1044606501@GENIA Treebank@formal@@1@S@Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line.@@@@1@25@@oe@19-12-2010
1044606502@GENIA Treebank@formal@@1@S@Expression of the class A macrophage scavenger receptor (MSR) contributes to the uptake of modified low density lipoproteins (LDL) by macrophages and transformation of these cells into lipid-laden foam cells, which characterize atherosclerosis.@@@@1@39@@oe@19-12-2010
1044606503@GENIA Treebank@formal@@1@S@Many environmental factors, in particular, proinflammatory cytokines and growth factors, can exert regulatory effects on MSR expression, whereas intracellular accumulation of cholesterol itself does not influence MSR levels to any considerable extent.@@@@1@37@@oe@19-12-2010
1044606504@GENIA Treebank@formal@@1@S@In the present study, by using an in vitro model, we examined whether stimulation with interleukin-6 (IL-6), an immunoregulatory, multipotential cytokine, modulates the expression and activities of the MSR in macrophages.@@@@1@39@@oe@19-12-2010
1044606505@GENIA Treebank@formal@@1@S@When treated with IL-6, macrophages derived from peripheral monocytes and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 monocytic cells showed significantly reduced uptake and/or binding of the MSR ligand, acetylated LDL.@@@@1@35@@oe@19-12-2010
1044606506@GENIA Treebank@formal@@1@S@This effect was paralleled by a reduction in the expression of MSR protein and mRNA.@@@@1@16@@oe@19-12-2010
1044606507@GENIA Treebank@formal@@1@S@Analysis of MSR promoter activity in THP-1 cells transfected with an MSR promoter-reporter gene construct demonstrated decreased activity of the MSR promoter in IL-6-treated THP-1 macrophages.@@@@1@27@@oe@19-12-2010
1044606508@GENIA Treebank@formal@@1@S@Electrophoretic mobility gel shift assay also showed a reduction in the binding of a transcription factor to the MSR promoter AP-1/ets elements in IL-6-treated cells.@@@@1@26@@oe@19-12-2010
1044606509@GENIA Treebank@formal@@1@S@Thus, exposure to IL-6 may inhibit expression of the class A MSR in differentiated macrophages at transcriptional levels.@@@@1@20@@oe@19-12-2010
1044606510@GENIA Treebank@formal@@1@S@This result suggests that this cytokine may modulate foam cell formation during atherogenesis.@@@@1@14@@oe@19-12-2010
1044814401@GENIA Treebank@formal@@1@S@Immune responses to adenoviruses: viral evasion mechanisms and their implications for the clinic.@@@@1@15@@oe@19-12-2010
1044814402@GENIA Treebank@formal@@1@S@Adenoviruses encode proteins that block responses to interferons, intrinsic cellular apoptosis, killing by CD8(+) cytotoxic T lymphocytes and killing by the death ligands TNF, Fas ligand and TRAIL.@@@@1@32@@oe@19-12-2010
1044814403@GENIA Treebank@formal@@1@S@The viral proteins are believed to prolong acute and persistent adenovirus infections.@@@@1@13@@oe@19-12-2010
1044814404@GENIA Treebank@formal@@1@S@The proteins may prove useful in protecting adenovirus gene therapy vectors and transplanted cells from the immune system.@@@@1@19@@oe@19-12-2010
1044915701@GENIA Treebank@formal@@1@S@Myb-transformed hematopoietic cells as a model for monocyte differentiation into dendritic cells and macrophages.@@@@1@15@@oe@19-12-2010
1044915702@GENIA Treebank@formal@@1@S@Immune induction is effected through the interaction of antigen-presenting cells with specific receptors on the surface of thymus-derived lymphocytes.@@@@1@20@@oe@19-12-2010
1044915703@GENIA Treebank@formal@@1@S@Cells most able to ingest, process, and present antigen appear to be related to the mononuclear phagocyte/neutrophil series.@@@@1@21@@oe@19-12-2010
1044915704@GENIA Treebank@formal@@1@S@For example dendritic cells (DC) can be found in colonies of GM-CSF-responsive bone marrow cells, and under experimental conditions are routinely expanded as a population in vitro from GM-CSF-responsive progenitor cells.@@@@1@35@@oe@19-12-2010
1044915705@GENIA Treebank@formal@@1@S@To address the question of DC lineage and to determine what genes are involved in lineage commitment, we have generated a series of GM-CSF-responsive cell lines that can be induced to differentiate in a homogeneous manner in vitro.@@@@1@40@@oe@19-12-2010
1044915706@GENIA Treebank@formal@@1@S@The cloned cell lines are derived from 12-day fetal liver and are transformed with a truncated form of c-myb, which lacks the normal autoregulatory sequences.@@@@1@27@@oe@19-12-2010
1044915707@GENIA Treebank@formal@@1@S@As far as we know, these myb-transformed hemopoi-etic cells (MTHC) differ from normal only in the unregulated expression of myb, a gene whose expression is obligatory for proliferation of hemopoietic cells.@@@@1@36@@oe@19-12-2010
1044915708@GENIA Treebank@formal@@1@S@MTHC in the presence of TNF-alpha and IL-4 will differentiate into cells that have many of the properties of macrophages.@@@@1@21@@oe@19-12-2010
1044915709@GENIA Treebank@formal@@1@S@When the same MTHC lines are exposed to TNF-alpha in combination with IFN-gamma, the cells instead become DC.@@@@1@20@@oe@19-12-2010
1044915710@GENIA Treebank@formal@@1@S@The differentiated DC are potent presenters of antigen in mixed lymphocyte reactions and of soluble antigen to specific T cell lines.@@@@1@22@@oe@19-12-2010
1044915711@GENIA Treebank@formal@@1@S@Thus, cells with the properties of both macrophages and DC can be derived from a single type of GM-CSF-responsive progenitor cell.@@@@1@23@@oe@19-12-2010
1044915712@GENIA Treebank@formal@@1@S@We have used this MTHC system to analyze differences in gene expression as the cells mature along the DC and macrophage pathways.@@@@1@23@@oe@19-12-2010
1044915713@GENIA Treebank@formal@@1@S@A distinctive pattern of differentially expressed cDNAs is evident where macrophage-specific cDNAs are homologous to genes encoding cytoskeletal and cell-surface proteins, whereas the DC-specific cDNAs are homologous to signaling, chemokine, and IFN-gamma-inducible genes.@@@@1@37@@oe@19-12-2010
1044915714@GENIA Treebank@formal@@1@S@We discuss the utility of MTHC in analyzing the relationships between DC and macrophages, and suggest that DC and macrophages represent extreme phenotypes in a spectrum of antigen handling cells that are somewhat interchangeable, depending on their immediate environment.@@@@1@42@@oe@19-12-2010
