PMA , but not Ara-C or ceramides , activated ERK MAPKS , in Jurkat and EL4 .

PMA , but not Ara-C or ceramides , activated <protein>ERK MAPKS</protein> , in <cell_line>Jurkat</cell_line> and <cell_line>EL4</cell_line> .


PMA acted synergistically with ionomycin to activate JNK MAPKs in Jurkat and EL4 within 10 minutes .

PMA acted synergistically with ionomycin to activate <protein>JNK MAPKs</protein> in <cell_line>Jurkat</cell_line> and <cell_line>EL4</cell_line> within 10 minutes .


Ara-C activated JNKs only after prolonged incubation ( 90-120 minutes ) .

Ara-C activated <protein>JNKs</protein> only after prolonged incubation ( 90-120 minutes ) .


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> .


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 .


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> .


Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus ( EBV ) .


These simian EBV share considerable genetic , biologic , and epidemiologic features with human EBV , including virus-induced tumorigenesis .


However , latent , transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions .


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 .


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 .


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> .


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 .


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 .


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> .


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 .


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 .


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 .


Abnormalities for one or both probes were detected in 83/95 samples .


Relative 1p36 under-representation was found in 79/95 .

Relative <dna>1p36</dna> under-representation was found in 79/95 .


The clinical relevance of these alterations was studied by comparing the FISH results with several parameters currently used in breast-cancer pathology .


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 .


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> .


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 .


These associations were found to be statistically significant .


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 .


These results indicate the utility of this FISH technique for a better definition of the biological characteristics of ductal carcinomas .


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> .


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 ]


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 .


However , most attention has been focused on lipopolysaccharide ( LPS ) .


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> .


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 .


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 .


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 .


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 .


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 .


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 .


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 .


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 ]


Previous studies have suggested that gangliosides have an important role in cell signaling and recognition .


However , their specific function in these processes has not been clearly defined .


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 .


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 .


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> .


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 .


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 .


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> .


This treatment also caused increased tyrosine phosphorylation of specific protein substrates .


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 .


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> .


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> .


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> .


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> .


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 .


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 .


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 .


BCL-6 and the molecular pathogenesis of B-cell lymphoma .

<protein>BCL-6</protein> and the molecular pathogenesis of B-cell lymphoma .


The results presented identify the first genetic lesion associated with DLCL , the most clinically relevant form of NHL .


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 .


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 .


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 .


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 ) .


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 .


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 .


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 ) .


Pancreatic development and maturation of the islet B cell .

Pancreatic development and maturation of the <cell_type>islet B cell</cell_type> .


Studies of pluripotent islet cultures .

Studies of <cell_line>pluripotent islet cultures</cell_line> .


Pancreas organogenesis is a highly regulated process , in which two anlage evaginate from the primitive gut .


They later fuse , and , under the influence of the surrounding mesenchyme , the mature organ develops , being mainly composed of ductal , exocrine and endocrine compartments .


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 .


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 .


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 .


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 .


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 .


Octamer independent activation of transcription from the kappa immunoglobulin germline promoter .

Octamer independent activation of transcription from the <dna>kappa immunoglobulin germline promoter</dna> .


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> .


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 .


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 .


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> .


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> .


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 .


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> .


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> .


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> .


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 .


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> .


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> .


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> .


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> .


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> .


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 .


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> .


Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation .


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> .


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 .


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 .


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> .


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> .


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> .


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 .


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 .


Thus the suppression of CD11b/CD18 expression by tepoxalin may involve IL-8 .

Thus the suppression of <protein>CD11b/CD18</protein> expression by tepoxalin may involve <protein>IL-8</protein> .


Our results suggest that by inhibiting NF-kappa B activation , surface expression of several adhesion molecules can be modulated and that tepoxalin may be useful in treating selected adhesion mediated events such as leukocyte migration or atherosclerotic plaque formation .

Our results suggest that by inhibiting <protein>NF-kappa B</protein> activation , surface expression of several <protein>adhesion molecules</protein> can be modulated and that tepoxalin may be useful in treating selected adhesion mediated events such as leukocyte migration or atherosclerotic plaque formation .


Characterization of a CD43/leukosialin -mediated pathway for inducing apoptosis in human T-lymphoblastoid cells .

Characterization of a <protein>CD43/leukosialin</protein> -mediated pathway for inducing apoptosis in <cell_type>human T-lymphoblastoid cells</cell_type> .


The monoclonal antibody ( mAb ) J393 induces apoptosis in Jurkat T-cells .

The <protein>monoclonal antibody</protein> ( <protein>mAb</protein> ) <protein>J393</protein> induces apoptosis in <cell_line>Jurkat T-cells</cell_line> .


NH2 -terminal amino acid sequence analysis identified the 140-kDa surface antigen for mAb J393 as CD43/leukosialin , the major sialoglycoprotein of leukocytes .

<protein>NH2</protein> -terminal amino acid sequence analysis identified the <protein>140-kDa surface antigen</protein> for <protein>mAb J393</protein> as <protein>CD43/leukosialin</protein> , the major <protein>sialoglycoprotein</protein> of <cell_type>leukocytes</cell_type> .


While Jurkat cells co-expressed two discrete cell-surface isoforms of CD43 , recognized by mAb J393 and mAb G10-2 , respectively , only J393/CD43 signaled apoptosis .

While <cell_line>Jurkat cells</cell_line> co-expressed two discrete <protein>cell-surface isoforms</protein> of <protein>CD43</protein> , recognized by <protein>mAb J393</protein> and <protein>mAb G10-2</protein> , respectively , only <protein>J393/CD43</protein> signaled apoptosis .


J393/CD43 was found to be hyposialylated , bearing predominantly O-linked monosaccharide glycans , whereas G10-2/CD43 bore complex sialylated tetra- and hexasaccharide chains .

<protein>J393/CD43</protein> was found to be hyposialylated , bearing predominantly O-linked monosaccharide glycans , whereas <protein>G10-2/CD43</protein> bore complex sialylated tetra- and hexasaccharide chains .


Treatment with soluble , bivalent mAb J393 killed 25-50 % of the cell population , while concomitant engagement of either the CD3.TcR complex or the integrins CD18 and CD29 significantly potentiated this effect .

Treatment with soluble , bivalent <protein>mAb J393</protein> killed 25-50 % of the <cell_line>cell population</cell_line> , while concomitant engagement of either the <protein>CD3.TcR complex</protein> or the <protein>integrins</protein> <protein>CD18</protein> and <protein>CD29</protein> significantly potentiated this effect .


Treatment of Jurkat cells with mAb J393 induced tyrosine phosphorylation of specific protein substrates that underwent hyperphosphorylation upon antigen receptor costimulation .

Treatment of <cell_line>Jurkat cells</cell_line> with <protein>mAb J393</protein> induced tyrosine phosphorylation of specific <protein>protein substrates</protein> that underwent hyperphosphorylation upon <protein>antigen receptor</protein> costimulation .


Tyrosine kinase inhibition by herbimycin A diminished J393/CD43 -mediated apoptosis , whereas inhibition of phosphotyrosine phosphatase activity by bis ( maltolato ) oxovanadium-IV enhanced cell death .

