible cytokine-induced reduction in GR binding affinity and the second related to an irreversible reduction in GR number.@@@@1@37@@oe@19-12-2010 828280313@GENIA Treebank@formal@@1@S@These findings may have important implications for the design of alternative treatment approaches for recalcitrant asthma.@@@@1@17@@oe@19-12-2010 828282001@GENIA Treebank@formal@@1@S@Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic transcription factors.@@@@1@15@@oe@19-12-2010 828282002@GENIA Treebank@formal@@1@S@Skeletal myogenesis is regulated by a group of transcription factors (MyoD, myogenin, myf5, and myf6) that are "basic helix-loop-helix" proteins that bind to the promoters of muscle-specific genes and promote their expression.@@@@1@40@@oe@19-12-2010 828282003@GENIA Treebank@formal@@1@S@We have previously shown that after a mutation of Leu122 to Arg the DNA binding basic domain of MyoD confers c-myc-like functional characteristics to the protein.@@@@1@27@@oe@19-12-2010 828282004@GENIA Treebank@formal@@1@S@In this study we used single-strand conformation polymorphism analysis to determine whether such mutations occur naturally in rhabdomyosarcomas.@@@@1@19@@oe@19-12-2010 828282005@GENIA Treebank@formal@@1@S@We have found that the basic domains of all the myogenic factors remain unaltered in rhabdomyosarcomas.@@@@1@17@@oe@19-12-2010 828282006@GENIA Treebank@formal@@1@S@Selection against such mutations may be the result of functional redundancy of these myogenic transcription factors.@@@@1@17@@oe@19-12-2010 828303201@GENIA Treebank@formal@@1@S@Increased proliferation, cytotoxicity, and gene expression after stimulation of human peripheral blood T lymphocytes through a surface ganglioside (GD3) [published erratum appears in J Immunol 1994 Jul 15;153(2):910]@@@@1@41@@oe@19-12-2010 828303202@GENIA Treebank@formal@@1@S@Previous studies have suggested that gangliosides have an important role in cell signaling and recognition.@@@@1@16@@oe@19-12-2010 828303203@GENIA Treebank@formal@@1@S@However, their specific function in these processes has not been clearly defined.@@@@1@14@@oe@19-12-2010 828303204@GENIA Treebank@formal@@1@S@A mAb, R24, that reacts specifically with a cell surface ganglioside (GD3) has been demonstrated to stimulate proliferation of T cells derived from human peripheral blood.@@@@1@31@@oe@19-12-2010 828303205@GENIA Treebank@formal@@1@S@In this study, we have investigated the mechanisms by which the R24 mAb affects T cell functions.@@@@1@19@@oe@19-12-2010 828303206@GENIA Treebank@formal@@1@S@We have observed that the R24 mAb stimulates GD3+ T cell proliferation, cytotoxicity, and surface marker expression of IL-2R alpha-chain, IL-2R beta-chain, HLA-DR, CD11a, and CD11c.@@@@1@33@@oe@19-12-2010 828303207@GENIA Treebank@formal@@1@S@Additionally, IFN-gamma activity but not IL-1, IL-2, or IL-4 activity was present in culture supernatants 72 h after R24 stimulation.@@@@1@24@@oe@19-12-2010 828303208@GENIA Treebank@formal@@1@S@In some donors, increased IL-6 and TNF-alpha activity also was detected after R24 treatment.@@@@1@16@@oe@19-12-2010 828303209@GENIA Treebank@formal@@1@S@Furthermore, R24 treatment resulted in translocation of c-rel, but little or no NF kappa B p50 or p65, from the cytoplasm to the nucleus and an increase of NF kappa B binding complexes containing c-rel and p50.@@@@1@41@@oe@19-12-2010 828303210@GENIA Treebank@formal@@1@S@This treatment also caused increased tyrosine phosphorylation of specific protein substrates.@@@@1@12@@oe@19-12-2010 828303211@GENIA Treebank@formal@@1@S@R24-stimulated increases in proliferation, cytotoxicity, and cell surface protein expression could be blocked by cyclosporin and staurosporin, indicating that cyclophilin/calcineurin and protein kinase C may be involved in the R24 signaling pathway.@@@@1@36@@oe@19-12-2010 828303212@GENIA Treebank@formal@@1@S@Additionally, herbimycin A, a tyrosine kinase inhibitor, blocked the R24-stimulated increase in proliferation but not cytotoxicity at concentrations consistent with specificity for tyrosine kinases.@@@@1@28@@oe@19-12-2010 828303213@GENIA Treebank@formal@@1@S@These results suggest that multiple biochemical pathways are involved in the activation of human T cells by R24.@@@@1@19@@oe@19-12-2010 828947401@GENIA Treebank@formal@@1@S@The SCL protein displays cell-specific heterogeneity in size.@@@@1@9@@oe@19-12-2010 828947402@GENIA Treebank@formal@@1@S@SCL protein production was examined in a variety of hemopoietic cell lines by immunoblotting using specific polyclonal antisera.@@@@1@19@@oe@19-12-2010 828947403@GENIA Treebank@formal@@1@S@SCL protein was detected in erythroid, megakaryocyte, mast and early myeloid cell lines, as well as in several lymphoid leukemia cell lines which are known to harbor SCL gene rearrangements.@@@@1@34@@oe@19-12-2010 828947404@GENIA Treebank@formal@@1@S@In most cell lines, proteins of molecular weight 49 and 44 kDa were found, however two myeloid cell lines expressed only lower molecular weight species of 24 and 22 kDa.@@@@1@33@@oe@19-12-2010 828947405@GENIA Treebank@formal@@1@S@This size discrepancy appeared to be due to cell-specific translational regulation, since overexpression of a retrovirally transfected SCL gene yielded the higher molecular weight forms in most cell lines (GP+E-86, AT2.5, M1) but only the 22 kDa form in the myeloid cell line, WEHI-3B/D+.@@@@1@51@@oe@19-12-2010 828947406@GENIA Treebank@formal@@1@S@Overexpression of full-length SCL protein in the lymphoid cell lines, SupT1 and Raji, did not alter cell phenotype and there was no evidence for autoregulation of SCL transcription.@@@@1@31@@oe@19-12-2010 828947407@GENIA Treebank@formal@@1@S@The restricted pattern of SCL protein synthesis is consistent with the restricted expression of SCL mRNA documented previously.@@@@1@19@@oe@19-12-2010 828947408@GENIA Treebank@formal@@1@S@In addition, the present results indicate that SCL protein size was determined by regulation of translation in a cell-specific manner.@@@@1@22@@oe@19-12-2010 828981301@GENIA Treebank@formal@@1@S@Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product: implications for viral latency.@@@@1@26@@oe@19-12-2010 828981302@GENIA Treebank@formal@@1@S@Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of the adult T-cell leukemia, an aggressive and often fatal malignancy of activated human CD4 T cells.@@@@1@32@@oe@19-12-2010 828981303@GENIA Treebank@formal@@1@S@HTLV-I encodes an essential 40-kDa protein termed Tax that not only transactivates the long terminal repeat of this retrovirus but also induces an array of cellular genes.@@@@1@28@@oe@19-12-2010 828981304@GENIA Treebank@formal@@1@S@Tax-mediated transformation of T cells likely involves the deregulated expression of various cellular genes that normally regulate lymphocyte growth produced by altered activity of various endogenous host transcription factors.@@@@1@30@@oe@19-12-2010 828981305@GENIA Treebank@formal@@1@S@In particular, Tax is capable of modulating the expression or activity of various host transcription factors, including members of the NF-kappa B/Rel and CREB/ATF families, as well as the cellular factors HEB-1 and p67SRF.@@@@1@38@@oe@19-12-2010 828981306@GENIA Treebank@formal@@1@S@An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells.@@@@1@24@@oe@19-12-2010 828981307@GENIA Treebank@formal@@1@S@In this study, we demonstrate that HTLV-I Tax can physically associate with p100, the product of the Rel-related NF-kappa B2 gene, both in transfected cells and in HTLV-I-infected leukemic T-cell lines.@@@@1@35@@oe@19-12-2010 828981308@GENIA Treebank@formal@@1@S@Furthermore, the physical interaction of Tax with p100 leads to the inhibition of Tax-induced activation of the HTLV-I and human immunodeficiency virus type 1 long terminal repeats, reflecting p100-mediated cytoplasmic sequestration of the normally nuclearly expressed Tax protein.@@@@1@41@@oe@19-12-2010 828981309@GENIA Treebank@formal@@1@S@In contrast, a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100.@@@@1@22@@oe@19-12-2010 828981310@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@19-12-2010 829122801@GENIA Treebank@formal@@1@S@Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in anti-immunoglobulin-treated B cells.@@@@1@16@@oe@19-12-2010 829122802@GENIA Treebank@formal@@1@S@Initiation of the Epstein-Barr virus (EBV) lytic cycle is dependent on the transcription of the BZLF1 gene.@@@@1@20@@oe@19-12-2010 829122803@GENIA Treebank@formal@@1@S@The BZLF1 gene promoter (Zp) was activated by crosslinking of cell surface immunoglobulin (Ig) with anti-Ig antibody in B cells, even in the absence of other viral genes.@@@@1@34@@oe@19-12-2010 829122804@GENIA Treebank@formal@@1@S@We identified several anti-Ig response elements within Zp, which were originally defined as 12-O-tetradecanoylphorbol-13-acetate (TPA) response elements (ZI repeats and ZII, an AP-1-like domain).@@@@1@31@@oe@19-12-2010 829122805@GENIA Treebank@formal@@1@S@Since anti-Ig crosslinking leads to activation of protein kinase C (PKC) and an increase in intracellular calcium level, Zp was tested for the response to these cellular factors.@@@@1@32@@oe@19-12-2010 829122806@GENIA Treebank@formal@@1@S@Treatment with calcium ionophore A23187 increased Zp activity.@@@@1@9@@oe@19-12-2010 829122807@GENIA Treebank@formal@@1@S@When the calcium ionophore was used in conjunction with TPA, a PKC activator, the Zp induction was synergistically enhanced.@@@@1@22@@oe@19-12-2010 829122808@GENIA Treebank@formal@@1@S@1-(5-Isoquinolinyl sulfonyl)-2-methylpiperazine, an inhibitor of PKC, inhibited the anti-Ig inducibility of Zp.@@@@1@14@@oe@19-12-2010 829122809@GENIA Treebank@formal@@1@S@Calmodulin antagonists, compound R24571 and trifluoperazine, blocked the Zp activation with anti-Ig.@@@@1@15@@oe@19-12-2010 829122810@GENIA Treebank@formal@@1@S@These findings suggest that Zp responds directly to changes in the activity of both PKC and calcium/calmodulin-dependent protein kinase.@@@@1@20@@oe@19-12-2010 829122811@GENIA Treebank@formal@@1@S@Requirement of tyrosine kinase activation for the anti-Ig-mediated Zp activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin.@@@@1@23@@oe@19-12-2010 829122812@GENIA Treebank@formal@@1@S@These cellular gene regulatory molecules induced with anti-Ig may cooperatively play an important part in achieving efficient EBV activation as seen with anti-Ig treatment in B cells.@@@@1@28@@oe@19-12-2010 830229601@GENIA Treebank@formal@@1@S@Induction of phosphatidylinositol turnover and EGR-1 mRNA expression by crosslinking of surface IgM and IgD in the human B cell line B104.@@@@1@23@@oe@19-12-2010 830229602@GENIA Treebank@formal@@1@S@We have previously shown that a human B lymphoma cell line, B104, expressed surface IgM (sIgM) and surface IgD (sIgD), and that crosslinking of sIgM and sIgD by anti-IgM antibody (Ab) and anti-IgD Ab, respectively, induced Ca2+ influx to almost the same degree, whereas only sIgM-crosslinking caused B104 cell death.@@@@1@63@@oe@19-12-2010 830229603@GENIA Treebank@formal@@1@S@Here, we investigated the accumulation of cyclic AMP (cAMP), the hydrolysis of inositol phosphates, protein kinase C (PKC) activity and the induction of Egr-1 and c-fos mRNA expression by sIgM- and sIgD-crosslinking to examine differences in the signals mediated through sIgM and sIgD in B104 cells.@@@@1@54@@oe@19-12-2010 830229604@GENIA Treebank@formal@@1@S@Both sIgM- and sIgD-crosslinking with antibodies induced elevation of cAMP levels, phosphatidylinositol turnover, PKC activation and expression of Egr-1 and c-fos mRNA, although sIgM-crosslinking was more effective than sIgD-crosslinking, presumably due to the higher expression of sIgM than of sIgD.@@@@1@45@@oe@19-12-2010 830229605@GENIA Treebank@formal@@1@S@Egr-1 mRNA expression induced by sIgM- and sIgD-crosslinking was inhibited by H7, erbstatin and genistein, but not by HA1004.@@@@1@22@@oe@19-12-2010 830229606@GENIA Treebank@formal@@1@S@Erbstatin and genistein inhibited the sIg-crosslinking-induced Egr-1 mRNA expression in a dose-dependent manner parallel to that observed in the inhibition of sIg-crosslinking-induced protein tyrosine phosphorylation.@@@@1@26@@oe@19-12-2010 830229607@GENIA Treebank@formal@@1@S@Phorbol myristate acetate induced Egr-1 mRNA expression but forskolin and dibutyryl cyclic AMP did not.@@@@1@16@@oe@19-12-2010 830229608@GENIA Treebank@formal@@1@S@These findings suggest that the Egr-1 mRNA activating signals through sIgM and sIgD are protein tyrosine kinase- and PKC-dependent, but protein kinase A-independent.@@@@1@25@@oe@19-12-2010 830229609@GENIA Treebank@formal@@1@S@Cyclosporin A (CsA) and FK506 rescued B104 cells from death induced by anti-IgM Ab, but did not affect the expression of Egr-1 and c-fos mRNA, showing that CsA and FK506 affect signal transducers differently from or downstream to these molecules.@@@@1@45@@oe@19-12-2010 830229610@GENIA Treebank@formal@@1@S@The difference in signals transduced through sIgM and sIgD in B104 cells is discussed.@@@@1@15@@oe@19-12-2010 830798201@GENIA Treebank@formal@@1@S@G(Anh)MTetra, a natural bacterial cell wall breakdown product, induces interleukin-1 beta and interleukin-6 expression in human monocytes.@@@@1@20@@oe@19-12-2010 830798202@GENIA Treebank@formal@@1@S@A study of the molecular mechanisms involved in inflammatory cytokine expression [published erratum appears in J Biol Chem 1994 Jun 17;269(24):16983]@@@@1@30@@oe@19-12-2010 830798203@GENIA Treebank@formal@@1@S@It is believed that induction of cytokine expression by bacterial cell wall components plays a role in the development and course of sepsis.@@@@1@24@@oe@19-12-2010 830798204@GENIA Treebank@formal@@1@S@However, most attention has been focused on lipopolysaccharide (LPS).@@@@1@13@@oe@19-12-2010 830798205@GENIA Treebank@formal@@1@S@We studied the ability of N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D- isoglutamyl-m-diaminopimelyl-D-alanine (G(Anh)MTetra), a naturally occurring breakdown product of peptidoglycan that is produced by soluble lytic transglycosylase of Escherichia coli, to induce cytokine expression in human monocytes.@@@@1@36@@oe@19-12-2010 830798206@GENIA Treebank@formal@@1@S@G(Anh)MTetra was found to strongly induce interleukin (IL)-1 beta and IL-6 mRNA expression after 2 h and IL-1 beta and IL-6 protein secretion after 48 h of activation.@@@@1@32@@oe@19-12-2010 830798207@GENIA Treebank@formal@@1@S@The increase in mRNA accumulation was at least partly due to an increase in the transcription rates of the respective genes and was accompanied by a strong induction of nuclear factor-kappa B and activator protein-1 transcription factor expression.@@@@1@39@@oe@19-12-2010 830798208@GENIA Treebank@formal@@1@S@Experiments using inhibitors of protein kinase C, protein kinase A, and tyrosine kinase-dependent pathways revealed that G(Anh)MTetra-induced IL-1 beta and IL-6 mRNA expression involves activation of an H7-inhibitable pathway.@@@@1@32@@oe@19-12-2010 830798209@GENIA Treebank@formal@@1@S@By using the protein synthesis inhibitor cycloheximide, it was shown that G(Anh)MTetra-induced IL-6 mRNA expression depends on the synthesis of new protein, whereas G(Anh)MTetra-induced IL-1 beta mRNA accumulation does not.@@@@1@33@@oe@19-12-2010 830798210@GENIA Treebank@formal@@1@S@When responses to G(Anh)MTetra were compared with those to LPS and muramyldipeptide (MDP), it was found that the optimal response to G(Anh)MTetra induction was similar to that of LPS but significantly higher than the response to MDP.@@@@1@41@@oe@19-12-2010 830798211@GENIA Treebank@formal@@1@S@Furthermore, maximal G(Anh)MTetra-induced IL-1 beta and IL-6 mRNA expression could be enhanced by co-stimulation with LPS or MDP, suggesting that different receptors and/or transduction pathways were involved.@@@@1@30@@oe@19-12-2010 830798212@GENIA Treebank@formal@@1@S@These results indicate that G(Anh)MTetra induces IL-1 beta and IL-6 expression in human monocytes suggesting a possible role for G(Anh)MTetra in the release of cytokines during sepsis.@@@@1@28@@oe@19-12-2010 831485701@GENIA Treebank@formal@@1@S@1,25-Dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate synergistically induce monocytic cell differentiation: FOS and RB expression.@@@@1@17@@oe@19-12-2010 831485702@GENIA Treebank@formal@@1@S@1,25-dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate (TPA) interact synergistically to induce monocytic differentiation of U937 histiocytic lymphoma cells.@@@@1@21@@oe@19-12-2010 831485703@GENIA Treebank@formal@@1@S@Addition of TPA causes an otherwise ineffective dose of 1,25-dihydroxy vitamin D3 to induce differentiation.@@@@1@16@@oe@19-12-2010 831485704@GENIA Treebank@formal@@1@S@The induced differentiation depends on the simultaneous (vs. sequential) presence of both agents.@@@@1@16@@oe@19-12-2010 831485705@GENIA Treebank@formal@@1@S@The kinetics of induced differentiation are consistent with a G1 specific cellular response to initiate the metabolic cascade culminating in cell differentiation.@@@@1@23@@oe@19-12-2010 831485706@GENIA Treebank@formal@@1@S@The induced differentiation occurs with down-regulation of c-fos protein and an accompanying up-regulation of RB protein expression, consistent with a possible need for up-regulated RB expression to maintain a given differentiated phenotype and suppress transcriptional activators that might typically be associated with proliferation.@@@@1@45@@oe@19-12-2010 831685901@GENIA Treebank@formal@@1@S@Regulation of lymphoid-specific immunoglobulin mu heavy chain gene enhancer by ETS-domain proteins.@@@@1@13@@oe@19-12-2010 831685902@GENIA Treebank@formal@@1@S@The enhancer for the immunoglobulin mu heavy chain gene (IgH) activates a heterologous gene at the pre-B cell stage of B lymphocyte differentiation.@@@@1@26@@oe@19-12-2010 831685903@GENIA Treebank@formal@@1@S@A lymphoid-specific element, microB, is necessary for enhancer function in pre-B cells.@@@@1@15@@oe@19-12-2010 831685904@GENIA Treebank@formal@@1@S@A microB binding protein is encoded by the PU.1/Spi-1 proto-oncogene.@@@@1@11@@oe@19-12-2010 831685905@GENIA Treebank@formal@@1@S@Another sequence element, microA, was identified in the mu enhancer that binds the product of the ets-1 proto-oncogene.@@@@1@21@@oe@19-12-2010 831685906@GENIA Treebank@formal@@1@S@The microA motif was required for microB-dependent enhancer activity, which suggests that a minimal B cell-specific enhancer is composed of both the PU.1 and Ets-1 binding sites.@@@@1@29@@oe@19-12-2010 831685907@GENIA Treebank@formal@@1@S@Co-expression of both PU.1 and Ets-1 in nonlymphoid cells trans-activated reporter plasmids that contained the minimal mu enhancer.@@@@1@19@@oe@19-12-2010 831685908@GENIA Treebank@formal@@1@S@These results implicate two members of the Ets family in the activation of IgH gene expression.@@@@1@17@@oe@19-12-2010 831991201@GENIA Treebank@formal@@1@S@The p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms.@@@@1@15@@oe@19-12-2010 831991202@GENIA Treebank@formal@@1@S@Transcription factor NF-kappa B (p50/p65) is generally localized to the cytoplasm by its inhibitor I kappa B.@@@@1@20@@oe@19-12-2010 831991203@GENIA Treebank@formal@@1@S@Overproduced I kappa B, free from NF-kappa B, is rapidly degraded.@@@@1@14@@oe@19-12-2010 831991204@GENIA Treebank@formal@@1@S@Overexpression of p65 increases endogenous I kappa B protein in both carcinoma and lymphoid cells by two mechanisms: protein stabilization and increased transcription of I kappa B mRNA.@@@@1@30@@oe@19-12-2010 831991205@GENIA Treebank@formal@@1@S@In contrast, p65 delta, a naturally occurring splice variant, fails to markedly augment I kappa B protein levels.@@@@1@22@@oe@19-12-2010 831991206@GENIA Treebank@formal@@1@S@Both overexpressed p65 and coexpressed p50 are cytoplasmic, whereas p65 delta is partly nuclear, indicating that the I kappa B induced by p65 can maintain NF-kappa B in the cytoplasm.@@@@1@33@@oe@19-12-2010 831991207@GENIA Treebank@formal@@1@S@Thus, p65 and I kappa B are linked in an autoregulatory loop, ensuring that NF-kappa B is held in the cytoplasm until cells are specifically induced to translocate it to the nucleus.@@@@1@35@@oe@19-12-2010 832120401@GENIA Treebank@formal@@1@S@Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F.@@@@1@22@@oe@19-12-2010 832120402@GENIA Treebank@formal@@1@S@The transcription factor E2F activates the expression of multiple genes involved in cell proliferation, such as c-myc and the dihydrofolate reductase gene.@@@@1@24@@oe@19-12-2010 832120403@GENIA Treebank@formal@@1@S@Regulation of E2F involves its interactions with other cellular proteins, including the retinoblastoma protein (Rb), the Rb-related protein p107, cyclin A, and cdk2.@@@@1@30@@oe@19-12-2010 832120404@GENIA Treebank@formal@@1@S@We undertook a detailed analysis of E2F DNA-binding activities and their cell cycle behavior in primary human T cells.@@@@1@20@@oe@19-12-2010 832120405@GENIA Treebank@formal@@1@S@Three E2F DNA-binding activities were identified in resting (G0) T cells with mobilities in gel shift assays distinct from those of previously defined E2F complexes.@@@@1@28@@oe@19-12-2010 832120406@GENIA Treebank@formal@@1@S@One of these activities was found to be a novel, less abundant, Rb-E2F complex.@@@@1@17@@oe@19-12-2010 832120407@GENIA Treebank@formal@@1@S@The most prominent E2F activity in resting T cells (termed complex X) was abundant in both G0 and G1 but disappeared as cells entered S phase, suggesting a possible role in negatively regulating E2F function.@@@@1@39@@oe@19-12-2010 832120408@GENIA Treebank@formal@@1@S@Complex X could be dissociated by adenovirus E1A with a requirement for an intact E1A conserved region 2.@@@@1@19@@oe@19-12-2010 832120409@GENIA Treebank@formal@@1@S@However, X failed to react with a variety of antibodies against Rb or p107, implicating the involvement of an E1A-binding protein other than Rb or p107.@@@@1@29@@oe@19-12-2010 832120410@GENIA Treebank@formal@@1@S@In addition to these novel E2F complexes, three distinct forms of unbound (free) E2F were resolved in gel shift experiments.@@@@1@24@@oe@19-12-2010 832120411@GENIA Treebank@formal@@1@S@These species showed different cell cycle kinetics.@@@@1@8@@oe@19-12-2010 832120412@GENIA Treebank@formal@@1@S@UV cross-linking experiments suggested that a distinct E2F DNA-binding protein is uniquely associated with the S-phase p107 complex and is not associated with Rb.@@@@1@25@@oe@19-12-2010 832120413@GENIA Treebank@formal@@1@S@Together, these results suggest that E2F consists of multiple, biochemically distinct DNA-binding proteins which function at different points in the cell cycle.@@@@1@25@@oe@19-12-2010 832595001@GENIA Treebank@formal@@1@S@Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: application for diagnosis, genetic counseling, and therapy.@@@@1@27@@oe@19-12-2010 832595002@GENIA Treebank@formal@@1@S@Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes, a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males.@@@@1@31@@oe@19-12-2010 832595003@GENIA Treebank@formal@@1@S@In this report, we address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis, genetic counseling, and molecular subclassification of affected patients and their families.@@@@1@34@@oe@19-12-2010 832595004@GENIA Treebank@formal@@1@S@DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied.@@@@1@20@@oe@19-12-2010 832595005@GENIA Treebank@formal@@1@S@Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing.@@@@1@25@@oe@19-12-2010 832595006@GENIA Treebank@formal@@1@S@Female family members were also studied to identify heterozygote carriers.@@@@1@11@@oe@19-12-2010 832595007@GENIA Treebank@formal@@1@S@Point mutations in the AR gene were identified in all six patients, and all mutations caused amino acid substitutions.@@@@1@21@@oe@19-12-2010 832595008@GENIA Treebank@formal@@1@S@One patient with incomplete androgen insensitivity was a mosaic for the mutation.@@@@1@13@@oe@19-12-2010 832595009@GENIA Treebank@formal@@1@S@Four of the five mothers, as well as a young sister of one patient, were carriers of the mutation present in the affected child.@@@@1@27@@oe@19-12-2010 832595010@GENIA Treebank@formal@@1@S@Our data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome.@@@@1@20@@oe@19-12-2010 832595011@GENIA Treebank@formal@@1@S@Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy, and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance.@@@@1@33@@oe@19-12-2010 832595012@GENIA Treebank@formal@@1@S@The identification of carriers is of substantial clinical importance for genetic counseling.@@@@1@13@@oe@19-12-2010 833089801@GENIA Treebank@formal@@1@S@Nuclear factor kappa B, a mediator of lipopolysaccharide effects.@@@@1@11@@oe@19-12-2010 833089802@GENIA Treebank@formal@@1@S@Exposure of certain cell types to bacterial lipopolysaccharide (LPS) leads to activation of nuclear factor kappa B (NF-kappa B), an inducible transcription factor.@@@@1@29@@oe@19-12-2010 833089803@GENIA Treebank@formal@@1@S@One of NF-kappa B's unique properties is its posttranslational activation via release of an inhibitory subunit, called inhibitor of NF-kappa B (I kappa B), from a sequestered cytoplasmic form.@@@@1@35@@oe@19-12-2010 833089804@GENIA Treebank@formal@@1@S@This event is also triggered under various other conditions of biomedical importance.@@@@1@13@@oe@19-12-2010 833089805@GENIA Treebank@formal@@1@S@Other bacterial toxins, tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), T cell mitogens, UV light, gamma rays and oxidative stress were reported to induce NF-kappa B.@@@@1@35@@oe@19-12-2010 833089806@GENIA Treebank@formal@@1@S@The activated form of NF-kappa B, which is rapidly taken up into nuclei, initiates transcription from immediate early genes in a wide variety of cell types.@@@@1@29@@oe@19-12-2010 833089807@GENIA Treebank@formal@@1@S@Most of the target genes for NF-kappa B are of relevance for the immune response and can be grouped into those encoding cytokines, cell surface receptors, acute phase proteins and viral genomes, such as that of human immunodeficiency virus type 1 (HIV-1).@@@@1@48@@oe@19-12-2010 833089808@GENIA Treebank@formal@@1@S@We will discuss recent experimental evidences suggesting that LPS might share a pathway of NF-kappa B activation with other inducers of the factor.@@@@1@24@@oe@19-12-2010 833089809@GENIA Treebank@formal@@1@S@This common pathway may involve reactive oxygen intermediates (ROI) as messenger molecules.@@@@1@15@@oe@19-12-2010 833249201@GENIA Treebank@formal@@1@S@Human T cell transcription factor GATA-3 stimulates HIV-1 expression.@@@@1@10@@oe@19-12-2010 833249202@GENIA Treebank@formal@@1@S@A family of transcriptional activating proteins, the GATA factors, has been shown to bind to a consensus motif through a highly conserved C4 zinc finger DNA binding domain.@@@@1@31@@oe@19-12-2010 833249203@GENIA Treebank@formal@@1@S@One member of this multigene family, GATA-3, is most abundantly expressed in T lymphocytes, a cellular target for human immunodeficiency virus type 1 (HIV-1) infection and replication.@@@@1@33@@oe@19-12-2010 833249204@GENIA Treebank@formal@@1@S@In vitro DNase I footprinting analysis revealed six hGATA-3 binding sites in the U3 region (the transcriptional regulatory domain) of the HIV-1 LTR.@@@@1@26@@oe@19-12-2010 833249205@GENIA Treebank@formal@@1@S@Cotransfection of an hGATA-3 expression plasmid with a reporter plasmid whose transcription is directed by the HIV-1 LTR resulted in 6- to 10-fold stimulation of LTR-mediated transcription, whereas site specific mutation of these GATA sites resulted in virtual abrogation of the activation by hGATA-3.@@@@1@46@@oe@19-12-2010 833249206@GENIA Treebank@formal@@1@S@Further, deletion of the hGATA-3 transcriptional activation domain abolished GATA-dependent HIV-1 trans-activation, showing that the stimulation of viral transcription observed is a direct effect of cotransfected hGATA-3.@@@@1@30@@oe@19-12-2010 833249207@GENIA Treebank@formal@@1@S@Introduction of the HIV-1 plasmids in which the GATA sites have been mutated into human T lymphocytes also caused a significant reduction in LTR-mediated transcription at both the basal level and in (PHA- plus PMA-) stimulated T cells.@@@@1@41@@oe@19-12-2010 833249208@GENIA Treebank@formal@@1@S@These observations suggest that in addition to its normal role in T lymphocyte gene regulation, hGATA-3 may also play a significant role in HIV-1 transcriptional activation.@@@@1@28@@oe@19-12-2010 833591301@GENIA Treebank@formal@@1@S@Analysis of the preexisting and nuclear forms of nuclear factor of activated T cells.@@@@1@15@@oe@19-12-2010 833591302@GENIA Treebank@formal@@1@S@The nuclear factor of activated T cells (NF-AT)3 is an inducible DNA-binding protein that is essential for transcriptional induction of the IL-2 gene during T cell activation.@@@@1@31@@oe@19-12-2010 833591303@GENIA Treebank@formal@@1@S@NF-AT is thought to consist of two components: a ubiquitous, inducible nuclear component that we have identified as Fos and Jun proteins, and a preexisting, T cell-specific component (NF-ATp) which is the target for the immunosuppressive agents cyclosporin A (CsA) and FK506.@@@@1@51@@oe@19-12-2010 833591304@GENIA Treebank@formal@@1@S@We have previously shown that nuclear extracts from activated T cells form two inducible NF-AT complexes with an oligonucleotide corresponding to the distal NF-AT site of the murine IL-2 promoter, although hypotonic extracts of unstimulated T cells form a single complex containing NF-ATp.@@@@1@45@@oe@19-12-2010 833591305@GENIA Treebank@formal@@1@S@We show that the ability to detect NF-ATp in a gel shift assay, which is essential for purification and biochemical studies of this protein, is strikingly dependent on the precise sequence of the NF-AT oligonucleotide used as the labeled probe.@@@@1@43@@oe@19-12-2010 833591306@GENIA Treebank@formal@@1@S@Moreover we present evidence that the component that forms the faster-migrating ("lower") nuclear NF-AT complex is derived by a calcium-dependent, cyclosporin-sensitive, posttranslational modification of NF-ATp, and that Fos and Jun proteins stabilize its interaction with DNA.@@@@1@44@@oe@19-12-2010 833591307@GENIA Treebank@formal@@1@S@The results are discussed in the context of a model relating the two nuclear NF-AT complexes to NF-ATp.@@@@1@19@@oe@19-12-2010 834471401@GENIA Treebank@formal@@1@S@Enhancing effect of 17 beta-estradiol on human NK cell activity.@@@@1@11@@oe@19-12-2010 834471402@GENIA Treebank@formal@@1@S@The in vitro effect of 17 beta-estradiol on NK activity was studied.@@@@1@13@@oe@19-12-2010 834471403@GENIA Treebank@formal@@1@S@The proliferation and NK activity of YT-N17 (a human NK-like cell line) were enhanced by 17 beta-estradiol (E2), and the enhancement was blocked by tamoxifen (Tx), an antagonist of E2.@@@@1@39@@oe@19-12-2010 834471404@GENIA Treebank@formal@@1@S@On the contrary, other steroid hormones such as Tx, progesterone, and testosterone had no effect.@@@@1@19@@oe@19-12-2010 834471405@GENIA Treebank@formal@@1@S@YT-N17 contained 11.8 fmol/mg protein of estrogen receptor (mean of two independent assays), a value which was 5-10-fold higher than that of other hematopoietic cell lines.@@@@1@30@@oe@19-12-2010 834471406@GENIA Treebank@formal@@1@S@An enhancement of NK activity by E2 was also seen in large granular lymphocytes obtained from normal subjects, and it was again suppressed by Tx.@@@@1@27@@oe@19-12-2010 834471407@GENIA Treebank@formal@@1@S@These data suggest that E2 is one of the activating factors for NK/LGL cells.@@@@1@15@@oe@19-12-2010 838134901@GENIA Treebank@formal@@1@S@The Epstein-Barr virus nuclear antigen 2 interacts with an EBNA2 responsive cis-element of the terminal protein 1 gene promoter.@@@@1@20@@oe@19-12-2010 838134902@GENIA Treebank@formal@@1@S@The Epstein-Barr virus protein EBNA2 acts as a transcriptional activator of cellular and viral genes and plays a crucial role in the immortalization of human primary B-cells by EBV.@@@@1@30@@oe@19-12-2010 838134903@GENIA Treebank@formal@@1@S@We have shown previously that EBNA2 transactivates the promoters of the latent membrane antigens LMP, TP1 and TP2.@@@@1@20@@oe@19-12-2010 838134904@GENIA Treebank@formal@@1@S@The promoter of the TP1 gene was chosen as a model system to study the molecular mechanism of EBNA2 mediated transactivation.@@@@1@22@@oe@19-12-2010 838134905@GENIA Treebank@formal@@1@S@To identify an EBNA2 dependent cis-acting element, various TP1 promoter-reporter gene constructs were transfected in the absence and presence of an EBNA2 expression vector into the established B-cell line BL41-P3HR1.@@@@1@32@@oe@19-12-2010 838134906@GENIA Treebank@formal@@1@S@We were able to delineate an 81 bp EBNA2 responsive region between -258 and -177 relative to the TP1 RNA start site.@@@@1@23@@oe@19-12-2010 838134907@GENIA Treebank@formal@@1@S@The element worked in either orientation and could mediate EBNA2 dependent transactivation on a heterologous promoter.@@@@1@17@@oe@19-12-2010 838134908@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays revealed three specific protein-DNA complexes formed with sequences of the EBNA2 responsive element.@@@@1@18@@oe@19-12-2010 838134909@GENIA Treebank@formal@@1@S@Two of these were not cell type specific, but the third was detected only in EBNA2 positive cell extracts.@@@@1@21@@oe@19-12-2010 838134910@GENIA Treebank@formal@@1@S@Gel-shift analysis in the presence of EBNA2 specific monoclonal antibodies revealed that EBNA2 is a component of the third complex.@@@@1@21@@oe@19-12-2010 838134911@GENIA Treebank@formal@@1@S@Thus, these experiments demonstrate that EBNA2 interacts with an EBNA2 responsive cis-element of the TP1 promoter.@@@@1@18@@oe@19-12-2010 838332301@GENIA Treebank@formal@@1@S@The interleukin 2 CD28-responsive complex contains at least three members of the NF kappa B family: c-Rel, p50, and p65.@@@@1@24@@oe@19-12-2010 838332302@GENIA Treebank@formal@@1@S@Optimal activation of T cells requires at least two signals.@@@@1@11@@oe@19-12-2010 838332303@GENIA Treebank@formal@@1@S@One signal can be delivered by the antigen-specific T-cell receptor, and the second signal is provided by the costimulatory molecule(s) delivered by the antigen-presenting cell.@@@@1@30@@oe@19-12-2010 838332304@GENIA Treebank@formal@@1@S@CD28 is a T-cell surface molecule and stimulation through this protein plays an important role in delivering the second activation signal.@@@@1@22@@oe@19-12-2010 838332305@GENIA Treebank@formal@@1@S@In this report, we show that in human peripheral blood T cells, CD28-mediated signal transduction involves the rel family proteins--c-Rel, p50, and p65.@@@@1@30@@oe@19-12-2010 838332306@GENIA Treebank@formal@@1@S@Treatment of peripheral blood T cells with phorbol 12-myristate 13-acetate (PMA) and anti-CD28 monoclonal antibody (mAb) results in augmentation of nuclear c-Rel, p50, and p65, and this augmentation can occur in the presence of the immunosuppressant cyclosporin A.@@@@1@46@@oe@19-12-2010 838332307@GENIA Treebank@formal@@1@S@It is also shown in this report that, in response to PMA/anti-CD28 mAb or anti-CD3/anti-CD28 mAb, c-Rel, p50, and p65 are associated with CD28-responsive element present in the promoter of the human interleukin 2 gene.@@@@1@40@@oe@19-12-2010 838332308@GENIA Treebank@formal@@1@S@The functional significance of c-Rel involvement in the CD28-responsive complex is demonstrated by transient transfection analysis, where cotransfection of c-Rel augments the level of expression of a chloramphenicol acetyltransferase reporter gene linked to the CD28-responsive element.@@@@1@38@@oe@19-12-2010 838591601@GENIA Treebank@formal@@1@S@The lytic transition of Epstein-Barr virus is imitated by recombinant B-cells.@@@@1@12@@oe@19-12-2010 838591602@GENIA Treebank@formal@@1@S@Lytic transition of Epstein-Barr virus (EBV) is initiated by distinct immediate early regulators of the viral cycle, in synchronization to temporary, permissive conditions during host cell differentiation.@@@@1@32@@oe@19-12-2010 838591603@GENIA Treebank@formal@@1@S@We developed eukaryotic vectors suitable to imitate the processes involved in lytic transition in cell culture systems.@@@@1@18@@oe@19-12-2010 838591604@GENIA Treebank@formal@@1@S@Two stable B cell lines were established: R59Z activator cells were used to induce lytic EBV expression in a constitutive manner by the production of the BZLF 1 trans-activator (Zta).@@@@1@34@@oe@19-12-2010 838591605@GENIA Treebank@formal@@1@S@R7-57 reporter cells, on the other hand, signaled induced activity of the lytic origin of EBV replication (ori Lyt).@@@@1@24@@oe@19-12-2010 838591606@GENIA Treebank@formal@@1@S@Different modes, like chemical induction, lytic superinfection with EBV and single gene trans-activation converted the recombinant ori Lyt element in R7-57 reporter cells.@@@@1@26@@oe@19-12-2010 838591607@GENIA Treebank@formal@@1@S@BZLF 1, transiently expressed in R7-57 reporter cells, was the only EBV trans-activator found, sufficient in inducing the viral lytic cycle.@@@@1@25@@oe@19-12-2010 838591608@GENIA Treebank@formal@@1@S@Basing on these experiments, trans-cellular activation of EBV was tested by cocultivation of BZLF 1-expressing R59Z activator cells with the R7-57 reporter line.@@@@1@25@@oe@19-12-2010 838591609@GENIA Treebank@formal@@1@S@No lytic effect on the reporter cells could be measured, neither by cocultivation of activator cells nor by coincubation of BZLF 1-containing cell lysates.@@@@1@26@@oe@19-12-2010 838591610@GENIA Treebank@formal@@1@S@Latency breaking activity, however, was transferred from activator to reporter cells when active, exogenous virus was added.@@@@1@21@@oe@19-12-2010 838591611@GENIA Treebank@formal@@1@S@The cell system described in these experiments provides a tool for the detection of EBV reactivation and demonstrates the potential of the lytic regulatory gene BZLF 1.@@@@1@28@@oe@19-12-2010 838693301@GENIA Treebank@formal@@1@S@Hypertension in pregnancy.@@@@1@4@@oe@19-12-2010 838693302@GENIA Treebank@formal@@1@S@Pregnancy-induced hypertension (PIH) is a frequent cause of maternal and neonatal morbidity and mortality.@@@@1@17@@oe@19-12-2010 838693303@GENIA Treebank@formal@@1@S@In the present study we focused on the pathophysiology of PIH, mainly on the role of mineralocorticoids, reversed blood pressure patterns, and the resulting necessity of continuous monitoring of the preeclamptic mother.@@@@1@36@@oe@19-12-2010 838693304@GENIA Treebank@formal@@1@S@Problems of antihypertensive therapy are discussed and the first results of a pilot study with Urapidil are presented.@@@@1@19@@oe@19-12-2010 838693305@GENIA Treebank@formal@@1@S@To examine the role of mineralocorticoids in the pathophysiology of PIH, we studied plasma aldosterone and 18-hydroxy-corticosterone (18-OH-B) levels in 25 women with PIH and in 25 healthy pregnant women.@@@@1@34@@oe@19-12-2010 838693306@GENIA Treebank@formal@@1@S@Furthermore, we evaluated the mineralocorticoid receptor (MR) count in mononuclear leukocytes in the 2 groups.@@@@1@19@@oe@19-12-2010 838693307@GENIA Treebank@formal@@1@S@The MR-count was significantly decreased in the PIH-group.@@@@1@9@@oe@19-12-2010 838693308@GENIA Treebank@formal@@1@S@The values of plasma aldosterone and 18-OH-B were also low.@@@@1@11@@oe@19-12-2010 838693309@GENIA Treebank@formal@@1@S@These results cannot be explained by receptor down-regulation due to higher level of mineralocorticoids of the zona glomerulosa.@@@@1@20@@oe@19-12-2010 838693310@GENIA Treebank@formal@@1@S@Perhaps deoxycorticosterone or a hitherto unknown mineralocorticoid is responsible for the hypertension and altered MR-status.@@@@1@16@@oe@19-12-2010 838693311@GENIA Treebank@formal@@1@S@The first results of continuous blood pressure measurements with a noninvasive, real-time blood pressure monitor (Finapres) are presented.@@@@1@22@@oe@19-12-2010 838693312@GENIA Treebank@formal@@1@S@The comparison of the obtained values with intraarterial measurements demonstrates a good correlation between the two methods.@@@@1@18@@oe@19-12-2010 838693313@GENIA Treebank@formal@@1@S@We also report on the first experiences with Urapidil in the treatment of hypertension in severe preeclampsia.@@@@1@18@@oe@19-12-2010 838693314@GENIA Treebank@formal@@1@S@The data show that hypertension in preeclamptic women can be treated by Urapidil without side effects or reflex-tachycardia.@@@@1@19@@oe@19-12-2010 838693315@GENIA Treebank@formal@@1@S@Further studies will have to prove if Urapidil is suited for prepartal treatment of PIH as well.@@@@1@18@@oe@19-12-2010 838752101@GENIA Treebank@formal@@1@S@A chimeric type II/type I interleukin-1 receptor can mediate interleukin-1 induction of gene expression in T cells.@@@@1@20@@oe@19-12-2010 838752102@GENIA Treebank@formal@@1@S@The type I interleukin-1 receptor (IL-1R) is capable of transducing a signal resulting in promoter activation in T cells.@@@@1@22@@oe@19-12-2010 838752103@GENIA Treebank@formal@@1@S@This signal transduction is dependent on the cytoplasmic domain, which consists of 213 amino acids.@@@@1@17@@oe@19-12-2010 838752104@GENIA Treebank@formal@@1@S@In contrast to the type I receptor, the type II IL-1R has a small cytoplasmic tail, and it is not clear whether this receptor is a signal-transducing or a regulatory molecule.@@@@1@34@@oe@19-12-2010 838752105@GENIA Treebank@formal@@1@S@Here we report that the type II IL-1R does not mediate gene activation in Jurkat cells.@@@@1@17@@oe@19-12-2010 838752106@GENIA Treebank@formal@@1@S@However, a hybrid receptor composed of the extracellular and transmembrane regions of the human type II interleukin-1 fused to the cytoplasmic domain of the human type I IL-1R was capable of transducing a signal across the membrane resulting in a pattern of gene activation identical to that mediated by the type I IL-1R.@@@@1@55@@oe@19-12-2010 838752107@GENIA Treebank@formal@@1@S@Our results indicated that the extracellular domain of the type II IL-1R was capable of functionally interacting with interleukin-1 and transmitting the resulting signal to a heterologous cytoplasmic domain.@@@@1@30@@oe@19-12-2010 838789301@GENIA Treebank@formal@@1@S@Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection.@@@@1@23@@oe@19-12-2010 838789302@GENIA Treebank@formal@@1@S@The multiple biological activities of tumor necrosis factor (TNF) are mediated by two distinct cell surface receptors of 55 kd (TNFRp55) and 75 kd (TNFRp75).@@@@1@32@@oe@19-12-2010 838789303@GENIA Treebank@formal@@1@S@Using gene targeting, we generated a TNFRp55-deficient mouse strain.@@@@1@11@@oe@19-12-2010 838789304@GENIA Treebank@formal@@1@S@Cells from TNFRp55-/-mutant mice lack expression of TNFRp55 but display normal numbers of high affinity TNFRp75 molecules.@@@@1@18@@oe@19-12-2010 838789305@GENIA Treebank@formal@@1@S@Thymocyte development and lymphocyte populations are unaltered, and clonal deletion of potentially self-reactive T cells is not impaired.@@@@1@20@@oe@19-12-2010 838789306@GENIA Treebank@formal@@1@S@However, TNF signaling is largely abolished, as judged by the failure of TNF to induce NF-kappa B in T lymphocytes from TNFRp55-deficient mice.@@@@1@26@@oe@19-12-2010 838789307@GENIA Treebank@formal@@1@S@The loss of TNFRp55 function renders mice resistant to lethal dosages of either lipopolysaccharides or S. aureus enterotoxin B.@@@@1@20@@oe@19-12-2010 838789308@GENIA Treebank@formal@@1@S@In contrast, TNFRp55-deficient mice are severely impaired to clear L. monocytogenes and readily succumb to infection.@@@@1@18@@oe@19-12-2010 838789309@GENIA Treebank@formal@@1@S@Thus, the 55 kd TNFR plays a decisive role in the host's defense against microorganisms and their pathogenic factors.@@@@1@22@@oe@19-12-2010 838908501@GENIA Treebank@formal@@1@S@A concatenated form of Epstein-Barr viral DNA in lymphoblastoid cell lines induced by transfection with BZLF1.@@@@1@17@@oe@19-12-2010 838908502@GENIA Treebank@formal@@1@S@The replicative form of Epstein-Barr virus (EBV) DNA was studied using two lymphoblastoid cell lines, X50-7 and 6F11, which are latently infected by Epstein-Barr virus.@@@@1@30@@oe@19-12-2010 838908503@GENIA Treebank@formal@@1@S@The lytic cycle of EBV infection was induced by transfection of the cells with the BRLF1/BZLF1 coding region of the P3HR-1 defective genome.@@@@1@24@@oe@19-12-2010 838908504@GENIA Treebank@formal@@1@S@We combined two techniques to identify the productive replicative form of Epstein-Barr viral DNA in the lytic cycle-induced cells.@@@@1@20@@oe@19-12-2010 838908505@GENIA Treebank@formal@@1@S@Restriction enzyme analysis followed by Southern blot hybridization identified a significant increase in the fused fragment encompassing both ends of EBV DNA.@@@@1@23@@oe@19-12-2010 838908506@GENIA Treebank@formal@@1@S@This indicates an increase in either episomal DNA or concatameric linear DNA.@@@@1@13@@oe@19-12-2010 838908507@GENIA Treebank@formal@@1@S@Southern blot analysis of in situ lysing gels revealed that the cellular content of linear EBV DNA was also increased significantly after the initiation of the viral lytic cycle, while the amount of circular DNA remained approximately constant.@@@@1@40@@oe@19-12-2010 838908508@GENIA Treebank@formal@@1@S@We propose from these results that the source of the fused fragment encompassing both ends of EBV DNA is a concatenated linear EBV DNA molecule, and that such a concatenated molecule most likely represents a replicative form of EBV DNA in productively infected cells.@@@@1@46@@oe@19-12-2010 838994001@GENIA Treebank@formal@@1@S@Differential contribution of herpes simplex virus type 1 gene products and cellular factors to the activation of human immunodeficiency virus type 1 provirus.@@@@1@24@@oe@19-12-2010 838994002@GENIA Treebank@formal@@1@S@We have previously reported that infection with herpes simplex virus type 1 (HSV-1) activates expression of the human immunodeficiency virus type 1 (HIV-1) provirus in T cells.@@@@1@32@@oe@19-12-2010 838994003@GENIA Treebank@formal@@1@S@Activation of the HIV-1 provirus correlated with the activation of binding of 55- and 85-kDa proteins to the kappa B enhancer and binding of the 50-kDa HLP-1 protein to the LBP-1 sequences of the HIV-1 long terminal repeat.@@@@1@39@@oe@19-12-2010 838994004@GENIA Treebank@formal@@1@S@Further examination of this system has shown that the inhibition of HSV-1 replication by the antiviral drug acyclovir does not inhibit HSV-1-mediated induction of HIV-1 provirus.@@@@1@27@@oe@19-12-2010 838994005@GENIA Treebank@formal@@1@S@Surprisingly, the NF-kappa B and HLP-1 binding activities were substantially inhibited in acyclovir-treated cells.@@@@1@16@@oe@19-12-2010 838994006@GENIA Treebank@formal@@1@S@In the transient-transfection assay, ICP0, but not ICP4, activated the HIV-1 long terminal repeat promoter region and the effect of ICP0 was greatly enhanced in the presence of the NF-kappa B binding proteins, suggesting that induction of the HIV-1 provirus involves cooperation between the HSV-1-activated cellular factor, NF-kappa B, and the virus-encoded transactivator, ICP0.@@@@1@62@@oe@19-12-2010 839209201@GENIA Treebank@formal@@1@S@Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate.@@@@1@17@@oe@19-12-2010 839209202@GENIA Treebank@formal@@1@S@We have previously shown that minimally oxidized LDL (MM-LDL) activated endothelial cells to increase their interaction with monocytes but not neutrophils, inducing monocyte but not neutrophil binding and synthesis of monocyte chemotactic protein-1 and monocyte colony-stimulating factor (M-CSF).@@@@1@44@@oe@19-12-2010 839209203@GENIA Treebank@formal@@1@S@In the present studies we have examined the signaling pathways by which this monocyte-specific response is induced.@@@@1@18@@oe@19-12-2010 839209204@GENIA Treebank@formal@@1@S@Both induction of monocyte binding and mRNA levels for M-CSF by MM-LDL were not inhibited in protein kinase C-depleted endothelial cells.@@@@1@22@@oe@19-12-2010 839209205@GENIA Treebank@formal@@1@S@A number of our studies indicate that cAMP is the second messenger for the effects of MM-LDL cited above.@@@@1@20@@oe@19-12-2010 839209206@GENIA Treebank@formal@@1@S@Incubation of endothelial cells with MM-LDL caused a 173% increase in intracellular cAMP levels.@@@@1@16@@oe@19-12-2010 839209207@GENIA Treebank@formal@@1@S@Agents which increased cAMP levels, including cholera toxin, pertussis toxin, dibutyryl cAMP, and isoproterenol mimicked the actions of MM-LDL.@@@@1@24@@oe@19-12-2010 839209208@GENIA Treebank@formal@@1@S@Agents which elevated cAMP were also shown to activate NF kappa B, suggesting a role for this transcription factor in activation of monocyte-endothelial interactions.