1044916901@GENIA Treebank@formal@@1@S@Dendritic cells and the pathogenesis of rheumatoid arthritis.@@@@1@9@@oe@19-12-2010
1044916902@GENIA Treebank@formal@@1@S@Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease in which unknown arthrogenic autoantigen is presented to CD4+ T cells.@@@@1@23@@oe@19-12-2010
1044916903@GENIA Treebank@formal@@1@S@The strong association of the disease with an epitope within the HLA-DR chain shared between various alleles of HLA-DR4 and DR1 emphasizes the importance of antigen presentation.@@@@1@28@@oe@19-12-2010
1044916904@GENIA Treebank@formal@@1@S@This immune response predominantly occurs in the synovial tissue and fluid of the joints and autoreactive T cells are readily demonstrable in both the synovial compartment and blood.@@@@1@29@@oe@19-12-2010
1044916905@GENIA Treebank@formal@@1@S@Circulating dendritic cells (DC) are phenotypically and functionally identical with normal peripheral blood (PB) DC.@@@@1@20@@oe@19-12-2010
1044916906@GENIA Treebank@formal@@1@S@In the synovial tissue, fully differentiated perivascular DC are found in close association with T cells and with B cell follicles, sometimes containing follicular DC.@@@@1@28@@oe@19-12-2010
1044916907@GENIA Treebank@formal@@1@S@These perivascular DC migrate across the activated endothelium from blood and receive differentiative signals within the joint from monocyte-derived cytokines and CD40-ligand+ T cells.@@@@1@25@@oe@19-12-2010
1044916908@GENIA Treebank@formal@@1@S@In the SF, DC manifest an intermediate phenotype, similar to that of monocyte-derived DC in vitro.@@@@1@19@@oe@19-12-2010
1044916909@GENIA Treebank@formal@@1@S@Like a delayed-type hypersensitivity response, the rheumatoid synovium represents an effector site.@@@@1@14@@oe@19-12-2010
1044916910@GENIA Treebank@formal@@1@S@DC at many effector sites have a characteristic pattern of infiltration and differentiation.@@@@1@14@@oe@19-12-2010
1044916911@GENIA Treebank@formal@@1@S@It is important to note that the effector response is not self-limiting in RA autoimmune inflammation.@@@@1@17@@oe@19-12-2010
1044916912@GENIA Treebank@formal@@1@S@In this article, we argue that the presentation of self-antigen by DC and by autoantibody-producing B cells is critical for the perpetuation of the autoimmune response.@@@@1@28@@oe@19-12-2010
1044916913@GENIA Treebank@formal@@1@S@Permanently arresting this ongoing immune response with either pharmaceutical agents or immunotherapy is a major challenge for immunology.@@@@1@19@@oe@19-12-2010
1044944201@GENIA Treebank@formal@@1@S@Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD.@@@@1@18@@oe@19-12-2010
1044944202@GENIA Treebank@formal@@1@S@Central to the bone-sparing effect of estrogen (E(2)) is its ability to block the monocytic production of the osteoclastogenic cytokine TNF-alpha (TNF).@@@@1@30@@oe@19-12-2010
1044944203@GENIA Treebank@formal@@1@S@However, the mechanism by which E(2) downregulates TNF production is presently unknown.@@@@1@17@@oe@19-12-2010
1044944204@GENIA Treebank@formal@@1@S@Transient transfection studies in HeLa cells, an E(2) receptor-negative line, suggest that E(2) inhibits TNF gene expression through an effect mediated by estrogen receptor beta (ERbeta).@@@@1@37@@oe@19-12-2010
1044944205@GENIA Treebank@formal@@1@S@We also report that in RAW 264.7 cells, an E(2) receptor-positive murine monocytic line, E(2) downregulates cytokine-induced TNF gene expression by decreasing the activity of the Jun NH(2)-terminal kinase (JNK).@@@@1@41@@oe@19-12-2010
1044944206@GENIA Treebank@formal@@1@S@The resulting diminished phosphorylation of c-Jun and JunD at their NH(2)-termini decreases the ability of these nuclear proteins to autostimulate the expression of the c-Jun and JunD genes, thus leading to lower production of c-Jun and JunD.@@@@1@39@@oe@19-12-2010
1044944207@GENIA Treebank@formal@@1@S@The consequent decrease in the nuclear levels of c-Jun and JunD leads to diminished binding of c-Jun/c-Fos and JunD/c-Fos heterodimers to the AP-1 consensus sequence in the TNF promoter and, thus, to decreased transactivation of the TNF gene.@@@@1@41@@oe@19-12-2010
1044977601@GENIA Treebank@formal@@1@S@TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues.@@@@1@10@@oe@19-12-2010
1044977602@GENIA Treebank@formal@@1@S@AIDS-related non-Hodgkin's lymphoma (AIDS NHL) comprises a diverse and heterogeneous group of high-grade B cell tumors.@@@@1@20@@oe@19-12-2010
1044977603@GENIA Treebank@formal@@1@S@Certain classes of AIDS NHL are associated with alterations in oncogenes or tumor-suppressor genes or infections by oncogenic herpesviruses.@@@@1@20@@oe@19-12-2010
1044977604@GENIA Treebank@formal@@1@S@However, the clinically significant class of AIDS NHL designated immunoblastic lymphoma plasmacytoid (AIDS IBLP) lacks any consistent genetic alterations.@@@@1@23@@oe@19-12-2010
1044977605@GENIA Treebank@formal@@1@S@We identified the TCL1 oncogene from a set of AIDS IBLP-associated cDNA fragments generated by subtractive hybridization with non-AIDS IBLP.@@@@1@21@@oe@19-12-2010
1044977606@GENIA Treebank@formal@@1@S@Aberrant TCL1 expression has been implicated in T cell leukemia/lymphoma development, and its expression also has been seen in many established B cell tumor lines.@@@@1@27@@oe@19-12-2010
1044977607@GENIA Treebank@formal@@1@S@However, TCL1 expression has not been reported in AIDS NHL.@@@@1@12@@oe@19-12-2010
1044977608@GENIA Treebank@formal@@1@S@We find that TCL1 is expressed in the majority of AIDS IBLP tumors examined.@@@@1@15@@oe@19-12-2010
1044977609@GENIA Treebank@formal@@1@S@TCL1 protein expression is restricted to tumor cells in AIDS IBLP tissue samples analyzed with immunohistochemical staining.@@@@1@18@@oe@19-12-2010
1044977610@GENIA Treebank@formal@@1@S@Hyperplastic lymph node and tonsil also exhibit strong TCL1 protein expression in mantle zone B cells and in rare interfollicular zone cells, whereas follicle-center B cells (centroblasts and centrocytes) show weaker expression.@@@@1@36@@oe@19-12-2010
1044977611@GENIA Treebank@formal@@1@S@These results establish TCL1 as the most prevalent of all of the surveyed oncogenes associated with AIDS IBLP.@@@@1@19@@oe@19-12-2010
