In contrast , IL-4 induces different C epsilon GAS DNA-protein binding complexes in both T and NK cells .

In contrast , <protein>IL-4</protein> induces different <protein>C epsilon GAS DNA-protein binding complexes</protein> in both T and <cell_type>NK cells</cell_type> .


Moreover , IL-4 costimulation with IL-2 or IL-12 does not alter their own preferential GAS -like DNA binding patterns when C epsilon- , Fc gamma RI- , and SIE GAS motif containing oligonucleotide probes are compared , suggesting that induction of GAS-like DNA-protein binding complexes by IL-2 , IL-4 , and IL-12 is highly selective and represents one important factor in determining specific gene activation .

Moreover , <protein>IL-4</protein> costimulation with <protein>IL-2</protein> or <protein>IL-12</protein> does not alter their own preferential <dna>GAS</dna> -like DNA binding patterns when <dna>C epsilon- , Fc gamma RI- , and SIE GAS motif</dna> containing oligonucleotide probes are compared , suggesting that induction of <protein>GAS-like DNA-protein binding complexes</protein> by <protein>IL-2</protein> , <protein>IL-4</protein> , and <protein>IL-12</protein> is highly selective and represents one important factor in determining specific gene activation .


In addition , IL-6 and IL-2 synergistically induce homo- and heterodimerized STAT1 alpha and STAT3 in both NK and T cells , consistent with their reported synergism in modulating perforin gene expression .

In addition , <protein>IL-6</protein> and <protein>IL-2</protein> synergistically induce homo- and heterodimerized <protein>STAT1 alpha</protein> and <protein>STAT3</protein> in both <cell_type>NK and T cells</cell_type> , consistent with their reported synergism in modulating <dna>perforin gene</dna> expression .


We further demonstrated that IL-2 , -7 , and -15 induce multiple STAT proteins , including STAT5a , STAT5b , STAT1 alpha , STAT3 , and another unidentified Fc gamma RI GAS DNA-binding protein .

We further demonstrated that <protein>IL-2 , -7 , and -15</protein> induce <protein>multiple STAT proteins</protein> , including <protein>STAT5a</protein> , <protein>STAT5b</protein> , <protein>STAT1 alpha</protein> , <protein>STAT3</protein> , and another unidentified <protein>Fc gamma RI GAS DNA-binding protein</protein> .


Finally , we observed that activated STAT5a and STAT5b proteins form distinct Fc gamma RI GAS binding patterns in T and NK cells , suggesting that they might have different roles in gene regulation .

Finally , we observed that activated <protein>STAT5a</protein> and <protein>STAT5b</protein> proteins form distinct Fc gamma RI GAS binding patterns in <cell_type>T and NK cells</cell_type> , suggesting that they might have different roles in gene regulation .


Our data provide evidence that the differential responses in gene expression and cell activation seen in primary NK and T cells on direct stimulation with different cytokines may be a direct result of distinct activation of STAT transcription factors .

Our data provide evidence that the differential responses in gene expression and cell activation seen in primary <cell_type>NK and T cells</cell_type> on direct stimulation with different <protein>cytokines</protein> may be a direct result of distinct activation of <protein>STAT transcription factors</protein> .


A regulatory element in the CD95 ( APO-1/Fas ) ligand promoter is essential for responsiveness to TCR -mediated activation .

A <dna>regulatory element</dna> in the <dna>CD95 ( APO-1/Fas ) ligand promoter</dna> is essential for responsiveness to <protein>TCR</protein> -mediated activation .


Expression of the CD95 ( APO-1/Fas ) ligand ( CD95L ) in activated T cells is a major cause of T cell activation-induced apoptosis .

Expression of the <protein>CD95 ( APO-1/Fas ) ligand</protein> ( <protein>CD95L</protein> ) in <cell_type>activated T cells</cell_type> is a major cause of T cell activation-induced apoptosis .


To study the molecular mechanisms of transcriptional control of CD95L expression in T cells , we investigated the human CD95L promoter in Jurkat T cells .

To study the molecular mechanisms of transcriptional control of <protein>CD95L</protein> expression in <cell_type>T cells</cell_type> , we investigated the <dna>human CD95L promoter</dna> in <cell_line>Jurkat T cells</cell_line> .


Deletion studies revealed that the CD95L proximal promoter sequence from -220 to the transcription start site is essential for T cell stimulation-induced expression of CD95L .

Deletion studies revealed that the <dna>CD95L proximal promoter sequence</dna> from <dna>-220</dna> to the <dna>transcription start site</dna> is essential for T cell stimulation-induced expression of <protein>CD95L</protein> .


In this study , we discovered a novel regulatory element located at -120 of the CD95L promoter which contains DNA binding sites for SP-1 and a yet unknown inducible factor .