<protein>Tyrosine kinase</protein> inhibition by herbimycin A diminished <protein>J393/CD43</protein> -mediated apoptosis , whereas inhibition of <protein>phosphotyrosine phosphatase</protein> activity by bis ( maltolato ) oxovanadium-IV enhanced cell death .


Signal transduction through tyrosine kinase activation may lead to altered gene expression , as J393/ CD43 ligation prompted decreases in the nuclear localization of the transcriptional regulatory protein NF-kappaB and proteins binding the interferon-inducible regulatory element .

Signal transduction through tyrosine kinase activation may lead to altered gene expression , as J393/ <protein>CD43</protein> ligation prompted decreases in the nuclear localization of the <protein>transcriptional regulatory protein</protein> <protein>NF-kappaB</protein> and proteins binding the <dna>interferon-inducible regulatory element</dna> .


Since peripheral blood T-lymphocytes express cryptic epitopes for mAb J393 , these findings demonstrate the existence of a tightly regulated CD43 -mediated pathway for inducing apoptosis in human T-cell lineages .

Since <cell_type>peripheral blood T-lymphocytes</cell_type> express <protein>cryptic epitopes</protein> for <protein>mAb J393</protein> , these findings demonstrate the existence of a tightly regulated <protein>CD43</protein> -mediated pathway for inducing apoptosis in <cell_type>human T-cell lineages</cell_type> .


Sterol dependent LDL-receptor gene transcription in lymphocytes from normal and CML patients .

Sterol dependent <dna>LDL-receptor gene</dna> transcription in <cell_type>lymphocytes</cell_type> from normal and CML patients .


Sterol regulatory element ( SRE ) has been recognized to regulate various key genes coding for especially low density lipoprotein ( LDL ) -receptor , 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase and HMG-CoA synthase known to play a crucial role in the cholesterol feedback mechanism .

<dna>Sterol regulatory element</dna> ( <dna>SRE</dna> ) has been recognized to regulate various key <dna>genes</dna> coding for especially <protein>low density lipoprotein ( LDL ) -receptor</protein> , <protein>3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase</protein> and <protein>HMG-CoA synthase</protein> known to play a crucial role in the cholesterol feedback mechanism .


The deranged cholesterol feedback mechanism has been widely recognised in initiation as well as progression of various types of cancers including chronic myeloid leukaemia ( CML ) .


Consequently , the present study was addressed to understand this phenomenon and revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects as well as its absence in lymphocytes from untreated CML patients .

Consequently , the present study was addressed to understand this phenomenon and revealed the existence of a <protein>unique 47 kDa protein factor</protein> having affinity for this <dna>SRE sequence</dna> in <cell_type>lymphocytes</cell_type> from normal subjects as well as its absence in <cell_type>lymphocytes</cell_type> from untreated CML patients .


However , this factor appeared when the CML patients achieved complete haematological remission ( CHR ) through alpha-interferon therapy .

However , this factor appeared when the CML patients achieved complete haematological remission ( CHR ) through <protein>alpha-interferon</protein> therapy .


Further , an inverse relationship was also observed between sterol modulated LDL-receptor gene transcription and the binding affinity of this 47 kDa factor to the SRE sequence .

Further , an inverse relationship was also observed between sterol modulated <dna>LDL-receptor gene</dna> transcription and the binding affinity of this <protein>47 kDa factor</protein> to the <dna>SRE sequence</dna> .


Based upon these results we propose that alpha-interferon through its receptor initiates phosphatidic acid dependent signalling which in turn regulates the affinity of 47 kDa sterol regulatory element binding factor as well as LDL-receptor gene transcription in lymphocytes from CML patients .

Based upon these results we propose that <protein>alpha-interferon</protein> through its receptor initiates phosphatidic acid dependent signalling which in turn regulates the affinity of <protein>47 kDa sterol regulatory element binding factor</protein> as well as <dna>LDL-receptor gene</dna> transcription in <cell_type>lymphocytes</cell_type> from CML patients .


Multiple prolactin-responsive elements mediate G1 and S phase expression of the interferon regulatory factor-1 gene .

Multiple <dna>prolactin-responsive elements</dna> mediate G1 and S phase expression of the <dna>interferon regulatory factor-1 gene</dna> .


The interferon regulatory factor-1 ( IRF-1 ) gene is both an immediate-early G1 phase gene and an S phase gene inducible by PRL in rat Nb2 T lymphocytes .

The <dna>interferon regulatory factor-1 ( IRF-1 ) gene</dna> is both an <dna>immediate-early G1 phase gene</dna> and an <dna>S phase gene</dna> inducible by <protein>PRL</protein> in <cell_line>rat Nb2 T lymphocytes</cell_line> .


To understand the mechanism by which PRL regulates the biphasic expression of IRF-1 , we cloned the rat IRF-1 gene and functionally characterized the IRF-1 promoter .

To understand the mechanism by which <protein>PRL</protein> regulates the biphasic expression of <protein>IRF-1</protein> , we cloned the <dna>rat IRF-1 gene</dna> and functionally characterized the <dna>IRF-1 promoter</dna> .


Upon transfection into Nb2 T cells , 1.7 kilobases ( kb ) of IRF-1 5'-flanking DNA linked to a chloramphenicol acetyl transferase ( CAT ) reporter gene mediated a 30-fold induction of CAT enzyme activity in response to 24 h of PRL stimulation .

Upon transfection into <cell_line>Nb2 T cells</cell_line> , 1.7 kilobases ( kb ) of <dna>IRF-1 5'-flanking DNA</dna> linked to a <dna>chloramphenicol acetyl transferase ( CAT ) reporter gene</dna> mediated a 30-fold induction of <protein>CAT enzyme</protein> activity in response to 24 h of <protein>PRL</protein> stimulation .


Deletion mutants containing 1.3 , 0.6 , and 0.2 kb 5'-flanking DNA were incrementally less transcriptionally active , although 0.2 kb still mediated a 12-fold induction by PRL .

Deletion mutants containing <dna>1.3 , 0.6 , and 0.2 kb 5'-flanking DNA</dna> were incrementally less transcriptionally active , although 0.2 kb still mediated a 12-fold induction by <protein>PRL</protein> .


The sequence between -1.7 and -0.2 kb linked to a heterologous thymidine kinase promoter failed to respond to PRL stimulation , suggesting that the activity of upstream PRL response elements may require an interaction with promoter-proximal elements .

The sequence between -1.7 and -0.2 kb linked to a <dna>heterologous thymidine kinase promoter</dna> failed to respond to <protein>PRL</protein> stimulation , suggesting that the activity of <dna>upstream PRL response elements</dna> may require an interaction with <dna>promoter-proximal elements</dna> .


By assaying CAT enzyme activity across a 24-h PRL induction time course , we were able to assign G1 vs. S phase PRL responses of the IRF-1 gene to different regions of the IRF-1 5'-flanking and promoter DNA .

By assaying <protein>CAT enzyme</protein> activity across a 24-h <protein>PRL</protein> induction time course , we were able to assign G1 vs. S phase <protein>PRL</protein> responses of the <dna>IRF-1 gene</dna> to different regions of the <protein>IRF-1</protein> <dna>5'-flanking</dna> and <dna>promoter DNA</dna> .