1044977612@GENIA Treebank@formal@@1@S@They also indicate that abundant TCL1 expression in quiescent mantle zone B cells is down-regulated in activated germinal center follicular B cells in parallel to the known expression pattern of BCL-2.@@@@1@32@@oe@19-12-2010
1044977613@GENIA Treebank@formal@@1@S@High-level expression in nonproliferating B cells suggests that TCL1 may function in protecting naive preactivated B cells from apoptosis.@@@@1@20@@oe@19-12-2010
1045552301@GENIA Treebank@formal@@1@S@Gender and vascular reactivity.@@@@1@5@@oe@19-12-2010
1045552302@GENIA Treebank@formal@@1@S@Estrogen receptors are found on vascular endothelial and smooth muscle cells; their expression is influenced by exposure to the hormone.@@@@1@22@@oe@19-12-2010
1045552303@GENIA Treebank@formal@@1@S@Estrogen receptors influence non-genomic events, which are rapid in onset and genomic events, which are longer acting responses.@@@@1@21@@oe@19-12-2010
1045552304@GENIA Treebank@formal@@1@S@Estrogens affect vascular tone indirectly by modulating release of endothelium-derived vasoactive factors and directly by modulating intracellular calcium in vascular smooth muscle cells.@@@@1@24@@oe@19-12-2010
1045552305@GENIA Treebank@formal@@1@S@Estrogens indirectly affect thrombotic events and inflammation by altering platelet aggregation and leukocyte adherence and migration, respectively.@@@@1@19@@oe@19-12-2010
1045552306@GENIA Treebank@formal@@1@S@Estrogens also influence production of mitogens which, when released at sites of vascular injury, affect vascular remodeling.@@@@1@20@@oe@19-12-2010
1045552307@GENIA Treebank@formal@@1@S@Although estrogens initiate vascular responses, genomic sex may influence and/or limit expression of estrogen receptors and therefore actions of sex steroid hormones throughout the vasculature.@@@@1@27@@oe@19-12-2010
1045876901@GENIA Treebank@formal@@1@S@Dephosphorylation of ZAP-70 and inhibition of T cell activation by activated SHP1.@@@@1@13@@oe@19-12-2010
1045876902@GENIA Treebank@formal@@1@S@Studies with motheaten mice, which lack the SHP1 protein tyrosine phosphatase, indicate that this enzyme plays an important negative role in T cell antigen receptor (TCR) signaling.@@@@1@32@@oe@19-12-2010
1045876903@GENIA Treebank@formal@@1@S@The physiological substrates for SHP1 in T lymphocytes, however, have remained unclear or controversial.@@@@1@17@@oe@19-12-2010
1045876904@GENIA Treebank@formal@@1@S@To define these targets for SHP1 we have compared the effects of constitutively active and inactive mutants of SHP1 on TCR signaling.@@@@1@23@@oe@19-12-2010
1045876905@GENIA Treebank@formal@@1@S@Expression of wild-type SHP1 had a very small effect on the TCR-induced tyrosine phosphorylation of ZAP-70 and Syk, even when SHP1 was overexpressed 20 - 100-fold over endogenous SHP1.@@@@1@29@@oe@19-12-2010
1045876906@GENIA Treebank@formal@@1@S@Inactive SHP1-D421A and wild-type SHP2 were without effects.@@@@1@9@@oe@19-12-2010
1045876907@GENIA Treebank@formal@@1@S@Constitutively active SHP1-DeltaSH2 had a more pronounced effect on ZAP-70 and Syk, even when expressed at near physiological levels.@@@@1@21@@oe@19-12-2010
1045876908@GENIA Treebank@formal@@1@S@SHP1-DeltaSH2 also inhibited events downstream of ZAP-70 and Syk, such as activation of the mitogen-activated protein kinase Erk2 and the transcriptional activation of the interleukin-2 gene.@@@@1@28@@oe@19-12-2010
1045876909@GENIA Treebank@formal@@1@S@In contrast, a constitutively active SHP2-DeltaSH2 had no statistically significant effect (although it caused a slight augmentation in some individual experiments).@@@@1@25@@oe@19-12-2010
1045876910@GENIA Treebank@formal@@1@S@None of the constructs influenced the anti-CD3-induced tyrosine phosphorylation of the TCR zeta-chain or phospholipase Cgamma1, indicating that Src family kinase function was intact.@@@@1@26@@oe@19-12-2010
1045876911@GENIA Treebank@formal@@1@S@Taken together, our findings support the notion that ZAP-70 and Syk can be direct substrates for SHP1 in intact cells.@@@@1@22@@oe@19-12-2010
1045876912@GENIA Treebank@formal@@1@S@However, the two SH2 domains of SHP1 did not facilitate its recognition of ZAP-70 and Syk as substrates in intact cells.@@@@1@23@@oe@19-12-2010
1045876913@GENIA Treebank@formal@@1@S@Therefore, we suggest that SHP1 is not actively recruited to inhibit TCR signaling induced by ligation of this receptor alone.@@@@1@22@@oe@19-12-2010
1045876914@GENIA Treebank@formal@@1@S@Instead, we propose that ligation of a distinct inhibitory receptor leads to the recruitment of SHP1 via its SH2 domains, activation of SHP1 and subsequently inhibition of TCR signals if the inhibitory receptor is juxtaposed to the TCR.@@@@1@41@@oe@19-12-2010
1045934801@GENIA Treebank@formal@@1@S@Classification of IVS1-10T-->C as a polymorphism of BRCA1.@@@@1@11@@oe@19-12-2010
1045934802@GENIA Treebank@formal@@1@S@Mutations inactivating the tumor suppressor gene BRCA1 may be responsible for disease for up to 80% of familial ovarian cancer cases.@@@@1@23@@oe@19-12-2010
1045934803@GENIA Treebank@formal@@1@S@In this syndrome, tumorigenesis classically initiates from an inherited mutation in one allele followed by somatic deletion of the normal allele.@@@@1@23@@oe@19-12-2010
1045934804@GENIA Treebank@formal@@1@S@Sequencing of BRCA1 amplified from genomic DNA of lymphocytes and microdissected ovarian tumor cells of a familial ovarian cancer patient revealed three, rare heterozygous DNA variations (2418delA, 233G-->A, and IVS1-10T-->C) in both tumor and constitutional (lymphocyte) DNA.@@@@1@49@@oe@19-12-2010
1045934805@GENIA Treebank@formal@@1@S@Thus, both copies of BRCA1 were retained in tumor.@@@@1@11@@oe@19-12-2010
1045934806@GENIA Treebank@formal@@1@S@Haplotype analysis of the patient and four siblings assigned 2418delA to one copy of BRCA1 and 233G-->A and IVS1-10T-->C to the other.@@@@1@27@@oe@19-12-2010
1045934807@GENIA Treebank@formal@@1@S@The DNA change, 2418delA, is considered a mutation that inactivated one BRCA1 allele because it caused a frameshift and generation of a premature stop codon, resulting in synthesis of a truncated peptide as evidenced by an in vitro protein truncation test.@@@@1@45@@oe@19-12-2010