@@@@1@26@@oe@19-12-2010 839209209@GENIA Treebank@formal@@1@S@Although endothelial leukocyte adhesion molecule (ELAM) mRNA synthesis can be regulated by NF kappa B, ELAM was not expressed and ELAM mRNA was only slightly elevated in response to MM-LDL.@@@@1@34@@oe@19-12-2010 839209210@GENIA Treebank@formal@@1@S@We present evidence that induction of neutrophil binding by LPS is actually suppressed by agents that elevated cAMP levels.@@@@1@20@@oe@19-12-2010 839243701@GENIA Treebank@formal@@1@S@Costimulation of cAMP and protein kinase C pathways inhibits the CD3-dependent T cell activation and leads to a persistent expression of the AP-1 transcription factor.@@@@1@26@@oe@19-12-2010 839243702@GENIA Treebank@formal@@1@S@The effects mediated by a combined stimulation of cAMP- and protein kinase C (PKC)-dependent pathways have been investigated in different cellular systems, and it has been shown that they may complement each other in activating cell proliferation and differentiation.@@@@1@44@@oe@19-12-2010 839243703@GENIA Treebank@formal@@1@S@In this report, we show that upon the stimulation of both pathways T lymphocytes became refractory to activation via the CD3/T cell receptor (TcR) complex.@@@@1@29@@oe@19-12-2010 839243704@GENIA Treebank@formal@@1@S@T cells preincubated with phorbol 12-myristate 13-acetate (PMA) and dibutyryl cAMP (Bt2cAMP) displayed a deficient proliferative ability in response to anti-CD3 mAb stimulation, whereas lymphocytes treated individually with either Bt2cAMP or PMA responded comparably to untreated samples.@@@@1@43@@oe@19-12-2010 839243705@GENIA Treebank@formal@@1@S@We detected an association between the reduced mitogenic response and low expression of both interleukin-2 (IL-2) and the alpha chain (CD25) of the IL-2 receptor (IL-2R).@@@@1@33@@oe@19-12-2010 839243706@GENIA Treebank@formal@@1@S@Analysis of intracellular Ca2+ mobilization suggested that the CD3/TcR-dependent signal transduction was impaired in PMA/Bt2cAMP-treated cells.@@@@1@17@@oe@19-12-2010 839243707@GENIA Treebank@formal@@1@S@Remarkably, we observed that these samples displayed a persistent expression of the c-fos protooncogene, associated to an increased AP-1 DNA-binding activity, whereas no variations of CREB or NF-kB were detected.@@@@1@34@@oe@19-12-2010 839243708@GENIA Treebank@formal@@1@S@Neither Bt2cAMP nor PMA individually mediated these sustained effects, which therefore appear as a consequence of the interplay between both metabolic stimuli.@@@@1@24@@oe@19-12-2010 839243709@GENIA Treebank@formal@@1@S@Altogether, the data provide the evidence that both pathways complement each other in regulating gene expression and, conversely, downregulate the TcR transduction mechanisms.@@@@1@27@@oe@19-12-2010 839518801@GENIA Treebank@formal@@1@S@Tumor necrosis factor receptor expression and signal transduction in HIV-1-infected cells.@@@@1@12@@oe@19-12-2010 839518802@GENIA Treebank@formal@@1@S@OBJECTIVE: To examine the inter-relationship between HIV-1 infection and the cell surface receptors for tumor necrosis factor (TNF)-alpha, an immunoregulatory cytokine that can enhance HIV-1 replication.@@@@1@32@@oe@19-12-2010 839518803@GENIA Treebank@formal@@1@S@DESIGN: Infected promyelocytic and promonocytic cells were examined because they normally express both types of TNF receptors.@@@@1@19@@oe@19-12-2010 839518804@GENIA Treebank@formal@@1@S@METHODS: TNF receptor surface expression was determined by specific monoclonal antibody recognition and flow cytometry, and signal transduction was detected by gel shift analysis.@@@@1@27@@oe@19-12-2010 839518805@GENIA Treebank@formal@@1@S@HIV-1 activation and expression was quantitated by reverse transcriptase assay.@@@@1@11@@oe@19-12-2010 839518806@GENIA Treebank@formal@@1@S@RESULTS: In the OM-10.1 promyelocytic model of chronic infection, TNF-alpha-induced HIV-1 expression also resulted in a substantial increase in 75 kd TNF receptor (TR75) expression although 55 kD TNF receptor (TR55) levels were not dramatically altered.@@@@1@43@@oe@19-12-2010 839518807@GENIA Treebank@formal@@1@S@A series of uninfected parental HL-60 subclones all reduced TR75 surface expression in response to TNF-alpha treatment.@@@@1@18@@oe@19-12-2010 839518808@GENIA Treebank@formal@@1@S@Enhanced TR75 expression on OM-10.1 cells followed the same TNF-alpha-dose dependency as that observed for HIV-1 production.@@@@1@18@@oe@19-12-2010 839518809@GENIA Treebank@formal@@1@S@An increase in TR75 expression was also evident during the peak of an acute HIV-1 infection of HL-60 promyelocytes.@@@@1@20@@oe@19-12-2010 839518810@GENIA Treebank@formal@@1@S@Although TR55 expression was unaltered during TNF-alpha-induced HIV activation, this receptor was still involved in the viral activation process.@@@@1@21@@oe@19-12-2010 839518811@GENIA Treebank@formal@@1@S@Antibody cross-linking of TR55, in the absence of exogenous TNF-alpha, induced maximal HIV-1 expression, an up-modulation of surface TR75, and nuclear NF-kappa B activity in OM-10.1 cultures.@@@@1@32@@oe@19-12-2010 839518812@GENIA Treebank@formal@@1@S@Surprisingly, this was the case even when an antagonistic anti-TR55 antibody was used.@@@@1@15@@oe@19-12-2010 839518813@GENIA Treebank@formal@@1@S@Anti-TR55 antibody cross-linking in chronically infected U1 promonocytic cultures could only partially substitute for TNF-alpha-induced HIV-1 expression.@@@@1@18@@oe@19-12-2010 839518814@GENIA Treebank@formal@@1@S@CONCLUSIONS: Our results demonstrated that HIV-1 infection can selectively influence the surface expression of TNF receptors, potentially influencing its own expression and altering normal immunoregulatory signal transduction.@@@@1@30@@oe@19-12-2010 841964401@GENIA Treebank@formal@@1@S@Human immunodeficiency viruses containing heterologous enhancer/promoters are replication competent and exhibit different lymphocyte tropisms.@@@@1@15@@oe@19-12-2010 841964402@GENIA Treebank@formal@@1@S@The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) contains binding sites for nuclear factor kappa B (NF-kappa B) and the constitutively expressed transcription factor Sp1, both of which are highly conserved in HIV and simian immunodeficiency virus isolates.@@@@1@49@@oe@19-12-2010 841964403@GENIA Treebank@formal@@1@S@To delineate the effects of these motifs on the replicative capacity of HIV and to explore the possibility of extending the virus host range, known heterologous enhancer/promoters were inserted into the HIV-1 LTR in place of the NF-kappa B and Sp1 binding sites.@@@@1@45@@oe@19-12-2010 841964404@GENIA Treebank@formal@@1@S@The effects of these substitutions on viral replication in transfected HeLa cells and on HIV infection of human peripheral blood lymphocytes or continuous T-leukemia cell lines were evaluated.@@@@1@29@@oe@19-12-2010 841964405@GENIA Treebank@formal@@1@S@HIVs in which the NF-kappa B/Sp1 enhancer plus the downstream TATA element were replaced with heterologous enhancer/promoters were also constructed.@@@@1@22@@oe@19-12-2010 841964406@GENIA Treebank@formal@@1@S@Viruses containing the human cytomegalovirus immediate-early enhancer exhibited infectious kinetics similar to that of wild-type HIV in activated human peripheral blood lymphocytes and AA2 cells but replicated less efficiently in H9 and CEM cells.@@@@1@35@@oe@19-12-2010 841964407@GENIA Treebank@formal@@1@S@These studies indicate that heterologous enhancer elements are capable of restoring Tat responsiveness to the HIV LTR in the context of directing reporter gene expression as well as in the production of infectious progeny virions.@@@@1@36@@oe@19-12-2010 841993101@GENIA Treebank@formal@@1@S@Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors [published erratum appears in Proc Natl Acad Sci U S A 1993 Apr 15;90(8):3775]@@@@1@45@@oe@19-12-2010 841993102@GENIA Treebank@formal@@1@S@Ionizing radiation triggers a signal in human B-lymphocyte precursors that is intimately linked to an active protein-tyrosine kinase regulatory pathway.@@@@1@21@@oe@19-12-2010 841993103@GENIA Treebank@formal@@1@S@We show that in B-lymphocyte precursors, irradiation with gamma-rays leads to (i) stimulation of phosphatidylinositol turnover; (ii) downstream activation by covalent modification of multiple serine-specific protein kinases, including protein kinase C; and (iii) activation of nuclear factor kappa B.@@@@1@50@@oe@19-12-2010 841993104@GENIA Treebank@formal@@1@S@All of the radiation-induced signals were effectively prevented by the protein-tyrosine kinase inhibitors genistein and herbimycin A.@@@@1@18@@oe@19-12-2010 841993105@GENIA Treebank@formal@@1@S@Thus, tyrosine phosphorylation is an important and perhaps mandatory proximal step in the activation of the protein kinase C signaling cascade in human B-lymphocyte precursors.@@@@1@27@@oe@19-12-2010 841993106@GENIA Treebank@formal@@1@S@Our report expands current knowledge of the radiation-induced signaling cascade by clarifying the chronological sequence of biochemical events that follow irradiation.@@@@1@22@@oe@19-12-2010 842227401@GENIA Treebank@formal@@1@S@A human putative lymphocyte G0/G1 switch gene homologous to a rodent gene encoding a zinc-binding potential transcription factor.@@@@1@19@@oe@19-12-2010 842227402@GENIA Treebank@formal@@1@S@G0S24 is a member of a set of genes (putative G0/G1 switch regulatory genes) that are expressed transiently within 1-2 hr of the addition of lectin or cycloheximide to human blood mononuclear cells.@@@@1@36@@oe@19-12-2010 842227403@GENIA Treebank@formal@@1@S@Comparison of a full-length cDNA sequence with the corresponding genomic sequence reveals an open reading frame of 326 amino acids, distributed across two exons.@@@@1@26@@oe@19-12-2010 842227404@GENIA Treebank@formal@@1@S@Potential phosphorylation sites include the sequence PSPTSPT, which resembles an RNA polymerase II repeat reported to be a target of the cell cycle control kinase cdc2.@@@@1@28@@oe@19-12-2010 842227405@GENIA Treebank@formal@@1@S@Comparison of the derived protein sequence with those of rodent homologs allows classification into three groups.@@@@1@17@@oe@19-12-2010 842227406@GENIA Treebank@formal@@1@S@Group 1 contains G0S24 and the rat and mouse TIS11 genes (also known as TTP, Nup475, and Zfp36).@@@@1@23@@oe@19-12-2010 842227407@GENIA Treebank@formal@@1@S@Members of this group have three tetraproline repeats.@@@@1@9@@oe@19-12-2010 842227408@GENIA Treebank@formal@@1@S@Groups 1 and 2 have a serine-rich region and an "arginine element" (RRLPIF) at the carboxyl terminus.@@@@1@22@@oe@19-12-2010 842227409@GENIA Treebank@formal@@1@S@All groups contain cysteine- and histidine-rich putative zinc finger domains and a serine-phenylalanine "SFS" domain similar to part of the large subunit of eukaryotic RNA polymerase II.@@@@1@30@@oe@19-12-2010 842227410@GENIA Treebank@formal@@1@S@Comparison of group 1 human and mouse genomic sequences shows high conservation in the 5' flank and exons.@@@@1@19@@oe@19-12-2010 842227411@GENIA Treebank@formal@@1@S@A CpG island suggests expression in the germ line.@@@@1@10@@oe@19-12-2010 842227412@GENIA Treebank@formal@@1@S@G0S24 has potential sites for transcription factors in the 5' flank and intron; these include a serum response element.@@@@1@21@@oe@19-12-2010 842227413@GENIA Treebank@formal@@1@S@Protein and genomic sequences show similarities with those of a variety of proteins involved in transcription, suggesting that the G0S24 product has a similar role.@@@@1@27@@oe@19-12-2010 842245901@GENIA Treebank@formal@@1@S@Interleukin-4 inhibits the lipopolysaccharide-induced expression of c-jun and c-fos messenger RNA and activator protein-1 binding activity in human monocytes.@@@@1@20@@oe@19-12-2010 842245902@GENIA Treebank@formal@@1@S@We studied the effect of interleukin-4 (IL-4) on the lipopolysaccharide (LPS) induction of two immediate early genes c-fos and c-jun.@@@@1@25@@oe@19-12-2010 842245903@GENIA Treebank@formal@@1@S@These genes encode proteins that form the dimeric complex activator protein-1 (AP-1), which is active as a transcriptional factor.@@@@1@23@@oe@19-12-2010 842245904@GENIA Treebank@formal@@1@S@Maximal accumulation of either c-fos and c-jun messenger RNA (mRNA) occurred 30 minutes after LPS addition.@@@@1@19@@oe@19-12-2010 842245905@GENIA Treebank@formal@@1@S@When cells were treated with IL-4 for 5 hours before LPS activation, both the c-fos and the c-jun mRNA expression was decreased.@@@@1@24@@oe@19-12-2010 842245906@GENIA Treebank@formal@@1@S@The inhibition of c-fos and c-jun expression by IL-4 in LPS-treated cells was shown to be due to a lower transcription rate of the c-fos and c-jun genes.@@@@1@29@@oe@19-12-2010 842245907@GENIA Treebank@formal@@1@S@IL-4 did not affect the stability of the c-fos and c-jun transcripts.@@@@1@13@@oe@19-12-2010 842245908@GENIA Treebank@formal@@1@S@Finally, using electrophoretic mobility shift assays, evidence was obtained that IL-4 inhibits LPS-induced expression of AP-1 protein.@@@@1@20@@oe@19-12-2010 842245909@GENIA Treebank@formal@@1@S@These data indicate that IL-4 suppresses the induction of transcription factors in human activated monocytes.@@@@1@16@@oe@19-12-2010 842399301@GENIA Treebank@formal@@1@S@Ras oncogene transformation of human B lymphoblasts is associated with lymphocyte activation and with a block of differentiation.@@@@1@19@@oe@19-12-2010 842399302@GENIA Treebank@formal@@1@S@The p21ras small GTP binding proteins participate in signal transduction from cell surface receptors and affect neoplastic transformation and development in many different cell types.@@@@1@26@@oe@19-12-2010 842399303@GENIA Treebank@formal@@1@S@In the present study, we examined the relationship between ras transformation and differentiation of human B lymphocytes.@@@@1@19@@oe@19-12-2010 842399304@GENIA Treebank@formal@@1@S@We show that the constitutive expression of the T24 Ha-ras oncogene in EBV-immortalized B lymphoblasts was associated with the induction of the interleukin 2 receptor alpha subunit, with an impaired immunoglobulin gene expression, altered adhesion properties and increased survival in serum-free medium.@@@@1@45@@oe@19-12-2010 842399305@GENIA Treebank@formal@@1@S@Since induction of the IL-2 receptor alpha subunit is a hallmark of lymphocyte activation, we suggest that p21ras naturally triggers B cell activation.@@@@1@25@@oe@19-12-2010 842399306@GENIA Treebank@formal@@1@S@The ras-transformed lymphocytes displayed a fully functional IL-2r, as assessed by c-fos induction following treatment with IL-2; nevertheless, they were not growth stimulated by this lymphokine.@@@@1@30@@oe@19-12-2010 842399307@GENIA Treebank@formal@@1@S@The decreased expression of immunoglobulin genes indicates that the ras oncogene blocks terminal differentiation to plasma cells, possibly by inhibiting the activity of lymphocyte-specific transcription factors.@@@@1@28@@oe@19-12-2010 842399308@GENIA Treebank@formal@@1@S@Somewhat unexpectedly, the constitutive p21ras activity did not cause an increased DNA binding of transcription factors PEA1 (AP1), PEA3, Oct-2 or NF-kB.@@@@1@28@@oe@19-12-2010 842410101@GENIA Treebank@formal@@1@S@Transcription factor GATA-1 and erythroid development.@@@@1@7@@oe@19-12-2010 842410102@GENIA Treebank@formal@@1@S@In summary, we derived an experimental system that allows us to dissect the function of GATA-1 in red cell development at a genetic level.@@@@1@26@@oe@19-12-2010 842410103@GENIA Treebank@formal@@1@S@We have established the essential nature of GATA-1 during both primitive and definitive erythropoiesis.@@@@1@15@@oe@19-12-2010 842410104@GENIA Treebank@formal@@1@S@By ablating the expression of the endogenous GATA-1 gene, we are in a position to introduce a variety of constructs that harbor subtle modifications in flanking or protein-coding sequences.@@@@1@31@@oe@19-12-2010 842410105@GENIA Treebank@formal@@1@S@We can now study regulatory regions and functional domains of the protein in the context of a true erythroid environment, experiments that have not been possible heretofore.@@@@1@29@@oe@19-12-2010 842410106@GENIA Treebank@formal@@1@S@Although the assay involves the dramatic loss of red cell production, it should be possible to define important regulatory domains that can then be assayed using less stringent systems, such as cell-free extracts for in vitro transcription.@@@@1@40@@oe@19-12-2010 842410107@GENIA Treebank@formal@@1@S@The ideal situation would be analyses conducted in GATA-1- erythroid cells.@@@@1@12@@oe@19-12-2010 842410108@GENIA Treebank@formal@@1@S@However, these cells have been impossible to generate given the requirement of GATA-1 for Epo receptor expression and red cell viability (C. Simon and S. Orkin, unpublished observations).@@@@1@33@@oe@19-12-2010 842410109@GENIA Treebank@formal@@1@S@It may be possible to produce such cells by first expressing the Epo receptor under the influence of a constitutive promoter and then targeting the GATA-1 gene.@@@@1@28@@oe@19-12-2010 842410110@GENIA Treebank@formal@@1@S@If GATA-1- red cells were available, the analyses would involve the actual transcription of or chromatin structure surrounding the globin genes.@@@@1@23@@oe@19-12-2010 842410111@GENIA Treebank@formal@@1@S@Structure-function studies of the GATA-1 protein could be greatly simplified and a larger number of mutants studied.@@@@1@18@@oe@19-12-2010 842410112@GENIA Treebank@formal@@1@S@However, the ES cell system can be used as an alternative until targeted erythroleukemia cells become available.@@@@1@19@@oe@19-12-2010 842410113@GENIA Treebank@formal@@1@S@Other applications involve the introduction of other GATA-binding protein family members to determine whether they rescue the mutation.@@@@1@19@@oe@19-12-2010 842410114@GENIA Treebank@formal@@1@S@If they cannot, chimeric proteins can be tested to identify which amino acids distinguish the different family members.@@@@1@21@@oe@19-12-2010 842410115@GENIA Treebank@formal@@1@S@We feel that these experiments are vital to understanding the function of GATA-1 during erythroid ontogeny.@@@@1@17@@oe@19-12-2010 842410116@GENIA Treebank@formal@@1@S@How does GATA-1 regulate red cell genes like globin or the Epo receptor?@@@@1@14@@oe@19-12-2010 842410117@GENIA Treebank@formal@@1@S@Once we identify the functional domains of the GATA-binding proteins, we hope to learn what proteins GATA-1 binds to in the basic transcription machinery or in chromatin.@@@@1@29@@oe@19-12-2010 842410118@GENIA Treebank@formal@@1@S@Is GATA-1 necessary for globin gene switching?@@@@1@8@@oe@19-12-2010 842410119@GENIA Treebank@formal@@1@S@GATA-1 may be modified differently during development so that the locus control region can interact with different globin promoters.@@@@1@20@@oe@19-12-2010 842410120@GENIA Treebank@formal@@1@S@We may find that one region of the protein is required for embryonic expression and another for adult globin gene expression.@@@@1@22@@oe@19-12-2010 842798301@GENIA Treebank@formal@@1@S@Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type I (HTLV-I) tax and HTLV-II tax proteins.@@@@1@26@@oe@19-12-2010 842798302@GENIA Treebank@formal@@1@S@The human T-cell leukemia virus type I (HTLV-I) and HTLV-II Tax proteins are potent transactivators of viral and cellular gene expression.@@@@1@24@@oe@19-12-2010 842798303@GENIA Treebank@formal@@1@S@Using deletion mutants, the downstream parathyroid hormone-related protein (PTHrP) promoter is shown to be responsive to both HTLV-I and HTLV-II Tax as well as the AP1/c-jun proto-oncogene.@@@@1@31@@oe@19-12-2010 842798304@GENIA Treebank@formal@@1@S@Transactivation of PTHrP by Tax was seen in T cells but not in B-cell lines or fibroblasts.@@@@1@18@@oe@19-12-2010 842798305@GENIA Treebank@formal@@1@S@A carboxy terminal Tax deletion mutant was deficient in transactivation of both the PTHrP and IL2R alpha promoters but not the HTLV-I long terminal repeat (LTR).@@@@1@29@@oe@19-12-2010 842798306@GENIA Treebank@formal@@1@S@Exogenous provision of NFkB rescued IL2R alpha expression but not the PTHrP promoter.@@@@1@14@@oe@19-12-2010 842798307@GENIA Treebank@formal@@1@S@Thus, HTLV-I Tax, HTLV-II Tax, and c-jun transactivate PTHrP and may contribute to the pathogenesis of hypercalcemia in adult T-cell leukemia.@@@@1@25@@oe@19-12-2010 843006901@GENIA Treebank@formal@@1@S@The c-rel protooncogene product represses NF-kappa B p65-mediated transcriptional activation of the long terminal repeat of type 1 human immunodeficiency virus.@@@@1@22@@oe@19-12-2010 843006902@GENIA Treebank@formal@@1@S@The long terminal repeat (LTR) of the type 1 human immunodeficiency virus (HIV-1) and the 5' regulatory region of the gene encoding the interleukin 2 receptor alpha subunit (IL-2R alpha) share functional kappa B enhancer elements involved in the regulation of these inducible transcription units during T-cell activation.@@@@1@55@@oe@19-12-2010 843006903@GENIA Treebank@formal@@1@S@These kappa B enhancer elements are recognized by a structurally related family of interactive proteins that includes p50, p65, and the product of the c-rel protooncogene (c-Rel).@@@@1@32@@oe@19-12-2010 843006904@GENIA Treebank@formal@@1@S@Recent biochemical studies have shown that p65 and p50 form the prototypical NF-kappa B complex, which is rapidly translocated from the cytoplasm to the nucleus during T-cell activation.@@@@1@30@@oe@19-12-2010 843006905@GENIA Treebank@formal@@1@S@This intracellular signaling complex potently stimulates kappa B-directed transcription from either the HIV-1 LTR or the IL-2R alpha promoter via the strong transactivation domain present in p65.@@@@1@28@@oe@19-12-2010 843006906@GENIA Treebank@formal@@1@S@We now demonstrate that nuclear expression of human c-Rel, which is induced by either phorbol ester or tumor necrosis factor alpha with delayed kinetics relative to p65, markedly represses p65-mediated activation of these transcription units.@@@@1@38@@oe@19-12-2010 843006907@GENIA Treebank@formal@@1@S@These inhibitory effects of c-Rel correlate with its DNA-binding activity but not with its ability to heterodimerize with p50, suggesting that c-Rel inhibition involves competition with p50/p65 for occupancy of the kappa B enhancer element.@@@@1@37@@oe@19-12-2010 843006908@GENIA Treebank@formal@@1@S@Together, these findings suggest that one function of c-Rel is as a physiologic repressor of the HIV-1 LTR and IL-2R alpha promoters, serving to efficiently counter the strong transcriptional activating effects of p65.@@@@1@36@@oe@19-12-2010 843723501@GENIA Treebank@formal@@1@S@Replication of type 1 human immunodeficiency viruses containing linker substitution mutations in the -201 to -130 region of the long terminal repeat.@@@@1@23@@oe@19-12-2010 843723502@GENIA Treebank@formal@@1@S@In previous transfection analyses using the chloramphenicol acetyltransferase reporter gene system, we determined that linker substitution (LS) mutations between -201 and -130 (relative to the transcription start site) of the human immunodeficiency virus type 1 long terminal repeat (LTR) caused moderate decreases in LTR transcriptional activity in a T-cell line (S.L.Zeichner, J.Y.H. Kim, and J.C.Alwine, J.Virol.65:2436-2444, 1991).@@@@1@74@@oe@19-12-2010 843723503@GENIA Treebank@formal@@1@S@In order to confirm the significance of this region in the context of viral replication, we constructed several of these LS mutations (-201 to - 184, -183 to -166, -165 to -148, and -148 to -130) in proviruses and prepared viral stocks by cocultivation of transfected RD cells with CEMx174 cells.@@@@1@57@@oe@19-12-2010 843723504@GENIA Treebank@formal@@1@S@In addition, two mutations between -93 and -76 and between -75 and -58 were utilized, since they affect the nuclear factor kappa B (NF-kappa B)- and Sp1-binding sites and were expected to diminish viral replication.@@@@1@41@@oe@19-12-2010 843723505@GENIA Treebank@formal@@1@S@Our results suggest that while transfection analyses offer an adequate approximation of the effects of the LS mutations, the analysis of viral replication using a mutant viral stock presents a more accurate picture, which is sometimes at variance with the transfection results.