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800 | Ara-C activated JNKs only after prolonged incubation ( 90-120 minutes ) . | Ara-C activated <protein>JNKs</protein> only after prolonged incubation ( 90-120 minutes ) . |
801 | Thus , ceramide is not a positive signal for ERK activation in T-cell lines . | Thus , ceramide is not a positive signal for <protein>ERK</protein> activation in <cell_line>T-cell lines</cell_line> . |
802 | The effects of Ara-C on JNK activity may be mediated through secondary response pathways . | The effects of Ara-C on <protein>JNK</protein> activity may be mediated through secondary response pathways . |
803 | Comparative analysis identifies conserved tumor necrosis factor receptor-associated factor 3 binding sites in the human and simian Epstein-Barr virus oncogene LMP1 . | Comparative analysis identifies conserved <dna>tumor necrosis factor receptor-associated factor 3 binding sites</dna> in the <dna>human and simian Epstein-Barr virus oncogene LMP1</dna> . |
804 | Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus ( EBV ) . | Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus ( EBV ) . |
805 | These simian EBV share considerable genetic , biologic , and epidemiologic features with human EBV , including virus-induced tumorigenesis . | These simian EBV share considerable genetic , biologic , and epidemiologic features with human EBV , including virus-induced tumorigenesis . |
806 | However , latent , transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions . | However , latent , transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions . |
807 | We have cloned the latent membrane protein 1 ( LMP1 ) homologs from the simian EBV naturally infecting baboons ( cercopithicine herpesvirus 12 , herpesvirus papio ) and rhesus monkeys ( cercopithicine herpesvirus 15 ) for a comparative study with the human EBV oncogene . | We have cloned the <protein>latent membrane protein 1 ( LMP1 ) homologs</protein> from the simian EBV naturally infecting baboons ( cercopithicine herpesvirus 12 , herpesvirus papio ) and rhesus monkeys ( cercopithicine herpesvirus 15 ) for a comparative study with the human EBV oncogene . |
808 | The transmembrane domains are well conserved , but there is striking sequence divergence of the carboxy-terminal cytoplasmic domain essential for B-cell immortalization and interaction with the tumor necrosis factor receptor signaling pathway . | The transmembrane domains are well conserved , but there is striking sequence divergence of the <protein>carboxy-terminal cytoplasmic domain</protein> essential for <cell_type>B-cell</cell_type> immortalization and interaction with the <protein>tumor necrosis factor receptor</protein> signaling pathway . |
809 | Nevertheless , the simian EBV LMP1s retain most functions in common with EBV LMP1 , including the ability to induce NF- ( kappa ) B activity in human cells , to bind the tumor necrosis factor-associated factor 3 ( TRAF3 ) in vitro , and to induce expression of tumor necrosis factor-responsive genes , such as ICAM1 , in human B lymphocytes . | Nevertheless , the <protein>simian EBV LMP1s</protein> retain most functions in common with EBV <protein>LMP1</protein> , including the ability to induce <protein>NF- ( kappa ) B</protein> activity in <cell_type>human cells</cell_type> , to bind the <protein>tumor necrosis factor-associated factor 3</protein> ( <protein>TRAF3</protein> ) in vitro , and to induce expression of <dna>tumor necrosis factor-responsive genes</dna> , such as <dna>ICAM1</dna> , in <cell_type>human B lymphocytes</cell_type> . |
810 | Multiple TRAF3 binding sites containing a PXQXT/S core sequence can be identified in the simian EBV LMP1s by an in vitro binding assay . | Multiple <dna>TRAF3 binding sites</dna> containing a <dna>PXQXT/S core sequence</dna> can be identified in the <protein>simian EBV LMP1s</protein> by an in vitro binding assay . |
811 | A PXQXT/S-containing sequence is also present in the cytoplasmic domain of the Hodgkin 's disease marker , CD30 , and binds TRAF3 in vitro . | A <dna>PXQXT/S-containing sequence</dna> is also present in the <protein>cytoplasmic domain</protein> of the Hodgkin 's disease marker , <protein>CD30</protein> , and binds <protein>TRAF3</protein> in vitro . |
812 | The last 13 amino acids containing a PXQXT/S sequence are highly conserved in human and simian EBV LMP1 but do not bind TRAF3 , suggesting a distinct role for this conserved region of LMP1 . | The <protein>last 13 amino acids</protein> containing a <dna>PXQXT/S sequence</dna> are highly conserved in human and simian EBV <protein>LMP1</protein> but do not bind <protein>TRAF3</protein> , suggesting a distinct role for this conserved region of <protein>LMP1</protein> . |