1045934808@GENIA Treebank@formal@@1@S@The DNA variation, 233G-->A, does not result in an amino acid change, and is considered a benign polymorphism.@@@@1@24@@oe@19-12-2010
1045934809@GENIA Treebank@formal@@1@S@IVS1-10T-->C is a unique BRCA1 change that occurs in the last nucleotide of a consensus sequence for a branch site critical for RNA splicing.@@@@1@27@@oe@19-12-2010
1045934810@GENIA Treebank@formal@@1@S@Therefore, we investigated whether IVS1-10T-->C deleteriously affected BRCA1 splicing or expression, and thereby inactivated the other BRCA1 allele.@@@@1@23@@oe@19-12-2010
1045934811@GENIA Treebank@formal@@1@S@Using the technique of reverse transcription-polymerase chain reaction (PCR) with RNA isolated from lymphoid cell lines of the patient and of controls, no evidence was found that IVS1-10TC abnormally disrupted mRNA splicing or caused the absence of BRCA1 mRNA.@@@@1@43@@oe@19-12-2010
1045934812@GENIA Treebank@formal@@1@S@Thus, IVS1-10T-->C is not harmful to BRCA1 function, and is classified a benign polymorphism.@@@@1@19@@oe@19-12-2010
1045934813@GENIA Treebank@formal@@1@S@Retention of the normal BRCA1 allele in the tumor with the heterozygous germline BRCA1 mutation, 2418delA, indicated that mutational inactivation of both BRCA1 alleles was not required for tumorigenesis.@@@@1@32@@oe@19-12-2010
1045934814@GENIA Treebank@formal@@1@S@It is possible that the normal allele may be functionally inactivated by a nonmutational mechanism.@@@@1@16@@oe@19-12-2010
1046249201@GENIA Treebank@formal@@1@S@Human T-cell lymphotrophic virus type-I tax gene induces secretion of human macrophage inflammatory protein-1alpha.@@@@1@15@@oe@19-12-2010
1046249202@GENIA Treebank@formal@@1@S@Human T-cell lymphotropic virus I (HTLV-I) encodes for a 40-kDa protein, Tax, which is important for the immortalization of T cells.@@@@1@26@@oe@19-12-2010
1046249203@GENIA Treebank@formal@@1@S@Tax has been shown to transactivate several cellular genes.@@@@1@10@@oe@19-12-2010
1046249204@GENIA Treebank@formal@@1@S@In this study, we show that MIP-1alpha is selectively expressed and secreted in the tax transfected Jurkat cell line upon mitogen stimulation.@@@@1@24@@oe@19-12-2010
1046249205@GENIA Treebank@formal@@1@S@Expression of MIP-1alpha-R mRNA in these cells suggests an autocrine role for this chemokine in HTLV-I infected T-cells.@@@@1@19@@oe@19-12-2010
1046249206@GENIA Treebank@formal@@1@S@Induced MIP-1alpha expression and secretion in PMA/PHA stimulated tax transfected cells correlate with the noninduction of MNP-1 transcription factor, which is intimately involved in downmodulating the MIP-1alpha gene.@@@@1@30@@oe@19-12-2010
1046249207@GENIA Treebank@formal@@1@S@Copyright 1999 Academic Press.@@@@1@5@@oe@19-12-2010
1046856001@GENIA Treebank@formal@@1@S@The beta-globin promoter is important for recruitment of erythroid Kruppel-like factor to the locus control region in erythroid cells.@@@@1@20@@oe@19-12-2010
1046856002@GENIA Treebank@formal@@1@S@Erythroid Kruppel-like factor (EKLF), which binds to the CACCC box in the beta-globin promoter, is required for the expression of the beta-globin gene in adult erythroid cells.@@@@1@32@@oe@19-12-2010
1046856003@GENIA Treebank@formal@@1@S@It was recently demonstrated that EKLF is also required for the activity of the beta-globin locus control region (LCR) 5'HS3.@@@@1@23@@oe@19-12-2010
1046856004@GENIA Treebank@formal@@1@S@Some evidence suggests that the LCR and the beta-globin promoter interact in adult erythroid cells, and the network of protein-protein interactions that exists between these two elements may regulate how EKLF is recruited to the LCR.@@@@1@38@@oe@19-12-2010
1046856005@GENIA Treebank@formal@@1@S@In this report, we use the PIN*POINT assay to study the role of the promoter on the recruitment of EKLF to 5'HS2 and 5'HS3 of the LCR.@@@@1@29@@oe@19-12-2010
1046856006@GENIA Treebank@formal@@1@S@We find that recruitment of EKLF to 5'HS2 requires the TATA box, but recruitment to 5'HS3 depends on the CACCC and TATA boxes of the beta-globin promoter.@@@@1@29@@oe@19-12-2010
1046856007@GENIA Treebank@formal@@1@S@Furthermore, recruitment of EKLF to 5'HS3 only occurred in beta-globin-expressing murine erythroid leukemia cells, whereas recruitment of EKLF to 5'HS2 occurred in both gamma-globin-expressing K562 cells and murine erythroid leukemia cells.@@@@1@34@@oe@19-12-2010
1046856008@GENIA Treebank@formal@@1@S@Unlike EKLF, Sp1, which also binds to CACCC boxes, is not recruited to 5'HS3.@@@@1@18@@oe@19-12-2010
1046856009@GENIA Treebank@formal@@1@S@We have also examined how one 5'HS affects the recruitment of EKLF to another 5'HS.@@@@1@16@@oe@19-12-2010
1046856010@GENIA Treebank@formal@@1@S@We have found that the recruitment of EKLF to 5'HS3 depends on the presence of 5'HS2 in cis, but the recruitment to 5'HS2 does not depend on 5'HS3.@@@@1@30@@oe@19-12-2010
1046856011@GENIA Treebank@formal@@1@S@Based on these results, we present a model that illustrates how EKLF may be recruited to the beta-globin locus.@@@@1@21@@oe@19-12-2010
1047132601@GENIA Treebank@formal@@1@S@E1A oncogene induction of cellular susceptibility to killing by cytolytic lymphocytes through target cell sensitization to apoptotic injury.@@@@1@19@@oe@19-12-2010
1047132602@GENIA Treebank@formal@@1@S@E1A oncogene expression increases mammalian cell susceptibility to lysis by cytolytic lymphocytes (CLs) at a stage in this intercellular interaction that is independent of cell surface recognition events.@@@@1@31@@oe@19-12-2010
1047132603@GENIA Treebank@formal@@1@S@Since CLs can induce either apoptotic or necrotic cell death, we asked whether E1A sensitization to injury-induced apoptosis is sufficient to explain E1A-induced cytolytic susceptibility.@@@@1@27@@oe@19-12-2010
1047132604@GENIA Treebank@formal@@1@S@Mouse, rat, hamster, and human cells that were rendered cytolytic susceptible by E1A were also sensitized to CL-induced and chemically induced apoptosis.@@@@1@26@@oe@19-12-2010
1047132605@GENIA Treebank@formal@@1@S@In contrast, E1A-positive cells were no more susceptible to injury-induced necrosis than E1A-negative cells.@@@@1@16@@oe@19-12-2010