In this study , we discovered a novel <dna>regulatory element</dna> located at <dna>-120</dna> of the <dna>CD95L promoter</dna> which contains <dna>DNA binding sites</dna> for <protein>SP-1</protein> and a yet unknown <protein>inducible factor</protein> .


Mutation analysis demonstrated that binding of the inducible factor to the -120 region is crucial for the biological function of the CD95L promoter upon T cell stimulation .

Mutation analysis demonstrated that binding of the inducible factor to the <dna>-120 region</dna> is crucial for the biological function of the <dna>CD95L promoter</dna> upon T cell stimulation .


The DNA sequence at -120 also contains two DNA motifs homologous to the binding site for NF-AT .

The DNA sequence at <dna>-120</dna> also contains two <dna>DNA motifs</dna> homologous to the binding site for <protein>NF-AT</protein> .


NF-AT does not directly bind to this element .

<protein>NF-AT</protein> does not directly bind to this element .


However , cotransfection studies with an NF-AT expression vector showed that NF-AT may confer a strong inducible activity to the CD95L promoter at this regulatory region .

However , cotransfection studies with an <dna>NF-AT expression vector</dna> showed that <protein>NF-AT</protein> may confer a strong inducible activity to the <dna>CD95L promoter</dna> at this <dna>regulatory region</dna> .


Our data also show that the immunosuppressive agent cyclosporin A down-regulates CD95L transcription by inhibiting the function of this positive regulatory element

Our data also show that the immunosuppressive agent cyclosporin A down-regulates <protein>CD95L</protein> transcription by inhibiting the function of this positive <dna>regulatory element</dna>


A nongenomic mechanism for progesterone-mediated immunosuppression : inhibition of K+ channels , Ca2+ signaling , and gene expression in T lymphocytes .

A nongenomic mechanism for progesterone-mediated immunosuppression : inhibition of <protein>K+ channels</protein> , Ca2+ signaling , and gene expression in <cell_type>T lymphocytes</cell_type> .


The mechanism by which progesterone causes localized suppression of the immune response during pregnancy has remained elusive .


Using human T lymphocytes and T cell lines , we show that progesterone , at concentrations found in the placenta , rapidly and reversibly blocks voltage-gated and calcium-activated K+ channels ( KV and KCa , respectively ) , resulting in depolarization of the membrane potential .

Using <cell_type>human T lymphocytes</cell_type> and <cell_line>T cell lines</cell_line> , we show that progesterone , at concentrations found in the placenta , rapidly and reversibly blocks <protein>voltage-gated and calcium-activated K+ channels</protein> ( <protein>KV</protein> and <protein>KCa</protein> , respectively ) , resulting in depolarization of the membrane potential .


As a result , Ca2+ signaling and nuclear factor of activated T cells ( NF-AT ) -driven gene expression are inhibited .

As a result , Ca2+ signaling and <protein>nuclear factor of activated T cells</protein> ( <protein>NF-AT</protein> ) -driven gene expression are inhibited .


Progesterone acts distally to the initial steps of T cell receptor ( TCR ) -mediated signal transduction , since it blocks sustained Ca2+ signals after thapsigargin stimulation , as well as oscillatory Ca2+ signals , but not the Ca2+ transient after TCR stimulation .

Progesterone acts distally to the initial steps of <protein>T cell receptor</protein> ( <protein>TCR</protein> ) -mediated signal transduction , since it blocks sustained Ca2+ signals after thapsigargin stimulation , as well as oscillatory Ca2+ signals , but not the Ca2+ transient after <protein>TCR</protein> stimulation .


K+ channel blockade by progesterone is specific ; other steroid hormones had little or no effect , although the progesterone antagonist RU 486 also blocked KV and KCa channels .

K+ channel blockade by progesterone is specific ; other steroid hormones had little or no effect , although the progesterone antagonist RU 486 also blocked <protein>KV</protein> and <protein>KCa</protein> channels .


Progesterone effectively blocked a broad spectrum of K+ channels , reducing both Kv1.3 and charybdotoxin-resistant components of KV current and KCa current in T cells , as well as blocking several cloned KV channels expressed in cell lines .

Progesterone effectively blocked a broad spectrum of <protein>K+ channels</protein> , reducing both <protein>Kv1.3</protein> and <protein>charybdotoxin-resistant components</protein> of <protein>KV</protein> current and <protein>KCa</protein> current in <cell_type>T cells</cell_type> , as well as blocking several <protein>cloned KV channels</protein> expressed in <cell_line>cell lines</cell_line> .


Progesterone had little or no effect on a cloned voltage-gated Na+ channel , an inward rectifier K+ channel , or on lymphocyte Ca2+ and Cl- channels .