813 | The conserved TRAF3 binding sites in LMP1 and the CD30 Hodgkin 's disease marker provides further evidence that a TRAF3 -mediated signal transduction pathway may be important in malignant transformation . | The conserved <dna>TRAF3 binding sites</dna> in <protein>LMP1</protein> and the <protein>CD30 Hodgkin 's disease marker</protein> provides further evidence that a <protein>TRAF3</protein> -mediated signal transduction pathway may be important in malignant transformation . |
814 | Chromosome 1 aneusomy with 1p36 under-representation is related to histologic grade , DNA aneuploidy , high c-erb B-2 and loss of bcl-2 expression in ductal breast carcinoma . | <dna>Chromosome 1</dna> aneusomy with <dna>1p36</dna> under-representation is related to histologic grade , DNA aneuploidy , high <protein>c-erb B-2</protein> and loss of <dna>bcl-2</dna> expression in ductal breast carcinoma . |
815 | Chromosome 1 abnormalities with loss of 1p36 have been investigated in 95 breast-cancer samples by means of a dual-target fluorescence in-situ hybridization ( FISH ) technique using the pUC 1.77 and p1-79 probes , specific for the 1q12 and 1p36 regions , respectively . | <dna>Chromosome 1</dna> abnormalities with loss of <dna>1p36</dna> have been investigated in 95 breast-cancer samples by means of a dual-target fluorescence in-situ hybridization ( FISH ) technique using the <dna>pUC 1.77</dna> and <dna>p1-79 probes</dna> , specific for the <dna>1q12 and 1p36 regions</dna> , respectively . |
816 | Abnormalities for one or both probes were detected in 83/95 samples . | Abnormalities for one or both probes were detected in 83/95 samples . |
817 | Relative 1p36 under-representation was found in 79/95 . | Relative <dna>1p36</dna> under-representation was found in 79/95 . |
818 | The clinical relevance of these alterations was studied by comparing the FISH results with several parameters currently used in breast-cancer pathology . | The clinical relevance of these alterations was studied by comparing the FISH results with several parameters currently used in breast-cancer pathology . |
819 | Distinct patterns of chromosome 1 abnormalities were found among the histologic types of breast carcinoma . | Distinct patterns of <dna>chromosome 1</dna> abnormalities were found among the histologic types of breast carcinoma . |
820 | Lobular or mucinous samples showed few or no alterations , whereas most ductal samples had high chromosome 1 polysomy with under-representation of 1p36 . | Lobular or mucinous samples showed few or no alterations , whereas most ductal samples had high <dna>chromosome 1</dna> polysomy with under-representation of <dna>1p36</dna> . |
821 | In ductal carcinomas , chromosome 1 alterations increased with histologic grade , DNA aneuploidy , loss of bcl-2 and high c-erb B-2 expression . | In ductal carcinomas , <dna>chromosome 1</dna> alterations increased with histologic grade , DNA aneuploidy , loss of bcl-2 and high <protein>c-erb B-2</protein> expression . |
822 | These associations were found to be statistically significant . | These associations were found to be statistically significant . |
823 | No correlation between chromosome 1 alterations and nuclear grade , age , size , lymph-node involvement , hormonal receptor presence , proliferation activity or p53 protein expression was detected . | No correlation between <dna>chromosome 1</dna> alterations and nuclear grade , age , size , lymph-node involvement , hormonal receptor presence , proliferation activity or <protein>p53</protein> protein expression was detected . |
824 | These results indicate the utility of this FISH technique for a better definition of the biological characteristics of ductal carcinomas . | These results indicate the utility of this FISH technique for a better definition of the biological characteristics of ductal carcinomas . |
825 | G ( Anh ) MTetra , a natural bacterial cell wall breakdown product , induces interleukin-1 beta and interleukin-6 expression in human monocytes . | G ( Anh ) MTetra , a natural bacterial cell wall breakdown product , induces <protein>interleukin-1 beta</protein> and <protein>interleukin-6</protein> expression in <cell_type>human monocytes</cell_type> . |
826 | A study of the molecular mechanisms involved in inflammatory cytokine expression [ published erratum appears in J Biol Chem 1994 Jun 17 ; 269 ( 24 ) : 16983 ] | A study of the molecular mechanisms involved in <protein>inflammatory cytokine</protein> expression [ published erratum appears in J Biol Chem 1994 Jun 17 ; 269 ( 24 ) : 16983 ] |