The 0.2-kb IRF-CAT construct was induced by PRL stimulation during the G1 phase of the cell cycle .

The 0.2-kb <dna>IRF-CAT construct</dna> was induced by <protein>PRL</protein> stimulation during the G1 phase of the cell cycle .


In contrast , the 1.7-kb IRF- CAT construct was inducible by PRL during both G1 and S phase of the cell cycle .

In contrast , the 1.7-kb IRF- <protein>CAT</protein> construct was inducible by <protein>PRL</protein> during both G1 and S phase of the cell cycle .


Hence , the PRL -induced biphasic expression of the IRF-1 gene appears to be controlled by separate PRL-responsive elements : elements in the first 0.2 kb of the IRF-1 promoter region act during early activation , and elements between 0.2 and 1.7 kb act in concert with the proximal 0.2-kb region during S phase progression .

Hence , the <protein>PRL</protein> -induced biphasic expression of the <dna>IRF-1 gene</dna> appears to be controlled by separate <dna>PRL-responsive elements</dna> : elements in the first 0.2 kb of the <dna>IRF-1 promoter region</dna> act during early activation , and elements between 0.2 and 1.7 kb act in concert with the proximal 0.2-kb region during S phase progression .


Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in anti-immunoglobulin-treated B cells .

Regulation of the <dna>BZLF1 promoter</dna> of Epstein-Barr virus by second messengers in <cell_line>anti-immunoglobulin-treated B cells</cell_line> .


Initiation of the Epstein-Barr virus ( EBV ) lytic cycle is dependent on the transcription of the BZLF1 gene .

Initiation of the Epstein-Barr virus ( EBV ) lytic cycle is dependent on the transcription of the <dna>BZLF1 gene</dna> .


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 .

The <dna>BZLF1 gene promoter</dna> ( <dna>Zp</dna> ) was activated by crosslinking of <protein>cell surface immunoglobulin</protein> ( <protein>Ig</protein> ) with <protein>anti-Ig antibody</protein> in <cell_type>B cells</cell_type> , even in the absence of other viral genes .


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 ) .

We identified several anti-Ig response elements within <dna>Zp</dna> , which were originally defined as <dna>12-O-tetradecanoylphorbol-13-acetate ( TPA ) response elements</dna> ( ZI repeats and <dna>ZII</dna> , an <dna>AP-1-like domain</dna> ) .


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 .

Since anti-Ig crosslinking leads to activation of <protein>protein kinase C</protein> ( <protein>PKC</protein> ) and an increase in intracellular calcium level , <dna>Zp</dna> was tested for the response to these <protein>cellular factors</protein> .


Treatment with calcium ionophore A23187 increased Zp activity .

Treatment with calcium ionophore A23187 increased <dna>Zp</dna> activity .


When the calcium ionophore was used in conjunction with TPA , a PKC activator , the Zp induction was synergistically enhanced .

When the calcium ionophore was used in conjunction with TPA , a <protein>PKC</protein> activator , the <dna>Zp</dna> induction was synergistically enhanced .


1- ( 5-Isoquinolinyl sulfonyl ) -2-methylpiperazine , an inhibitor of PKC , inhibited the anti-Ig inducibility of Zp .

1- ( 5-Isoquinolinyl sulfonyl ) -2-methylpiperazine , an inhibitor of <protein>PKC</protein> , inhibited the <protein>anti-Ig</protein> inducibility of <dna>Zp</dna> .


Calmodulin antagonists , compound R24571 and trifluoperazine , blocked the Zp activation with anti-Ig .

Calmodulin antagonists , compound R24571 and trifluoperazine , blocked the <dna>Zp</dna> activation with <protein>anti-Ig</protein> .


These findings suggest that Zp responds directly to changes in the activity of both PKC and calcium/calmodulin-dependent protein kinase .

These findings suggest that <dna>Zp</dna> responds directly to changes in the activity of both <protein>PKC</protein> and <protein>calcium/calmodulin-dependent protein kinase</protein> .


Requirement of tyrosine kinase activation for the anti-Ig -mediated Zp activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin .

Requirement of <protein>tyrosine kinase</protein> activation for the <protein>anti-Ig</protein> -mediated <dna>Zp</dna> activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin .


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 .

These <protein>cellular gene regulatory molecules</protein> induced with anti-Ig may cooperatively play an important part in achieving efficient EBV activation as seen with <protein>anti-Ig</protein> treatment in <cell_type>B cells</cell_type> .


The SCL protein displays cell-specific heterogeneity in size .

The <protein>SCL protein</protein> displays cell-specific heterogeneity in size .


SCL protein production was examined in a variety of hemopoietic cell lines by immunoblotting using specific polyclonal antisera .

<protein>SCL protein</protein> production was examined in a variety of <cell_line>hemopoietic cell lines</cell_line> by immunoblotting using specific polyclonal antisera .


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 .

<protein>SCL protein</protein> was detected in <cell_line>erythroid , megakaryocyte , mast and early myeloid cell lines</cell_line> , as well as in several <cell_line>lymphoid leukemia cell lines</cell_line> which are known to harbor <dna>SCL gene rearrangements</dna> .


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 .

In most cell lines , proteins of molecular weight 49 and 44 kDa were found , however two myeloid cell lines expressed only lower <protein>molecular weight species of 24 and 22 kDa</protein> .


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+ .

This size discrepancy appeared to be due to cell-specific translational regulation , since overexpression of a retrovirally transfected <dna>SCL gene</dna> yielded the higher molecular weight forms in most <cell_line>cell lines</cell_line> ( <cell_line>GP+E-86</cell_line> , <cell_line>AT2.5</cell_line> , <cell_line>M1</cell_line> ) but only the <protein>22 kDa form</protein> in the <cell_line>myeloid cell line</cell_line> , <cell_line>WEHI-3B/D+</cell_line> .


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 .

Overexpression of full-length <protein>SCL protein</protein> in the <cell_line>lymphoid cell lines</cell_line> , SupT1 and Raji , did not alter cell phenotype and there was no evidence for autoregulation of <protein>SCL</protein> transcription .


The restricted pattern of SCL protein synthesis is consistent with the restricted expression of SCL mRNA documented previously .

The restricted pattern of <protein>SCL protein</protein> synthesis is consistent with the restricted expression of <rna>SCL mRNA</rna> documented previously .


In addition , the present results indicate that SCL protein size was determined by regulation of translation in a cell-specific manner .

In addition , the present results indicate that <protein>SCL protein</protein> size was determined by regulation of translation in a cell-specific manner .


Description and functional implications of a novel mutation in the sex-determining gene SRY .

Description and functional implications of a novel mutation in the <dna>sex-determining gene</dna> <dna>SRY</dna> .


The sex-determining gene SRY was screened for molecular alteration in an XY sex-reversed female by single-strand conformation polymorphism ( SSCP ) technique .

The sex-determining gene <dna>SRY</dna> was screened for molecular alteration in an XY sex-reversed female by single-strand conformation polymorphism ( SSCP ) technique .


An A-to-G transition was detected which leads to an exchange of a tyrosine by a cysteine in the SRY protein .

An A-to-G transition was detected which leads to an exchange of a tyrosine by a cysteine in the <protein>SRY protein</protein> .