@@@@1@45@@oe@19-12-2010 843723506@GENIA Treebank@formal@@1@S@Three mutants (-201/-184 NXS, -165/-148 NXS, and -147/-130 NXS) had effects on viral replication that were much more severe than the effects predicted from their performance in transfection analyses, and the effects of two LS mutations (-201/-184 NXS and -183/-166 NXS) were not predicted by their effects in transfection.@@@@1@57@@oe@19-12-2010 843723507@GENIA Treebank@formal@@1@S@In addition, we observed cell type-specific permissiveness to replication of some mutant viruses.@@@@1@15@@oe@19-12-2010 843723508@GENIA Treebank@formal@@1@S@In the cell types tested, the LS mutations indicated an apparent requirement not only for the intact NF-kappa B and SP1-binding sites but also for several regions between -201 and -130 not previously associated with viral infectivity.@@@@1@39@@oe@19-12-2010 844137701@GENIA Treebank@formal@@1@S@Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3).@@@@1@23@@oe@19-12-2010 844137702@GENIA Treebank@formal@@1@S@Inducible expression of human immunodeficiency virus (HIV) is regulated by a cellular transcription factor, nuclear factor kappa B (NF-kappa B).@@@@1@26@@oe@19-12-2010 844137703@GENIA Treebank@formal@@1@S@NF-kappa B is composed of distinct subunits; five independent genes, NFKB1(p105), NFKB2(p100), RelA(p65), c-rel and relB, that encode related proteins that bind to kappa B DNA elements have been isolated.@@@@1@37@@oe@19-12-2010 844137704@GENIA Treebank@formal@@1@S@We have previously found that NFKB2(p49/p52) acts in concert with RelA(p65) to stimulate the HIV enhancer in Jurkat T-leukemia cells.@@@@1@21@@oe@19-12-2010 844137705@GENIA Treebank@formal@@1@S@Here we examine the biochemical basis for the transcriptional regulation of HIV by NFKB2.@@@@1@15@@oe@19-12-2010 844137706@GENIA Treebank@formal@@1@S@Using Scatchard analysis, we have determined the dissociation constants of homodimeric p49 and heterodimeric p49/p65 for binding to the HIV kappa B site.@@@@1@25@@oe@19-12-2010 844137707@GENIA Treebank@formal@@1@S@p49 has a approximately 18-fold-lower affinity for the HIV kappa B site (KD = 69.1 pM) than does the approximately 50-kDa protein NFKB1(p50) derived from p105 (KD = 3.9 pM).@@@@1@35@@oe@19-12-2010 844137708@GENIA Treebank@formal@@1@S@In contrast, the affinity of heterodimeric NFKB2(p49)/RelA(p65) for this site is approximately 6-fold higher (KD = 11.8 pM) than that of p49 alone.@@@@1@27@@oe@19-12-2010 844137709@GENIA Treebank@formal@@1@S@Consistent with these findings, in vitro transcription was stimulated 18-fold by the addition of preformed, heterodimeric NFKB2(p49)/RelA(p65) protein.@@@@1@21@@oe@19-12-2010 844137710@GENIA Treebank@formal@@1@S@Transcriptional activation of the HIV enhancer was also subject to regulation by recently cloned I kappa B-alpha(MAD-3).@@@@1@21@@oe@19-12-2010 844137711@GENIA Treebank@formal@@1@S@Recombinant I kappa B-alpha(MAD-3) inhibited the DNA binding activity of p65, p49/p65, and p50/p65 but stimulated the binding of NFKB2(p49) or NFKB1(p50).@@@@1@28@@oe@19-12-2010 844137712@GENIA Treebank@formal@@1@S@Functional activation of an HIV reporter plasmid by p49/p65 in transiently transfected Jurkat T-leukemia cells was also inhibited by coexpression of MAD-3.@@@@1@23@@oe@19-12-2010 844137713@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@19-12-2010 844677401@GENIA Treebank@formal@@1@S@Expression of the Tat protein of HIV1 in human promonocytic U937 cells.@@@@1@13@@oe@19-12-2010 844677402@GENIA Treebank@formal@@1@S@Numerous studies have shown that, upon HIV1 infection, human promonocytic U937 cells were induced to differentiate, as indicated, for example, by increased expression of adhesion molecules.@@@@1@32@@oe@19-12-2010 844677403@GENIA Treebank@formal@@1@S@One of the viral proteins involved in this process might be the Tat protein.@@@@1@15@@oe@19-12-2010 844677404@GENIA Treebank@formal@@1@S@Indeed, this viral protein, which is essential for productive infection, has also been shown to display growth-stimulating properties and immunomodulatory activities.@@@@1@25@@oe@19-12-2010 844677405@GENIA Treebank@formal@@1@S@In order to apprehend the role of the HIV1 tat gene in inducing the differentiation of HIV1-infected U937 cells, we have successfully introduced this gene into U937 cells by infecting them with retroviral particles transducing tat.@@@@1@38@@oe@19-12-2010 844677406@GENIA Treebank@formal@@1@S@The effect of the Tat protein constitutively expressed by these cells upon their differentiation was then evaluated by looking for the expression of the c-fos and of the c-fms proto-oncogenes which are linked to the differentiation of myelomonoblastic cells.@@@@1@40@@oe@19-12-2010 844677407@GENIA Treebank@formal@@1@S@Northern blot analysis revealed in these cells, an increase in the transcription of these two proto-oncogenes, and this increase was amplified after treatment with phorbol myristate acetate.@@@@1@30@@oe@19-12-2010 844677408@GENIA Treebank@formal@@1@S@No such increase was observed in control U937 cells.@@@@1@10@@oe@19-12-2010 844677409@GENIA Treebank@formal@@1@S@These results indicate that, among HIV1 gene products, the Tat protein appears to trigger monocytic differentiation, and suggests that this viral protein directs progenitors of the monocyte/macrophage lineage towards a differentiation stage in which production of viral antigens and virions might be more efficient.@@@@1@48@@oe@19-12-2010 845411401@GENIA Treebank@formal@@1@S@Transcription factor jun-B is target of autoreactive T-cells in IDDM.@@@@1@11@@oe@19-12-2010 845411402@GENIA Treebank@formal@@1@S@Target antigens defined by autoantibodies in IDDM include insulin, a putative glycolipid that reacts with islet cell antibodies, and a 64,000-M(r) protein recently identified as glutamic acid decarboxylase.@@@@1@31@@oe@19-12-2010 845411403@GENIA Treebank@formal@@1@S@In addition, some IDDM sera that contain antibodies to glutamic acid decarboxylase also coprecipitate a 38,000-M(r) protein from islets.@@@@1@21@@oe@19-12-2010 845411404@GENIA Treebank@formal@@1@S@This study used a high titer anti-38,000-M(r) serum to screen bacteriophage lambda cDNA expression libraries and identified human islet and placental clones encoding jun-B, the nuclear transcription protein, of predicted 38,000 M(r).@@@@1@35@@oe@19-12-2010 845411405@GENIA Treebank@formal@@1@S@Peripheral blood T-cells exhibited significant proliferation in response to a recombinant fragment of jun-B (amino acids 1-180) in 12 of 17 (71%) recent-onset IDDM subjects, 8 of 16 (50%) ICA-positive first-degree relatives of IDDM subjects who were at risk, 3 of 12 (25%) other autoimmune disease subjects, and 0 of 10 healthy control subjects.@@@@1@69@@oe@19-12-2010 845411406@GENIA Treebank@formal@@1@S@Proliferation to tetanus toxoid did not differ significantly between the groups.@@@@1@12@@oe@19-12-2010 845411407@GENIA Treebank@formal@@1@S@Responses to jun-B were not related to age, sex, or human leukocyte antigen status.@@@@1@17@@oe@19-12-2010 845411408@GENIA Treebank@formal@@1@S@Thus, autoreactive T-cells identify a novel antigen, p38 jun-B, in IDDM and appear to indicate subjects at risk for the development of clinical disease.@@@@1@28@@oe@19-12-2010 845562701@GENIA Treebank@formal@@1@S@Interaction between NF-kappa B- and serum response factor-binding elements activates an interleukin-2 receptor alpha-chain enhancer specifically in T lymphocytes.@@@@1@20@@oe@19-12-2010 845562702@GENIA Treebank@formal@@1@S@We find that a short enhancer element containing the NF-kappa B binding site from the interleukin-2 receptor alpha-chain gene (IL-2R alpha) is preferentially activated in T cells.@@@@1@30@@oe@19-12-2010 845562703@GENIA Treebank@formal@@1@S@The IL-2R alpha enhancer binds NF-kappa B poorly and is only weakly activated by the NF-kappa B site alone.@@@@1@20@@oe@19-12-2010 845562704@GENIA Treebank@formal@@1@S@Serum response factor (SRF) binds to a site adjacent to the NF-kappa B site in the IL-2R enhancer, and both sites together have strong transcriptional activity specifically in T cells.@@@@1@34@@oe@19-12-2010 845562705@GENIA Treebank@formal@@1@S@Surprisingly, the levels of SRF constitutively expressed in T cells are consistently higher than in other cell types.@@@@1@20@@oe@19-12-2010 845562706@GENIA Treebank@formal@@1@S@Overexpression of SRF in B cells causes the IL-2R enhancer to function as well as it does in T cells, suggesting that the high level of SRF binding in T cells is functionally important.@@@@1@36@@oe@19-12-2010 845594101@GENIA Treebank@formal@@1@S@The transcriptionally active factors mediating the effect of the HTLV-I Tax transactivator on the IL-2R alpha kappa B enhancer include the product of the c-rel proto-oncogene.@@@@1@27@@oe@19-12-2010 845594102@GENIA Treebank@formal@@1@S@The transactivator HTLV-I Tax activates the promoter of the gene coding for the interleukin 2 alpha-chain receptor (IL-2R alpha) via a kappa B site that can bind several protein species of the rel family.@@@@1@37@@oe@19-12-2010 845594103@GENIA Treebank@formal@@1@S@Tax1 strongly activates the enhancer activity of this motif, in both epithelial HeLa and lymphoid Jurkat cells.@@@@1@19@@oe@19-12-2010 845594104@GENIA Treebank@formal@@1@S@This activation was not observed in undifferentiated embryocarcinoma F9 cells.@@@@1@11@@oe@19-12-2010 845594105@GENIA Treebank@formal@@1@S@Overexpression of the p50, p65 and Rel proteins in these cells showed that significant activation of the IL-2R alpha kappa B site was observed only with Rel and Rel plus p65.@@@@1@33@@oe@19-12-2010 845594106@GENIA Treebank@formal@@1@S@Moreover, whereas both Tax and phorbol 12-myristate 13-acetate (PMA) are able to efficiently induce the binding of NF-kappa B to the IL-2R alpha kappa B site, PMA is functionally inactive.@@@@1@35@@oe@19-12-2010 845594107@GENIA Treebank@formal@@1@S@Using the DNA affinity precipitation assay, we observed that Tax1 is able to efficiently induce the binding of Rel, whereas PMA is not.@@@@1@26@@oe@19-12-2010 845594108@GENIA Treebank@formal@@1@S@This established a clear difference between both stimuli, indicating that Rel is the functionally active factor.@@@@1@18@@oe@19-12-2010 845594109@GENIA Treebank@formal@@1@S@We conclude from these results that the functional activity of members of the rel family is regulated by their interaction with DNA and that Rel can be a potent transcriptional activator on specific kappa B sites.@@@@1@37@@oe@19-12-2010 845858101@GENIA Treebank@formal@@1@S@p105 and p98 precursor proteins play an active role in NF-kappa B-mediated signal transduction.@@@@1@15@@oe@19-12-2010 845858102@GENIA Treebank@formal@@1@S@The Rel/NF-kappa B family of transcription factors is composed of two distinct subgroups, proteins that undergo proteolytic processing and contain SWI6/ankyrin repeats in their carboxyl termini (p105, p98), and those without such repeats that do not require processing (p65, c-Rel, RelB, and Dorsal).@@@@1@54@@oe@19-12-2010 845858103@GENIA Treebank@formal@@1@S@We demonstrate that the p105 and p98 precursors share functional properties with the I kappa B proteins, which also contain SWI6/ankyrin repeats.@@@@1@24@@oe@19-12-2010 845858104@GENIA Treebank@formal@@1@S@Both p105 and p98 were found to form stable complexes with other Rel/NF-kappa B family members, including p65 and c-Rel.@@@@1@22@@oe@19-12-2010 845858105@GENIA Treebank@formal@@1@S@Association with the precursors is sufficient for cytoplasmic retention of either p65 or c-Rel, both of which are otherwise nuclear.@@@@1@22@@oe@19-12-2010 845858106@GENIA Treebank@formal@@1@S@These complexes undergo stimulus-responsive processing to produce active p50/c-Rel and p55/c-Rel complexes.@@@@1@13@@oe@19-12-2010 845858107@GENIA Treebank@formal@@1@S@These observations suggest a second pathway leading to NF-kappa B induction, in which processing of the precursors rather than phosphorylation of I kappa B plays a major role.@@@@1@30@@oe@19-12-2010 846016901@GENIA Treebank@formal@@1@S@Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha.@@@@1@16@@oe@19-12-2010 846016902@GENIA Treebank@formal@@1@S@The NK-kappa B transcription factor complex is sequestered in the cytoplasm by the inhibitory protein I kappa B-alpha (MAD-3).@@@@1@22@@oe@19-12-2010 846016903@GENIA Treebank@formal@@1@S@Various cellular stimuli relieve this inhibition by mechanisms largely unknown, leading to NF-kappa B nuclear localization and transactivation of its target genes.@@@@1@24@@oe@19-12-2010 846016904@GENIA Treebank@formal@@1@S@It is demonstrated here with human T lymphocytes and monocytes that different stimuli, including tumor necrosis factor alpha and phorbol 12-myristate 13-acetate, cause rapid degradation of I kappa B-alpha, with concomitant activation of NF-kappa B, followed by a dramatic increase in I kappa B-alpha mRNA and protein synthesis.@@@@1@53@@oe@19-12-2010 846016905@GENIA Treebank@formal@@1@S@Transfection studies reveal that the I kappa B-alpha mRNA and the encoded protein are potently induced by NF-kappa B and by homodimers of p65 and of c-Rel.@@@@1@28@@oe@19-12-2010 846016906@GENIA Treebank@formal@@1@S@We propose a model in which NF-kappa B and I kappa B-alpha mutually regulate each other in a cycle: saturating amounts of the inhibitory I kappa B-alpha protein are destroyed upon stimulation, allowing rapid activation of NF-kappa B.@@@@1@41@@oe@19-12-2010 846016907@GENIA Treebank@formal@@1@S@Subsequently, I kappa B-alpha mRNA and protein levels are quickly induced by the activated NF-kappa B.@@@@1@18@@oe@19-12-2010 846016908@GENIA Treebank@formal@@1@S@This resurgence of I kappa B-alpha protein acts to restore an equilibrium in which NF-kappa B is again inhibited.@@@@1@20@@oe@19-12-2010 846266201@GENIA Treebank@formal@@1@S@Induced myeloid differentiation of K562 cells with downregulation of erythroid and megakaryocytic transcription factors: a novel experimental model for hemopoietic lineage restriction.@@@@1@24@@oe@19-12-2010 846266202@GENIA Treebank@formal@@1@S@The human erythroleukemia cell line K562 can be induced to differentiate along the erythroid and megakaryocytic lineages.@@@@1@18@@oe@19-12-2010 846266203@GENIA Treebank@formal@@1@S@Here we demonstrate that hexamethylene bisacetamide (HMBA) induced K562 cells to differentiate along a third pathway.@@@@1@19@@oe@19-12-2010 846266204@GENIA Treebank@formal@@1@S@This was accompanied by downregulation of two transcription factors normally expressed in erythroid, mast and megakaryocyte lineages.@@@@1@19@@oe@19-12-2010 846266205@GENIA Treebank@formal@@1@S@Northern analysis demonstrated coordinate downregulation of alpha globin and gamma globin in addition to the two lineage-restricted transcription factors, SCL and GATA-1.@@@@1@24@@oe@19-12-2010 846266206@GENIA Treebank@formal@@1@S@Proliferation of the K562 cells was also suppressed.@@@@1@9@@oe@19-12-2010 846266207@GENIA Treebank@formal@@1@S@Clonal assay showed that the suppression was irreversible and appeared analogous to the commitment of murine erythroleukemia (MEL) cells to terminal differentiation.@@@@1@25@@oe@19-12-2010 846266208@GENIA Treebank@formal@@1@S@In contrast to MEL cells, however, K562 cells acquired a macrophage-like morphology and exhibited a complete failure to generate benzidine-positive cells.@@@@1@24@@oe@19-12-2010 846266209@GENIA Treebank@formal@@1@S@Electron microscopy revealed a marked increase in granules resembling those specific for eosinophils.@@@@1@14@@oe@19-12-2010 846266210@GENIA Treebank@formal@@1@S@Surface marker analysis showed that HMBA-induced cells expressed reduced levels of glycophorin A, CD5, CD7 and CD11b.@@@@1@20@@oe@19-12-2010 846266211@GENIA Treebank@formal@@1@S@No upregulation of megakaryocyte or lymphoid markers occurred.@@@@1@9@@oe@19-12-2010 846266212@GENIA Treebank@formal@@1@S@Thus the response of K562 cells to HMBA may provide a useful experimental system for studying the molecular mechanisms responsible for downmodulation of lineage-restricted transcription factors during hemopoietic lineage commitment.@@@@1@31@@oe@19-12-2010 846847001@GENIA Treebank@formal@@1@S@A protein of the AP-1 family is a component of nuclear factor of activated T cells.@@@@1@17@@oe@19-12-2010 846847002@GENIA Treebank@formal@@1@S@Nuclear factor of activated T cells (NF-AT) is a transcriptional activator involved in the induction of IL-2 gene expression.@@@@1@22@@oe@19-12-2010 846847003@GENIA Treebank@formal@@1@S@The response element for NF-AT is a sequence localized between -285/-254 in the IL-2 regulatory region.@@@@1@17@@oe@19-12-2010 846847004@GENIA Treebank@formal@@1@S@The composition of NF-AT protein is still not fully elucidated.@@@@1@11@@oe@19-12-2010 846847005@GENIA Treebank@formal@@1@S@We demonstrate that, in normal human T cells, an AP-1 protein is a component of the NF-AT protein complex.@@@@1@22@@oe@19-12-2010 846847006@GENIA Treebank@formal@@1@S@This was evidenced by the ability of the AP-1 site to compete with the NF-AT site for binding to NF-AT and by the capacity of immobilized anti-Jun and anti-Fos antibodies to deplete NF-AT-binding activity from nuclear extracts of activated T cells.@@@@1@42@@oe@19-12-2010 846847007@GENIA Treebank@formal@@1@S@There was no detectable binding of in vitro translated Jun/Fos heterodimer (AP-1) to the NF-AT sequence, and the NF-AT sequence was unable to inhibit the binding of Jun/Fos to the AP-1 sequence.@@@@1@36@@oe@19-12-2010 846847008@GENIA Treebank@formal@@1@S@The presence of an AP-1 protein in the NF-AT protein complex may regulate NF-AT-binding activity through protein-protein interaction.@@@@1@19@@oe@19-12-2010 847116701@GENIA Treebank@formal@@1@S@Immobilization and recovery of fusion proteins and B-lymphocyte cells using magnetic separation.@@@@1@13@@oe@19-12-2010 847116702@GENIA Treebank@formal@@1@S@A new approach to facilitate immobilization and affinity purification of recombinant proteins and selected human B lymphocytes has been developed.@@@@1@21@@oe@19-12-2010 847116703@GENIA Treebank@formal@@1@S@Using magnetic beads with attached DNA containing the Escherichia coli lac operator, fusion proteins comprising the DNA-binding lac repressor could be affinity-purified and recovered by gentle elution conditions, such as with a lactose analogue or by enzymatic means using either deoxyribonuclease (DNase) or restriction endonucleases.@@@@1@50@@oe@19-12-2010 847116704@GENIA Treebank@formal@@1@S@The results show for the first time that a DNA-binding protein can be used for affinity purification of fusion proteins as exemplified by the specific and gentle recovery of beta-galactosidase and alkaline phosphatase from bacterial lysates using immunomagnetic separation.@@@@1@40@@oe@19-12-2010 847116705@GENIA Treebank@formal@@1@S@The approach was further extended to cell separation by the efficient recovery and elution of human CD37 B lymphocytes from peripheral blood.@@@@1@23@@oe@19-12-2010 847406801@GENIA Treebank@formal@@1@S@Lymphocytes from the site of disease suggest adenovirus is one cause of persistent or recurrent inflammatory arthritis.@@@@1@18@@oe@19-12-2010 847406802@GENIA Treebank@formal@@1@S@The assessment of synovial lymphocyte reactivity to adenovirus antigen stimulation was undertaken in patients with persistent or recurrent inflammatory arthritis.@@@@1@21@@oe@19-12-2010 847406803@GENIA Treebank@formal@@1@S@The 3H-thymidine uptake procedure was employed, incorporating multiple microbiological antigens.@@@@1@12@@oe@19-12-2010 847406804@GENIA Treebank@formal@@1@S@Five patients were found with repeated maximal responses to adenovirus antigen; in one of these adenovirus nucleotide sequences were present in a synovial biopsy specimen.@@@@1@27@@oe@19-12-2010 847406805@GENIA Treebank@formal@@1@S@It is concluded that adenovirus may be one cause of persistent or recurrent inflammatory arthritis.@@@@1@16@@oe@19-12-2010 849245101@GENIA Treebank@formal@@1@S@[The trend of molecular biology study on eosinophils]@@@@1@10@@oe@19-12-2010 849245102@GENIA Treebank@formal@@1@S@Recently, many investigators have been interested in the study on eosinophil biology since genes association with eosinophils such as interleukin-5 or eosinophil granule proteins (EPO, ECP, EDN, MBP, and CLC), were isolated.@@@@1@41@@oe@19-12-2010 849245103@GENIA Treebank@formal@@1@S@However, the molecular basis for the commitment of progenitors to the eosinophil lineage has not been determined.@@@@1@19@@oe@19-12-2010 849245104@GENIA Treebank@formal@@1@S@The mechanism by which eosinophil-specific genes encoding primary and secondary granule proteins (e.g. ECP, EDN, EPO, MBP, and CLC) are expressed and regulated during eosinophilopoiesis is also unknown.@@@@1@35@@oe@19-12-2010 849245105@GENIA Treebank@formal@@1@S@In this paper, I described the characterization of genes encoding eosinophil granule proteins and the mRNA expression of GATA-1 binding transcription factor during eosinophil differentiation.@@@@1@27@@oe@19-12-2010 849618801@GENIA Treebank@formal@@1@S@Oxidoreductive regulation of nuclear factor kappa B.@@@@1@8@@oe@19-12-2010 849618802@GENIA Treebank@formal@@1@S@Involvement of a cellular reducing catalyst thioredoxin.@@@@1@8@@oe@19-12-2010 849618803@GENIA Treebank@formal@@1@S@We have investigated an oxidoreductive regulatory pathway for the DNA binding activity of a pleiotropic cellular transcription factor, nuclear factor kappa B (NF kappa B), has been investigated by using NF kappa B prepared from the nucleus and the cytosol of the primary human T lymphocytes.@@@@1@51@@oe@19-12-2010 849618804@GENIA Treebank@formal@@1@S@We show that a cellular reducing catalyst thioredoxin (Trx) plays a major role in activation of the DNA binding of NF kappa B in vitro and stimulation of transcription from the NF kappa B-dependent gene expression.@@@@1@39@@oe@19-12-2010 849618805@GENIA Treebank@formal@@1@S@We demonstrate evidence suggesting that redox regulation of NF kappa B by Trx might be exerted at a step after dissociation of the inhibitory molecule I kappa B, a cytosolic-anchoring protein for NF kappa B.@@@@1@37@@oe@19-12-2010 849618806@GENIA Treebank@formal@@1@S@To examine the effect of Trx in intact cells, we performed transient assay with a chloramphenicol acetyltransferase-expressing plasmid under the control of human immunodeficiency virus (HIV) long terminal repeat and an effector plasmid expressing human Trx.@@@@1@40@@oe@19-12-2010 849618807@GENIA Treebank@formal@@1@S@The promoter activity from HIV long terminal repeat was greatly augmented by co-transfecting the Trx-expressing plasmid, whose effect was dependent on the NF kappa B-binding sites.@@@@1@28@@oe@19-12-2010 849618808@GENIA Treebank@formal@@1@S@These findings have suggested that cysteine residue(s) of NF kappa B might be involved in the DNA-recognition by NF kappa B and that the redox control mechanism mediated by Trx might have a regulatory role in the NF kappa B-mediated gene expression.@@@@1@46@@oe@19-12-2010 849618809@GENIA Treebank@formal@@1@S@These results may also provide a clue to understanding of the molecular process of AIDS pathogenesis and its possible biochemical intervention.@@@@1@22@@oe@19-12-2010 850061501@GENIA Treebank@formal@@1@S@Calcium dependent activation of the NF-AT transcription factor by p59fyn.@@@@1@11@@oe@19-12-2010 850061502@GENIA Treebank@formal@@1@S@A reporter gene under the control of a T-cell antigen receptor element was activated in Jurkat cells by antigen receptor triggering or by a combination of phorbol myristate acetate, which activates protein kinase C, and a calcium ionophore.@@@@1@41@@oe@19-12-2010 850061503@GENIA Treebank@formal@@1@S@Both these signals were necessary for expression of the reporter gene.@@@@1@12@@oe@19-12-2010 850061504@GENIA Treebank@formal@@1@S@When co-transfected with a construct capable of overexpressing the tyrosine kinase p59fyn, the reporter gene was activated by PMA alone.@@@@1@22@@oe@19-12-2010 850061505@GENIA Treebank@formal@@1@S@Thus p59fyn could replace the calcium ionophore but not activation of protein kinase C.@@@@1@15@@oe@19-12-2010 850061506@GENIA Treebank@formal@@1@S@The activation by p59fyn plus PMA was blocked by EGTA and by the immunosuppressant drug cyclosporin A.@@@@1@18@@oe@19-12-2010 850530901@GENIA Treebank@formal@@1@S@Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells.@@@@1@20@@oe@19-12-2010 850530902@GENIA Treebank@formal@@1@S@Many effects of lipopolysaccharide (LPS) on gene expression, including that of human immunodeficiency virus (HIV), in monocytic cells are mediated by activation of kappa B DNA-binding proteins.@@@@1@34@@oe@19-12-2010 850530903@GENIA Treebank@formal@@1@S@However, the specific members of the NF-kappa B/Rel transcription factor family involved in the LPS response, and the mechanisms through which LPS-generated signals are transduced remain unclear.@@@@1@30@@oe@19-12-2010 850530904@GENIA Treebank@formal@@1@S@Here we show that LPS induces nuclear expression of c-Rel/p50 heterodimers as well as p50/p65 (NF-kappa B) kappa B DNA-binding complexes in human monocytic THP-1 cells.@@@@1@29@@oe@19-12-2010 850530905@GENIA Treebank@formal@@1@S@Nuclear localization of these proteins occurred concomitantly with a rapid decrease in their cytosolic levels and was independent of phorbol ester-sensitive protein kinase C.@@@@1@25@@oe@19-12-2010 850530906@GENIA Treebank@formal@@1@S@Within 24 h following LPS stimulation there was a striking increase in the levels of c-Rel, p105, and p50 in the cytosol.@@@@1@25@@oe@19-12-2010 850530907@GENIA Treebank@formal@@1@S@The increased levels of these proteins correlated with increases in the amounts of their mRNAs during LPS activation of THP-1 cells.@@@@1@22@@oe@19-12-2010 850530908@GENIA Treebank@formal@@1@S@LPS activation of THP-1 cells resulted in phosphorylation of MAD3 (an I kappa B-like protein), a rapid increase in MAD3 mRNA, and an increase in MAD3 protein by 2 h.@@@@1@35@@oe@19-12-2010 850530909@GENIA Treebank@formal@@1@S@Thus, LPS activation of human monocytic cells results in nuclear expression of c-Rel/p50 and p50/p65 (NF-kappa B) and induces phosphorylation of MAD3.@@@@1@26@@oe@19-12-2010 850584701@GENIA Treebank@formal@@1@S@Induction of CD8 antigen and suppressor activity by glucocorticoids in a CEM human leukemic cell clone.@@@@1@17@@oe@19-12-2010 850584702@GENIA Treebank@formal@@1@S@The relationship between glucocorticoid effect and regulation of cell surface antigens was investigated in two models of leukemic cell lines, CEM C7 denoted (r+, ly+) and CEM C1 (r+, ly-).@@@@1@38@@oe@19-12-2010 850584703@GENIA Treebank@formal@@1@S@The reactivity of murine monoclonal antibodies, anti-CD4-FITC, anti-CD8-FITC, anti-CD2-FITC and anti-calla-FITC, were analyzed using flow cytometry.@@@@1@21@@oe@19-12-2010 850584704@GENIA Treebank@formal@@1@S@The suppressor function was determined using [3H]thymidine incorporation into phytohemagglutinin-activated peripheral blood lymphocytes.@@@@1@14@@oe@19-12-2010 850584705@GENIA Treebank@formal@@1@S@Dexamethasone treatment of a human leukemic cell clone CEM C7 caused an increase in a subset of cells expressing the surface antigen CD8, which is present on suppressor and cytotoxic T-lymphocytes.@@@@1@33@@oe@19-12-2010 850584706@GENIA Treebank@formal@@1@S@By comparison, there was no modification of the expression of CD4 antigen, which is expressed at high levels in these cells.@@@@1@24@@oe@19-12-2010 850584707@GENIA Treebank@formal@@1@S@After two days of treatment with 5 x 10(-8) M dexamethasone, CEM C7 cells showed a two-fold increase in suppressor activity compared to untreated cells.@@@@1@27@@oe@19-12-2010 850584708@GENIA Treebank@formal@@1@S@In contrast, there was no regulation by glucocorticoids of either the CD8 or CD4 antigens in the leukemic clone CEM C1.@@@@1@23@@oe@19-12-2010 850584709@GENIA Treebank@formal@@1@S@Furthermore, no modification of the suppressor function in CEM C1 cells by dexamethasone was observed.@@@@1@17@@oe@19-12-2010 850584710@GENIA Treebank@formal@@1@S@In the human leukemic cells studied here, the ability to induce CD8 antigen expression in a CD4+ cells correlates with the ability to induce cell lysis in a glucocorticoid receptor positive cell population.@@@@1@35@@oe@19-12-2010 850835801@GENIA Treebank@formal@@1@S@Proliferation index as a prognostic marker in breast cancer.@@@@1@10@@oe@19-12-2010 850835802@GENIA Treebank@formal@@1@S@BACKGROUND.@@@@1@2@@oe@19-12-2010 850835803@GENIA Treebank@formal@@1@S@The proliferative activity of tumors has been extensively investigated with different approaches, among which the use of the monoclonal antibody Ki-67 represents an easy and reliable means of assessing cell proliferation.@@@@1@33@@oe@19-12-2010 850835804@GENIA Treebank@formal@@1@S@In this study, the proliferative activity of 129 primary breast cancers was investigated, and the results were related to prognosis.@@@@1@23@@oe@19-12-2010 850835805@GENIA Treebank@formal@@1@S@METHODS.@@@@1@2@@oe@19-12-2010 850835806@GENIA Treebank@formal@@1@S@Tumor samples, obtained from 129 patients who underwent surgery between January 1987 and December 1988, were processed for staining by an immunohistochemical procedure (avidin-biotin complex).@@@@1@30@@oe@19-12-2010 850835807@GENIA Treebank@formal@@1@S@The median time of observation was 42 months (range, 31-55 months).@@@@1@15@@oe@19-12-2010 850835808@GENIA Treebank@formal@@1@S@Life-table analysis (Mantel-Cox) was used to assess the probability of disease-free survival (DFS) and overall survival (OS).@@@@1@24@@oe@19-12-2010 850835809@GENIA Treebank@formal@@1@S@RESULTS.@@@@1@2@@oe@19-12-2010 850835810@GENIA Treebank@formal@@1@S@Tumors with high Ki-67 proliferation indices (> 20%) were associated with a higher 4-year probability of relapse of disease (55.3% versus 79.1%; P = 0.003) and death (71% versus 95.6%; P = 0.00005) when compared with tumors with low Ki-67 values.@@@@1@55@@oe@19-12-2010 850835811@GENIA Treebank@formal@@1@S@In addition, this proliferative parameter maintained its prognostic significance when the patients were stratified according to lymph node involvement, menopausal status, and nuclear estrogen receptor content.@@@@1@30@@oe@19-12-2010 850835812@GENIA Treebank@formal@@1@S@CONCLUSIONS.@@@@1@2@@oe@19-12-2010 850835813@GENIA Treebank@formal@@1@S@Tumor proliferative activity as evaluated by the monoclonal antibody Ki-67 seems to be an effective indicator of prognosis in breast cancer for DFS and OS.@@@@1@26@@oe@19-12-2010 851151901@GENIA Treebank@formal@@1@S@Glucocorticoid receptors in mononuclear cells of patients with sepsis.@@@@1@10@@oe@19-12-2010 851151902@GENIA Treebank@formal@@1@S@Glucocorticoid receptor (GR) hormone-binding activity was studied by a whole-cell method in mononuclear cells (MNC) from peripheral blood of 7 patients during the hemodynamic compensatory phase of sepsis.@@@@1@33@@oe@19-12-2010 851151903@GENIA Treebank@formal@@1@S@4 patients were receiving dopamine, which did not affect the GR count.@@@@1@14@@oe@19-12-2010 851151904@GENIA Treebank@formal@@1@S@The patients' plasma cortisol concentrations were normal or slightly elevated.@@@@1@12@@oe@19-12-2010 851151905@GENIA Treebank@formal@@1@S@Despite a wide range, the mean GR count and affinity in MNC from septic patients did not differ from those in normal controls, suggesting that glucocorticoids could still be effective in the hemodynamic compensatory phase of sepsis.@@@@1@40@@oe@19-12-2010 851507501@GENIA Treebank@formal@@1@S@Transcriptional activation of the macrophage colony-stimulating factor gene by IL-2 is associated with secretion of bioactive macrophage colony-stimulating factor protein by monocytes and involves activation of the transcription factor NF-kappa B.@@@@1@32@@oe@19-12-2010 851507502@GENIA Treebank@formal@@1@S@Human peripheral blood monocytes (Mo) constitutively display the beta-chain of the receptor for IL-2, whereas expression of the IL-2R alpha-chain is not constitutive but inducible with IL-2.@@@@1@31@@oe@19-12-2010 851507503@GENIA Treebank@formal@@1@S@Here we report that binding of human IL-2 to its binding site leads to transcriptional activation of the macrophage CSF (M-CSF) gene in Mo resulting in accumulation of M-CSF mRNA and subsequent release of bioactive M-CSF protein as demonstrated by ELISA and inhibition of IL-2 induced release of an activity-stimulating growth of monocyte-type colonies by a neutralizing anti-M-CSF antibody.@@@@1@62@@oe@19-12-2010 851507504@GENIA Treebank@formal@@1@S@Transcriptional activation of the M-CSF gene by IL-2 is preceded by enhanced binding activity of the transcription factor NF-kappa B to its recognition sequence in the 5' regulatory enhancer region of the M-CSF gene.@@@@1@35@@oe@19-12-2010 851507505@GENIA Treebank@formal@@1@S@Moreover, using a heterologous promoter (herpes thymidine kinase) construct containing the NF-kappa B consensus sequence, it is shown that NF-kappa B binding by an IL-2-induced monocyte-derived nuclear protein confers reporter gene (human growth hormone) activity.@@@@1@42@@oe@19-12-2010 851507506@GENIA Treebank@formal@@1@S@Taken together, our findings indicate that IL-2 induces gene expression of M-CSF in human blood-derived Mo and provide evidence for involvement of NF-kappa B in transcriptional regulation of this gene.@@@@1@32@@oe@19-12-2010 852236101@GENIA Treebank@formal@@1@S@Synergy between signal transduction pathways is obligatory for expression of c-fos in B and T cell lines: implication for c-fos control via surface immunoglobulin and T cell antigen receptors.@@@@1@31@@oe@19-12-2010 852236102@GENIA Treebank@formal@@1@S@Expression of the protooncogene c-fos is controlled by three main regulatory pathways involving kinase C, cAMP, and calcium.@@@@1@21@@oe@19-12-2010 852236103@GENIA Treebank@formal@@1@S@Kinase C mediates its effects via phosphorylation of serum response factor (SRF) which interacts with the serum response element (SRE); cAMP and calcium mediate their effects via phosphorylation of CREB (cAMP regulatory element binding protein) presumably by activation of a protein kinase A or calmodulin-regulated kinase.@@@@1@54@@oe@19-12-2010 852236104@GENIA Treebank@formal@@1@S@We have examined the function of these elements in Burkitt's lymphoma cells (Ramos and Daudi) as well as a T lymphocytic cell line (Jurkat).@@@@1@30@@oe@19-12-2010 852236105@GENIA Treebank@formal@@1@S@We have found that stimulation of any one of these pathways alone has little or no effect on c-fos induction.@@@@1@21@@oe@19-12-2010 852236106@GENIA Treebank@formal@@1@S@However, kinase C activation (PMA stimulation) combined with either cAMP (forskolin plus MIX) or calcium stimulation (ionophore) leads to greatly enhanced c-fos induction.@@@@1@31@@oe@19-12-2010 852236107@GENIA Treebank@formal@@1@S@By contrast, cAMP in the presence of calcium shows no synergy in c-fos induction.@@@@1@16@@oe@19-12-2010 852236108@GENIA Treebank@formal@@1@S@Okadaic acid augments PMA- as well as calcium-mediated activation of c-fos, and has little or no effect when combined with cAMP.@@@@1@23@@oe@19-12-2010 852236109@GENIA Treebank@formal@@1@S@The main difference between Ramos (B cells) and Jurkat (T cells) in the regulation of c-fos is that cAMP plus calcium is strongly synergistic in Jurkat and is without effect in Ramos.@@@@1@37@@oe@19-12-2010 852236110@GENIA Treebank@formal@@1@S@Analysis of AP-1 activity using gel mobility shift assays confirms that the requirements for synergy in c-fos mRNA induction are paralleled by requirements for synergy in induction of AP-1 activity.@@@@1@31@@oe@19-12-2010 852236111@GENIA Treebank@formal@@1@S@Signaling in B cells due to anti-Ig stimulation involves both kinase C activation and release of intracellular calcium, and results in c-fos mRNA induction.@@@@1@26@@oe@19-12-2010 852236112@GENIA Treebank@formal@@1@S@Our results indicate that synergy between the kinase C activation and calcium is needed for efficient c-fos induction since neither of these two alone induces c-fos well.@@@@1@28@@oe@19-12-2010 852236113@GENIA Treebank@formal@@1@S@That synergy of signaling pathways is relevant for the anti-Ig induction of c-fos is supported by the fact that cAMP-inducing agents and okadaic acid further enhance anti-Ig induction of c-fos.@@@@1@31@@oe@19-12-2010 852236114@GENIA Treebank@formal@@1@S@These results suggest that cell-specific patterns of synergy are an essential feature for c-fos induction and may be relevant for c-fos control through B and T cell antigen receptors.@@@@1@30@@oe@19-12-2010 852910801@GENIA Treebank@formal@@1@S@Hemoglobin switching in humans is accompanied by changes in the ratio of the transcription factors, GATA-1 and SP1.@@@@1@20@@oe@19-12-2010 852910802@GENIA Treebank@formal@@1@S@BACKGROUND: Understanding the mechanism of developmental regulation of hemoglobin switching has scientific as well as clinical relevance because of the influence of fetal hemoglobin (HbF) production in adulthood on the clinical manifestation of thalassemia and sickle cell anemia.@@@@1@42@@oe@19-12-2010 852910803@GENIA Treebank@formal@@1@S@We have previously found that the normal developmental patterns of globin gene expression are recapitulated in an experimental system of primary cultures that support differentiation of erythroid progenitors.@@@@1@29@@oe@19-12-2010 852910804@GENIA Treebank@formal@@1@S@We further found that high activities of the transcriptional activators, GATA-1 and SP1, are associated with normal adult erythroid differentiation.@@@@1@23@@oe@19-12-2010 852910805@GENIA Treebank@formal@@1@S@MATERIALS AND METHODS: In the present work, we have studied, the activities of GATA-1 and SP1 during differentiation of cultured erythroid progenitors derived from cord blood and from fetal livers, as well as from beta zero-thalassemia patients.@@@@1@42@@oe@19-12-2010 852910806@GENIA Treebank@formal@@1@S@RESULTS: The results showed high GATA-1 binding activity and very low SP1 activity in the fetal liver cultures.@@@@1@20@@oe@19-12-2010 852910807@GENIA Treebank@formal@@1@S@This pattern was in contrast to cultures derived from normal adult peripheral blood, in which both GATA-1 and SP1 activities were high.@@@@1@24@@oe@19-12-2010 852910808@GENIA Treebank@formal@@1@S@Cord blood cultures showed an additive combination of "adult" and "fetal" patterns.@@@@1@17@@oe@19-12-2010 852910809@GENIA Treebank@formal@@1@S@The progenitors derived from a beta zero-thalassemia patient with high HbF production showed "fetal" pattern.@@@@1@18@@oe@19-12-2010 852910810@GENIA Treebank@formal@@1@S@On the other hand, in cultures of 2 beta zero-thalassemia patients without high HbF, "adult" pattern was observed.@@@@1@23@@oe@19-12-2010 852910811@GENIA Treebank@formal@@1@S@CONCLUSIONS: In the present work, we show that human fetal and adult erythroid progenitors are distinct in their transcription factors, and that the commitment to fetal or adult program occurs at a very early differentiation stage.@@@@1@40@@oe@19-12-2010 852910812@GENIA Treebank@formal@@1@S@Our studies also demonstrate that under anemic stress, recruitment of fetal progenitors may occur in adulthood.@@@@1@18@@oe@19-12-2010 852965701@GENIA Treebank@formal@@1@S@Transcriptional activation and repression, two properties of the lymphoid-specific transcription factor Oct-2a.@@@@1@14@@oe@19-12-2010 852965702@GENIA Treebank@formal@@1@S@The lymphoid-specific transcription factor Oct-2a contains two transcriptional activation domains which are located within the N-terminal and C-terminal regions.@@@@1@20@@oe@19-12-2010 852965703@GENIA Treebank@formal@@1@S@To study their differential activation properties, we linked the isolated effector domains to the GAL4 DNA-binding domain.@@@@1@19@@oe@19-12-2010 852965704@GENIA Treebank@formal@@1@S@We have shown that both activating regions of Oct-2a, isolated from their natural context, can activate transcription as promoter factors.@@@@1@23@@oe@19-12-2010 852965705@GENIA Treebank@formal@@1@S@In contrast to the C-terminus, activation by the N-terminal domain is dependent on a yet unidentified factor(s) binding to the simian virus 40 enhancer.@@@@1@29@@oe@19-12-2010 852965706@GENIA Treebank@formal@@1@S@The results obtained by duplication of activation domains or their mixed combination suggest that the domains are functionally independent.@@@@1@20@@oe@19-12-2010 852965707@GENIA Treebank@formal@@1@S@However, activation from a remote position could only be achieved with the C-terminus of Oct-2a in B cells.@@@@1@20@@oe@19-12-2010 852965708@GENIA Treebank@formal@@1@S@In lymphoid cells, higher activation levels were observed, suggesting that distinct B-cell-specific cofactors in concert with the effector domains of Oct-2a might be involved in mediating transcription from proximal and remote positions.@@@@1@35@@oe@19-12-2010 852965709@GENIA Treebank@formal@@1@S@Furthermore, we identified a repression domain at the N-terminus of Oct-2a.@@@@1@13@@oe@19-12-2010 852965710@GENIA Treebank@formal@@1@S@When transferred to a potent activator, transcriptional stimulation was inhibited efficiently.@@@@1@13@@oe@19-12-2010 852965711@GENIA Treebank@formal@@1@S@These results underscore the modular structure of Oct-2a with separable domains for activation and repression and suggest that Oct-2a might have complex regulatory functions in vivo.@@@@1@27@@oe@19-12-2010 853015601@GENIA Treebank@formal@@1@S@Circumvention of tolerance for the nuclear T cell protein TCF-1 by immunization of TCF-1 knock-out mice.@@@@1@17@@oe@19-12-2010 853015602@GENIA Treebank@formal@@1@S@Molecular events that underlie the well-defined phenotypic changes of the differentiating thymocyte are poorly understood.@@@@1@16@@oe@19-12-2010 853015603@GENIA Treebank@formal@@1@S@A candidate gene to control thymocyte differentiation, T cell factor-1 (TCF-1)* encodes a DNA-binding protein.@@@@1@20@@oe@19-12-2010 853015604@GENIA Treebank@formal@@1@S@Its mRNA expression pattern is complex during embryogenesis, yet restricted to lymphocytes postnatally.@@@@1@15@@oe@19-12-2010 853015605@GENIA Treebank@formal@@1@S@Expression studies on TCF-1 protein have been hampered by the difficulty to raise antibodies due to extreme evolutionary conservation.@@@@1@20@@oe@19-12-2010 853015606@GENIA Treebank@formal@@1@S@TCF-1 knock-out mice, generated recently in our laboratory, have strongly decreased numbers of thymocytes, but are otherwise normal.@@@@1@22@@oe@19-12-2010 853015607@GENIA Treebank@formal@@1@S@We have used these mice to generate anti-TCF-1 antibodies.@@@@1@10@@oe@19-12-2010 853015608@GENIA Treebank@formal@@1@S@By immunization with a recombinant fusion protein, we show that TCF-1 knock-out mice readily yield antiserum titers against human and mouse TCF-1 protein.@@@@1@25@@oe@19-12-2010 853015609@GENIA Treebank@formal@@1@S@Wild-type littermates remain unresponsive to TCF-1 while they mount a high-titer antibody response to the fusion protein, Maltose Binding Protein (MBP).@@@@1@25@@oe@19-12-2010 853015610@GENIA Treebank@formal@@1@S@Subsequently, TCF-1-specific hybridomas could be prepared from the spleens of immunized knock-out mice.@@@@1@15@@oe@19-12-2010 853015611@GENIA Treebank@formal@@1@S@This study illustrates the almost complete tolerance of mice for human TCF-1 and demonstrates that this tolerance is readily broken by gene knock-out.@@@@1@24@@oe@19-12-2010 853015612@GENIA Treebank@formal@@1@S@Furthermore, the usefulness of knock-out mice for the generation of monoclonal antibodies against the gene product of interest is underscored.@@@@1@22@@oe@19-12-2010 853048301@GENIA Treebank@formal@@1@S@Solution structure of the sequence-specific HMG box of the lymphocyte transcriptional activator Sox-4.@@@@1@14@@oe@19-12-2010 853048302@GENIA Treebank@formal@@1@S@Two groups of HMG box proteins are distinguished.@@@@1@9@@oe@19-12-2010 853048303@GENIA Treebank@formal@@1@S@Proteins in the first group contain multiple HMG boxes, are non-sequence-specific, and recognize structural features as found in cruciform DNA and cross-over DNA.@@@@1@26@@oe@19-12-2010 853048304@GENIA Treebank@formal@@1@S@The abundant chromosomal protein HMG-1 belongs to this subgroup.@@@@1@10@@oe@19-12-2010 853048305@GENIA Treebank@formal@@1@S@Proteins in the second group carry a single HMG box with affinity for the minor groove of the heptamer motif AACAAAG or variations thereof.@@@@1@25@@oe@19-12-2010 853048306@GENIA Treebank@formal@@1@S@A solution structure for the non-sequence-specific C-terminal HMG box of HMG-1 has recently been proposed.@@@@1@16@@oe@19-12-2010 853048307@GENIA Treebank@formal@@1@S@Now, we report the solution structure of the sequence-specific HMG-box of the SRY-related protein Sox-4.@@@@1@17@@oe@19-12-2010 853048308@GENIA Treebank@formal@@1@S@NMR analysis demonstrated the presence of three alpha-helices (Val10-Gln22, Glu30-Leu41 and Phe50-Tyr65) connected by loop regions (Ser23-Ala49 and Leu42-Pro49).@@@@1@25@@oe@19-12-2010 853048309@GENIA Treebank@formal@@1@S@Helices I and II are positioned in an antiparallel mode and form one arm of the HMG box.@@@@1@19@@oe@19-12-2010 853048310@GENIA Treebank@formal@@1@S@Helix III is less rigid, makes an average angle of about 90 degrees with helices I and II, and constitutes the other arm of the molecule.@@@@1@29@@oe@19-12-2010 853048311@GENIA Treebank@formal@@1@S@As in HMG1B, the overall structure of the Sox-4 HMG box is L-shaped and is maintained by a cluster of conserved, mainly aromatic residues.@@@@1@27@@oe@19-12-2010 853735401@GENIA Treebank@formal@@1@S@A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity through its binding to an osteoblast-specific cis-acting element.@@@@1@17@@oe@19-12-2010 853735402@GENIA Treebank@formal@@1@S@To identify osteoblast-specific cis-acting elements and trans-acting factors, we initiated an analysis of the promoter of a mouse osteocalcin gene, an osteoblast-specific gene.@@@@1@26@@oe@19-12-2010 853735403@GENIA Treebank@formal@@1@S@In this promoter, we identified two osteoblast-specific cis-acting elements (Ducy, P.and Karsenty, G.(1995) Mol.Cell.Biol.15, 1858-1869).@@@@1@26@@oe@19-12-2010 853735404@GENIA Treebank@formal@@1@S@The sequence of one of these elements, OSE2, is identical to the DNA-binding site of the PEBP2 alpha/AML-1 transcription factors, the mammalian homologues of the Drosophila Runt protein.@@@@1@32@@oe@19-12-2010 853735405@GENIA Treebank@formal@@1@S@Here we show, using nuclear extracts, recombinant protein, and a specific antiserum against AML-1 proteins in DNA-binding assays, that one member of this family, AML-1B, binds specifically to OSE2 and is immunologically related to OSF2, the factor present in osteoblast nuclear extracts that binds to OSE2.@@@@1@54@@oe@19-12-2010 853735406@GENIA Treebank@formal@@1@S@By DNA cotransfection experiments, we also demonstrate that AML-1B can increase the activity of a short osteocalcin promoter through its binding to OSE2.@@@@1@25@@oe@19-12-2010 853735407@GENIA Treebank@formal@@1@S@Lastly, the different mobilities of osteoblast nuclear extract-DNA complexes compared with T-cell nuclear extract-DNA complexes, along with the inability of OSF2 to be upregulated by retinoic acid, unlike the other PEBP2 alpha factors, suggest that OSF2 is a new member of this family of transcription factors.@@@@1@51@@oe@19-12-2010 853735408@GENIA Treebank@formal@@1@S@Thus, this study demonstrates that AML-1B can increase gene expression of an osteoblast-specific gene through its binding to an osteoblast-specific cis-acting element and presents evidence that OSF2 is a member of the PEBP2 alpha/AML-1 family of transcription factors.@@@@1@40@@oe@19-12-2010 854820001@GENIA Treebank@formal@@1@S@The number of glucocorticoid receptors in peripheral human lymphocytes is elevated by a zinc containing trace element preparation.@@@@1@19@@oe@19-12-2010 854820002@GENIA Treebank@formal@@1@S@A trace element preparation (Beres Drops Plus, BDP) elevates the number of glucocorticoid receptors (gcR) in peripheral lymphocytes isolated both from healthy blood donors and rheumatoid arthritis patients.@@@@1@34@@oe@19-12-2010 854820003@GENIA Treebank@formal@@1@S@This enhancement by BDP was found either for constitutive expression of gcRs or in experiments when the lymphocytes were stimulated by interleukin (IL)-6.@@@@1@27@@oe@19-12-2010 854820004@GENIA Treebank@formal@@1@S@There was no significant effect of BDP on IL-1 and tumour necrosis factor alpha (TNF alpha)-induced changes of gcRs.@@@@1@23@@oe@19-12-2010 854820005@GENIA Treebank@formal@@1@S@The effect of BDP was greatly dependent on the presence of Zn++ ions in the preparation, since the augmenting effect was abolished if BDP did not contain zinc.@@@@1@30@@oe@19-12-2010 855079701@GENIA Treebank@formal@@1@S@Inhibition of lipopolysaccharide-induced monocyte interleukin-1 receptor antagonist synthesis by cortisol: involvement of the mineralocorticoid receptor.