827 | It is believed that induction of cytokine expression by bacterial cell wall components plays a role in the development and course of sepsis . | It is believed that induction of <protein>cytokine</protein> expression by bacterial cell wall components plays a role in the development and course of sepsis . |
828 | However , most attention has been focused on lipopolysaccharide ( LPS ) . | However , most attention has been focused on lipopolysaccharide ( LPS ) . |
829 | 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 . | 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 <protein>lytic transglycosylase</protein> of Escherichia coli , to induce <protein>cytokine</protein> expression in <cell_type>human monocytes</cell_type> . |
830 | 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 . | G ( Anh ) MTetra was found to strongly induce <protein>interleukin ( IL ) -1 beta</protein> and <rna>IL-6 mRNA</rna> expression after 2 h and <protein>IL-1 beta</protein> and <protein>IL-6 protein</protein> secretion after 48 h of activation . |
831 | 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 . | The increase in mRNA accumulation was at least partly due to an increase in the transcription rates of the respective <dna>genes</dna> and was accompanied by a strong induction of nuclear factor-kappa B and activator protein-1 transcription factor expression . |
832 | 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 . | Experiments using inhibitors of <protein>protein kinase C</protein> , <protein>protein kinase A</protein> , and tyrosine kinase-dependent pathways revealed that G ( Anh ) MTetra-induced <protein>IL-1 beta</protein> and <rna>IL-6 mRNA</rna> expression involves activation of an H7-inhibitable pathway . |
833 | 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 . | By using the protein synthesis inhibitor cycloheximide , it was shown that G ( Anh ) MTetra-induced <rna>IL-6 mRNA</rna> expression depends on the synthesis of new protein , whereas G ( Anh ) MTetra-induced <protein>IL-1 beta</protein> mRNA accumulation does not . |
834 | 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 . | 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 . |
835 | 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 . | Furthermore , maximal G ( Anh ) MTetra-induced <protein>IL-1 beta</protein> and <rna>IL-6 mRNA</rna> expression could be enhanced by co-stimulation with LPS or MDP , suggesting that different receptors and/or transduction pathways were involved . |
836 | 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 . | These results indicate that G ( Anh ) MTetra induces <protein>IL-1 beta</protein> and <protein>IL-6</protein> expression in <cell_type>human monocytes</cell_type> suggesting a possible role for G ( Anh ) MTetra in the release of <protein>cytokines</protein> during sepsis . |
837 | 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 ] | Increased proliferation , cytotoxicity , and gene expression after stimulation of <cell_type>human peripheral blood T lymphocytes</cell_type> through a surface ganglioside ( GD3 ) [ published erratum appears in J Immunol 1994 Jul 15 ; 153 ( 2 ) : 910 ] |
838 | Previous studies have suggested that gangliosides have an important role in cell signaling and recognition . | Previous studies have suggested that gangliosides have an important role in cell signaling and recognition . |
839 | However , their specific function in these processes has not been clearly defined . | However , their specific function in these processes has not been clearly defined . |
840 | 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 . | A <protein>mAb</protein> , <protein>R24</protein> , that reacts specifically with a cell surface ganglioside ( GD3 ) has been demonstrated to stimulate proliferation of <cell_type>T cells</cell_type> derived from human peripheral blood . |
841 | In this study , we have investigated the mechanisms by which the R24 mAb affects T cell functions . | In this study , we have investigated the mechanisms by which the <protein>R24 mAb</protein> affects T cell functions . |
842 | 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 . | We have observed that the <protein>R24 mAb</protein> stimulates GD3+ T cell proliferation , cytotoxicity , and surface marker expression of <protein>IL-2R alpha-chain</protein> , <protein>IL-2R beta-chain</protein> , <protein>HLA-DR</protein> , <protein>CD11a</protein> , and <protein>CD11c</protein> . |