Progesterone had little or no effect on a <protein>cloned voltage-gated Na+ channel</protein> , an inward rectifier <protein>K+ channel</protein> , or on <protein>lymphocyte Ca2+ and Cl- channels</protein> .


We propose that direct inhibition of K+ channels in T cells by progesterone contributes to progesterone-induced immunosuppression .

We propose that direct inhibition of <protein>K+ channels</protein> in <cell_type>T cells</cell_type> by progesterone contributes to progesterone-induced immunosuppression .


A mouse carrying genetic defect in the choice between T and B lymphocytes .

A mouse carrying genetic defect in the choice between <cell_type>T and B lymphocytes</cell_type> .


Transgenic mice with human CD3epsilon gene have been shown to exhibit early arrest of T cell development in the thymus .

Transgenic mice with <dna>human CD3epsilon gene</dna> have been shown to exhibit early arrest of T cell development in the thymus .


The present study shows that , instead of T cells , B cells are generated in the thymus of a line , tg epsilon26 , of the human CD3epsilon transgenic mice .

The present study shows that , instead of <cell_type>T cells</cell_type> , <cell_type>B cells</cell_type> are generated in the thymus of a line , tg epsilon26 , of the human CD3epsilon transgenic mice .


The accumulation of mature B cells in the thymus was found only in tg epsilon26 mice , not in other human CD3epsilon transgenic mouse lines or other T cell-deficient mice , including CD3-epsilon knockout mice and TCR-beta/TCR-delta double knockout mice .

The accumulation of <cell_type>mature B cells</cell_type> in the thymus was found only in tg epsilon26 mice , not in other <cell_line>human CD3epsilon transgenic mouse lines</cell_line> or other T cell-deficient mice , including CD3-epsilon knockout mice and TCR-beta/TCR-delta double knockout mice .


Hanging drop-mediated transfer into 2-deoxyguanosine-treated thymus lobes showed that lymphoid progenitor cells rather than thymus stromal cells were responsible for abnormal B cell development in tg epsilon26 thymus , and that tg epsilon26 fetal liver cells were destined to become B cells in normal thymus even in the presence of normal progenitor cells undergoing T cell development .

Hanging drop-mediated transfer into 2-deoxyguanosine-treated thymus lobes showed that <cell_type>lymphoid progenitor cells</cell_type> rather than thymus stromal cells were responsible for abnormal B cell development in <protein>tg epsilon26</protein> thymus , and that <cell_type>tg epsilon26 fetal liver cells</cell_type> were destined to become <cell_type>B cells</cell_type> in normal thymus even in the presence of <cell_type>normal progenitor cells</cell_type> undergoing T cell development .


These results indicate that lymphoid progenitor cells in tg epsilon26 mice are genetically defective in thymic choice between T cells and B cells , generating B cells even in normal thymus environment .

These results indicate that <cell_type>lymphoid progenitor cells</cell_type> in <protein>tg epsilon26</protein> mice are genetically defective in thymic choice between <cell_type>T cells</cell_type> and <cell_type>B cells</cell_type> , generating <cell_type>B cells</cell_type> even in normal thymus environment .


Interestingly , tg epsilon26 thymocytes expressed GATA-3 and TCF-1 , but not LEF-1 and PEBP-2alpha , among T cell-specific transcription factors that are involved in early T cell development , indicating that GATA-3 and TCF-1 expressed during thymocyte development do not necessarily determine the cell fate into T cell lineage .

Interestingly , <cell_type>tg epsilon26 thymocytes</cell_type> expressed <protein>GATA-3</protein> and <protein>TCF-1</protein> , but not <protein>LEF-1</protein> and <protein>PEBP-2alpha</protein> , among <protein>T cell-specific transcription factors</protein> that are involved in early T cell development , indicating that <protein>GATA-3</protein> and <protein>TCF-1</protein> expressed during thymocyte development do not necessarily determine the cell fate into <cell_type>T cell lineage</cell_type> .


Thus , tg epsilon26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective .

Thus , <protein>tg epsilon26</protein> mice provide a novel mouse model in that lineage choice between <cell_type>T and B lymphocytes</cell_type> is genetically defective .


Downstream activation of a TATA-less promoter by Oct-2 , Bob1 , and NF-kappaB directs expression of the homing receptor BLR1 to mature B cells .

Downstream activation of a <dna>TATA-less promoter</dna> by <protein>Oct-2</protein> , Bob1 , and <protein>NF-kappaB</protein> directs expression of the <protein>homing receptor BLR1</protein> to <cell_type>mature B cells</cell_type> .


The chemokine receptor , BLR1 , is a major regulator of the microenvironmental homing of B cells in lymphoid organs .

The <protein>chemokine receptor</protein> , <protein>BLR1</protein> , is a major regulator of the microenvironmental homing of <cell_type>B cells</cell_type> in lymphoid organs .