@@@@1@17@@oe@19-12-2010 855079702@GENIA Treebank@formal@@1@S@Glucocorticoids, as a part of their physiological role in the control of inflammatory and immune processes, suppress the expression of interleukin-1 (IL-1) and other cytokines.@@@@1@30@@oe@19-12-2010 855079703@GENIA Treebank@formal@@1@S@Human monocyte IL-1 receptor antagonist (IL-1ra) messenger ribonucleic acid (mRNA) expression and protein secretion are inhibited by dexamethasone.@@@@1@23@@oe@19-12-2010 855079704@GENIA Treebank@formal@@1@S@We have now further studied the regulation of IL-1ra by the major physiological human glucocorticoid, cortisol.@@@@1@18@@oe@19-12-2010 855079705@GENIA Treebank@formal@@1@S@We found that cortisol incubation induced a decrease in IL-1ra mRNA expression and a significant inhibition of IL-1ra protein secretion in cell cultures of human peripheral monocytes stimulated with the bacterial endotoxin lipopolysaccharide (LPS).@@@@1@37@@oe@19-12-2010 855079706@GENIA Treebank@formal@@1@S@Oral administration of 276 mumol cortisol to normal subjects also decreased LPS-induced IL-1ra synthesis in cultured monocytes.@@@@1@18@@oe@19-12-2010 855079707@GENIA Treebank@formal@@1@S@By coincubating the monocytes with either the mineralocorticoid antagonist spironolactone or the glucocorticoid receptor antagonist RU 38486, the in vitro cortisol-induced inhibition of LPS-stimulated IL-1ra secretion was partially reversed.@@@@1@31@@oe@19-12-2010 855079708@GENIA Treebank@formal@@1@S@The mineralocorticoid aldosterone exerted a significant decrease in LPS-induced monocyte IL-1ra secretion in vitro, which was blocked by coincubation with spironolactone.@@@@1@23@@oe@19-12-2010 855079709@GENIA Treebank@formal@@1@S@In addition, the expression of mineralocorticoid receptor mRNA in human monocytes was observed by PCR of reversed transcribed RNA.@@@@1@21@@oe@19-12-2010 855079710@GENIA Treebank@formal@@1@S@Our results further indicate that corticosteroids physiologically control the IL-1/IL-1ra system during inflammatory or immune processes.@@@@1@17@@oe@19-12-2010 855079711@GENIA Treebank@formal@@1@S@Moreover, we provide evidence that, in addition to a glucocorticoid receptor-mediated effect, the mineralocorticoid receptor is involved in the inhibition of monocyte IL-1ra secretion by cortisol.@@@@1@30@@oe@19-12-2010 855209701@GENIA Treebank@formal@@1@S@E2F-1 blocks terminal differentiation and causes proliferation in transgenic megakaryocytes.@@@@1@11@@oe@19-12-2010 855209702@GENIA Treebank@formal@@1@S@The transcription factor E2F-1 plays a central role in the cell cycle through its ability to activate genes involved in cell division.@@@@1@23@@oe@19-12-2010 855209703@GENIA Treebank@formal@@1@S@E2F-1 activity is regulated by a number of proteins, including the retinoblastoma susceptibility gene product, cyclin-dependent kinases, and their inhibitors, proteins that have been implicated in the control of certain developmental processes.@@@@1@37@@oe@19-12-2010 855209704@GENIA Treebank@formal@@1@S@To investigate a potential role of E2F-1 in differentiation, we assayed the ability of megakaryocytes to form platelets in an in vivo transgenic model.@@@@1@26@@oe@19-12-2010 855209705@GENIA Treebank@formal@@1@S@E2F-1 expression in megakaryocytes blocked differentiation during maturation, resulting in severe thrombocytopenia.@@@@1@14@@oe@19-12-2010 855209706@GENIA Treebank@formal@@1@S@Ultrastructural analysis of megakaryocytes revealed abnormal development characterized by hyperdemarcation of cytoplasmic membranes and reduced numbers of alpha granules.@@@@1@20@@oe@19-12-2010 855209707@GENIA Treebank@formal@@1@S@Administration of megakaryocyte growth and development factor or interleukin 6 could not overcome the differentiation block.@@@@1@17@@oe@19-12-2010 855209708@GENIA Treebank@formal@@1@S@Additionally, E2F-1 caused massive megakaryocyte accumulation in both normal and ectopic sites, first evident in E15 embryonic liver.@@@@1@21@@oe@19-12-2010 855209709@GENIA Treebank@formal@@1@S@Furthermore, significant apoptosis was observed in transgenic megakaryocytes.@@@@1@10@@oe@19-12-2010 855209710@GENIA Treebank@formal@@1@S@These data indicate that E2F-1 can prevent terminal differentiation, probably through its cell cycle-stimulatory activity.@@@@1@17@@oe@19-12-2010 855445101@GENIA Treebank@formal@@1@S@Immunophenotype of intraductal carcinoma.@@@@1@5@@oe@19-12-2010 855445102@GENIA Treebank@formal@@1@S@OBJECTIVE--Mammography and breast-conserving therapy have focused attention on the classification of intraductal carcinoma (IDC) and emphasized the prognostic importance of comedo versus noncomedo variants.@@@@1@29@@oe@19-12-2010 855445103@GENIA Treebank@formal@@1@S@We used histochemical markers to define the immunophenotype of 43 IDCs with respect to comedo versus noncomedo status and patterns of angiogenesis.@@@@1@23@@oe@19-12-2010 855445104@GENIA Treebank@formal@@1@S@RESULTS--Reactions in comedo carcinomas were significantly negative for estrogen receptor and progesterone receptor, and positive for p53 and HER-2/neu more often than the noncomedo variant.@@@@1@29@@oe@19-12-2010 855445105@GENIA Treebank@formal@@1@S@All seven IDCs associated with Paget's disease showed positive reactions for HER-2/neu.@@@@1@14@@oe@19-12-2010 855445106@GENIA Treebank@formal@@1@S@Basement membrane immunoreactivity for type IV collagen and laminin was discontinuous in most examples of IDC regardless of type, with a trend toward more intense staining in comedo than in noncomedo carcinomas.@@@@1@34@@oe@19-12-2010 855445107@GENIA Treebank@formal@@1@S@Periductal angiogenesis was not significantly related to the type of IDC but was more pronounced with comedo carcinomas.@@@@1@19@@oe@19-12-2010 855445108@GENIA Treebank@formal@@1@S@CONCLUSIONS--These observations indicate that there are immunophenotypic correlates to the current structural classification of IDC.@@@@1@18@@oe@19-12-2010 855445109@GENIA Treebank@formal@@1@S@The immunophenotype of IDC is helpful in subclassifying an IDC and could prove useful as a prognostic indicator for local control in patients treated by breast-conserving therapy.@@@@1@28@@oe@19-12-2010 855546401@GENIA Treebank@formal@@1@S@Thrombopoietin induces tyrosine phosphorylation of Stat3 and Stat5 in human blood platelets.@@@@1@13@@oe@19-12-2010 855546402@GENIA Treebank@formal@@1@S@Thrombopoietin is known to be essential for megakaryocytopoiesis and thrombopoiesis.@@@@1@11@@oe@19-12-2010 855546403@GENIA Treebank@formal@@1@S@Recently, we and others have shown that thrombopoietin induces rapid tyrosine phosphorylation of Jak2 and other proteins in human platelets and BaF3 cells, genetically engineered to express c-Mpl, a receptor for thrombopoietin.@@@@1@36@@oe@19-12-2010 855546404@GENIA Treebank@formal@@1@S@The Jak family of tyrosine kinases are known to mediate some of the effects of cytokines or hematopoietic growth factors by recruitment and tyrosine phosphorylation of a variety of Stat (signal transducers and activators of transcription) proteins.@@@@1@40@@oe@19-12-2010 855546405@GENIA Treebank@formal@@1@S@Hence, we have investigated whether Stat proteins are present in platelets and, if so, whether they become tyrosine phosphorylated in response to thrombopoietin.@@@@1@27@@oe@19-12-2010 855546406@GENIA Treebank@formal@@1@S@We immunologically identified Stat1, Stat2, Stat3, and Stat5 in human platelet lysates.@@@@1@16@@oe@19-12-2010 855546407@GENIA Treebank@formal@@1@S@Thrombopoietin induced tyrosine phosphorylation of Stat3 and Stat5 in these cells.@@@@1@12@@oe@19-12-2010 855546408@GENIA Treebank@formal@@1@S@Thrombopoietin also induced tyrosine phosphorylation of Stat3 and Stat5 in FDCP-2 cells genetically engineered to constitutively express human c-Mpl.@@@@1@20@@oe@19-12-2010 855546409@GENIA Treebank@formal@@1@S@Thus, our data indicate that Stat3 and Stat5 may be involved in signal transduction after ligand binding to c-Mpl and that this event may have a role in megakaryopoiesis/thrombopoiesis or possibly a mature platelet function such as aggregation.@@@@1@40@@oe@19-12-2010 855546701@GENIA Treebank@formal@@1@S@Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease.@@@@1@15@@oe@19-12-2010 855546702@GENIA Treebank@formal@@1@S@The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is rearranged in about 30% diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas.@@@@1@34@@oe@19-12-2010 855546703@GENIA Treebank@formal@@1@S@These findings suggest that BCL-6 may play a role in regulating differentiation of normal germinal center B cells and that its deregulated expression caused by rearrangements may contribute to lymphomagenesis.@@@@1@31@@oe@19-12-2010 855546704@GENIA Treebank@formal@@1@S@This prompted us to investigate the expression of the BCL-6 protein in Hodgkin's disease (HD), focusing on the nodular lymphocyte predominance subtype (NLPHD), which differs from classical HD by virtue of the B-cell nature of the malignant cell population (so-called L&H cells) and its relationship with germinal centers.@@@@1@60@@oe@19-12-2010 855546705@GENIA Treebank@formal@@1@S@Forty-one HD samples (19 NLPHD, 12 nodular sclerosis, and 10 mixed cellularity) were immunostained with the monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive and a formalin-resistant epitope on the aminoterminal region of the BCL-6 gene product, respectively.@@@@1@46@@oe@19-12-2010 855546706@GENIA Treebank@formal@@1@S@Strong nuclear positivity for the BCL-6 protein was detected in tumor (L&H) cells in all cases of NLPHD.@@@@1@23@@oe@19-12-2010 855546707@GENIA Treebank@formal@@1@S@In contrast, BCL-6 was expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about 30% of classical HD cases.@@@@1@25@@oe@19-12-2010 855546708@GENIA Treebank@formal@@1@S@Notably, the nuclei of reactive CD3+/CD4+ T cells nearby to and rosetting around L&H cells in NLPHD were also strongly BCL-6+, but lacked CD40 ligand (CD40L) expression.@@@@1@34@@oe@19-12-2010 855546709@GENIA Treebank@formal@@1@S@This staining pattern clearly differed from that of classical HD, whose cellular background was made up of CD3+/CD4+ T cells showing the BCL-6-/CD40L+ phenotype.@@@@1@26@@oe@19-12-2010 855546710@GENIA Treebank@formal@@1@S@These results further support the concept that NLPHD is an histogenetically distinct, B-cell-derived subtype of HD and suggest a role for BCL-6 in its development.@@@@1@27@@oe@19-12-2010 855639201@GENIA Treebank@formal@@1@S@Selective effects of DNA damaging agents on HIV long terminal repeat activation and virus replication in vitro.@@@@1@18@@oe@19-12-2010 855639202@GENIA Treebank@formal@@1@S@Much attention has recently focused on the observation that UV light can activate the long terminal repeat (LTR) of the human immunodeficiency virus (HIV).@@@@1@29@@oe@19-12-2010 855639203@GENIA Treebank@formal@@1@S@Although the mechanism of LTR activation remains obscure, several lines of investigation have suggested that it is a result of activation of the NF-kappa B transcription factor(s) following signaling events related to generalized DNA damage.@@@@1@40@@oe@19-12-2010 855639204@GENIA Treebank@formal@@1@S@In this report, we present data demonstrating that HIV LTR activation is not a general consequence of cellular DNA damage, but rather a process unique to specific genotoxic stimuli, and that it does not necessarily depend on activation of NF-kappa B.@@@@1@45@@oe@19-12-2010 855639205@GENIA Treebank@formal@@1@S@Furthermore, we demonstrate that several of these agents can significantly increase HIV replication and accelerate CD4-positive lymphocyte cytotoxicity in vitro.@@@@1@22@@oe@19-12-2010 855639206@GENIA Treebank@formal@@1@S@These findings, therefore, could have clinical significance to AIDS patients with malignancies who are undergoing radiotherapy and chemotherapy.@@@@1@21@@oe@19-12-2010 855703201@GENIA Treebank@formal@@1@S@NF-M (chicken C/EBP beta) induces eosinophilic differentiation and apoptosis in a hematopoietic progenitor cell line.@@@@1@18@@oe@19-12-2010 855703202@GENIA Treebank@formal@@1@S@CAAT/enhancer binding proteins (C/EBPs) are transcriptional activators implicated in the differentiation processes of various cell lineages.@@@@1@19@@oe@19-12-2010 855703203@GENIA Treebank@formal@@1@S@We have shown earlier that NF-M, the chicken homolog of C/EBP beta, is specifically expressed in myelomonocytic and eosinophilic cells of the hematopoietic system.@@@@1@27@@oe@19-12-2010 855703204@GENIA Treebank@formal@@1@S@To investigate the role of NF-M in hematopoietic cell lineage commitment, we constructed a conditional form of the protein by fusing it to the hormone binding domain of the human estrogen receptor.@@@@1@34@@oe@19-12-2010 855703205@GENIA Treebank@formal@@1@S@This construct was stably expressed in a multipotent progenitor cell line transformed by the Myb-Ets oncoprotein.@@@@1@17@@oe@19-12-2010 855703206@GENIA Treebank@formal@@1@S@We report here that both NF-M-dependent promoter constructs and resident genes could be activated by addition of beta-estradiol to the NF-M-estrogen receptor expressing progenitors.@@@@1@25@@oe@19-12-2010 855703207@GENIA Treebank@formal@@1@S@At the same time, we observed a down-regulation of progenitor-specific surface markers and the up-regulation of differentiation markers restricted to the eosinophil and myeloid lineages.@@@@1@27@@oe@19-12-2010 855703208@GENIA Treebank@formal@@1@S@In addition to the onset of differentiation, cell death was induced with typical apoptotic features.@@@@1@17@@oe@19-12-2010 855703209@GENIA Treebank@formal@@1@S@Our results suggest that NF-M plays an important role in commitment along the eosinophil lineage and in the induction of apoptosis.@@@@1@22@@oe@19-12-2010 855801101@GENIA Treebank@formal@@1@S@HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression in glial cells.@@@@1@13@@oe@19-12-2010 855801102@GENIA Treebank@formal@@1@S@Involvement of Janus kinase/signal transducer and activator of transcription and protein kinase C signaling pathways.@@@@1@16@@oe@19-12-2010 855801103@GENIA Treebank@formal@@1@S@It is well established that the two major glial cells in the central nervous system (CNS), astrocytes and microglia, are key participants in mediating the neurologic dysfunction associated with HIV infection of the CNS.@@@@1@39@@oe@19-12-2010 855801104@GENIA Treebank@formal@@1@S@In this study, we investigated the ability of the major envelope glycoprotein of HIV, glycoprotein 120 (gp120), to regulate intercellular adhesion molecule-1 (ICAM-1) expression in glial cells, because ICAM-1 is important in mediating immune responsiveness in the CNS, facilitating entry of HIV-infected cells into the CNS, and promoting syncytia formation.@@@@1@61@@oe@19-12-2010 855801105@GENIA Treebank@formal@@1@S@Our results indicate that gp120 enhances ICAM-1 gene expression in primary rat astrocytes, primary human astrocytes, a human astroglioma cell line CRT, and primary rat microglia.@@@@1@30@@oe@19-12-2010 855801106@GENIA Treebank@formal@@1@S@The signal transduction events involved in gp120-mediated enhancement of ICAM-1 appear to involve activation of both protein kinase C and tyrosine kinase, because inhibitors of protein kinase C and tyrosine kinase abrogate gp120-mediated ICAM-1 expression in both astrocytes and microglia.@@@@1@42@@oe@19-12-2010 855801107@GENIA Treebank@formal@@1@S@Moreover, gp120 induces tyrosine phosphorylation of signal transducer and activator of transcription (STAT-1 alpha) as well as the Janus kinase (JAK2) in glial cells.@@@@1@30@@oe@19-12-2010 855801108@GENIA Treebank@formal@@1@S@We also demonstrate that gp120-mediated ICAM-1 expression has functional significance, as it enhances the ability of monocytic cells to bind to gp120-stimulated human astrocytes in an ICAM-1/beta 2 integrin-dependent fashion.@@@@1@32@@oe@19-12-2010 855801109@GENIA Treebank@formal@@1@S@These results provide new insights into how gp120 can influence the involvement of glial cells in the pathogenesis of AIDS dementia complex.@@@@1@23@@oe@19-12-2010 856295501@GENIA Treebank@formal@@1@S@Fas ligation induces apoptosis and Jun kinase activation independently of CD45 and Lck in human T cells.@@@@1@18@@oe@19-12-2010 856295502@GENIA Treebank@formal@@1@S@Stimulation through the Fas/APO-1 receptor results in apoptosis through an incompletely characterized signaling pathway.@@@@1@15@@oe@19-12-2010 856295503@GENIA Treebank@formal@@1@S@More is known regarding signal transduction events that occur after ligation of the T-cell antigen receptor (TCR).@@@@1@20@@oe@19-12-2010 856295504@GENIA Treebank@formal@@1@S@It has been shown that TCR stimulation requires both the membrane tyrosine phosphatase, CD45, and the Src-family kinase, Lck, to result in cellular activation.@@@@1@29@@oe@19-12-2010 856295505@GENIA Treebank@formal@@1@S@Although prior studies suggest a role for protein tyrosine kinases and phosphatases in Fas signaling, we report here that Fas ligation induces apoptosis in T cells deficient in either CD45 or Lck.@@@@1@34@@oe@19-12-2010 856295506@GENIA Treebank@formal@@1@S@Further, in normal and CD45- or Lck-deficient cell lines, Fas stimulation results in activation of Jun kinase (JNK), a proposed mediator of stress activation pathways.@@@@1@31@@oe@19-12-2010 856295507@GENIA Treebank@formal@@1@S@Previous studies have also demonstrated a role for endogenous ceramide release in Fas-mediated apoptosis.@@@@1@15@@oe@19-12-2010 856295508@GENIA Treebank@formal@@1@S@We show that stimulation with a synthetic ceramide analog results in JNK activation as well as apoptosis, suggesting ceramide release occurs proximal to JNK activation in Fas signaling.@@@@1@30@@oe@19-12-2010 856295509@GENIA Treebank@formal@@1@S@Our data suggest that although CD45 and Lck are not required for Fas signaling, JNK activation may play an important role transducing distal signals that lead to apoptosis after Fas ligation.@@@@1@33@@oe@19-12-2010 856531701@GENIA Treebank@formal@@1@S@Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma.@@@@1@11@@oe@19-12-2010 856531702@GENIA Treebank@formal@@1@S@Although their precise mechanism of action remains to be elucidated, glucocorticoids represent the most effective therapy in the treatment of asthma.@@@@1@23@@oe@19-12-2010 856531703@GENIA Treebank@formal@@1@S@Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes, including glucocorticoid receptor itself.@@@@1@25@@oe@19-12-2010 856531704@GENIA Treebank@formal@@1@S@The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days.@@@@1@47@@oe@19-12-2010 856531705@GENIA Treebank@formal@@1@S@mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase, by polymerase chain reaction using a semiquantitative competitive hybridization assay.@@@@1@26@@oe@19-12-2010 856531706@GENIA Treebank@formal@@1@S@All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment (per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41, P < 0.02), and a significant decrease for glucocorticoid receptor mRNA expression (P < 0.02) was observed in their monocytes.@@@@1@52@@oe@19-12-2010 856531707@GENIA Treebank@formal@@1@S@This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression, following corticosteroid treatment.@@@@1@21@@oe@19-12-2010 856695101@GENIA Treebank@formal@@1@S@Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9.@@@@1@20@@oe@19-12-2010 856695102@GENIA Treebank@formal@@1@S@Campomelic dysplasia (CMPD1) and autosomal XY sex reversal (SRA1) are caused by mutations in the SRY-related gene SOX9 on 17q.@@@@1@25@@oe@19-12-2010 856695103@GENIA Treebank@formal@@1@S@Unexpectedly, the 17q breakpoints in four CMPD1 translocation cases previously analyzed by us and others map 50 kb or more from SOX9.@@@@1@24@@oe@19-12-2010 856695104@GENIA Treebank@formal@@1@S@Here, we present clinical, cytogenetic, and molecular data from a new CMPD1/SRA1 patient with t(6;17)(q14;q24).@@@@1@19@@oe@19-12-2010 856695105@GENIA Treebank@formal@@1@S@Fluorescence in situ hybridization has shown that the 17q breakpoint in this case maps to the same region as the breakpoints in the other translocation cases, at least 130 kb from SOX9.@@@@1@34@@oe@19-12-2010 856695106@GENIA Treebank@formal@@1@S@Likewise, the breakpoints in two of the previously described cases also map more than 130 kb and, as shown by pulsed field gel electrophoresis analysis, at most 400 kb or 690 kb from SOX9.@@@@1@38@@oe@19-12-2010 856695107@GENIA Treebank@formal@@1@S@By using a SOX9 coding sequence polymorphism, expression of both SOX9 alleles has been demonstrated by the reverse transcriptase polymerase chain reaction in lymphoblastoid cells from one of the translocation cases.@@@@1@33@@oe@19-12-2010 857021501@GENIA Treebank@formal@@1@S@Expression of either the TCL1 oncogene, or transcripts from its homologue MTCP1/c6.1B, in leukaemic and non-leukaemic T cells from ataxia telangiectasia patients.@@@@1@25@@oe@19-12-2010 857021502@GENIA Treebank@formal@@1@S@Patients with the recessively inherited disorder ataxia telangiectasia (A-T) have a high level of specific chromosome translocations which can be easily observed in peripheral T cells and show a greatly increased predisposition to leukaemia/lymphoma, mainly of T cell origin.@@@@1@43@@oe@19-12-2010 857021503@GENIA Treebank@formal@@1@S@Some translocation cells proliferate into a large clone and may develop into T cell prolymphocytic leukaemia (T-PLL).@@@@1@20@@oe@19-12-2010 857021504@GENIA Treebank@formal@@1@S@By the time of diagnosis of T-PLL, the clone contains many more genetic changes in the form of additional translocations.@@@@1@22@@oe@19-12-2010 857021505@GENIA Treebank@formal@@1@S@T-PLL is also seen in non-A-T individuals where expression of either TCL1 (at 14q32) or the c6.1B/MTCP1 A1 transcript (at-Xq28) has been demonstrated in just a few instances.@@@@1@33@@oe@19-12-2010 857021506@GENIA Treebank@formal@@1@S@We show here, that expression of TCL1 occurs in leukaemic T cells from A-T patients with chromosome 14 rearrangements.@@@@1@21@@oe@19-12-2010 857021507@GENIA Treebank@formal@@1@S@Expression of TCL1 also occurs in the preleukaemic clone cells of A-T patients containing the primary translocation alone.@@@@1@19@@oe@19-12-2010 857021508@GENIA Treebank@formal@@1@S@Some expression of TCL1 could also be detected in randomly selected A-T patients without large cytogenetic clones and without any evidence of leukaemic change.@@@@1@25@@oe@19-12-2010 857021509@GENIA Treebank@formal@@1@S@We also show that expression of the B1 transcript from a second gene, MTCP1, occurred at a relatively high level only in two T-PLL tumours from A-T patients with t(X;14) translocations whereas the MTCP1/A1 transcript is much more widely expressed in both tumour and non tumour cells of A-T and non-A-T individuals.@@@@1@55@@oe@19-12-2010 857292501@GENIA Treebank@formal@@1@S@Aspirin-like drugs can protect human T lymphocytes against benzoquinone cytotoxicity: evidence for a NAD(P)H:quinone reductase-dependent mechanism.@@@@1@18@@oe@19-12-2010 857292502@GENIA Treebank@formal@@1@S@Benzene toxicity towards lymphocytes is thought to be mediated by metabolites of benzene including benzoquinone (BQ).@@@@1@19@@oe@19-12-2010 857292503@GENIA Treebank@formal@@1@S@NAD(P)H:quinone reductase (QR) is known to protect against BQ toxicity.@@@@1@13@@oe@19-12-2010 857292504@GENIA Treebank@formal@@1@S@The expression of the QR gene is regulated by the transcription factor AP-1.@@@@1@14@@oe@19-12-2010 857292505@GENIA Treebank@formal@@1@S@We had previously found that aspirin-like drugs (ALD) induce AP-1 in human T lymphocytes.@@@@1@17@@oe@19-12-2010 857292506@GENIA Treebank@formal@@1@S@It was therefore hypothesized that ALD would protect lymphocytes against BQ toxicity by inducing QR.@@@@1@16@@oe@19-12-2010 857292507@GENIA Treebank@formal@@1@S@Molt-4 cells (M4), a human T lymphocyte cell line, were incubated with different concentrations of two ALD, flurbiprofen and sodium diclofenac, and then exposed to BQ.@@@@1@33@@oe@19-12-2010 857292508@GENIA Treebank@formal@@1@S@Toxicity was measured by viability (trypan blue exclusion).@@@@1@11@@oe@19-12-2010 857292509@GENIA Treebank@formal@@1@S@Both drugs protected the cells against BQ cytotoxicity in a dose-dependent manner, e.g., sodium diclofenac at 15 microM reduced the fraction of BQ-treated dead cells by 70%.