843 | Additionally , IFN-gamma activity but not IL-1 , IL-2 , or IL-4 activity was present in culture supernatants 72 h after R24 stimulation . | Additionally , <protein>IFN-gamma</protein> activity but not IL-1 , IL-2 , or IL-4 activity was present in culture supernatants 72 h after <protein>R24</protein> stimulation . |
844 | In some donors , increased IL-6 and TNF-alpha activity also was detected after R24 treatment . | In some donors , increased <protein>IL-6</protein> and <protein>TNF-alpha</protein> activity also was detected after <protein>R24</protein> treatment . |
845 | 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 . | Furthermore , <protein>R24</protein> treatment resulted in translocation of <protein>c-rel</protein> , but little or no <protein>NF kappa B p50</protein> or <protein>p65</protein> , from the cytoplasm to the nucleus and an increase of <protein>NF kappa B binding complexes</protein> containing <protein>c-rel</protein> and <protein>p50</protein> . |
846 | This treatment also caused increased tyrosine phosphorylation of specific protein substrates . | This treatment also caused increased tyrosine phosphorylation of specific protein substrates . |
847 | 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 . | <protein>R24</protein> -stimulated increases in proliferation , cytotoxicity , and cell surface protein expression could be blocked by cyclosporin and staurosporin , indicating that <protein>cyclophilin/calcineurin</protein> and <protein>protein kinase C</protein> may be involved in the <protein>R24</protein> signaling pathway . |
848 | 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 . | Additionally , herbimycin A , a <protein>tyrosine kinase</protein> inhibitor , blocked the <protein>R24</protein> -stimulated increase in proliferation but not cytotoxicity at concentrations consistent with specificity for <protein>tyrosine kinases</protein> . |
849 | These results suggest that multiple biochemical pathways are involved in the activation of human T cells by R24 . | These results suggest that multiple biochemical pathways are involved in the activation of <cell_type>human T cells</cell_type> by <protein>R24</protein> . |
850 | Genes encoding general initiation factors for RNA polymerase II transcription are dispersed in the human genome . | Genes encoding <protein>general initiation factors</protein> for <protein>RNA polymerase II</protein> transcription are dispersed in the <dna>human genome</dna> . |
851 | General transcription factors are required for accurate initiation of transcription by RNA polymerase II . | <protein>General transcription factors</protein> are required for accurate initiation of transcription by <protein>RNA polymerase II</protein> . |
852 | Human cDNAs encoding subunits of these factors have been cloned and sequenced . | <dna>Human cDNAs</dna> encoding subunits of these factors have been cloned and sequenced . |
853 | Using fluorescence in situ hybridization ( FISH ) , we show here that the genes encoding the TATA-box binding protein ( TBP ) , TFIIB , TFIIE alpha , TFIIE beta , RAP30 , RAP74 and the 62 kDa subunit , of TFIIH are located at the human chromosomal bands 6q26-27 , 1p21-22 , 3q21-24 , 8p12 , 13q14 , 19p13.3 and 11p14-15.1 , respectively . | Using fluorescence in situ hybridization ( FISH ) , we show here that the <dna>genes</dna> encoding the <protein>TATA-box binding protein</protein> ( <protein>TBP</protein> ) , <protein>TFIIB</protein> , <protein>TFIIE alpha</protein> , <protein>TFIIE beta</protein> , <protein>RAP30</protein> , <protein>RAP74</protein> and the <protein>62 kDa subunit</protein> , of <protein>TFIIH</protein> are located at the <dna>human chromosomal bands 6q26-27 , 1p21-22 , 3q21-24 , 8p12 , 13q14 , 19p13.3 and 11p14-15.1</dna> , respectively . |
854 | This dispersed localization of a group of functionally related gene provides insights into the molecular mechanism of human genome evolution and their possible involvement in human diseases . | This dispersed localization of a group of functionally related gene provides insights into the molecular mechanism of <dna>human genome</dna> evolution and their possible involvement in human diseases . |
855 | BCL-6 and the molecular pathogenesis of B-cell lymphoma . | <protein>BCL-6</protein> and the molecular pathogenesis of B-cell lymphoma . |
856 | The results presented identify the first genetic lesion associated with DLCL , the most clinically relevant form of NHL . | The results presented identify the first genetic lesion associated with DLCL , the most clinically relevant form of NHL . |