In vitro studies identify three essential elements of the TATA-less blr1 core promoter that confer cell type- and differentiation-specific expression in the B cells of both humans and mice , a functional promoter region ( -36 with respect to the transcription start site ) , a NF-kappaB motif ( +44 ) , and a noncanonical octamer motif ( +157 ) .

In vitro studies identify three essential elements of the <dna>TATA-less blr1 core promoter</dna> that confer cell type- and differentiation-specific expression in the <cell_type>B cells</cell_type> of both humans and mice , a <dna>functional promoter region</dna> ( -36 with respect to the <dna>transcription start site</dna> ) , a <dna>NF-kappaB motif</dna> ( +44 ) , and a <dna>noncanonical octamer motif</dna> ( +157 ) .


The importance of these sites was confirmed by in vivo studies in gene-targeted mice deficient of either Oct-2 , Bob1 , or both NF-kappaB subunits p50 and p52 .

The importance of these sites was confirmed by in vivo studies in gene-targeted mice deficient of either <protein>Oct-2</protein> , <protein>Bob1</protein> , or both <protein>NF-kappaB</protein> subunits p50 and p52 .


In all of these animals , the expression of BLR1 was reduced or absent .

In all of these animals , the expression of <protein>BLR1</protein> was reduced or absent .


In mice deficient only of p52/NF-kappaB , BLR1 expression was unaffected .

In mice deficient only of <protein>p52/NF-kappaB</protein> , <protein>BLR1</protein> expression was unaffected .


Thus our data demonstrate that BLR1 is a target gene for Oct-2 , Bob1 , and members of the NF-kappaB/Rel family and provides a link to the impaired B cell functions in mice deficient for these factors .

Thus our data demonstrate that <protein>BLR1</protein> is a target gene for <protein>Oct-2</protein> , <protein>Bob1</protein> , and members of the <protein>NF-kappaB/Rel family</protein> and provides a link to the impaired B cell functions in mice deficient for these factors .


CD4 promoter transactivation by human herpesvirus 6 .

<dna>CD4 promoter</dna> transactivation by human herpesvirus 6 .


The observation that human herpesvirus 6 ( HHV-6 ) can induce CD4 gene transcription and expression in CD4 ( - ) cells was reported several years ago ( P.Lusso , A.De Maria , M.Malnati , F.Lori , S.E.DeRocco , M. Baseler , and R.C.Gallo , Nature 349 : 533-535 , 1991 ) and subsequently confirmed ( P.Lusso , M.S.Malnati , A.Garzino-Demo , R.W.Crowley , E. O.Long , and R.C.Gallo , Nature 362 : 458-462 , 1993 ; G.Furlini , M. Vignoli , E.Ramazzotti , M.C.Re , G.Visani , and M.LaPlaca , Blood 87 : 4737-4745 , 1996 ) .

The observation that human herpesvirus 6 ( HHV-6 ) can induce <dna>CD4 gene</dna> transcription and expression in <cell_line>CD4 ( - ) cells</cell_line> was reported several years ago ( P.Lusso , A.De Maria , M.Malnati , F.Lori , S.E.DeRocco , M. Baseler , and R.C.Gallo , Nature 349 : 533-535 , 1991 ) and subsequently confirmed ( P.Lusso , M.S.Malnati , A.Garzino-Demo , R.W.Crowley , E. O.Long , and R.C.Gallo , Nature 362 : 458-462 , 1993 ; G.Furlini , M. Vignoli , E.Ramazzotti , M.C.Re , G.Visani , and M.LaPlaca , Blood 87 : 4737-4745 , 1996 ) .


Our objective was to identify the mechanisms underlying such phenomena .


Using reporter gene constructs driven by the CD4 promoter , we report that HHV-6 can efficiently transactivate such genetic elements .

Using <dna>reporter gene constructs</dna> driven by the <dna>CD4 promoter</dna> , we report that HHV-6 can efficiently transactivate such <dna>genetic elements</dna> .


Activation of the CD4 promoter occurs in the presence of the viral DNA polymerase inhibitor phosphonoformic acid , which limits expression to the immediate-early and early classes of viral genes .

Activation of the <dna>CD4 promoter</dna> occurs in the presence of the viral DNA polymerase inhibitor phosphonoformic acid , which limits expression to the <dna>immediate-early and early classes of viral genes</dna> .


Using deletion mutants and specific CD4 promoter mutants , we identified an ATF/CRE binding site located at nucleotides -67 to -60 upstream of the CD4 gene transcription start site that is important for HHV-6 transactivation .

Using deletion mutants and specific <dna>CD4 promoter mutants</dna> , we identified an <dna>ATF/CRE binding site</dna> located at <dna>nucleotides -67 to -60 upstream</dna> of the <dna>CD4 gene transcription start site</dna> that is important for HHV-6 transactivation .