The affected tyrosine residue located at the C terminus of the DNA binding protein is evolutionarily strongly conserved among the members of the HMG box containing proteins .

The affected tyrosine residue located at the <protein>C terminus</protein> of the <protein>DNA binding protein</protein> is evolutionarily strongly conserved among the members of the <protein>HMG box containing proteins</protein> .


Using gel shift assay and peptide synthesis such a mutation is shown to abolish the SRY protein DNA binding ability .

Using gel shift assay and peptide synthesis such a mutation is shown to abolish the <dna>SRY</dna> protein DNA binding ability .


The involvement of this particular amino acid in the binding specificity is also discussed .


Induction of tyrosine phosphorylation and T-cell activation by vanadate peroxide , an inhibitor of protein tyrosine phosphatases .

Induction of tyrosine phosphorylation and <cell_type>T-cell</cell_type> activation by vanadate peroxide , an inhibitor of <protein>protein tyrosine phosphatases</protein> .


Rapid tyrosine phosphorylation of key cellular proteins is a crucial event in the transduction of activation signals to T-lymphocytes .

Rapid tyrosine phosphorylation of key cellular proteins is a crucial event in the transduction of activation signals to <cell_type>T-lymphocytes</cell_type> .


The regulatory role of protein tyrosine phosphatases ( PTPases ) in this process was explored by studying the effects of a powerful PTPase inhibitor , vanadate peroxide ( pervanadate ) , on the activation cascade of Jurkat human leukaemic T-cells .

The regulatory role of <protein>protein tyrosine phosphatases</protein> ( <protein>PTPases</protein> ) in this process was explored by studying the effects of a powerful <protein>PTPase</protein> inhibitor , vanadate peroxide ( pervanadate ) , on the activation cascade of <cell_line>Jurkat human leukaemic T-cells</cell_line> .


Pervanadate induced activation of the tyrosine kinases lck and fyn ( 4- and 3-fold respectively ) and a dramatic increase in tyrosine phosphorylation of cellular proteins , notably phospholipase C gamma 1 .

Pervanadate induced activation of the <protein>tyrosine kinases</protein> <protein>lck</protein> and <protein>fyn</protein> ( 4- and 3-fold respectively ) and a dramatic increase in tyrosine phosphorylation of <protein>cellular proteins</protein> , notably <protein>phospholipase C gamma 1</protein> .


After this event , we observed a rise in intracellular Ca2+ concentration , corresponding to an influx .


This effect required surface expression of the CD45 PTPase and was not observed in CD45-deficient variants of Jurkat cells .

This effect required surface expression of the <protein>CD45 PTPase</protein> and was not observed in <cell_line>CD45-deficient variants</cell_line> of <cell_line>Jurkat cells</cell_line> .


In the CD45-negative variant , the effect of pervanadate on tyrosine phosphorylation was globally decreased and some phosphorylated substrates were specifically missing .

In the <cell_line>CD45-negative variant</cell_line> , the effect of pervanadate on tyrosine phosphorylation was globally decreased and some phosphorylated substrates were specifically missing .


Pervanadate also stimulated transcription of the c-fos gene and accumulation of its mRNA as well as several other hallmarks of T-lymphocyte activation such as surface expression of the CD69 antigen and the interleukin 2 receptor alpha-chain ( CD25 ) .

Pervanadate also stimulated transcription of the <dna>c-fos gene</dna> and accumulation of its <rna>mRNA</rna> as well as several other hallmarks of <cell_type>T-lymphocyte</cell_type> activation such as surface expression of the CD69 antigen and the interleukin 2 receptor alpha-chain ( CD25 ) .


Pervanadate synergized with signals delivered by T-cell antigen receptor engagement or by a phorbol ester to induce interleukin 2 production .

Pervanadate synergized with signals delivered by <cell_type>T-cell</cell_type> <protein>antigen receptor</protein> engagement or by a phorbol ester to induce interleukin 2 production .


Pervanadate activated NF-kappa B , as shown by an increase in DNA-binding activity of this transcription factor .

<protein>Pervanadate activated NF-kappa B</protein> , as shown by an increase in DNA-binding activity of this <protein>transcription factor</protein> .


We thus conclude that PTPases play a crucial role in the negative regulation of signal transduction culminating in T-lymphocyte activation .

We thus conclude that <protein>PTPases</protein> play a crucial role in the negative regulation of signal transduction culminating in <cell_type>T-lymphocyte</cell_type> activation .


Moreover , induction of tyrosine phosphorylation appears sufficient per se to initiate a complete activation programme .


Activation of nuclear factor-kappaB via T cell receptor requires a Raf kinase and Ca2+ influx .

Activation of <protein>nuclear factor-kappaB</protein> via <protein>T cell receptor</protein> requires a <protein>Raf kinase</protein> and Ca2+ influx .


Functional synergy between Raf and calcineurin .

Functional synergy between <protein>Raf</protein> and <protein>calcineurin</protein> .


Signals transduced via the TCR activate the transcription factor nuclear factor-kappaB ( NF-kappaB ) , which , in turn , is critical to the transcriptional induction of many genes important for the proliferation and expression of a differentiated phenotype .

Signals transduced via the <protein>TCR</protein> activate the <protein>transcription factor</protein> <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) , which , in turn , is critical to the transcriptional induction of many genes important for the proliferation and expression of a differentiated phenotype .


Treatment of T cells with the protein kinase C activator PMA in combination with Ca2+ ionophores mimics this process , and the two agents are often substituted for TCR stimulation , bypassing the TCR .

Treatment of <cell_type>T cells</cell_type> with the <protein>protein kinase C</protein> activator PMA in combination with Ca2+ ionophores mimics this process , and the two agents are often substituted for <protein>TCR</protein> stimulation , bypassing the <protein>TCR</protein> .


Here we identify intracellular signaling components involved in activation of NF-kappaB following TCR stimulation .

Here we identify intracellular signaling components involved in activation of <protein>NF-kappaB</protein> following <protein>TCR</protein> stimulation .


TCR signaling was triggered by treating Jurkat T cells with PHA or anti-CD3 Abs , and NF-kappaB activation was monitored by electrophoretic mobility shift assays and/or by kappaB -dependent reporter assays .

<protein>TCR</protein> signaling was triggered by treating <cell_line>Jurkat T cells</cell_line> with <protein>PHA</protein> or <protein>anti-CD3 Abs</protein> , and <protein>NF-kappaB</protein> activation was monitored by electrophoretic mobility shift assays and/or by <protein>kappaB</protein> -dependent reporter assays .


Contrary to the idea that protein kinase C is involved in TCR -mediated activation of NF-kappaB , high doses of staurosporine did not interfere with activation of NF-kappaB by PHA , while the same dose of staurosporine completely blocked activation by PMA .

Contrary to the idea that <protein>protein kinase C</protein> is involved in <protein>TCR</protein> -mediated activation of <protein>NF-kappaB</protein> , high doses of staurosporine did not interfere with activation of <protein>NF-kappaB</protein> by <protein>PHA</protein> , while the same dose of staurosporine completely blocked activation by PMA .


PHA -induced kappaB-dependent reporter activity was , however , effectively blocked by a dominant negative form of Raf-1 , suggesting a critical role for a Raf kinase .