857 | Although no proof yet exists of a role for these lesions in DLCL pathogenesis , the feature of the BCL-6 gene product , its specific pattern of expression in B cells , and the clustering of lesions disrupting its regulatory domain strongly suggest that deregulation of BCL-6 expression may contribute to DLCL development . | Although no proof yet exists of a role for these lesions in DLCL pathogenesis , the feature of the <protein>BCL-6 gene product</protein> , its specific pattern of expression in <cell_type>B cells</cell_type> , and the clustering of lesions disrupting its regulatory domain strongly suggest that deregulation of <protein>BCL-6</protein> expression may contribute to DLCL development . |
858 | A more precise definition of the role of BCL-6 in normal and neoplastic B-cell development is the goal of ongoing study of transgenic mice engineered either to express BCL-6 under heterologous promoters or lacking BCL-6 function due to targeted deletions . | A more precise definition of the role of <protein>BCL-6</protein> in normal and neoplastic B-cell development is the goal of ongoing study of transgenic mice engineered either to express <protein>BCL-6</protein> under <dna>heterologous promoters</dna> or lacking <protein>BCL-6</protein> function due to targeted deletions . |
859 | In addition to contributing to the understanding of DLCL pathogenesis , the identification of BCL-6 lesions may have relevant clinical implications . | In addition to contributing to the understanding of DLCL pathogenesis , the identification of <protein>BCL-6</protein> lesions may have relevant clinical implications . |
860 | DLCL represent a heterogeneous group of neoplasms which are treated homogeneously despite the fact that only 50 % of patients experience long-term disease-free survival ( Schneider et al. 1990 ) . | DLCL represent a heterogeneous group of neoplasms which are treated homogeneously despite the fact that only 50 % of patients experience long-term disease-free survival ( Schneider et al. 1990 ) . |
861 | The fact that BCL-6 rearrangements identify biologically and clinically distinct subsets of DLCL suggests that these lesions may be useful as markers in selection of differential therapeutic strategies based on different risk groups . | The fact that <protein>BCL-6</protein> rearrangements identify biologically and clinically distinct subsets of DLCL suggests that these lesions may be useful as markers in selection of differential therapeutic strategies based on different risk groups . |
862 | Furthermore , the BCL-6 rearrangements can be used to identify and monitor the malignant clone with sensitive PCR-based techniques . | Furthermore , the <protein>BCL-6</protein> rearrangements can be used to identify and monitor the <cell_type>malignant clone</cell_type> with sensitive PCR-based techniques . |
863 | Since clinical remission has been observed in a significant fraction of DLCL cases , these markers may serve as critical tools for sensitive monitoring of minimal residual disease and early diagnosis of relapse ( Gribben et al. 1993 ) . | Since clinical remission has been observed in a significant fraction of DLCL cases , these markers may serve as critical tools for sensitive monitoring of minimal residual disease and early diagnosis of relapse ( Gribben et al. 1993 ) . |
864 | Pancreatic development and maturation of the islet B cell . | Pancreatic development and maturation of the <cell_type>islet B cell</cell_type> . |
865 | Studies of pluripotent islet cultures . | Studies of <cell_line>pluripotent islet cultures</cell_line> . |
866 | Pancreas organogenesis is a highly regulated process , in which two anlage evaginate from the primitive gut . | Pancreas organogenesis is a highly regulated process , in which two anlage evaginate from the primitive gut . |
867 | They later fuse , and , under the influence of the surrounding mesenchyme , the mature organ develops , being mainly composed of ductal , exocrine and endocrine compartments . | They later fuse , and , under the influence of the surrounding mesenchyme , the mature organ develops , being mainly composed of ductal , exocrine and endocrine compartments . |
868 | Early buds are characterized by a branching morphogenesis of the ductal epithelium from which endocrine and exocrine precursor cells bud to eventually form the two other compartments . | Early buds are characterized by a branching morphogenesis of the ductal epithelium from which <cell_type>endocrine and exocrine precursor cells</cell_type> bud to eventually form the two other compartments . |