The ATF/CRE site is also essential for CD4 promoter activation by forskolin , an activator of adenylate cyclase .

The <dna>ATF/CRE site</dna> is also essential for <dna>CD4 promoter</dna> activation by forskolin , an activator of adenylate cyclase .


Using electrophoretic mobility shift assays and specific antibodies , we showed that CREB-1 binds specifically to the -79 to -52 region of the CD4 promoter .

Using electrophoretic mobility shift assays and specific antibodies , we showed that <protein>CREB-1</protein> binds specifically to the <dna>-79 to -52 region</dna> of the <dna>CD4 promoter</dna> .


Last , we have identified two open reading frames ( ORFs ) of HHV-6 , U86 and U89 from the immediate-early locus A , that can transactivate the CD4 promoter in HeLa cells .

Last , we have identified two <dna>open reading frames</dna> ( <dna>ORFs</dna> ) of HHV-6 , <dna>U86</dna> and <dna>U89</dna> from the immediate-early locus A , that can transactivate the <dna>CD4 promoter</dna> in <cell_line>HeLa cells</cell_line> .


However , transactivation of the CD4 promoter by ORFs U86 and U89 is independent of the CRE element , suggesting that additional HHV-6 ORFs are likely to contribute to CD4 gene activation .

However , transactivation of the <dna>CD4 promoter</dna> by <dna>ORFs</dna> <dna>U86</dna> and <dna>U89</dna> is independent of the <dna>CRE element</dna> , suggesting that additional <dna>HHV-6 ORFs</dna> are likely to contribute to <dna>CD4 gene</dna> activation .


Taken together , our results will help to understand the complex interactions occurring between HHV-6 and the CD4 promoter and provide additional information regarding the class of transcription factors involved in the control of CD4 gene expression .

Taken together , our results will help to understand the complex interactions occurring between HHV-6 and the <dna>CD4 promoter</dna> and provide additional information regarding the class of <protein>transcription factors</protein> involved in the control of <dna>CD4 gene</dna> expression .


The PEBP2betaMYH11 fusion created by Inv ( 16 ) ( p13 ; q22 ) in myeloid leukemia impairs neutrophil maturation and contributes to granulocytic dysplasia .

The <protein>PEBP2betaMYH11</protein> fusion created by <dna>Inv ( 16 ) ( p13 ; q22 )</dna> in myeloid leukemia impairs neutrophil maturation and contributes to granulocytic dysplasia .


Chromosomal translocations involving the genes encoding the alpha and beta subunits of the Pebp2/Cbf transcription factor have been associated with human acute myeloid leukemia and the preleukemic condition , myelodysplasia .

Chromosomal translocations involving the genes encoding the <protein>alpha and beta subunits</protein> of the <protein>Pebp2/Cbf transcription factor</protein> have been associated with human acute myeloid leukemia and the preleukemic condition , myelodysplasia .


Inv ( 16 ) ( p13 ; q22 ) fuses the gene encoding the beta subunit of Pebp2 to the MYH11 gene encoding a smooth muscle myosin heavy chain ( Smmhc ) .

<dna>Inv ( 16 ) ( p13 ; q22 )</dna> fuses the gene encoding the <protein>beta subunit</protein> of <protein>Pebp2</protein> to the <dna>MYH11 gene</dna> encoding a <protein>smooth muscle myosin heavy chain</protein> ( <protein>Smmhc</protein> ) .


To examine the effect of the inv ( 16 ) ( p13 ; q22 ) on myelopoiesis , we used the hMRP8 promoter element to generate transgenic mice expressing the Pebp2beta Smmhc chimeric fusion protein in myeloid cells .

To examine the effect of the <dna>inv ( 16 ) ( p13 ; q22 )</dna> on myelopoiesis , we used the <dna>hMRP8 promoter element</dna> to generate transgenic mice expressing the <protein>Pebp2beta</protein> <protein>Smmhc chimeric fusion protein</protein> in <cell_type>myeloid cells</cell_type> .


Neutrophil maturation was impaired in PEBP2betaMYH11 transgenic mice .

Neutrophil maturation was impaired in <protein>PEBP2betaMYH11</protein> transgenic mice .


Although the transgenic mice had normal numbers of circulating neutrophils , their bone marrow contained increased numbers of immature neutrophilic cells , which exhibited abnormal characteristics .

Although the transgenic mice had normal numbers of <cell_type>circulating neutrophils</cell_type> , their bone marrow contained increased numbers of <cell_type>immature neutrophilic cells</cell_type> , which exhibited abnormal characteristics .


In addition , PEBP2betaMYH11 inhibited neutrophilic differentiation in colonies derived from hematopoietic progenitors .