1047132606@GENIA Treebank@formal@@1@S@Similar to induction of cytolytic susceptibility and in contrast to other E1A activities, cellular sensitization to chemically induced apoptosis depended on high-level E1A oncoprotein expression.@@@@1@27@@oe@19-12-2010
1047132607@GENIA Treebank@formal@@1@S@Loss of both cytolytic susceptibility and sensitization to chemically induced apoptosis was coselected during in vivo selection of E1A-positive sarcoma cells for increased tumorigenicity.@@@@1@25@@oe@19-12-2010
1047132608@GENIA Treebank@formal@@1@S@Furthermore, E1A mutant proteins that cannot bind the cellular transcriptional coactivator, p300, and that fail to induce cytolytic susceptibility also failed to sensitize cells to injury-induced apoptosis.@@@@1@32@@oe@19-12-2010
1047132609@GENIA Treebank@formal@@1@S@These data indicate that E1A induces susceptibility to killer cell-induced lysis through sensitization of cells to injury-induced apoptosis.@@@@1@19@@oe@19-12-2010
1047132610@GENIA Treebank@formal@@1@S@Copyright 1999 Academic Press.@@@@1@5@@oe@19-12-2010
1047234301@GENIA Treebank@formal@@1@S@Polyamines in human breast cancer and its relations to classical prognostic features: clinical implications.@@@@1@16@@oe@19-12-2010
1047234302@GENIA Treebank@formal@@1@S@Experimental evidence suggest an important role of polyamines in breast cancer development.@@@@1@13@@oe@19-12-2010
1047234303@GENIA Treebank@formal@@1@S@Polyamines have been determined in tissue and erythrocyte samples from 100 patients with primary invasive breast cancer and 30 patients with fibroadenomas.@@@@1@23@@oe@19-12-2010
1047234304@GENIA Treebank@formal@@1@S@Statistical analysis was performed in order to determine the prognostic value of the polyamine patterns of tumor tissues and erythrocytes in comparison with clinical and histological prognostic factors.@@@@1@29@@oe@19-12-2010
1047234305@GENIA Treebank@formal@@1@S@In malignant tissues, polyamine levels were significantly higher than in benign tissues.@@@@1@14@@oe@19-12-2010
1047234306@GENIA Treebank@formal@@1@S@They correlated with markers of tumor aggressivity (axillary node involvement and especially with markers of high mitotic rate as Ki-67 staining, histological grade).@@@@1@27@@oe@19-12-2010
1047234307@GENIA Treebank@formal@@1@S@No correlation was found between estrogen and progesterone status, tumor size and polyamine concentrations.@@@@1@16@@oe@19-12-2010
1047234308@GENIA Treebank@formal@@1@S@Erythrocyte polyamines levels were identical between cancer patients and controls.@@@@1@11@@oe@19-12-2010
1047234309@GENIA Treebank@formal@@1@S@The knowledge of the polyamine pattern in breast cancer could become useful in clinical practice particularly if polyamine metabolism is targeted as a therapeutic approach.@@@@1@26@@oe@19-12-2010
1047759901@GENIA Treebank@formal@@1@S@An activation-responsive element in single C motif-1/lymphotactin promoter is a site of constitutive and inducible DNA-protein interactions involving nuclear factor of activated T cell.@@@@1@25@@oe@19-12-2010
1047759902@GENIA Treebank@formal@@1@S@Single C motif-1 (SCM-1)/lymphotactin is a C-type chemokine whose expression is activation dependent, cyclosporin A sensitive and restricted to CD8+ T cells, double-negative thymocytes, gammadelta-type T cells, and NK cells.@@@@1@38@@oe@19-12-2010
1047759903@GENIA Treebank@formal@@1@S@In humans, there are two highly homologous genes encoding SCM-1alpha and SCM-1beta.@@@@1@14@@oe@19-12-2010
1047759904@GENIA Treebank@formal@@1@S@Here we examined the regulatory mechanism of the SCM-1 genes.@@@@1@11@@oe@19-12-2010
1047759905@GENIA Treebank@formal@@1@S@The luciferase reporter gene under the control of the 5' flanking region of 0.7 kb was strongly induced upon activation with anti-CD3 or PHA plus PMA only in SCM-1-producer T cell lines through a cyclosporin A-sensitive mechanism.@@@@1@38@@oe@19-12-2010
1047759906@GENIA Treebank@formal@@1@S@An element termed E1 located at -108 to -95 nt relative to the major transcription start site was found to be critical for the promoter activity.@@@@1@27@@oe@19-12-2010
1047759907@GENIA Treebank@formal@@1@S@In electrophoretic mobility shift assays using the E1 oligonucleotide as probe, nuclear extracts from unstimulated T and B cell lines formed a constitutive complex termed complex I, while nuclear extracts from stimulated SCM-1-producer T cell lines formed a higher mobility complex termed complex II with a concomitant decrease in complex I.@@@@1@54@@oe@19-12-2010
1047759908@GENIA Treebank@formal@@1@S@The shift from complex I to complex II seen only in SCM-1-producer T cell lines upon activation was completely suppressed by cyclosporin A.@@@@1@24@@oe@19-12-2010
1047759909@GENIA Treebank@formal@@1@S@Both complexes were critically dependent on the NF-AT core sequence TTTCC in the E1 element and were partially supershifted by anti-NF-ATp.@@@@1@22@@oe@19-12-2010
1047759910@GENIA Treebank@formal@@1@S@One-hybrid assays in yeast isolated NF-ATp as an E1 binding protein, and transfection of NF-ATp into T and B cell lines strongly enhanced the activation-dependent SCM-1 promoter activity.@@@@1@30@@oe@19-12-2010
1047759911@GENIA Treebank@formal@@1@S@Collectively, a unique mechanism involving NF-ATp appears to regulate the cell type-specific and activation-dependent expression of the SCM-1 genes.@@@@1@21@@oe@19-12-2010
1047762101@GENIA Treebank@formal@@1@S@Glucocorticoids induce apoptosis in human monocytes: potential role of IL-1 beta.@@@@1@13@@oe@19-12-2010
1047762102@GENIA Treebank@formal@@1@S@Glucocorticoids (GC) are potent anti-inflammatory and immunosuppressive agents that act on a variety of immune cells, including monocytes and macrophages.@@@@1@24@@oe@19-12-2010
1047762103@GENIA Treebank@formal@@1@S@However, the exact cellular mechanisms underlying this anti-inflammatory capacity are still unknown.@@@@1@14@@oe@19-12-2010
1047762104@GENIA Treebank@formal@@1@S@In our study, we determined the induction of apoptosis by GC in human monocytes.@@@@1@16@@oe@19-12-2010
1047762105@GENIA Treebank@formal@@1@S@Peripheral blood monocytes were isolated by density centrifugation methods with a purity of >90% and were cultured in RPMI 1640 medium.@@@@1@24@@oe@19-12-2010