<protein>PHA</protein> -induced kappaB-dependent reporter activity was , however , effectively blocked by a dominant negative form of <protein>Raf-1</protein> , suggesting a critical role for a <protein>Raf kinase</protein> .


The TCR -mediated activation of NF-kappaB was also dependent on a Ca2+ influx , because the Ca2+ channel blocker , SK & F 96365 , as well as other agents that prevented the Ca2+ influx , inhibited NF-kappaB activation .

The <protein>TCR</protein> -mediated activation of <protein>NF-kappaB</protein> was also dependent on a Ca2+ influx , because the Ca2+ channel blocker , SK & F 96365 , as well as other agents that prevented the Ca2+ influx , inhibited <protein>NF-kappaB</protein> activation .


Cotransfection of a constitutively active form of calcineurin largely substituted for the Ca2+ requirement and reversed the blockade by SK & F 96365 .

Cotransfection of a constitutively active form of <protein>calcineurin</protein> largely substituted for the Ca2+ requirement and reversed the blockade by SK & F 96365 .


Consistent with these observations , coexpression of constitutively active forms of Raf-1 and calcineurin synergistically induced kappaB -dependent reporter activity , suggesting a physiologically relevant functional interaction between the kinase and the phosphatase .

Consistent with these observations , coexpression of constitutively active forms of <protein>Raf-1</protein> and <protein>calcineurin</protein> synergistically induced <protein>kappaB</protein> -dependent reporter activity , suggesting a physiologically relevant functional interaction between the <protein>kinase</protein> and the <protein>phosphatase</protein> .


Synergistic interactions between overlapping binding sites for the serum response factor and ELK-1 proteins mediate both basal enhancement and phorbol ester responsiveness of primate cytomegalovirus major immediate-early promoters in monocyte and T-lymphocyte cell types .

Synergistic interactions between <dna>overlapping binding sites</dna> for the <protein>serum response factor</protein> and <protein>ELK-1 proteins</protein> mediate both basal enhancement and phorbol ester responsiveness of <dna>primate cytomegalovirus major immediate-early promoters</dna> in monocyte and <cell_type>T-lymphocyte</cell_type> cell types .


Cytomegalovirus ( CMV ) infection is nonpermissive or persistent in many lymphoid and myeloid cell types but can be activated in differentiated macrophages .

Cytomegalovirus ( CMV ) infection is nonpermissive or persistent in many <cell_type>lymphoid and myeloid cell types</cell_type> but can be activated in <cell_type>differentiated macrophages</cell_type> .


We have shown elsewhere that both the major immediate-early gene ( MIE ) and lytic cycle infectious progeny virus expression can be induced in otherwise nonpermissive monocyte-like U-937 cell cultures infected with either human CMV ( HCMV ) or simian CMV ( SCMV ) by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .

We have shown elsewhere that both the <dna>major immediate-early gene</dna> ( <dna>MIE</dna> ) and lytic cycle infectious progeny virus expression can be induced in otherwise nonpermissive <cell_line>monocyte-like U-937 cell cultures</cell_line> infected with either human CMV ( HCMV ) or simian CMV ( SCMV ) by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .


Two multicopy basal enhancer motifs within the SCMV MIE enhancer , namely , 11 copies of the 16-bp cyclic AMP response element ( CRE ) and 3 copies of novel 17-bp serum response factor ( SRF ) binding sites referred to as the SNE ( SRF/NFkappaB-like element ) , as well as four classical NFkappaB sites within the HCMV version , contribute to TPA responsiveness in transient assays in monocyte and T-cell types .

Two <dna>multicopy basal enhancer motifs</dna> within the SCMV <dna>MIE enhancer</dna> , namely , 11 copies of the 16-bp <dna>cyclic AMP response element</dna> ( <dna>CRE</dna> ) and 3 copies of novel 17-bp <dna>serum response factor ( SRF ) binding sites</dna> referred to as the <dna>SNE</dna> ( <dna>SRF/NFkappaB-like element</dna> ) , as well as four classical <dna>NFkappaB sites</dna> within the HCMV version , contribute to TPA responsiveness in transient assays in <cell_type>monocyte and T-cell types</cell_type> .


The SCMV SNE sites contain potential overlapping core recognition binding motifs for SRF , Rel/NFkappaB , ETS , and YY1 class transcription factors but fail to respond to either serum or tumor necrosis factor alpha .

The <dna>SCMV SNE sites</dna> contain potential overlapping core recognition binding motifs for <protein>SRF</protein> , <protein>Rel/NFkappaB</protein> , <protein>ETS</protein> , and <protein>YY1 class transcription factors</protein> but fail to respond to either <protein>serum or tumor necrosis factor alpha</protein> .


Therefore , to evaluate the mechanism of TPA responsiveness of the SNE motifs and of a related 16-bp SEE ( SRF/ETS element ) motif found in the HCMV and chimpanzee CMV MIE enhancers , we have examined the functional responses and protein binding properties of multimerized wild-type and mutant elements added upstream to the SCMV MIE or simian virus 40 minimal promoter regions in the U-937 , K-562 , HL-60 , THP-1 , and Jurkat cell lines .

Therefore , to evaluate the mechanism of TPA responsiveness of the <dna>SNE motifs</dna> and of a related 16-bp <dna>SEE</dna> ( <dna>SRF/ETS element</dna> ) motif found in the <dna>HCMV and chimpanzee CMV MIE enhancers</dna> , we have examined the functional responses and protein binding properties of <dna>multimerized wild-type and mutant elements</dna> added upstream to the <dna>SCMV MIE</dna> or <dna>simian virus 40 minimal promoter regions</dna> in the <cell_line>U-937</cell_line> , <cell_line>K-562</cell_line> , <cell_line>HL-60</cell_line> , <cell_line>THP-1</cell_line> , and <cell_line>Jurkat cell lines</cell_line> .


Unlike classical NFkappaB sites , neither the SNE nor the SEE motif responded to phosphatase inhibition by okadaic acid .

Unlike classical <dna>NFkappaB sites</dna> , neither the <dna>SNE</dna> nor the <dna>SEE motif</dna> responded to phosphatase inhibition by okadaic acid .


However , the TPA responsiveness of both CMV elements proved to involve synergistic interactions between the core SRF binding site ( CCATATATGG ) and the adjacent inverted ETS binding motifs ( TTCC ) , which correlated directly with formation of a bound tripartite complex containing both the cellular SRF and ELK-1 proteins .

However , the TPA responsiveness of both <dna>CMV elements</dna> proved to involve synergistic interactions between the core <dna>SRF binding site</dna> ( CCATATATGG ) and the adjacent inverted <dna>ETS binding motifs</dna> ( TTCC ) , which correlated directly with formation of a bound <protein>tripartite complex</protein> containing both the cellular <protein>SRF</protein> and <protein>ELK-1 proteins</protein> .


This protein complex was more abundant in U-937 , K-562 , and HeLa cell extracts than in Raji , HF , BALB/c 3T3 , or HL-60 cells , but the binding activity was altered only twofold after TPA treatment .

This <protein>protein complex</protein> was more abundant in U-937 , K-562 , and HeLa cell extracts than in <cell_line>Raji</cell_line> , <cell_line>HF</cell_line> , <cell_line>BALB/c 3T3</cell_line> , or <cell_line>HL-60 cells</cell_line> , but the binding activity was altered only twofold after TPA treatment .