869 | The three compartments are thought to be of common endodermal origin ; in contrast to earlier hypotheses , which suggested that the endocrine compartment was of neuroectodermal origin . | The three compartments are thought to be of common endodermal origin ; in contrast to earlier hypotheses , which suggested that the endocrine compartment was of neuroectodermal origin . |
870 | It is thus generally believed that the pancreatic endocrine-lineage possesses the ability to mature along a differentiation pathway that shares many characteristics with those of neuronal differentiation . | It is thus generally believed that the pancreatic endocrine-lineage possesses the ability to mature along a differentiation pathway that shares many characteristics with those of neuronal differentiation . |
871 | During recent years , studies of insulin-gene regulation and , in particular , the tissue-specific transcriptional control of insulin-gene activity have provided information on pancreas development in general . | During recent years , studies of <dna>insulin-gene</dna> regulation and , in particular , the tissue-specific transcriptional control of <dna>insulin-gene</dna> activity have provided information on pancreas development in general . |
872 | The present review summarizes these findings , with a special focus on our own studies on pluripotent endocrine cultures of rat pancreas . | The present review summarizes these findings , with a special focus on our own studies on <cell_line>pluripotent endocrine cultures</cell_line> of rat pancreas . |
873 | Octamer independent activation of transcription from the kappa immunoglobulin germline promoter . | Octamer independent activation of transcription from the <dna>kappa immunoglobulin germline promoter</dna> . |
874 | Previous analyses of immunoglobulin V region promoters has led to the discovery of a common octamer motif which is functionally important in the tissue-specific and developmentally regulated transcriptional activation of immunoglobulin genes . | Previous analyses of <dna>immunoglobulin V region promoters</dna> has led to the discovery of a common <dna>octamer motif</dna> which is functionally important in the tissue-specific and developmentally regulated transcriptional activation of <dna>immunoglobulin genes</dna> . |
875 | The germline promoters ( Ko ) located upstream of the J region gene segments of the kappa locus also contain an octamer motif ( containing a single base pair mutation and referred to as the variant octamer ) which has been shown previously to bind Oct-1 and Oct-2 transcription factors in vitro . | The <dna>germline promoters</dna> ( <dna>Ko</dna> ) located upstream of the <dna>J region gene segments</dna> of the <dna>kappa locus</dna> also contain an <dna>octamer motif</dna> ( containing a single <dna>base pair mutation</dna> and referred to as the variant octamer ) which has been shown previously to bind <protein>Oct-1</protein> and <protein>Oct-2</protein> <protein>transcription factors</protein> in vitro . |
876 | To further elucidate the role of this variant octamer motif in the regulation of germline transcription from the unrearranged kappa locus , we have quantitated the relative binding affinity of Oct-1 and Oct-2 for the variant octamer motif and determined the functional role of this octamer motif in transcriptional activation . | To further elucidate the role of this variant <dna>octamer motif</dna> in the regulation of <dna>germline</dna> transcription from the unrearranged <dna>kappa locus</dna> , we have quantitated the relative binding affinity of <protein>Oct-1</protein> and <protein>Oct-2</protein> for the variant <dna>octamer motif</dna> and determined the functional role of this <dna>octamer motif</dna> in transcriptional activation . |
877 | We find that , although the variant octamer motif binds Oct-1 and Oct-2 in vitro with 5-fold lower affinity than the consensus octamer motif , mutation of the variant octamer motif to either a consensus octamer or non-octamer motif has no effect on transcriptional activation from the germline promoter . | We find that , although the variant <dna>octamer motif</dna> binds <protein>Oct-1</protein> and <protein>Oct-2</protein> in vitro with 5-fold lower affinity than the <dna>consensus octamer motif</dna> , mutation of the variant <dna>octamer motif</dna> to either a <dna>consensus octamer</dna> or <dna>non-octamer motif</dna> has no effect on transcriptional activation from the <dna>germline promoter</dna> . |