In addition , <protein>PEBP2betaMYH11</protein> inhibited neutrophilic differentiation in colonies derived from <cell_type>hematopoietic progenitors</cell_type> .


Coexpression of both PEBP2betaMYH11 and activated NRAS induced a more severe phenotype characterized by abnormal nuclear morphology indicative of granulocytic dysplasia .

Coexpression of both <protein>PEBP2betaMYH11</protein> and <protein>activated NRAS</protein> induced a more severe phenotype characterized by abnormal nuclear morphology indicative of granulocytic dysplasia .


These results show that PEBP2betaMYH11 can impair neutrophil development and provide evidence that alterations of Pebp2 can contribute to the genesis of myelodysplasia .

These results show that <protein>PEBP2betaMYH11</protein> can impair neutrophil development and provide evidence that alterations of <protein>Pebp2</protein> can contribute to the genesis of myelodysplasia .


Human T cell leukemia virus-I ( HTLV-I ) Tax -mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state .

Human T cell leukemia virus-I ( HTLV-I ) <protein>Tax</protein> -mediated apoptosis in <cell_type>activated T cells</cell_type> requires an enhanced intracellular prooxidant state .


We have shown that an estradiol-dependent activation of human T cell leukemia virus-I Tax leads to the inhibition of cell proliferation and to the induction of apoptosis .

We have shown that an estradiol-dependent activation of human T cell leukemia virus-I <protein>Tax</protein> leads to the inhibition of cell proliferation and to the induction of apoptosis .


The present study demonstrates that a hormone-dependent activation of Tax promotes an enhanced prooxidant state in stably transfected Jurkat cells as measured by changes in the intracellular levels of glutathione and H2O2 ; these changes are followed by apoptotic cell death .

The present study demonstrates that a hormone-dependent activation of <protein>Tax</protein> promotes an enhanced prooxidant state in <cell_line>stably transfected Jurkat cells</cell_line> as measured by changes in the intracellular levels of glutathione and H2O2 ; these changes are followed by apoptotic cell death .


Additional stimulation of the CD3 /TCR pathway enhances the oxidative and apoptotic effects .

Additional stimulation of the <protein>CD3</protein> <protein>/TCR</protein> pathway enhances the oxidative and apoptotic effects .


Both Tax -mediated apoptosis and oxidative stress can be potently suppressed by antioxidants , as is seen with the administration of recombinant thioredoxin ( adult T cell leukemia-derived factor ) or pyrrolidine dithiocarbamate .

Both <protein>Tax</protein> -mediated apoptosis and oxidative stress can be potently suppressed by antioxidants , as is seen with the administration of <protein>recombinant thioredoxin</protein> ( <protein>adult T cell leukemia-derived factor</protein> ) or pyrrolidine dithiocarbamate .


Hormone-induced Tax activation induces a long-lasting activation of NF-kappaB , which is a major target of reactive oxygen intermediates .

Hormone-induced <protein>Tax</protein> activation induces a long-lasting activation of <protein>NF-kappaB</protein> , which is a major target of reactive oxygen intermediates .


The long-term exposure of Jurkat cells to hormone eventually results in a selection of cell clones that have lost Tax activity .

The long-term exposure of <cell_line>Jurkat cells</cell_line> to hormone eventually results in a selection of <cell_line>cell clones</cell_line> that have lost <protein>Tax</protein> activity .


A subsequent transfection of these apparently `` nonresponsive '' clones allows the recovery of Tax responses in these cells .

A subsequent transfection of these apparently <cell_line>`` nonresponsive '' clones</cell_line> allows the recovery of <protein>Tax</protein> responses in these cells .


Our observations indicate that changes in the intracellular redox status may be a determining factor in Tax -mediated DNA damage , apoptosis , and selection against the long-term expression of Tax function .

Our observations indicate that changes in the intracellular redox status may be a determining factor in <protein>Tax</protein> -mediated DNA damage , apoptosis , and selection against the long-term expression of <protein>Tax</protein> function .


An allosteric drug , o , o'-bismyristoyl thiamine disulfide , suppresses HIV-1 replication through prevention of nuclear translocation of both HIV-1 Tat and NF-kappa B .

An allosteric drug , o , o'-bismyristoyl thiamine disulfide , suppresses HIV-1 replication through prevention of nuclear translocation of both <protein>HIV-1 Tat</protein> and <protein>NF-kappa B</protein> .


The efficacy of o , o'-bismyristoyl thiamine disulfide ( BMT ) was examined in detail against HIV-1 laboratory isolates ( HTLV-IIIB , JRFL , and MN ) , primary isolates ( KMT and KMO ) , and simian immunodeficiency virus ( SIVmac251 ) in vitro .


BMT inhibited the replication of HIV-1 in both laboratory and primary isolates in vitro .