1047762106@GENIA Treebank@formal@@1@S@Monocyte apoptosis was determined by four independent methods, including annexin-V staining, TUNEL, DNA-laddering, and typical morphology by means of transmission electron microscopy.@@@@1@27@@oe@19-12-2010
1047762107@GENIA Treebank@formal@@1@S@TNF-alpha and IL-1beta were measured by ELISA.@@@@1@8@@oe@19-12-2010
1047762108@GENIA Treebank@formal@@1@S@GC receptor was blocked with mifepristone.@@@@1@7@@oe@19-12-2010
1047762109@GENIA Treebank@formal@@1@S@Caspase 3 was inhibited with caspase-3 inhibitor (DEVD-CHO).@@@@1@11@@oe@19-12-2010
1047762110@GENIA Treebank@formal@@1@S@Stimulation with different GC at therapeutic concentrations resulted in monocyte apoptosis in a time- and dose-dependent manner.@@@@1@18@@oe@19-12-2010
1047762111@GENIA Treebank@formal@@1@S@Necrosis was excluded by propidium iodide staining.@@@@1@8@@oe@19-12-2010
1047762112@GENIA Treebank@formal@@1@S@Proinflammatory cytokines such as IL-1beta and TNF-alpha were down-regulated by GC treatment.@@@@1@13@@oe@19-12-2010
1047762113@GENIA Treebank@formal@@1@S@Continuous treatment of monocytes with IL-1beta, but not with TNF-alpha, could almost completely prevent GC-induced cell death.@@@@1@20@@oe@19-12-2010
1047762114@GENIA Treebank@formal@@1@S@The addition of mifepristone or caspase-3 inhibitor could partially abrogate GC-induced apoptosis as well as GC-induced inhibition of IL-1beta.@@@@1@20@@oe@19-12-2010
1047762115@GENIA Treebank@formal@@1@S@This is the first study to demonstrate induction of apoptosis by GC in human monocytes.@@@@1@16@@oe@19-12-2010
1047762116@GENIA Treebank@formal@@1@S@GC-induced monocyte apoptosis may be partially mediated through effects on IL-1beta production.@@@@1@13@@oe@19-12-2010
1047762117@GENIA Treebank@formal@@1@S@It is conceivable that GC exert their anti-inflammatory capacity in various diseases, at least in part, by the induction of apoptosis in monocytes.@@@@1@26@@oe@19-12-2010
1047965001@GENIA Treebank@formal@@1@S@Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction.@@@@1@14@@oe@19-12-2010
1047965002@GENIA Treebank@formal@@1@S@An early event in acute and chronic inflammation and associated diseases such as atherosclerosis and rheumatoid arthritis is the induced expression of specific adhesion molecules on the surface of endothelial cells (ECs), which subsequently bind leukocytes.@@@@1@40@@oe@19-12-2010
1047965003@GENIA Treebank@formal@@1@S@Peroxisome proliferator-activated receptors (PPARs), members of the nuclear receptor superfamily of transcription factors, are activated by fatty acid metabolites, peroxisome proliferators, and thiazolidinediones and are now recognized as important mediators in the inflammatory response.@@@@1@41@@oe@19-12-2010
1047965004@GENIA Treebank@formal@@1@S@Whether PPAR activators influence the inflammatory responses of ECs is unknown.@@@@1@12@@oe@19-12-2010
1047965005@GENIA Treebank@formal@@1@S@We show that the PPAR activators 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), Wyeth 14643, ciglitazone, and troglitazone, but not BRL 49653, partially inhibit the induced expression of vascular cell adhesion molecule-1 (VCAM-1), as measured by ELISA, and monocyte binding to human aortic endothelial cells (HAECs) activated by phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide.@@@@1@78@@oe@19-12-2010
1047965006@GENIA Treebank@formal@@1@S@The "natural" PPAR activator 15d-PGJ(2) had the greatest potency and was the only tested molecule capable of partially inhibiting the induced expression of E-selectin and neutrophil-like HL60 cell binding to PMA-activated HAECs.@@@@1@38@@oe@19-12-2010
1047965007@GENIA Treebank@formal@@1@S@Intracellular adhesion molecule-1 induction by PMA was unaffected by any of the molecules tested.@@@@1@15@@oe@19-12-2010
1047965008@GENIA Treebank@formal@@1@S@Both PPAR-alpha and PPAR-gamma mRNAs were detected in HAECs by using reverse transcription-polymerase chain reaction and a ribonuclease protection assay; however, we have yet to determine which, if any, of the PPARs are mediating this process.@@@@1@41@@oe@19-12-2010
1047965009@GENIA Treebank@formal@@1@S@These results suggest that certain PPAR activators may help limit chronic inflammation mediated by VCAM-1 and monocytes without affecting acute inflammation mediated by E-selectin and neutrophil binding.@@@@1@28@@oe@19-12-2010
1047965101@GENIA Treebank@formal@@1@S@9-cis retinoic acid induces monocyte chemoattractant protein-1 secretion in human monocytic THP-1 cells.@@@@1@14@@oe@19-12-2010
1047965102@GENIA Treebank@formal@@1@S@Monocyte migration and activation are regulated by monocyte chemoattractant protein-1 (MCP-1).@@@@1@14@@oe@19-12-2010
1047965103@GENIA Treebank@formal@@1@S@Prior studies have shown MCP-1 expression is modulated by a variety of ligands that act through extracellular receptors.@@@@1@19@@oe@19-12-2010
1047965104@GENIA Treebank@formal@@1@S@In the current study, we show 9-cis retinoic acid (RA), a ligand for the nuclear hormone receptor retinoid X receptor (RXR) and retinoic acid receptor (RAR), markedly induces the expression of MCP-1.@@@@1@42@@oe@19-12-2010
1047965105@GENIA Treebank@formal@@1@S@In human THP-1 monocytic leukemia cells cultured with RA (0.05 to 500 nmol/L), MCP-1 expression was induced rapidly, significantly, and dose-dependently by as much as 165-fold.@@@@1@32@@oe@19-12-2010
1047965106@GENIA Treebank@formal@@1@S@MCP-1 RNA level was also increased in RA-treated cells.@@@@1@10@@oe@19-12-2010
1047965107@GENIA Treebank@formal@@1@S@Expression of PPARgamma, a heterodimer partner of RXR, is also markedly induced by RA in THP-1 cells.@@@@1@20@@oe@19-12-2010
1047965108@GENIA Treebank@formal@@1@S@However, BRL49653, a PPARgamma ligand, failed to induce MCP-1 secretion either alone or to modify the expression level induced by RA.@@@@1@25@@oe@19-12-2010
1047965109@GENIA Treebank@formal@@1@S@In contrast, BRL49653 significantly increased MCP-1 (biotinylated MCP-1) binding to THP-1 cells, whereas RA had no effect.@@@@1@22@@oe@19-12-2010
1047965110@GENIA Treebank@formal@@1@S@Other peroxisome proliferator activated receptor (PPAR) ligands, 15d-PGJ(2) and troglitazone (PPARgamma) , Wy14,643 (PPARalpha), and PD195599 (PPARbeta) inhibited the induction of MCP-1 by RA.@@@@1@40@@oe@19-12-2010