878 | We also find significant differences in activation of germline and V region promoters by kappa enhancers . | We also find significant differences in activation of <dna>germline</dna> and <dna>V region promoters</dna> by <dna>kappa enhancers</dna> . |
879 | Our results suggest that the germline promoters and V region promoters differ in their dependence on octamer for activation and respond differently to enhancer activation . | Our results suggest that the <dna>germline promoters</dna> and <dna>V region promoters</dna> differ in their dependence on <dna>octamer</dna> for activation and respond differently to enhancer activation . |
880 | These findings have important implications in regulation of germline transcription as well as concomitant activation of the V-J recombination of the kappa light chain locus . | These findings have important implications in regulation of <dna>germline</dna> transcription as well as concomitant activation of the V-J recombination of the <dna>kappa light chain locus</dna> . |
881 | Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells from human monocytes . | Generation of <cell_type>CD1+RelB+ dendritic cells</cell_type> and <cell_type>tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells</cell_type> from <cell_type>human monocytes</cell_type> . |
882 | We previously showed that granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and macrophage colony-stimulating factor ( M-CSF ) stimulate the differentiation of human monocytes into two phenotypically distinct types of macrophages . | We previously showed that <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) and <protein>macrophage colony-stimulating factor</protein> ( <protein>M-CSF</protein> ) stimulate the differentiation of <cell_type>human monocytes</cell_type> into two phenotypically distinct types of <cell_type>macrophages</cell_type> . |
883 | However , in vivo , not only CSF but also many other cytokines are produced under various conditions . | However , in vivo , not only <protein>CSF</protein> but also many other <protein>cytokines</protein> are produced under various conditions . |
884 | Those cytokines may modulate the differentiation of monocytes by CSFs . | Those <protein>cytokines</protein> may modulate the differentiation of <cell_type>monocytes</cell_type> by <protein>CSFs</protein> . |
885 | In the present study , we showed that CD14+ adherent human monocytes can differentiate into CD1+relB+ dendritic cells ( DC ) by the combination of GM-CSF plus interleukin-4 ( IL-4 ) and that they differentiate into tartrate-resistant acid phosphatase ( TRAP ) -positive osteoclast-like multinucleated giant cells ( MGC ) by the combination of M-CSF plus IL-4 . | In the present study , we showed that <cell_type>CD14+ adherent human monocytes</cell_type> can differentiate into <cell_type>CD1+relB+ dendritic cells</cell_type> ( <cell_type>DC</cell_type> ) by the combination of <protein>GM-CSF</protein> plus <protein>interleukin-4</protein> ( <protein>IL-4</protein> ) and that they differentiate into <cell_type>tartrate-resistant acid phosphatase ( TRAP ) -positive osteoclast-like multinucleated giant cells</cell_type> ( <cell_type>MGC</cell_type> ) by the combination of <protein>M-CSF</protein> plus <protein>IL-4</protein> . |
886 | However , the monocyte-derived DC were not terminally differentiated cells ; they could still convert to macrophages in response to M-CSF . | However , the <cell_line>monocyte-derived DC</cell_line> were not <cell_line>terminally differentiated cells</cell_line> ; they could still convert to <cell_type>macrophages</cell_type> in response to <protein>M-CSF</protein> . |
887 | Tumor necrosis factor-alpha ( TNF-alpha ) stimulated the terminal differentiation of the DC by downregulating the expression of the M-CSF receptor , cfms mRNA , and aborting the potential to convert to macrophages . | <protein>Tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) stimulated the terminal differentiation of the <cell_type>DC</cell_type> by downregulating the expression of the <protein>M-CSF receptor</protein> , <rna>cfms mRNA</rna> , and aborting the potential to convert to <cell_type>macrophages</cell_type> . |
888 | In contrast to IL-4 , interferon-gamma ( IFN-gamma ) had no demonstrable effect on the differentiation of monocytes . | In contrast to <protein>IL-4</protein> , <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) had no demonstrable effect on the differentiation of <cell_type>monocytes</cell_type> . |