In addition , BMT exhibited antiviral activity against SIVmac251 .


Minimizing energy studies of BMT structure reveal that a trans-disulfide of thiamine ( holo drug ) disulfide ( TDS , protodrug ) is allosterically transited to the reactive twisted disulfide of BMT ( allo drug ) by o , o'-bismyristoyl esterification of TDS .


BMT inhibits nuclear translocation of both HIV-1 transactivator ( TAT ) and the cellular transcriptional nuclear factor-KB ( NF-kappa B ) , resulting in the suppression of HIV-1 replication .

BMT inhibits nuclear translocation of both <protein>HIV-1 transactivator</protein> ( <protein>TAT</protein> ) and the <protein>cellular transcriptional nuclear factor-KB</protein> ( <protein>NF-kappa B</protein> ) , resulting in the suppression of HIV-1 replication .


Glucocorticoid-induced apoptosis and regulation of NF-kappaB activity in human leukemic T cells .

Glucocorticoid-induced apoptosis and regulation of <protein>NF-kappaB</protein> activity in <cell_type>human leukemic T cells</cell_type> .


Glucocorticoid-induced apoptosis was investigated in glucocorticoid-sensitive 6TG1.1 and resistant ICR27TK.3 human leukemic T cells .

Glucocorticoid-induced apoptosis was investigated in <cell_line>glucocorticoid-sensitive 6TG1.1</cell_line> and <cell_line>resistant ICR27TK.3</cell_line> <cell_type>human leukemic T cells</cell_type> .


Following glucocorticoid treatment of 6TG1.1 cells , chromatin fragmentation was observed after a delay of 24 h .

Following glucocorticoid treatment of <cell_line>6TG1.1 cells</cell_line> , <dna>chromatin</dna> fragmentation was observed after a delay of 24 h .


Fragmentation was not observed in ICR27TK.3 cells containing mutant glucocorticoid receptors ( L753F ) that are activation-deficient but retain the ability to repress AP-1 activity .

Fragmentation was not observed in <cell_line>ICR27TK.3 cells</cell_line> containing <protein>mutant glucocorticoid receptors</protein> ( <cell_line>L753F</cell_line> ) that are activation-deficient but retain the ability to repress <protein>AP-1</protein> activity .


Nor was fragmentation observed after treatment with RU38486 , indicating that repression of AP-1 activity is not involved .

Nor was fragmentation observed after treatment with RU38486 , indicating that repression of <protein>AP-1</protein> activity is not involved .


As described in other systems , fragmentation required ongoing protein synthesis .


However , inhibition of protein synthesis with cycloheximide anytime during the first 18 h of steroid treatment was as effective in blocking chromatin fragmentation as inhibition for the entire period , suggesting that synthesis of a component with a rapid turnover rate is required .


Dexamethasone treatment completely blocked 12-O-tetradecanoylphorbol 13-acetate induction of nuclear factor-kappaB ( NF-kappaB ) activity and elicited an increase in the amount of immunoreactive IkappaB alpha in sensitive 6TG1.1 cells but not in resistant ICR27TK.3 cells .

Dexamethasone treatment completely blocked 12-O-tetradecanoylphorbol 13-acetate induction of <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) activity and elicited an increase in the amount of <protein>immunoreactive IkappaB alpha</protein> in sensitive <cell_line>6TG1.1 cells</cell_line> but not in resistant <cell_line>ICR27TK.3 cells</cell_line> .


In addition , mild detergent treatment of cell extracts indicated that a substantial amount of cytoplasmic NF-kappaB is complexed with IkappaB alpha or some other inhibitory factor. These results suggest that induction of a labile inhibitory factor such as IkappaB alpha may contribute to glucocorticoid-induced apoptosis .

In addition , mild detergent treatment of cell extracts indicated that a substantial amount of <protein>cytoplasmic NF-kappaB</protein> is complexed with <protein>IkappaB alpha</protein> or some other inhibitory factor. These results suggest that induction of a <protein>labile inhibitory factor</protein> such as <protein>IkappaB alpha</protein> may contribute to glucocorticoid-induced apoptosis .


Inhibition of HIV-1 replication by combination of a novel inhibitor of TNF-alpha with AZT .

Inhibition of HIV-1 replication by combination of a novel inhibitor of <protein>TNF-alpha</protein> with AZT .


The small molecule S9a was derived from an established tumor necrosis factor-alpha ( TNF-alpha ) inhibitor ( Canventol ) by replacement of the isopropylidine group with a phenyl ring .

The small molecule S9a was derived from an established <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) inhibitor ( Canventol ) by replacement of the isopropylidine group with a phenyl ring .


S9a at 10 to 100 nM inhibited HIV production as potently as 3'-azido-3'-deoxythymidine ( AZT ) , an inhibitor of viral reverse transcriptase .