1047965111@GENIA Treebank@formal@@1@S@RA's effect on MCP-1 expression in human elutriated monocytes were similar to that observed in the THP-1 cells.@@@@1@20@@oe@19-12-2010
1047965112@GENIA Treebank@formal@@1@S@These studies identify RA as a nuclear signal for MCP-1 induction in undifferentiated human monocytic cells.@@@@1@17@@oe@19-12-2010
1047965113@GENIA Treebank@formal@@1@S@These studies also suggest monocyte MCP-1 expression induced through RA may modulate cell migration.@@@@1@15@@oe@19-12-2010
1048256801@GENIA Treebank@formal@@1@S@Target structures of the CD8(+)-T-cell response to human cytomegalovirus: the 72-kilodalton major immediate-early protein revisited.@@@@1@17@@oe@19-12-2010
1048256802@GENIA Treebank@formal@@1@S@Cell-mediated immunity plays an essential role in the control of infection with the human cytomegalovirus (HCMV).@@@@1@19@@oe@19-12-2010
1048256803@GENIA Treebank@formal@@1@S@However, only a few CD8(+)-T-cell epitopes are known, with the majority being contained in the pp65 phosphoprotein, which is believed to dominate the CD8(+)-T-cell response to HCMV.@@@@1@31@@oe@19-12-2010
1048256804@GENIA Treebank@formal@@1@S@Here, we have readdressed the issue of CD8(+) T cells specific for the 72-kDa major immediate-early protein (IE-1), which is nonstructural but is found very early and throughout the replicative cycle.@@@@1@36@@oe@19-12-2010
1048256805@GENIA Treebank@formal@@1@S@Using a novel flow-cytometric assay, we were able to identify CD8(+)-T-cell epitopes (by IE-1 peptide-specific induction of cytokine synthesis) and simultaneously measure the frequency of cells directed against them.@@@@1@33@@oe@19-12-2010
1048256806@GENIA Treebank@formal@@1@S@For this purpose, 81 pentadecamer peptides covering the complete 491-amino-acid sequence of IE-1 were tested on peripheral blood mononuclear cells of anti-HCMV immunoglobulin G-seropositive donors.@@@@1@27@@oe@19-12-2010
1048256807@GENIA Treebank@formal@@1@S@At least 10 new epitopes were identified, and the fine specificity and presenting HLA molecule of the first of them was determined.@@@@1@24@@oe@19-12-2010
1048256808@GENIA Treebank@formal@@1@S@The frequencies of CD8(+) T cells directed against IE-1 were similar to those directed against pp65 in donors tested with known pp65-derived peptides.@@@@1@24@@oe@19-12-2010
1048256809@GENIA Treebank@formal@@1@S@Importantly, additional testing of a corresponding set of peptides covering the complete sequence of pp65 on 10 of these donors identified individuals whose CD8(+) T cells recognized IE-1 but not pp65 and vice versa, clearly illustrating that either protein may be a major target.@@@@1@47@@oe@19-12-2010
1048256810@GENIA Treebank@formal@@1@S@In summary, our results suggest that IE-1 is far more important as a CD8(+)-T-cell target than current opinion suggests.@@@@1@21@@oe@19-12-2010
1048587501@GENIA Treebank@formal@@1@S@Inhibition of protein phosphatase 2A induces serine/threonine phosphorylation, subcellular redistribution, and functional inhibition of STAT3.@@@@1@18@@oe@19-12-2010
1048587502@GENIA Treebank@formal@@1@S@Signal transducers and activators of transcription (STATs) are rapidly phosphorylated on tyrosine residues in response to cytokine and growth factor stimulation of cell surface receptors.@@@@1@28@@oe@19-12-2010
1048587503@GENIA Treebank@formal@@1@S@STATs hereafter are translocated to the nucleus where they act as transcription factors.@@@@1@14@@oe@19-12-2010
1048587504@GENIA Treebank@formal@@1@S@Recent reports suggest that serine phosphorylation of STATs also is involved in the regulation of STAT-mediated gene transcription.@@@@1@19@@oe@19-12-2010
1048587505@GENIA Treebank@formal@@1@S@Here, we studied the role of serine/threonine phosphatases in STAT3 signaling in human antigen-specific CD4(+) T cell lines and cutaneous T cell lymphoma lines, expressing a constitutively activated STAT3.@@@@1@32@@oe@19-12-2010
1048587506@GENIA Treebank@formal@@1@S@We show that an inhibitor of protein phosphatases (PPs) PP1/PP2A, calyculin A, induces (i) phosphorylation of STAT3 on serine and threonine residues, (ii) inhibition of STAT3 tyrosine phosphorylation and DNA binding activity, and (iii) relocation of STAT3 from the nucleus to the cytoplasm.@@@@1@56@@oe@19-12-2010
1048587507@GENIA Treebank@formal@@1@S@Similar results were obtained with other PP2A inhibitors (okadaic acid, endothall thioanhydride) but not with inhibitors of PP1 (tautomycin) or PP2B (cyclosporine A).@@@@1@31@@oe@19-12-2010
1048587508@GENIA Treebank@formal@@1@S@Pretreatment with the broad serine/threonine kinase inhibitor staurosporine partly blocked the calyculin A-induced STAT3 phosphorylation, whereas inhibitors of serine/threonine kinases, such as mitogen-activated protein kinase-1 extracellular-regulated kinase-kinase, mitogen-activated protein p38 kinase, and phosphatidylinositol 3-kinase, did not.@@@@1@42@@oe@19-12-2010
1048587509@GENIA Treebank@formal@@1@S@In conclusion, we provide evidence that PP2A plays a crucial role in the regulation of STAT3 phosphorylation and subcellular distribution in T cells.@@@@1@25@@oe@19-12-2010
1048587510@GENIA Treebank@formal@@1@S@Moreover, our findings suggest that the level of STAT3 phosphorylation is balanced between a staurosporine-sensitive kinase(s) and PP2A.@@@@1@23@@oe@19-12-2010
1049139401@GENIA Treebank@formal@@1@S@Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility.@@@@1@23@@oe@19-12-2010
1049139402@GENIA Treebank@formal@@1@S@To propel itself in infected cells, the pathogen Shigella flexneri subverts the Cdc42-controlled machinery responsible for actin assembly during filopodia formation.@@@@1@23@@oe@19-12-2010
1049139403@GENIA Treebank@formal@@1@S@Using a combination of bacterial motility assays in platelet extracts with Escherichia coli expressing the Shigella IcsA protein and in vitro analysis of reconstituted systems from purified proteins, we show here that the bacterial protein IcsA binds N-WASP and activates it in a Cdc42-like fashion.@@@@1@47@@oe@19-12-2010
1049139404@GENIA Treebank@formal@@1@S@Dramatic stimulation of actin assembly is linked to the formation of a ternary IcsA-N-WASP-Arp2/3 complex, which nucleates actin polymerization.@@@@1@21@@oe@19-12-2010