A 40-fold stimulation of chloramphenicol acetyltransferase activity mediated by four tandem repeats of the SNE could be induced within 2 h ( and up to 250-fold within 6 h ) after addition of TPA in DNA-transfected U-937 cells , indicating that the stimulation appeared likely to be a true protein kinase C -mediated signal transduction event rather than a differentiation response .

A 40-fold stimulation of <protein>chloramphenicol acetyltransferase</protein> activity mediated by four <dna>tandem repeats</dna> of the <dna>SNE</dna> could be induced within 2 h ( and up to 250-fold within 6 h ) after addition of TPA in <cell_line>DNA-transfected U-937 cells</cell_line> , indicating that the stimulation appeared likely to be a true <protein>protein kinase C</protein> -mediated signal transduction event rather than a differentiation response .


Slight differences in the sequence of the core SRF binding site compared with that of the classical c-Fos promoter serum response element , together with differences in the spacing between the SRF and ETS motifs , appear to account for the inability of the SCMV SNEs to respond to serum induction .

Slight differences in the sequence of the <dna>core SRF binding site</dna> compared with that of the classical <dna>c-Fos promoter serum response element</dna> , together with differences in the spacing between the <dna>SRF and ETS motifs</dna> , appear to account for the inability of the <dna>SCMV SNEs</dna> to respond to serum induction .


T-cell -directed TAL-1 expression induces T-cell malignancies in transgenic mice .

<cell_type>T-cell</cell_type> -directed <protein>TAL-1</protein> expression induces T-cell malignancies in transgenic mice .


The TAL-1 gene specifies for a basic domain-helix-loop-helix protein , which is involved in the control of normal hematopoiesis .

The <dna>TAL-1 gene</dna> specifies for a basic <protein>domain-helix-loop-helix protein</protein> , which is involved in the control of normal hematopoiesis .


In human pathology , the TAL-1 gene product is expressed in a high percentage of T-cell acute lymphoblastic leukemias in the pediatric age range ; however , it has not been established whether the expression has a causal role in oncogenesis .

In human pathology , the <protein>TAL-1 gene product</protein> is expressed in a high percentage of <cell_type>T-cell</cell_type> acute lymphoblastic leukemias in the pediatric age range ; however , it has not been established whether the expression has a causal role in oncogenesis .


In this report , we describe the phenotype of mouse transgenic lines obtained by inducing tal-1 protein expression in lymphoid tissues using the LCK promoter .

In this report , we describe the phenotype of <cell_line>mouse transgenic lines</cell_line> obtained by inducing <protein>tal-1 protein</protein> expression in lymphoid tissues using the <dna>LCK promoter</dna> .


The survival rate of tal-1 transgenic animals was much lower as compared with control mice .

The survival rate of <dna>tal-1</dna> transgenic animals was much lower as compared with control mice .


Histopathological analysis revealed lymphomas of T-cell type , often comprising a minor B-cell component .


Some mice showed marked splenic lymphocyte depletion .


Primary lymphocyte cultures showed partial independence from exogenous growth stimuli and increased resistance to low-serum apoptosis .

<cell_line>Primary lymphocyte cultures</cell_line> showed partial independence from exogenous growth stimuli and increased resistance to low-serum apoptosis .


To further unravel the tal-1 oncogenic potential , a strain of tal-1 transgenic mice was crossbred with p53-/- mice ; the survival rate in these animals was reduced by more than one-half when compared with that of tal-1 mice , and histopathological analysis revealed exclusively T-cell lymphomas .

To further unravel the <dna>tal-1</dna> oncogenic potential , a strain of <dna>tal-1</dna> transgenic mice was crossbred with p53-/- mice ; the survival rate in these animals was reduced by more than one-half when compared with that of <dna>tal-1</dna> mice , and histopathological analysis revealed exclusively <cell_type>T-cell</cell_type> lymphomas .


These data indicate that TAL-1 , expressed in T cells , is per se a potent oncogene , which may exert a key leukemogenetic role in the majority of T-cell acute lymphoblastic leukemias .

These data indicate that <protein>TAL-1</protein> , expressed in <cell_type>T cells</cell_type> , is per se a potent oncogene , which may exert a key leukemogenetic role in the majority of <cell_type>T-cell</cell_type> acute lymphoblastic leukemias .


Tissue and cell-type specific expression of the tuberous sclerosis gene , TSC2 , in human tissues .

Tissue and cell-type specific expression of the <dna>tuberous sclerosis gene</dna> , <dna>TSC2</dna> , in human tissues .


TSC2 is a gene on chromosome 16p13.3 associated with the autosomal dominant neurocutaneous disorder , tuberous sclerosis complex ( TSC ) .

<dna>TSC2</dna> is a gene on <dna>chromosome 16p13.3</dna> associated with the autosomal dominant neurocutaneous disorder , tuberous sclerosis complex ( TSC ) .


By using a partial nucleotide sequence from the cloned TSC2 and polymerase chain reaction methodology , we constructed a digoxigenin-labeled complementary DNA probe to examine TSC2 gene expression in autopsy- or biopsy-derived human tissues by in situ hybridization .

By using a partial nucleotide sequence from the cloned <dna>TSC2</dna> and polymerase chain reaction methodology , we constructed a <dna>digoxigenin-labeled complementary DNA probe</dna> to examine <dna>TSC2</dna> gene expression in autopsy- or biopsy-derived human tissues by in situ hybridization .


TSC2 messenger RNA was widely expressed in various cell types throughout the body , including epithelia , lymphocytes , and cells with endocrine functions , e.g. , adrenal cortex and anterior pituitary .

<rna>TSC2 messenger RNA</rna> was widely expressed in various cell types throughout the body , including epithelia , <cell_type>lymphocytes</cell_type> , and cells with endocrine functions , e.g. , adrenal cortex and anterior pituitary .


It was prominently and selectively ( within the central nervous system ) expressed in pyramidal cells of the cerebral cortex and other motor neurons , e.g. , in spinal cord and brainstem nuclei .

It was prominently and selectively ( within the central nervous system ) expressed in <cell_type>pyramidal cells</cell_type> of the cerebral cortex and other <cell_type>motor neurons</cell_type> , e.g. , in spinal cord and brainstem nuclei .


Visceral TSC2 expression was comparable in autopsy tissues from patients with and without TSC ; TSC2 messenger RNA expression was most prominent in cells with a rapid mitotic rate and turnover , e.g. , epithelia and lymphocytes , with central nervous system pyramidal cells and other neurons being an obvious exception , and/or in cells with important secretory/transport functions .

Visceral <dna>TSC2</dna> expression was comparable in autopsy tissues from patients with and without TSC ; <dna>TSC2</dna> messenger RNA expression was most prominent in cells with a rapid mitotic rate and turnover , e.g. , epithelia and <cell_type>lymphocytes</cell_type> , with central nervous system <cell_type>pyramidal cells</cell_type> and other neurons being an obvious exception , and/or in cells with important secretory/transport functions .


This widespread expression of the TSC2 gene supports the view that it encodes a protein vital to cell growth and metabolism or one that functions as a tumor/growth suppressor .