@@@@1@31@@oe@19-12-2010 857292510@GENIA Treebank@formal@@1@S@ALDs induced QR activity in the M4 cells in the same range of concentrations that protected the cells against BQ toxicity.@@@@1@22@@oe@19-12-2010 857292511@GENIA Treebank@formal@@1@S@The protective effect of ALD was significantly reduced by dicoumarol, a QR-specific inhibitor.@@@@1@15@@oe@19-12-2010 857292512@GENIA Treebank@formal@@1@S@Since human T cells and T cell lines do not metabolize arachidonic acid, our data suggest that ALD can protect human T lymphocytes against a metabolite of benzene by induction of QR activity.@@@@1@35@@oe@19-12-2010 857338101@GENIA Treebank@formal@@1@S@Human herpesvirus 6 variant A, but not variant B, infects EBV-positive B lymphoid cells, activating the latent EBV genome through a BZLF-1-dependent mechanism.@@@@1@27@@oe@19-12-2010 857338102@GENIA Treebank@formal@@1@S@Human herpesvirus 6, a predominantly T lymphotropic virus, has been recently shown to infect some EBV-positive B cell lines, and to induce in them the activation of the EBV lytic cycle.@@@@1@36@@oe@19-12-2010 857338103@GENIA Treebank@formal@@1@S@Here we have confirmed and extended such observations, showing that (1) this phenomenon is restricted to the variant A of HHV-6: in fact two isolates belonging to the HHV-6 variant B (BA92 and Z29) were neither able to infect any B cell line, independently of the EBV status, nor to induce the EBV genome expression.@@@@1@64@@oe@19-12-2010 857338104@GENIA Treebank@formal@@1@S@The only exception is represented by the P3HR1 cells, in which, however, the infection by the variant B does not determine induction of EBV antigens; (2) the presence of the EBV genome contributes to the susceptibility of the B cell lines to HHV-6 infection, increasing the binding sites and the percentage of infectable cells, as detected by immunoelectron microscopy; and (3) HHV-6 infected T cells, transfected with plasmids bearing the promoter regions of the EBV early genes BZLF1 and BMRF1, show a strong transactivation of these promoters.@@@@1@101@@oe@19-12-2010 857611101@GENIA Treebank@formal@@1@S@Identification of a physical interaction between calcineurin and nuclear factor of activated T cells (NFATp).@@@@1@18@@oe@19-12-2010 857611102@GENIA Treebank@formal@@1@S@In T lymphocytes, the calcium/calmodulin-dependent serine/threonine phosphatase, calcineurin, plays a pivotal role in transducing membrane-associated signals to the nucleus.@@@@1@23@@oe@19-12-2010 857611103@GENIA Treebank@formal@@1@S@One of the putative targets of calcineurin is the pre-existing, cytosolic component of the nuclear factor of activated T cells (NFATp; also referred to as NFAT1), which is one of several transcription factors required for the expression of interleukin 2.@@@@1@46@@oe@19-12-2010 857611104@GENIA Treebank@formal@@1@S@Inhibition of calcineurin by the immunosuppressive drugs cyclosporin A and FK506 prevents dephosphorylation of NFATp and its translocation to the nucleus.@@@@1@22@@oe@19-12-2010 857611105@GENIA Treebank@formal@@1@S@However, a physical interaction between calcineurin and NFATp has not been demonstrated.@@@@1@14@@oe@19-12-2010 857611106@GENIA Treebank@formal@@1@S@Here we demonstrate the binding of NFATp from lysates of T cells to immobilized calcineurin.@@@@1@16@@oe@19-12-2010 857611107@GENIA Treebank@formal@@1@S@Stimulation of T cells with calcium ionophore induced a shift in the molecular weight of NFATp that is due to its dephosphorylation.@@@@1@23@@oe@19-12-2010 857611108@GENIA Treebank@formal@@1@S@This dephosphorylation was inhibited by treatment of T cells with cyclosporin A or FK506 prior to stimulation.@@@@1@18@@oe@19-12-2010 857611109@GENIA Treebank@formal@@1@S@Of note, both the phosphorylated and the dephosphorylated form of NFATp bound to calcineurin.@@@@1@16@@oe@19-12-2010 857611110@GENIA Treebank@formal@@1@S@Furthermore, the binding of both forms of NFATp to calcineurin was inhibited by pretreatment of calcineurin with a complex of FK506 and its ligand FKBP12.@@@@1@27@@oe@19-12-2010 857611111@GENIA Treebank@formal@@1@S@Taken together these data strongly suggest a direct interaction of calcineurin with NFATp and that this interaction does not depend upon the phosphorylation sites of NFATp affected by activation.@@@@1@30@@oe@19-12-2010 857974801@GENIA Treebank@formal@@1@S@BSAP: a key regulator of B-cell development and differentiation.@@@@1@11@@oe@19-12-2010 857974802@GENIA Treebank@formal@@1@S@B-cell-specific activator protein (BSAP) is a recently identified member of the Pax-gene family of transcription factors; in the lymphoid system, BSAP is produced only in B cells.@@@@1@32@@oe@19-12-2010 857974803@GENIA Treebank@formal@@1@S@Here, Markus Neurath, Eckhard Stuber and Warren Strober describe the molecular structure of BSAP and focus on the ability of this protein to regulate the expression of B-cell-specific genes.@@@@1@32@@oe@19-12-2010 857974804@GENIA Treebank@formal@@1@S@They propose that BSAP is a key protein of B cells and that it not only influence B-cell development but also influences the balance between B-cell proliferation and immunoglobulin secretion at later stages of B-cell differentiation.@@@@1@37@@oe@19-12-2010 858037801@GENIA Treebank@formal@@1@S@Activation of JAK3, but not JAK1, is critical for IL-2-induced proliferation and STAT5 recruitment by a COOH-terminal region of the IL-2 receptor beta-chain.@@@@1@26@@oe@19-12-2010 858037802@GENIA Treebank@formal@@1@S@A number of cytokines and growth factors use the JAK-STAT pathway to signal from the cell membrane to the nucleus.@@@@1@21@@oe@19-12-2010 858037803@GENIA Treebank@formal@@1@S@While homodimerizing cytokine receptors may transmit signal via a single form of JAK (i.e. growth hormone receptors), several multicomponent cytokine receptors have been shown to require simultaneous activation of pairs of different JAK kinases (i.e. interferon receptors).@@@@1@43@@oe@19-12-2010 858037804@GENIA Treebank@formal@@1@S@Recent evidence for a preferential coupling of JAK3 to interleukin-2 receptor-gamma (IL-2R gamma) and JAK1 to IL-2R beta supports the concept of heterotrans-activation of JAK1 and JAK3 caused by IL-2-induced heterodimerization of their receptor partners.@@@@1@38@@oe@19-12-2010 858037805@GENIA Treebank@formal@@1@S@The present study verified the ability of IL-2 to cause tyrosine phosphorylation and activation of JAK1 and JAK3, but demonstrated that IL-2 stimulated JAK3 to a significantly larger extent than JAK1 in human T lymphocytes and the YT cell line.@@@@1@42@@oe@19-12-2010 858037806@GENIA Treebank@formal@@1@S@This conclusion was based upon several independent criteria, including more vigorous tyrosine phosphorylation of JAK3, more marked enzymatic activation of JAK3 as well as higher abundance of JAK3 in activated IL-2 receptor complexes.@@@@1@36@@oe@19-12-2010 858037807@GENIA Treebank@formal@@1@S@Furthermore, when human IL-2R beta was stably expressed in murine BA/F3 cells, robust IL-2-induced proliferation and JAK3 activation occurred without detectable involvement of either JAK1, JAK2 or TYK2.@@@@1@32@@oe@19-12-2010 858037808@GENIA Treebank@formal@@1@S@We therefore propose that IL-2 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL-2-induced heterodimerization of IL-2R beta and IL-2R gamma.@@@@1@28@@oe@19-12-2010 858037809@GENIA Treebank@formal@@1@S@Nonetheless, a membrane-proximal region of human IL-2R beta (Asn240-Leu335) was critical for JAK3 activation, and the amount of JAK3 present in activated IL-2 receptor complexes increased with time, suggesting that stabilization of JAK3 binding to the receptor complex relies on both IL-2R beta and IL-2R gamma.@@@@1@52@@oe@19-12-2010 858037810@GENIA Treebank@formal@@1@S@Moreover, STAT5 was found to be the predominant STAT transcription factor used by IL-2 in human T cells, and specifically required a COOH-terminal region of IL-2R beta (Ser386-Val525), while STAT5 recruitment was not correlated to activation of IL-2R gamma or JAK3.@@@@1@47@@oe@19-12-2010 859383101@GENIA Treebank@formal@@1@S@Inhibition of vitamin D receptor-retinoid X receptor-vitamin D response element complex formation by nuclear extracts of vitamin D-resistant New World primate cells.@@@@1@23@@oe@19-12-2010 859383102@GENIA Treebank@formal@@1@S@Most New World primate (NWP) genera evolved to require high circulating levels of steroid hormones and vitamin D.@@@@1@21@@oe@19-12-2010 859383103@GENIA Treebank@formal@@1@S@We hypothesized that an intracellular vitamin D binding protein (IDBP), present in both nuclear and cytoplasmic fractions of NWP cells, or another protein(s) may cause or contribute to the steroid hormone-resistant state in NWP by disruption of the receptor dimerization process and/or by interference of receptor complex binding to the consensus response elements present in the enhancer regions of steroid-responsive genes.@@@@1@69@@oe@19-12-2010 859383104@GENIA Treebank@formal@@1@S@We employed electromobility shift assay (EMSA) to screen for the presence of proteins capable of binding to the vitamin D response element (VDRE).@@@@1@28@@oe@19-12-2010 859383105@GENIA Treebank@formal@@1@S@Nuclear and post-nuclear extracts were prepared from two B-lymphoblastoid cell lines known to be representative of the vitamin D-resistant and wild type phenotypes, respectively.@@@@1@26@@oe@19-12-2010 859383106@GENIA Treebank@formal@@1@S@The extracts were compared for their ability to retard the migration of radiolabeled double stranded oligomers representative of the VDREs of the human osteocalcin and the mouse osteopontin gene promoters.@@@@1@31@@oe@19-12-2010 859383107@GENIA Treebank@formal@@1@S@A specific, retarded band containing VDR-RXR was identified when wild type cell but not when vitamin D-resistant cell nuclear extract was used in the binding reaction with either probe.@@@@1@31@@oe@19-12-2010 859383108@GENIA Treebank@formal@@1@S@In addition, vitamin D-resistant cell nuclear extract contained a protein(s) which was bound specifically to the VDRE and was capable of completely inhibiting VDR-RXR-VDRE complex formation; these effects were not demonstrated with nuclear extract from the wild type cell line or with the post-nuclear extract of the vitamin D-resistant cell line.@@@@1@57@@oe@19-12-2010 859383109@GENIA Treebank@formal@@1@S@We conclude that a VDRE-binding protein(s), distinct from IDBP and present in nuclear extract of cells from a prototypical vitamin D-resistant NWP, is capable of inhibiting normal VDR-RXR heterodimer binding to the VDRE.@@@@1@39@@oe@19-12-2010 859601701@GENIA Treebank@formal@@1@S@Characterization and purification of a protein kinase C substrate in human B cells.@@@@1@14@@oe@19-12-2010 859601702@GENIA Treebank@formal@@1@S@Identification as lymphocyte-specific protein 1 (LSP1).@@@@1@9@@oe@19-12-2010 859601703@GENIA Treebank@formal@@1@S@Incubation of B-chronic lymphocytic leukemia (B-CLL) cells with phorbol esters resulted in the phosphorylation of two major PKC substrates, MARCKS (myristoylated, alanine-rich C kinase substrate) and MRP (MARCKS-related protein), and of a third protein, with an apparent m.w. of 60,000 that was the most prominent protein kinase C substrate in these cells.@@@@1@63@@oe@19-12-2010 859601704@GENIA Treebank@formal@@1@S@p60 phosphorylation was time and PMA dose dependent, and was induced by cell-permeable diacylglycerol, but not by inactive phorbol esters.@@@@1@23@@oe@19-12-2010 859601705@GENIA Treebank@formal@@1@S@Two-dimensional electrophoretic analysis of the protein phosphorylation pattern from the B cell line CESS demonstrated the identity between the p60 protein expressed in this cell line and that expressed in B-CLL cells.@@@@1@33@@oe@19-12-2010 859601706@GENIA Treebank@formal@@1@S@p60 was purified from CESS cells and peptide microsequencing of this protein revealed that it was lymphocyte-specific protein 1 (LSP1), that is here characterized as the most prominent protein kinase C substrate in B cells.@@@@1@39@@oe@19-12-2010 859821001@GENIA Treebank@formal@@1@S@Cross-linking CD40 on B cells preferentially induces stress-activated protein kinases rather than mitogen-activated protein kinases.@@@@1@16@@oe@19-12-2010 859821002@GENIA Treebank@formal@@1@S@The B cell-associated surface molecule CD40 plays a key role in T cell-dependent B cell maturation, as individuals with defects in either CD40 or its ligand are impaired in immunoglobulin isotype class switching and germinal center formation.@@@@1@39@@oe@19-12-2010 859821003@GENIA Treebank@formal@@1@S@CD40 signaling activates downstream effectors, including the tyrosine protein kinase, Lyn, the phosphatidylinositol-3-kinase (PI-3 kinase), and the transcription factor, NF-kappa B.@@@@1@29@@oe@19-12-2010 859821004@GENIA Treebank@formal@@1@S@In this study, we demonstrate that stress-activated protein kinases (SAPK) are activated after CD40 cross-linking on various B cell lines or human tonsillar B cells.@@@@1@29@@oe@19-12-2010 859821005@GENIA Treebank@formal@@1@S@The activation is rapid and transient and is mediated through a cyclosporin A-insensitive pathway.@@@@1@15@@oe@19-12-2010 859821006@GENIA Treebank@formal@@1@S@Furthermore, this signaling pathway appears not to rely on protein kinase C.@@@@1@14@@oe@19-12-2010 859821007@GENIA Treebank@formal@@1@S@While CD40 ligation strongly activates the SAPKs (up to 25-fold), it does not affect members of the mitogen-activated protein kinase family (MAPK; ERK1 and ERK2).@@@@1@32@@oe@19-12-2010 859821008@GENIA Treebank@formal@@1@S@Consistent with these data, CD40 signals up-regulate c-jun but not c-fos mRNA and alter the transcription factor ATF2 but not the Raf-1 protein.@@@@1@25@@oe@19-12-2010 859821009@GENIA Treebank@formal@@1@S@In summary, CD40 signaling preferentially induces SAPK but not MAPK.@@@@1@12@@oe@19-12-2010 859848101@GENIA Treebank@formal@@1@S@Dehydroepiandrosterone modulation of lipopolysaccharide-stimulated monocyte cytotoxicity.@@@@1@7@@oe@19-12-2010 859848102@GENIA Treebank@formal@@1@S@Dehydroepiandrosterone (DHEA), the predominant androgen secreted by the adrenal cortex, can be converted to both potent androgens and estrogens.@@@@1@24@@oe@19-12-2010 859848103@GENIA Treebank@formal@@1@S@In addition to its role as a precursor for other steroid hormones, DHEA has been proposed to play an important role in immunity.@@@@1@25@@oe@19-12-2010 859848104@GENIA Treebank@formal@@1@S@This study has investigated DHEA modulation of LPS-induced monocyte cytotoxicity.@@@@1@11@@oe@19-12-2010 859848105@GENIA Treebank@formal@@1@S@Cytotoxicity markers assessed include tumor cell killing, IL-1 secretion, reactive oxygen intermediate release, nitric oxide synthetase activity as measured by the release of reactive nitrogen intermediates, complement receptor-1 cell surface protein, and TNF-alpha protein presence.@@@@1@41@@oe@19-12-2010 859848106@GENIA Treebank@formal@@1@S@Monocytes stimulated with LPS concentrations of 1.0 micrograms/ml displayed the above cytotoxic markers, whereas monocytes stimulated with DHEA alone or with LPS at a lower concentration of 0.2 ng/ml did not.@@@@1@33@@oe@19-12-2010 859848107@GENIA Treebank@formal@@1@S@However, when used simultaneously, DHEA and LPS 0.2 ng/ml displayed a synergistic effect on monocyte cytotoxicity against cancerous cell lines, IL-1 secretion, reactive nitrogen intermediate release, complement receptor-1 cell-surface protein, and TNF-alpha protein to levels comparable with levels obtained using LPS 1.0 microgram/ml.@@@@1@50@@oe@19-12-2010 859848108@GENIA Treebank@formal@@1@S@Finally, Scatchard plot analysis demonstrated the presence of a DHEA receptor in monocytes, suggesting that DHEA effects on LPS-stimulated monocytes are mediated through a receptor-dependent process.@@@@1@29@@oe@19-12-2010 860304501@GENIA Treebank@formal@@1@S@The involvement of p23, hsp90, and immunophilins in the assembly of progesterone receptor complexes.@@@@1@17@@oe@19-12-2010 860304502@GENIA Treebank@formal@@1@S@To better understand the assembly mechanism for the progesterone receptor (PR), we have developed cell-free systems for studying interactions of PR, hsp90, and other associated proteins.@@@@1@32@@oe@19-12-2010 860304503@GENIA Treebank@formal@@1@S@When PR is incubated in rabbit reticulocyte lysate, its association with hsp90, hsp70, the three immunophilins FKBP54, FKBP52 and CyP-40, and with p23 is observed.@@@@1@31@@oe@19-12-2010 860304504@GENIA Treebank@formal@@1@S@These interactions require ATP/Mg2+ and when ATP is limiting the PR complex is altered to one containing the proteins p60 and p48, but lacking immunophilins and p23.@@@@1@29@@oe@19-12-2010 860304505@GENIA Treebank@formal@@1@S@We have studied two pre-formed hsp90 complexes that may participate in the assembly of PR complexes.@@@@1@17@@oe@19-12-2010 860304506@GENIA Treebank@formal@@1@S@One contains hsp90 bound to hsp70 and p60 and this complex forms spontaneously in the absence of ATP.@@@@1@19@@oe@19-12-2010 860304507@GENIA Treebank@formal@@1@S@A second complex contains hsp90 bound to p23 plus the three immunophilins and some hsp70.@@@@1@16@@oe@19-12-2010 860304508@GENIA Treebank@formal@@1@S@The formation of this complex requires ATP.@@@@1@8@@oe@19-12-2010 860304509@GENIA Treebank@formal@@1@S@In further studies we have shown that purified hsp90 can bind to purified p23 and this interaction requires both ATP and molybdate.@@@@1@23@@oe@19-12-2010 860304510@GENIA Treebank@formal@@1@S@This explains, in part, the known effects of ATP and molybdate on assembly of PR complexes.@@@@1@19@@oe@19-12-2010 860594101@GENIA Treebank@formal@@1@S@Autocrine activation by interferon-gamma of STAT factors following T cell activation.@@@@1@12@@oe@19-12-2010 860594102@GENIA Treebank@formal@@1@S@The activation of T cells requires engagement of the T cell receptor/CD3 complex and co-stimulatory molecules, and results in the triggering of several signaling pathways which lead rapidly to the nuclear translocation of several transcription factors, such as nuclear factor (NF)-kappa B and NF-AT.@@@@1@50@@oe@19-12-2010 860594103@GENIA Treebank@formal@@1@S@A result of this activation process is the induction of a number of genes, including those encoding cytokines such as interleukin-2, tumor necrosis factor-alpha, and interferon (IFN)-gamma which have important immunoregulatory effects.@@@@1@39@@oe@19-12-2010 860594104@GENIA Treebank@formal@@1@S@We report here that a DNA-binding factor containing STAT1 also becomes activated in human peripheral blood T lymphocytes or Jurkat cells, although not until 1-2 h after stimulation.@@@@1@30@@oe@19-12-2010 860594105@GENIA Treebank@formal@@1@S@Activation is delayed a further 1-2 hr when mononuclear cell cultures are stimulated by an antigen which requires processing.@@@@1@20@@oe@19-12-2010 860594106@GENIA Treebank@formal@@1@S@Appearance of the STAT1 factor is significantly reduced in the presence of cyclosporin A, and blocked by cycloheximide, indicating that its activation is dependent upon a protein(s) synthesized in response to initial signaling events.@@@@1@40@@oe@19-12-2010 860594107@GENIA Treebank@formal@@1@S@Neutralizing antiserum against IFN-gamma, but not other cytokines tested, blocked activation of the factor almost completely, and IFN-gamma was found in the culture supernatants of stimulated cells at levels at which recombinant IFN-gamma could activate the factor in naive cells.@@@@1@44@@oe@19-12-2010 860594108@GENIA Treebank@formal@@1@S@Therefore, a STAT1 transcription factor is activated by IFN-gamma synthesized and released upon stimulation of T lymphocyte populations.@@@@1@20@@oe@19-12-2010 860594109@GENIA Treebank@formal@@1@S@While Jurkat cells both secrete and respond to IFN-gamma in an autocrine loop, it seems likely that the responding cells may differ from those synthesizing this cytokine in the mononuclear cell cultures in the light of the recent report that Th1 cells lack the IFN-gamma receptor chain necessary for activation of STAT1 (Pernis, A., Gupta, S., Gollob, K.J., Garfein, E., Coffman, R.L., Schindler, C., and Rothman, P., Science 1995. 269:245).@@@@1@91@@oe@19-12-2010 860794101@GENIA Treebank@formal@@1@S@Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of estrogen receptors in human peripheral monocytes.@@@@1@26@@oe@19-12-2010 860794102@GENIA Treebank@formal@@1@S@PROBLEM: The clinical significance of the differential expression of estrogen receptor (ER) in human monocytes was evaluated.@@@@1@21@@oe@19-12-2010 860794103@GENIA Treebank@formal@@1@S@METHOD: Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy.@@@@1@27@@oe@19-12-2010 860794104@GENIA Treebank@formal@@1@S@In addition, the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine.@@@@1@19@@oe@19-12-2010 860794105@GENIA Treebank@formal@@1@S@RESULTS: During menopause there is a significant decrease in the percentage of ER positive monocytes, and an increase in blood monocyte number, which declines following estrogen replacement therapy to values of the young.@@@@1@37@@oe@19-12-2010 860794106@GENIA Treebank@formal@@1@S@CONCLUSIONS: These findings suggest that estrogen modulates the monocyte numbers and its effects may be mediated through the ER in the monocytes.@@@@1@24@@oe@19-12-2010 860939301@GENIA Treebank@formal@@1@S@Herpesvirus saimiri immortalized gamma delta T cell line activated by IL-12.@@@@1@12@@oe@19-12-2010 860939302@GENIA Treebank@formal@@1@S@IL-12 is a novel heterodimeric cytokine important for the regulation and differentiation of lymphocytes and NK cells.@@@@1@18@@oe@19-12-2010 860939303@GENIA Treebank@formal@@1@S@Like other cytokines, IL-12 mediates its biologic activity through high-affinity receptors expressed on responsive cells.@@@@1@17@@oe@19-12-2010 860939304@GENIA Treebank@formal@@1@S@To date, a large number of receptors for IL-12 have been found only on PBMC following activation with PHA or IL-2.@@@@1@23@@oe@19-12-2010 860939305@GENIA Treebank@formal@@1@S@To gain further knowledge of the IL-12R complex and the IL-12 signal transduction pathway in cytotoxic T cells, we studied a number of human T cell lines that had been transformed to permanent growth with Herpesvirus saimiri, an oncogenic virus of nonhuman primates.@@@@1@46@@oe@19-12-2010 860939306@GENIA Treebank@formal@@1@S@This paper reports the expression of IL-12R on a human gamma delta T cell line that responds to IL-12 with enhanced cytolytic activity and increased expression of cytolytic effector molecules granzyme B and perforin.@@@@1@35@@oe@19-12-2010 860939307@GENIA Treebank@formal@@1@S@Using these T cells as a model of IL-12 signal transduction, we confirmed that these events involve members of the Janus kinase family of nonreceptor tyrosine kinases JAK2, TYK2, and signal transducer and activator of transcription 4.@@@@1@41@@oe@19-12-2010 860941801@GENIA Treebank@formal@@1@S@IL-13 induces phosphorylation and activation of JAK2 Janus kinase in human colon carcinoma cell lines: similarities between IL-4 and IL-13 signaling.@@@@1@23@@oe@19-12-2010 860941802@GENIA Treebank@formal@@1@S@We have recently reported that IL-13R may share a component with IL-4R.@@@@1@13@@oe@19-12-2010 860941803@GENIA Treebank@formal@@1@S@Here we report that both IL-4 and IL-13 share signaling events in human colon carcinoma cell lines (HT-29 and WiDr).@@@@1@23@@oe@19-12-2010 860941804@GENIA Treebank@formal@@1@S@IL-13 caused rapid phosphorylation of the three out of four members of the known Janus family of kinases (JAKs).@@@@1@22@@oe@19-12-2010 860941805@GENIA Treebank@formal@@1@S@We show that JAK2 kinase is rapidly phosphorylated and activated in response to IL-13.@@@@1@15@@oe@19-12-2010 860941806@GENIA Treebank@formal@@1@S@Within 1 min of activation, JAK2 was phosphorylated, and peaked in 10 min.@@@@1@16@@oe@19-12-2010 860941807@GENIA Treebank@formal@@1@S@In addition, IL-13 phosphorylated insulin response substrate-1, IL-4R p140, JAK1, and Tyk2, but not JAK3 kinase.@@@@1@22@@oe@19-12-2010 860941808@GENIA Treebank@formal@@1@S@IL-4 also stimulated all three kinases and substrates, but unlike in immune cells, IL-4 did not involve JAK3 activation for its signaling in colon cancer cell lines.@@@@1@30@@oe@19-12-2010 860941809@GENIA Treebank@formal@@1@S@Furthermore, JAK2 associated with the IL-4R p140 before and after stimulation with IL-13.