1049139405@GENIA Treebank@formal@@1@S@The Arp2/3 complex is essential in initiation of actin assembly and Shigella movement, as previously observed for Listeria monocytogenes.@@@@1@21@@oe@19-12-2010
1049139406@GENIA Treebank@formal@@1@S@Activation of N-WASP by IcsA unmasks two domains acting together in insertional actin polymerization.@@@@1@15@@oe@19-12-2010
1049139407@GENIA Treebank@formal@@1@S@The isolated COOH-terminal domain of N-WASP containing a verprolin-homology region, a cofilin-homology sequence, and an acidic terminal segment (VCA) interacts with G-actin in a unique profilin-like functional fashion.@@@@1@33@@oe@19-12-2010
1049139408@GENIA Treebank@formal@@1@S@Hence, when N-WASP is activated, its COOH-terminal domain feeds barbed end growth of filaments and lowers the critical concentration at the bacterial surface.@@@@1@26@@oe@19-12-2010
1049139409@GENIA Treebank@formal@@1@S@On the other hand, the NH(2)-terminal domain of N-WASP interacts with F-actin, mediating the attachment of the actin tail to the bacterium surface.@@@@1@26@@oe@19-12-2010
1049139410@GENIA Treebank@formal@@1@S@VASP is not involved in Shigella movement, and the function of profilin does not require its binding to proline-rich regions.@@@@1@22@@oe@19-12-2010
1049203801@GENIA Treebank@formal@@1@S@Immunocytochemical analysis of MNDA in tissue sections and sorted normal bone marrow cells documents expression only in maturing normal and neoplastic myelomonocytic cells and a subset of normal and neoplastic B lymphocytes.@@@@1@33@@oe@19-12-2010
1049203802@GENIA Treebank@formal@@1@S@The human myeloid cell nuclear differentiation antigen (MNDA) is a nuclear antigen known to be expressed in mature myelomonocytic cell lines.@@@@1@24@@oe@19-12-2010
1049203803@GENIA Treebank@formal@@1@S@An extensive immunocytochemical evaluation of fixed tissues confirmed MNDA expression in normal maturing granulocytes and monocytes and in acute nonlymphocytic leukemias and chronic myelogenous leukemia.@@@@1@26@@oe@19-12-2010
1049203804@GENIA Treebank@formal@@1@S@MNDA was not detected in normal tissue histiocytes but was found in activated macrophages and foreign body giant cells associated with inflammation.@@@@1@23@@oe@19-12-2010
1049203805@GENIA Treebank@formal@@1@S@Flow cytometric cell sorting of normal bone marrow established that MNDA is initially expressed in myeloid blast cells.@@@@1@19@@oe@19-12-2010
1049203806@GENIA Treebank@formal@@1@S@Examination of lymphoid tissues showed a low level of expression in a population of normal mande B lymphocytes but not in germinal center cells or plasma cells.@@@@1@28@@oe@19-12-2010
1049203807@GENIA Treebank@formal@@1@S@A subset of B cell neoplasms expressing MNDA included hairy cell leukemia, parafollicular (monocytoid) B cell lymphoma, mantle cell lymphoma, and small lymphocytic lymphoma.@@@@1@30@@oe@19-12-2010
1049203808@GENIA Treebank@formal@@1@S@Cell sorting of normal bone marrow showed MNDA expression in CD20+/CD10-/CD5- B cells.@@@@1@14@@oe@19-12-2010
1049203809@GENIA Treebank@formal@@1@S@MNDA was not detected in other normal bone marrow or all other nonhematopoietic cells.@@@@1@15@@oe@19-12-2010
1049203810@GENIA Treebank@formal@@1@S@The hematopoietic cell-specific pattern of MNDA expression was elucidated through a comprehensive analysis of normal and neoplastic tissues, and the results provide further evidence of the coexpression of B- and myeloid cell markers in neoplastic B cells and identify a normal B cell population that might be related to the cell of origin of a subset of B cell neoplasms.@@@@1@62@@oe@19-12-2010
1049953801@GENIA Treebank@formal@@1@S@Vitamin D analogs, 20-Epi-22-oxa-24a,26a,27a,-trihomo-1alpha,25(OH)2-vitamin D3, 1,24(OH)2-22-ene-24-cyclopropyl-vitamin D3 and 1alpha,25(OH)2-lumisterol3 prime NB4 leukemia cells for monocytic differentiation via nongenomic signaling pathways, involving calcium and calpain.@@@@1@29@@oe@19-12-2010
1049953802@GENIA Treebank@formal@@1@S@Side-chain modified vitamin D analogs including 20-Epi-22-oxa-24a,26a,27a-trihomo-1alpha,2 5-dihydroxyvitamin D3 (KH1060), and 1,24-dihydroxy-22-ene-24-cyclopropyl-vitamin D3 (MC903) were originally designed to aid in the treatment of hyperproliferative disorders including psoriasis and cancer.@@@@1@35@@oe@19-12-2010
1049953803@GENIA Treebank@formal@@1@S@Here we demonstrate that these analogs, as well as the 6-cis-locked conformer, 1alpha,25-dihydroxy-lumisterol3 (JN) prime NB4 cells for monocytic differentiation.@@@@1@25@@oe@19-12-2010
1049953804@GENIA Treebank@formal@@1@S@Previously, the action of MC903 and KH1060 was presumed to be mediated by the nuclear vitamin D receptor (VDRnuc).@@@@1@23@@oe@19-12-2010
1049953805@GENIA Treebank@formal@@1@S@Differentiation in response to all analogs was shown to be inhibited by 1beta,25-dihydroxyvitamin D3 (HL), the antagonist to the nongenomic activities of 1,25D3.@@@@1@27@@oe@19-12-2010
1049953806@GENIA Treebank@formal@@1@S@These data suggest that although MC903 and KH1060 may bind the VDRnuc, that the differentiative activities of these agents requires nongenomic signaling pathways.@@@@1@25@@oe@19-12-2010
1049953807@GENIA Treebank@formal@@1@S@Here we show that 1alpha,25(OH)2-d5-previtamin D3 (HF), JN, KH1060, and MC903 induce expression of PKC alpha and PKC delta and translocation of both isoforms to the particulate fraction, and PKC alpha to the nuclear fraction.@@@@1@42@@oe@19-12-2010
1049953808@GENIA Treebank@formal@@1@S@The full differentiation response with combinations of analogs and TPA was inhibited 50% by the membrane permeable Ca2+ chelator, 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) or calpain inhibitor I.@@@@1@31@@oe@19-12-2010
1049953809@GENIA Treebank@formal@@1@S@These data demonstrate that intracellular free calcium and the calcium-dependent protease, calpain play critical roles in monocytic differentiation.@@@@1@20@@oe@19-12-2010
1049953810@GENIA Treebank@formal@@1@S@Intracellular calcium appears to be most critical in the 1,25D3-priming stage of differentiation, while calpain is essential in the TPA maturation response.@@@@1@24@@oe@19-12-2010