This widespread expression of the <dna>TSC2 gene</dna> supports the view that it encodes a protein vital to cell growth and metabolism or one that functions as a tumor/growth suppressor .


Apoptosis signaling pathways in normal T cells : differential activity of Bcl-2 and IL-1beta-converting enzyme family protease inhibitors on glucocorticoid- and Fas-mediated cytotoxicity .

Apoptosis signaling pathways in normal <cell_type>T cells</cell_type> : differential activity of <protein>Bcl-2</protein> and <protein>IL-1beta-converting enzyme family</protein> protease inhibitors on glucocorticoid- and Fas-mediated cytotoxicity .


Fas -mediated apoptosis plays an important role in regulating the immune response in peripheral T cells .

<protein>Fas</protein> -mediated apoptosis plays an important role in regulating the immune response in <cell_type>peripheral T cells</cell_type> .


Restimulation of T cell blasts up-regulates Fas and Fas ligand expression , with subsequent interaction leading to cell death .

Restimulation of <cell_type>T cell blasts</cell_type> up-regulates <protein>Fas</protein> and <protein>Fas</protein> ligand expression , with subsequent interaction leading to cell death .


Overexpression of Bcl-2 in tumor cells blocks apoptosis induced by many stimuli , but inhibition of Fas -mediated killing has not been consistently observed .

Overexpression of <protein>Bcl-2</protein> in <cell_type>tumor cells</cell_type> blocks apoptosis induced by many stimuli , but inhibition of <protein>Fas</protein> -mediated killing has not been consistently observed .


To examine the behavior of Bcl-2 in normal cells , T cell blasts were transiently transfected with Bcl-2 and related gene products to determine the effect on apoptotic signaling .

To examine the behavior of <protein>Bcl-2</protein> in <cell_type>normal cells</cell_type> , <cell_type>T cell blasts</cell_type> were transiently transfected with <protein>Bcl-2</protein> and related <protein>gene products</protein> to determine the effect on apoptotic signaling .


Transient overexpression of Bcl-2 in mouse and human T cell blasts did not block Fas -mediated apoptosis , whereas etoposide- and glucocorticoid-induced cytotoxicity was potently inhibited .

Transient overexpression of <protein>Bcl-2</protein> in mouse and human <cell_type>T cell blasts</cell_type> did not block <protein>Fas</protein> -mediated apoptosis , whereas etoposide- and glucocorticoid-induced cytotoxicity was potently inhibited .


Expression of Bcl-xL and adenovirus E1B 19K did not interfere with anti- Fas killing .

Expression of <protein>Bcl-xL</protein> and <protein>adenovirus E1B 19K</protein> did not interfere with anti- <protein>Fas</protein> killing .


In contrast , interleukin-1beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked Fas -mediated apoptosis .

In contrast , interleukin-1beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked <protein>Fas</protein> -mediated apoptosis .


These results suggest that peripheral T cells use distinct apoptosis signaling pathways with differential sensitivity to Bcl-2 and interleukin-1beta-converting enzyme family protease inhibitors .

These results suggest that <cell_type>peripheral T cells</cell_type> use distinct apoptosis signaling pathways with differential sensitivity to <protein>Bcl-2</protein> and interleukin-1beta-converting enzyme family protease inhibitors .


Since T cells normally express Bcl-2 and Bcl-xL following activation , their inability to block Fas -mediated apoptosis may allow for the elimination of self-reactive cells and the appropriate regulation of immune responses .

Since <cell_type>T cells</cell_type> normally express <protein>Bcl-2</protein> and <protein>Bcl-xL</protein> following activation , their inability to block <protein>Fas</protein> -mediated apoptosis may allow for the elimination of <cell_type>self-reactive cells</cell_type> and the appropriate regulation of immune responses .


Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin .

Increased <protein>interleukin 2</protein> transcription in <cell_type>murine lymphocytes</cell_type> by ciprofloxacin .


The fluoroquinolone antibiotic , ciprofloxacin ( cipro ) , induces hyperproduction of interleukin 2 ( IL-2 ) and interferon-gamma ( IFN-gamma ) in stimulated human peripheral blood lymphocytes .

The fluoroquinolone antibiotic , ciprofloxacin ( cipro ) , induces hyperproduction of <protein>interleukin 2</protein> ( <protein>IL-2</protein> ) and <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) in stimulated <cell_type>human peripheral blood lymphocytes</cell_type> .


In this investigation an enhanced and prolonged IL-2 and IL-2 mRNA response was also detected in both stimulated ( T cell mitogens or alloantigens ) murine splenocytes and in the stimulated murine T cell line EL-4 in the presence of ciprofloxacin ( 5-80 micrograms/ml ) as compared to control cells without antibiotics .

In this investigation an enhanced and prolonged <protein>IL-2</protein> and <rna>IL-2 mRNA</rna> response was also detected in both stimulated ( <protein>T cell mitogens</protein> or <protein>alloantigens</protein> ) <cell_type>murine splenocytes</cell_type> and in the stimulated <cell_line>murine T cell line EL-4</cell_line> in the presence of ciprofloxacin ( 5-80 micrograms/ml ) as compared to control cells without antibiotics .


However , in contrast to human lymphocytes , IFN-gamma production was inhibited and IFN-gamma mRNA levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in murine splenocytes incubated with cipro ( 20 micrograms/ml ) .

However , in contrast to <cell_type>human lymphocytes</cell_type> , <protein>IFN-gamma</protein> production was inhibited and <rna>IFN-gamma mRNA</rna> levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in <cell_type>murine splenocytes</cell_type> incubated with cipro ( 20 micrograms/ml ) .


EL-4 cells were transfected with a plasmid containing the IL-2 promoter and enhancer region linked to the chloramphenicol acetyltransferase ( CAT ) reporter gene .

<cell_type>EL-4 cells</cell_type> were transfected with a plasmid containing the <dna>IL-2 promoter</dna> and <dna>enhancer region</dna> linked to the <dna>chloramphenicol acetyltransferase ( CAT ) reporter gene</dna> .


Analysis of CAT activity revealed that cipro enhanced IL-2 gene induction .

Analysis of <protein>CAT</protein> activity revealed that cipro enhanced IL-2 gene induction .


In addition , EL-4 cells incubated with ciprofloxacin showed an early peak and more activated nuclear factor of activated T cells ( NFAT-1 ) as compared to control cells without antibiotics .

In addition , <cell_type>EL-4 cells</cell_type> incubated with ciprofloxacin showed an early peak and more activated nuclear factor of <cell_type>activated T cells</cell_type> ( <protein>NFAT-1</protein> ) as compared to control cells without antibiotics .


Cipro did not affect the nuclear transcription factors AP-1 or NFIL-2A .

Cipro did not affect the <protein>nuclear transcription factors</protein> <protein>AP-1</protein> or <protein>NFIL-2A</protein> .


Taken together , cipro inhibited IFN-gamma synthesis , but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription .

Taken together , cipro inhibited <protein>IFN-gamma</protein> synthesis , but enhanced <protein>IL-2</protein> production in <cell_type>murine lymphocytes</cell_type> by means of influencing <protein>NFAT-1</protein> and causing an increased <protein>IL-2</protein> transcription .


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 .