889 | Rather , IFN-gamma antagonized the effect of IL-4 and suppressed the DC and MGC formation induced by GM-CSF + IL-4 and M-CSF + IL-4 , respectively . | Rather , <protein>IFN-gamma</protein> antagonized the effect of <protein>IL-4</protein> and suppressed the <cell_type>DC</cell_type> and <cell_type>MGC</cell_type> formation induced by <protein>GM-CSF</protein> + <protein>IL-4</protein> and <protein>M-CSF</protein> + <protein>IL-4</protein> , respectively . |
890 | Taken together , these results provide a new aspect to our knowledge of monocyte differentiation and provide evidence that human monocytes are flexible in their differentiation potential and are precursors not only of macrophages but also of CD1+relB+DC and TRAP-positive MGC . | Taken together , these results provide a new aspect to our knowledge of monocyte differentiation and provide evidence that <cell_type>human monocytes</cell_type> are flexible in their differentiation potential and are precursors not only of <cell_type>macrophages</cell_type> but also of <cell_type>CD1+relB+DC</cell_type> and <cell_type>TRAP-positive MGC</cell_type> . |
891 | Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation . | Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation . |
892 | The NF-kappa B inhibitor , tepoxalin , suppresses surface expression of the cell adhesion molecules CD62E , CD11b/CD18 and CD106 . | The <protein>NF-kappa B</protein> inhibitor , tepoxalin , suppresses surface expression of the <protein>cell adhesion molecules</protein> <protein>CD62E</protein> , <protein>CD11b/CD18</protein> and <protein>CD106</protein> . |
893 | Tepoxalin , a dual enzyme inhibitor of cyclooxygenase and 5-lipoxygenase has been shown to inhibit T-cell activation . | Tepoxalin , a dual enzyme inhibitor of <protein>cyclooxygenase</protein> and <protein>5-lipoxygenase</protein> has been shown to inhibit T-cell activation . |
894 | Its immunosuppressive property is distinct from cyclosporin because only tepoxalin , but not cyclosporin , suppresses NF-kappa B activation . | Its immunosuppressive property is distinct from cyclosporin because only tepoxalin , but not cyclosporin , suppresses <protein>NF-kappa B</protein> activation . |
895 | Here we report that tepoxalin selectively inhibits intercellular adhesion molecule-1 ( ICAM-1 , CD54 ) /MAC-1 ( CD11b/CD18 ) dependent adhesion of polymorphonuclear cells to IL-1 activated human umbilical vein endothelial cells . | Here we report that tepoxalin selectively inhibits <protein>intercellular adhesion molecule-1</protein> <protein>( ICAM-1 , CD54 ) /MAC-1</protein> ( <protein>CD11b/CD18</protein> ) dependent adhesion of <cell_type>polymorphonuclear cells</cell_type> to <protein>IL-1</protein> activated <cell_type>human umbilical vein endothelial cells</cell_type> . |
896 | The mechanism of inhibition is related to the surface expression of several cell adhesion molecules . | The mechanism of inhibition is related to the surface expression of several cell <protein>adhesion molecules</protein> . |
897 | Flow cytometry analyses on cultured cells that were treated with tepoxalin or antisense oligonucleotides to the P65/p50 subunit of NF-kappa B , and then stimulated with PMA , revealed a reduced expression of CD11b/CD18 on monocytic HL60 cells , and endothelial adhesion molecule-1 ( CD62E ) and vascular adhesion molecule-1 ( CD106 ) on human umbilical vein endothelial cells . | Flow cytometry analyses on cultured cells that were treated with tepoxalin or antisense oligonucleotides to the <protein>P65/p50 subunit</protein> of <protein>NF-kappa B</protein> , and then stimulated with PMA , revealed a reduced expression of <protein>CD11b/CD18</protein> on <cell_line>monocytic HL60 cells</cell_line> , and <protein>endothelial adhesion molecule-1</protein> ( <protein>CD62E</protein> ) and <protein>vascular adhesion molecule-1</protein> ( <protein>CD106</protein> ) on <cell_type>human umbilical vein endothelial cells</cell_type> . |
898 | Expression of other adhesion molecules such as lymphocyte function associated-antigen-1 ( CD11a/CD18 ) and CD54 were unaffected . | Expression of other <protein>adhesion molecules</protein> such as <protein>lymphocyte function associated-antigen-1</protein> ( <protein>CD11a/CD18</protein> ) and <protein>CD54</protein> were unaffected . |
899 | Tepoxalin also inhibited the secretion of a NF-kappa B regulated chemokine , IL-8 , a known inducer of CD11b/CD18 expression . | Tepoxalin also inhibited the secretion of a <protein>NF-kappa B regulated chemokine</protein> , <protein>IL-8</protein> , a known inducer of <protein>CD11b/CD18</protein> expression . |
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