@@@@1@15@@oe@19-12-2010 860941810@GENIA Treebank@formal@@1@S@Both IL-13 and IL-4 induced phosphorylation of IL-4 STAT (STAT6) but not STAT1, STAT3, or STAT5.@@@@1@21@@oe@19-12-2010 860941811@GENIA Treebank@formal@@1@S@125I-IL-13 did not bind to colon cancer cell lines, but unlabeled IL-13 competed for the binding of 125I-IL-4.@@@@1@20@@oe@19-12-2010 860941812@GENIA Treebank@formal@@1@S@Our data suggest that IL-13 utilizes IL-4R and its signaling pathway, and JAK2 may play an important role in the function of IL-4R and IL-13R in colon cancer cells.@@@@1@31@@oe@19-12-2010 861011601@GENIA Treebank@formal@@1@S@Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages.@@@@1@10@@oe@19-12-2010 861011602@GENIA Treebank@formal@@1@S@Activation of macrophages by bacterial lipopolysaccharide (LPS) induces transcription of genes that encode for proinflammatory regulators of the immune response.@@@@1@23@@oe@19-12-2010 861011603@GENIA Treebank@formal@@1@S@Previous work has suggested that activation of the transcription factor activator protein 1 (AP-1) is one LPS-induced event that mediates this response.@@@@1@25@@oe@19-12-2010 861011604@GENIA Treebank@formal@@1@S@Consistent with this notion, we found that LPS stimulated AP-1-mediated transcription of a transfected reporter gene in the murine macrophage cell line RAW 264.7.@@@@1@26@@oe@19-12-2010 861011605@GENIA Treebank@formal@@1@S@As AP-1 activity is regulated in part by activation of the c-Jun N-terminal kinase (JNK), which phosphorylates and subsequently increases the transcriptional activity of c-Jun, we examined whether LPS treatment of macrophages resulted in activation of this kinase.@@@@1@43@@oe@19-12-2010 861011606@GENIA Treebank@formal@@1@S@LPS treatment of RAW 264.7 cells, murine bone marrow-derived macrophages, and the human monocyte cell line THP-1 resulted in rapid activation of the p46 and p54 isoforms of JNK.@@@@1@32@@oe@19-12-2010 861011607@GENIA Treebank@formal@@1@S@Treatment with wild-type and rough mutant forms of LPS and synthetic lipid A resulted in JNK activation, while pretreatment with the tyrosine kinase inhibitor herbimycin A inhibited this response.@@@@1@31@@oe@19-12-2010 861011608@GENIA Treebank@formal@@1@S@Binding of LPS-LPS binding protein (LBP) complexes to CD14, a surface receptor that mediates many LPS responses, was found to be crucial, as pretreatment of THP-1 cells with the monoclonal antibody 60b, which blocks this binding, inhibited JNK activation.@@@@1@47@@oe@19-12-2010 861011609@GENIA Treebank@formal@@1@S@These results suggest that LPS activation of JNK in monocyte/macrophage cells is a CD14- and protein tyrosine phosphorylation-dependent event that may mediate the early activation of AP-1 in regulating LPS-triggered gene induction.@@@@1@33@@oe@19-12-2010 861724401@GENIA Treebank@formal@@1@S@C-terminal activating and inhibitory domains determine the transactivation potential of BSAP (Pax-5), Pax-2 and Pax-8.@@@@1@19@@oe@19-12-2010 861724402@GENIA Treebank@formal@@1@S@Pax-5 encodes the transcription factor BSAP which plays an essential role in early B cell development and midbrain patterning.@@@@1@20@@oe@19-12-2010 861724403@GENIA Treebank@formal@@1@S@In this study we have analysed the structural requirements for transcriptional activation by BSAP.@@@@1@15@@oe@19-12-2010 861724404@GENIA Treebank@formal@@1@S@In vitro mutagenesis and transient transfection experiments indicate that the C-terminal serine/threonine/proline-rich region of BSAP contains a potent transactivation domain of 55 amino acids which is active from promoter and enhancer positions.@@@@1@33@@oe@19-12-2010 861724405@GENIA Treebank@formal@@1@S@This transactivation domain was found to be inactivated by a naturally occurring frameshift mutation in one PAX-5 allele of the acute lymphoblastic leukemia cell line REH.@@@@1@27@@oe@19-12-2010 861724406@GENIA Treebank@formal@@1@S@The function of the transactivation domain is negatively regulated by adjacent sequences from the extreme C-terminus.@@@@1@17@@oe@19-12-2010 861724407@GENIA Treebank@formal@@1@S@The activating and inhibitory domains function together as an independent regulatory module in different cell types as shown by fusion to the GAL4 DNA binding domain.@@@@1@27@@oe@19-12-2010 861724408@GENIA Treebank@formal@@1@S@The same arrangement of positively and negatively acting sequences has been conserved in the mammalian Pax-2 and Pax-8, the zebrafish Pax-b as well as the sea urchin Pax-258 proteins.@@@@1@31@@oe@19-12-2010 861724409@GENIA Treebank@formal@@1@S@These data demonstrate that the transcriptional competence of a subfamily of Pax proteins is determined by a C-terminal regulatory module composed of activating and inhibitory sequences.@@@@1@27@@oe@19-12-2010 861776601@GENIA Treebank@formal@@1@S@Ubiquitinylation of transcription factors c-Jun and c-Fos using reconstituted ubiquitinylating enzymes.@@@@1@12@@oe@19-12-2010 861776602@GENIA Treebank@formal@@1@S@Recombinant c-Jun and c-Fos were ubiquitinylated by the ubiquitin carrier enzymes E214K, E220K, or E232K in the presence of the ubiquitin-activating enzyme, E1.@@@@1@27@@oe@19-12-2010 861776603@GENIA Treebank@formal@@1@S@Addition of ubiquitin protein ligase E3 substantially enhanced the E214K-mediated ubiquitinylation of c-Jun and c-Fos.@@@@1@16@@oe@19-12-2010 861776604@GENIA Treebank@formal@@1@S@Truncated c-Jun and c-Fos mutant proteins including wbJun and wbFos were also ubiquitinylated under the same conditions, suggesting the sites of ubiquitinylation are located within the dimerization and DNA binding domains of c-Jun and c-Fos.@@@@1@37@@oe@19-12-2010 861776605@GENIA Treebank@formal@@1@S@The E3-dependent ubiquitinylation of c-Jun was inhibited upon the heterodimerization of c-Jun with c-Fos.@@@@1@15@@oe@19-12-2010 861776606@GENIA Treebank@formal@@1@S@Further addition of E220K significantly enhanced ubiquitinylation of c-Jun in the heterodimer suggesting a regulatory role of E220K.@@@@1@19@@oe@19-12-2010 861776607@GENIA Treebank@formal@@1@S@Polyubiquitinylated c-Jun, wbFos, and wbJun, but not E220K-ubiquitinylated c-Jun, were readily degraded by the ATP-dependent 26 S multicatalytic proteases.@@@@1@24@@oe@19-12-2010 861776608@GENIA Treebank@formal@@1@S@These results suggest that the temporal control of c-Jun and c-Fos may be regulated through the ubiquitinylation pathways, and the ubiquitinylation of c-Jun and c-Fos may in turn be regulated in response to the heterodimerization between them and the cooperation between E220K and E3 mediated polyubiquitinylation.@@@@1@48@@oe@19-12-2010 861845601@GENIA Treebank@formal@@1@S@A new variant translocation in acute promyelocytic leukaemia: molecular characterization and clinical correlation.@@@@1@15@@oe@19-12-2010 861845602@GENIA Treebank@formal@@1@S@Translocation t(15;17)(q22;q21) is an acquired clonal cytogenetic change present in almost all cases of acute promelocytic leukemia (APL).@@@@1@21@@oe@19-12-2010 861845603@GENIA Treebank@formal@@1@S@The molecular genetic basis of the translocation supports its integral role in pathogenesis.@@@@1@14@@oe@19-12-2010 861845604@GENIA Treebank@formal@@1@S@We describe a patient with APL in whom the leukaemic clone was characterized by a true variant of the classical t(15;17).@@@@1@22@@oe@19-12-2010 861845605@GENIA Treebank@formal@@1@S@The patient whose disease had numerous atypical clinical features, had t(11;17)(q13;121).@@@@1@13@@oe@19-12-2010 861845606@GENIA Treebank@formal@@1@S@The chromosome 17 breakpoint was localized to intron 2 of RARA by Southern blotting, and there was no evidence at the molecular level for rearrangement at PML locus.@@@@1@30@@oe@19-12-2010 861845607@GENIA Treebank@formal@@1@S@These data, along with previous reports of rare variant translocations in APL, indicate that while dysregulation of RARA by gene fusion may be essential for the APL phenotype, the particular fusion partner may determine clinicopathological aspects, including presentation, response to treatment with all-trans retinoic acid (ATRA), and prognosis.@@@@1@57@@oe@19-12-2010 861845608@GENIA Treebank@formal@@1@S@This heterogeneity suggests that the variant fusion partners of RARA in APL encode factors with properties both common to and distinct from those of PML.@@@@1@26@@oe@19-12-2010 861845609@GENIA Treebank@formal@@1@S@Investigation of these factors promises to shed light on the complex development pathways involved in the regulation of haematopoiesis.@@@@1@20@@oe@19-12-2010 861983401@GENIA Treebank@formal@@1@S@Regulation of the nuclear factor of activated T cells in stably transfected Jurkat cell clones.@@@@1@16@@oe@19-12-2010 861983402@GENIA Treebank@formal@@1@S@Two Jurkat cell clones have been stably transfected with a reporter vector for the nuclear factor of activated T cells (NFAT).@@@@1@24@@oe@19-12-2010 861983403@GENIA Treebank@formal@@1@S@Upon stimulation, they express high levels of secreted heat stable placental alkaline phosphatase.@@@@1@15@@oe@19-12-2010 861983404@GENIA Treebank@formal@@1@S@With these clones, we demonstrated that NFAT activation induced by phorbol 12-myristate 13-acetate and ionomycin was inhibited by both cyclosporin A (CsA) (IC50 = 8 nM) and FK506 (IC50 = 160 pM), presumably by inhibition of calcineurin activity.@@@@1@47@@oe@19-12-2010 861983405@GENIA Treebank@formal@@1@S@Selective phosphatase inhibitors for protein phosphatase 1 (PP1) and 2A (PP2A) that do not inhibit calcineurin, such as okadaic acid and calyculin A, also inhibited NFAT activation with IC50s of 87 nM and 4 nM, respectively, suggesting that okadaic acid and related inhibitors may block NFAT activation through the inhibition of PP1, instead of PP2A.@@@@1@65@@oe@19-12-2010 861983406@GENIA Treebank@formal@@1@S@NFAT activation was also inhibited by agents that increase cAMP concentrations such as dibutyryl cAMP, forskolin and prostaglandin E2.@@@@1@21@@oe@19-12-2010 861983407@GENIA Treebank@formal@@1@S@These stable Jurkat cell clones provide a convenient and sensitive tool to study NFAT regulation.@@@@1@16@@oe@19-12-2010 862054601@GENIA Treebank@formal@@1@S@Age-related decreases in IL-2 production by human T cells are associated with impaired activation of nuclear transcriptional factors AP-1 and NF-AT.@@@@1@22@@oe@19-12-2010 862054602@GENIA Treebank@formal@@1@S@Although transcriptional factors AP-1 and nuclear factor of activated T cells (NF-AT) are important for the normal induction of IL-2, it is unknown if the age-related decline in IL-2 production by activated human T cells may be associated with aberrancies in transcriptional regulatory proteins.@@@@1@48@@oe@19-12-2010 862054603@GENIA Treebank@formal@@1@S@In the current studies, IL-2 production by T cells from elderly (mean 78 years) and young (mean 37 years) humans was measured in cultures stimulated with PHA, PHA plus PMA, crosslinked anti-CD3 mAB OKT3 plus PMA, or PMA plus ionomycin.@@@@1@49@@oe@19-12-2010 862054604@GENIA Treebank@formal@@1@S@Substantial decreases of IL-2 production were observed for cell cultures from 7 of 12 elderly individuals in response to the different stimuli, whereas the levels of IL-2 produced by stimulated T cells from other elderly individuals were equivalent to those observed for stimulated T cells of young subjects.@@@@1@50@@oe@19-12-2010 862054605@GENIA Treebank@formal@@1@S@Analyses of nuclear extracts by electrophoretic DNA mobility shift assays showed that decreased IL-2 production by stimulated T cells of elderly individuals was closely associated with impairments in the activation of both AP-1 and NF-AT.@@@@1@36@@oe@19-12-2010 862054606@GENIA Treebank@formal@@1@S@By contrast, T cells from elderly subjects with normal levels of IL-2 production exhibited normal activation of AP-1 and NF-AT.@@@@1@22@@oe@19-12-2010 862054607@GENIA Treebank@formal@@1@S@In addition, the results of competition experiments analyzing the normal components of NF-AT showed that the age-related reductions in stimulus-dependent NF-AT complexes corresponded to the slow migrating complexes that were composed of c-Fos/c-Jun AP-1.@@@@1@36@@oe@19-12-2010 862054608@GENIA Treebank@formal@@1@S@The resting and stimulated levels of NF kappa B were reduced in T cells from certain elderly individuals; however, alterations of NF kappa B did not correlate with changes in IL-2 expression.@@@@1@35@@oe@19-12-2010 862054609@GENIA Treebank@formal@@1@S@Thus, these results show that age-related impairments in the activation of AP-1 and NF-AT are closely associated with decreased expression of IL-2 and further suggest that aberrancies in the signaling pathways important for the induction of transcriptionally active c-Fos/c-Jun AP-1 may contribute to the impaired activation of NF-AT.@@@@1@50@@oe@19-12-2010 862297101@GENIA Treebank@formal@@1@S@cAMP inducibility of transcriptional repressor ICER in developing and mature human T lymphocytes [published erratum appears in Proc Natl Acad Sci U S A 1996 Jul 23;93(15):8154]@@@@1@36@@oe@19-12-2010 862297102@GENIA Treebank@formal@@1@S@Stimulation of the cAMP-dependent signaling pathway exerts an inhibitory effect on the proliferation and effector functions of T cells.@@@@1@20@@oe@19-12-2010 862297103@GENIA Treebank@formal@@1@S@The ability of T cells to form high intracellular levels of cAMP is acquired during development in the human thymus and is retained by the majority of mature peripheral T lymphocytes.@@@@1@32@@oe@19-12-2010 862297104@GENIA Treebank@formal@@1@S@Here we show that elevated cAMP levels in T cells correlate with the expression of the potent transcriptional repressor ICER (inducible cAMP early repressor) previously described in the hypothalamic-pituitary-gonadal axis.@@@@1@33@@oe@19-12-2010 862297105@GENIA Treebank@formal@@1@S@Further, in transcriptional assays in vivo, ICER inhibits calcineurin-mediated expression of the interleukin 2 promoter as well as Tax-mediated transactivation of the human T-lymphotropic virus type I (HTLV-I) promoter.@@@@1@34@@oe@19-12-2010 862297106@GENIA Treebank@formal@@1@S@Thus, the induction of ICER in T cells may play an important role in the cAMP-induced quiescence and the persistent latency of HTLV-I.@@@@1@25@@oe@19-12-2010 862722601@GENIA Treebank@formal@@1@S@Epstein-Barr virus nuclear antigen 2 (EBNA2)-oestrogen receptor fusion proteins complement the EBNA2-deficient Epstein-Barr virus strain P3HR1 in transformation of primary B cells but suppress growth of human B cell lymphoma lines.@@@@1@35@@oe@19-12-2010 862722602@GENIA Treebank@formal@@1@S@To develop a transformation system with a conditional Epstein-Barr virus nuclear antigen 2 (EBNA2) gene, we fused the hormone binding domain of the oestrogen receptor to the N or C terminus of EBNA2.@@@@1@37@@oe@19-12-2010 862722603@GENIA Treebank@formal@@1@S@In promoter transactivation as well as primary B cell transformation assays these chimeric EBNA2 proteins are able to substitute for wild-type EBNA2 in the presence of oestrogen.@@@@1@28@@oe@19-12-2010 862722604@GENIA Treebank@formal@@1@S@Here we provide evidence that this transformation is the result of double infection of a cell with two virions, the P3HR1 virus genome and a mini-EBV plasmid carrying the chimeric EBNA2 gene.@@@@1@34@@oe@19-12-2010 862722605@GENIA Treebank@formal@@1@S@Unexpectedly, expression of the same EBNA2-oestrogen receptor fusion protein in established human B cell lymphoma lines resulted in growth retardation or growth arrest upon the addition of oestrogen.@@@@1@30@@oe@19-12-2010 862722606@GENIA Treebank@formal@@1@S@By titrating the oestrogen concentration in these stably transfected cells, the growth retarding and the transactivating function of the chimeric proteins could not be dissociated.@@@@1@27@@oe@19-12-2010 862722607@GENIA Treebank@formal@@1@S@We propose that growth inhibition of established B cell lymphoma lines is a novel function of EBNA2 which has not been detected in the absence of an inducible system.@@@@1@30@@oe@19-12-2010 862722608@GENIA Treebank@formal@@1@S@It remains open whether the growth retarding property of the EBNA2-oestrogen receptor fusion protein in B cell lymphoma lines is due to unphysiologically high expression of the chimeric protein or to interference with a cellular programme driving proliferation in these cell lines.@@@@1@43@@oe@19-12-2010 862769501@GENIA Treebank@formal@@1@S@Identification of a herpesvirus Saimiri cis-acting DNA fragment that permits stable replication of episomes in transformed T cells.@@@@1@19@@oe@19-12-2010 862769502@GENIA Treebank@formal@@1@S@Herpesvirus saimiri is a lymphotropic herpesvirus capable of immortalizing and transforming T cells both in vitro and in vivo.@@@@1@20@@oe@19-12-2010 862769503@GENIA Treebank@formal@@1@S@Immortalized and transformed T cells harbor several copies of the viral genome as a persisting genome.@@@@1@17@@oe@19-12-2010 862769504@GENIA Treebank@formal@@1@S@The mapping of the cis-acting genetic cis-acting segment (oriP) required for viral episomal maintenance is reported here.@@@@1@20@@oe@19-12-2010 862769505@GENIA Treebank@formal@@1@S@Viral DNA fragments that potentially contain oriP were cloned into a plasmid that contains the hygromycin resistance gene.@@@@1@19@@oe@19-12-2010 862769506@GENIA Treebank@formal@@1@S@After several round of subcloning followed by transfection, oriP was mapped to a 1.955-kb viral segment.@@@@1@18@@oe@19-12-2010 862769507@GENIA Treebank@formal@@1@S@This viral fragment permits stable plasmid replication without deletion or rearrangement as well as episomal maintenance without integration or recombination.@@@@1@21@@oe@19-12-2010 862769508@GENIA Treebank@formal@@1@S@The function of oriP depends on a trans-acting factor(s) encoded by the viral genome.@@@@1@18@@oe@19-12-2010 862769509@GENIA Treebank@formal@@1@S@The 1.955-kb viral segment includes a dyad symmetry region located between two small nuclear RNA genes and is located upstream of the dihydrofolate reductase gene homolog.@@@@1@27@@oe@19-12-2010 862769510@GENIA Treebank@formal@@1@S@Therefore, this oriP contains novel elements distinct from those of other DNA viruses.@@@@1@15@@oe@19-12-2010 862770101@GENIA Treebank@formal@@1@S@Cyclic AMP-responsive element-dependent activation of Epstein-Barr virus zebra promoter by human herpesvirus 6.@@@@1@14@@oe@19-12-2010 862770102@GENIA Treebank@formal@@1@S@We have recently shown that infection of Epstein-Barr virus (EBV) genome-positive B cells by human herpesvirus 6 (HHV-6) results in the expression of the immediate-early EBV Zebra gene, followed by virus replication (L.Flamand, I.Stefanescu, D.V.Ablashi, and J.Menezes, J.Virol.67:6768-6777, 1993).@@@@1@54@@oe@19-12-2010 862770103@GENIA Treebank@formal@@1@S@Here we show that HHV-6 upregulates Zebra gene transcription through a cyclic AMP-responsive element (CRE) located within the Zebra promoter (Zp).@@@@1@26@@oe@19-12-2010 862770104@GENIA Treebank@formal@@1@S@Using human B- or T-cell lines transfected with ZpCat reporter gene constructs, we demonstrate that a region designated the ZII domain of Zp is the target of HHV-6 transactivation.@@@@1@31@@oe@19-12-2010 862770105@GENIA Treebank@formal@@1@S@Mutation of the consensus AP-1/CRE site within ZII abolished the inducibility of Zp by HHV-6, whereas positioning of the ZII domain upstream of the beta-globin minimal promoter conferred responsiveness following HHV-6 infection.@@@@1@34@@oe@19-12-2010 862770106@GENIA Treebank@formal@@1@S@Binding of these factors to ZII was prevented by oligonucleotides containing CRE but not by AP-1 consensus sequences.@@@@1@19@@oe@19-12-2010 862770107@GENIA Treebank@formal@@1@S@Antibodies against CRE-binding (CREB) protein but not against c-Fos or c-Jun were able to supershift the DNA-protein complex, identifying the nature of the transcription factor which binds to ZII as a member of the CREB family of proteins.@@@@1@42@@oe@19-12-2010 862770108@GENIA Treebank@formal@@1@S@Finally, transfection of CREB protein and protein kinase A expression vectors were found to activate Zp in Jurkat cells, suggesting that phosphorylated form of CREB protein can play a determining role in the EBV reactivation process.@@@@1@39@@oe@19-12-2010 862828401@GENIA Treebank@formal@@1@S@Genetic characterization of transactivation of the human T-cell leukemia virus type 1 promoter: Binding of Tax to Tax-responsive element 1 is mediated by the cyclic AMP-responsive members of the CREB/ATF family of transcription factors.@@@@1@36@@oe@19-12-2010 862828402@GENIA Treebank@formal@@1@S@To achieve a better understanding of the mechanism of transactivation by Tax of human T-cell leukemia virus type 1 Tax-responsive element 1 (TRE-1), we developed a genetic approach with Saccharomyces cerevisiae.@@@@1@35@@oe@19-12-2010 862828403@GENIA Treebank@formal@@1@S@We constructed a yeast reporter strain containing the lacZ gene under the control of the CYC1 promoter associated with three copies of TRE-1.@@@@1@24@@oe@19-12-2010 862828404@GENIA Treebank@formal@@1@S@Expression of either the cyclic AMP response element-binding protein (CREB) or CREB fused to the GAL4 activation domain (GAD) in this strain did not modify the expression of the reporter gene.@@@@1@36@@oe@19-12-2010 862828405@GENIA Treebank@formal@@1@S@Tax alone was also inactive.@@@@1@6@@oe@19-12-2010 862828406@GENIA Treebank@formal@@1@S@However, expression of the reporter gene was induced by coexpression of Tax and CREB.@@@@1@16@@oe@19-12-2010 862828407@GENIA Treebank@formal@@1@S@This effect was stronger with the GAD-CREB fusion protein.@@@@1@10@@oe@19-12-2010 862828408@GENIA Treebank@formal@@1@S@Analysis of different CREB mutants with this genetic system indicated that the C-terminal 92 amino acid residues, which include the basic domain and the leucine zipper, are necessary and sufficient to mediate transactivation by Tax.@@@@1@38@@oe@19-12-2010 862828409@GENIA Treebank@formal@@1@S@To identify cellular proteins binding to TRE-1 in a Tax-dependent manner, this strain was also used to screen a library of human cDNAs fused to GAD.@@@@1@28@@oe@19-12-2010 862828410@GENIA Treebank@formal@@1@S@Of five positive clones isolated from 0.75 x 10(6) yeast colonies, four were members of the CREB/activating transcription factor (ATF) family: CREB, two isoforms of the cyclic AMP-responsive element modulator (CREM), and ATF-1.@@@@1@42@@oe@19-12-2010 862828411@GENIA Treebank@formal@@1@S@Interestingly, these three proteins can be phosphorylated by protein kinase A and thus form a particular subgroup within the CREB/ATF family.@@@@1@23@@oe@19-12-2010 862828412@GENIA Treebank@formal@@1@S@Expression of ATF-2 in S. cerevisiae did not activate TRE-1 in the presence of Tax.@@@@1@16@@oe@19-12-2010 862828413@GENIA Treebank@formal@@1@S@This shows that in a eukaryotic nucleus, Tax specifically interacts with the basic domain-leucine zipper region of ATF-1, CREB, and CREM.@@@@1@25@@oe@19-12-2010 862828414@GENIA Treebank@formal@@1@S@The fifth clone identified in this screening corresponded to the Ku autoantigen p70 subunit.@@@@1@15@@oe@19-12-2010 862828415@GENIA Treebank@formal@@1@S@When fused to GAD, the C-terminal region of Ku was able to activate transcription via TRE-1 but this activation was not dependent on Tax.@@@@1@26@@oe@19-12-2010 863180901@GENIA Treebank@formal@@1@S@Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway.@@@@1@14@@oe@19-12-2010 863180902@GENIA Treebank@formal@@1@S@The mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex.@@@@1@27@@oe@19-12-2010 863180903@GENIA Treebank@formal@@1@S@Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene.@@@@1@32@@oe@19-12-2010 863180904@GENIA Treebank@formal@@1@S@IL-2 production by CsA-treated cells is therefore dramatically reduced.@@@@1@10@@oe@19-12-2010 863180905@GENIA Treebank@formal@@1@S@We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway.@@@@1@26@@oe@19-12-2010 863180906@GENIA Treebank@formal@@1@S@In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha-CD28 stimulation, and this activation was resistant to CsA.@@@@1@35@@oe@19-12-2010 863180907@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28.@@@@1@27@@oe@19-12-2010 863180908@GENIA Treebank@formal@@1@S@Peripheral blood T cells stimulated with PMA/alphaCD28 produced IL-2 in the presence of CsA.@@@@1@15@@oe@19-12-2010 863180909@GENIA Treebank@formal@@1@S@Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner.@@@@1@21@@oe@19-12-2010