Human T-cell leukemia virus type I <protein>Tax</protein> associates with and is negatively regulated by the <protein>NF-kappa B2 p100 gene product</protein> : implications for viral latency .


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 .

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 <cell_line>activated human CD4 T cells</cell_line> .


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 .

HTLV-I encodes an essential <protein>40-kDa protein</protein> termed <protein>Tax</protein> that not only transactivates the long terminal repeat of this retrovirus but also induces an array of <dna>cellular genes</dna> .


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 .

<protein>Tax</protein> -mediated transformation of <cell_type>T cells</cell_type> likely involves the deregulated expression of various <dna>cellular genes</dna> that normally regulate <cell_type>lymphocyte</cell_type> growth produced by altered activity of various endogenous host <protein>transcription factors</protein> .


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 .

In particular , <protein>Tax</protein> is capable of modulating the expression or activity of various host <protein>transcription factors</protein> , including members of the <protein>NF-kappa B/Rel</protein> and <protein>CREB/ATF families</protein> , as well as the <protein>cellular factors</protein> <protein>HEB-1</protein> and <protein>p67SRF</protein> .


An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells .

An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating <cell_type>primary leukemic T cells</cell_type> .


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 .

In this study , we demonstrate that HTLV-I <protein>Tax</protein> can physically associate with <protein>p100</protein> , the product of the <dna>Rel-related NF-kappa B2 gene</dna> , both in <cell_line>transfected cells</cell_line> and in <cell_line>HTLV-I-infected leukemic T-cell lines</cell_line> .


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 .

Furthermore , the physical interaction of <protein>Tax</protein> with <protein>p100</protein> leads to the inhibition of <protein>Tax</protein> -induced activation of the HTLV-I and <dna>human immunodeficiency virus type 1 long terminal repeats</dna> , reflecting <protein>p100</protein> -mediated cytoplasmic sequestration of the normally nuclearly expressed <protein>Tax protein</protein> .


In contrast , a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100 .

In contrast , a mutant of <protein>Tax</protein> that selectively fails to activate nuclear <protein>NF-kappa B</protein> expression does not associate with <protein>p100</protein> .


( ABSTRACT TRUNCATED AT 250 WORDS )


Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic transcription factors .

Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic <protein>transcription factors</protein> .


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 .

Skeletal myogenesis is regulated by a group of <protein>transcription factors</protein> ( <protein>MyoD</protein> , <protein>myogenin</protein> , <protein>myf5</protein> , and <protein>myf6</protein> ) that are <protein>`` basic helix-loop-helix '' proteins</protein> that bind to the <dna>promoters</dna> of <dna>muscle-specific genes</dna> and promote their expression .


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 .

We have previously shown that after a mutation of Leu122 to Arg the <protein>DNA binding basic domain</protein> of <protein>MyoD</protein> confers <dna>c-myc</dna> -like functional characteristics to the protein .


In this study we used single-strand conformation polymorphism analysis to determine whether such mutations occur naturally in rhabdomyosarcomas .


We have found that the basic domains of all the myogenic factors remain unaltered in rhabdomyosarcomas .

We have found that the <protein>basic domains</protein> of all the <protein>myogenic factors</protein> remain unaltered in rhabdomyosarcomas .


Selection against such mutations may be the result of functional redundancy of these myogenic transcription factors .

Selection against such mutations may be the result of functional redundancy of these <protein>myogenic transcription factors</protein> .


Function and activation of NF-kappa B in the immune system .

Function and activation of <protein>NF-kappa B</protein> in the immune system .


NF-kappa B is a ubiquitous transcription factor .

<protein>NF-kappa B</protein> is a <protein>ubiquitous transcription factor</protein> .


Nevertheless , its properties seem to be most extensively exploited in cells of the immune system .


Among these properties are NF-kappa B 's rapid posttranslational activation in response to many pathogenic signals , its direct participation in cytoplasmic/nuclear signaling , and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins .

Among these properties are <protein>NF-kappa B</protein> 's rapid posttranslational activation in response to many pathogenic signals , its direct participation in cytoplasmic/nuclear signaling , and its potency to activate transcription of a great variety of genes encoding <protein>immunologically relevant proteins</protein> .


In vertebrates , five distinct DNA binding subunits are currently known which might extensively heterodimerize , thereby forming complexes with distinct transcriptional activity , DNA sequence specificity , and cell type- and cell stage-specific distribution .

In vertebrates , five distinct <protein>DNA binding subunits</protein> are currently known which might extensively heterodimerize , thereby forming complexes with distinct transcriptional activity , DNA sequence specificity , and cell type- and cell stage-specific distribution .


The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates .

The activity of <protein>DNA binding NF-kappa B dimers</protein> is tightly controlled by <protein>accessory proteins</protein> called <protein>I kappa B subunits</protein> of which there are also five different species currently known in vertebrates .


I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes .

<protein>I kappa B proteins</protein> inhibit DNA binding and prevent nuclear uptake of <protein>NF-kappa B complexes</protein> .


An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus .

An exception is the <protein>Bcl-3 protein</protein> which in addition can function as a <protein>transcription activating subunit</protein> in th nucleus .


Other I kappa B proteins are rather involved in terminating NF-kappa B 's activity in the nucleus .

Other <protein>I kappa B proteins</protein> are rather involved in terminating <protein>NF-kappa B</protein> 's activity in the nucleus .


The intracellular events that lead to the inactivation of I kappa B , i.e. the activation of NF-kappa B , are complex .

The intracellular events that lead to the inactivation of <protein>I kappa B</protein> , i.e. the activation of <protein>NF-kappa B</protein> , are complex .


They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells ' redox status .


Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock , graft-vs-host reactions , acute inflammatory reactions , acute phase response , and radiation damage .

Interference with the activation or activity of <protein>NF-kappa B</protein> may be beneficial in suppressing toxic/septic shock , graft-vs-host reactions , acute inflammatory reactions , acute phase response , and radiation damage .


The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes .

The inhibition of <protein>NF-kappa B</protein> activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes .


Lack of T-cell-mediated recognition of the fusion region of the pml/RAR-alpha hybrid protein by lymphocytes of acute promyelocytic leukemia patients .

Lack of T-cell-mediated recognition of the fusion region of the <protein>pml/RAR-alpha hybrid protein</protein> by <cell_type>lymphocytes</cell_type> of acute promyelocytic leukemia patients .


In previous studies , it was shown that the fusion region of the pml/RAR-alpha protein , expressed by acute promyelocytic leukemia ( APL ) cells , can be specifically recognized in vitro by donor ( D. E. ) CD4 T cells in a HLA class II DR11-restricted fashion .

In previous studies , it was shown that the fusion region of the <protein>pml/RAR-alpha protein</protein> , expressed by <cell_line>acute promyelocytic leukemia ( APL ) cells</cell_line> , can be specifically recognized in vitro by donor ( D. E. ) <cell_line>CD4 T cells</cell_line> in a <protein>HLA class II</protein> DR11-restricted fashion .


We present here the results on the recognition of several pml/RAR-alpha peptides by APL patients expressing HLA DR11 .

We present here the results on the recognition of several pml/RAR-alpha peptides by APL patients expressing <protein>HLA DR11</protein> .