S9a at 10 to 100 nM inhibited HIV production as potently as 3'-azido-3'-deoxythymidine ( AZT ) , an inhibitor of <protein>viral reverse transcriptase</protein> .


Furthermore , S9a and AZT in combination , at noncytoxic concentrations strongly inhibited HIV-1 replication that was more than additive and substantially prolonged the appearance of virus both in acutely infected CD4+ lymphocytes ( SupT ) in culture and in peripheral blood mononuclear cells ( PBMCs ) infected with a primary HIV-1 isolate .

Furthermore , S9a and AZT in combination , at noncytoxic concentrations strongly inhibited HIV-1 replication that was more than additive and substantially prolonged the appearance of virus both in <cell_type>acutely infected CD4+ lymphocytes</cell_type> ( <cell_line>SupT</cell_line> ) in culture and in <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) infected with a primary HIV-1 isolate .


S9a inhibited TNF-alpha promoter-driven reporter gene activity .

S9a inhibited <protein>TNF-alpha</protein> promoter-driven <dna>reporter gene</dna> activity .


It was proposed that the mechanism of antiviral action of S9a was on the host cell , by blocking TNF-alpha transcription via a Tat -induced tar-independent loop , which decreases downstream NF-kappaB activation of HIV-1 long terminal repeat ( LTR ) .

It was proposed that the mechanism of antiviral action of S9a was on the host cell , by blocking <protein>TNF-alpha</protein> transcription via a <protein>Tat</protein> -induced tar-independent loop , which decreases downstream <protein>NF-kappaB</protein> activation of <dna>HIV-1 long terminal repeat</dna> ( <dna>LTR</dna> ) .


S9a was superior to the first generation compound Canventol , which was superior to the natural compound sarcophytol A , demonstrating that further structure-based enhancement of potency of these compounds is feasible .


This study suggests a therapeutic approach against AIDS by application of two drugs , one against a cellular and the other a viral target , which may provide an approach to the problem of frequent emergence of resistant variants to combinations of drugs that target only HIV genes .

This study suggests a therapeutic approach against AIDS by application of two drugs , one against a cellular and the other a viral target , which may provide an approach to the problem of frequent emergence of resistant variants to combinations of drugs that target only <dna>HIV genes</dna> .


Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells .

Highly polarized <protein>HLA class II antigen</protein> processing and presentation by <cell_type>human intestinal epithelial cells</cell_type> .


The high concentration of foreign antigen in the lumen of the gastrointestinal tract is separated from the underlying lymphocytes by a single cell layer of polarized epithelium .

The high concentration of <protein>foreign antigen</protein> in the <cell_type>lumen</cell_type> of the gastrointestinal tract is separated from the underlying <cell_type>lymphocytes</cell_type> by a single cell layer of polarized epithelium .


Intestinal epithelial cells can express HLA class II antigens and may function as antigen-presenting cells to CD4 ( + ) T cells within the intestinal mucosa .

<cell_type>Intestinal epithelial cells</cell_type> can express <protein>HLA class II antigens</protein> and may function as <cell_type>antigen-presenting cells to CD4 ( + ) T cells</cell_type> within the intestinal mucosa .


Using tetanus toxoid specific and HLA-DR-restricted T lymphocytes , we show that polarized intestinal epithelial cells directed to express HLA-DR molecules are able to initiate class II processing only after internalization of antigen from their apical surface .

Using <cell_type>tetanus toxoid specific and HLA-DR-restricted T lymphocytes</cell_type> , we show that <cell_type>polarized intestinal epithelial cells</cell_type> directed to express <protein>HLA-DR molecules</protein> are able to initiate class II processing only after internalization of antigen from their apical surface .


Coexpression of the class II transactivator CIITA in these cells , which stimulates highly efficient class II processing without the characteristic decline in barrier function seen in polarized monolayers treated with the proinflammatory cytokine gamma-IFN , facilitates antigen processing from the basolateral surface .

Coexpression of the <protein>class II transactivator CIITA</protein> in these cells , which stimulates highly efficient class II processing without the characteristic decline in barrier function seen in polarized monolayers treated with the <protein>proinflammatory cytokine gamma-IFN</protein> , facilitates antigen processing from the basolateral surface .


In both cases , peptide presentation to T cells via class II molecules was restricted to the basolateral surface .

In both cases , peptide presentation to <cell_type>T cells</cell_type> via <protein>class II molecules</protein> was restricted to the basolateral surface .


These data indicate a highly polarized functional architecture for antigen processing and presentation by intestinal epithelial cells , and suggest that the functional outcome of antigen processing by the intestinal epithelium is both dependent on the cellular surface at which the foreign antigen is internalized and by the underlying degree of mucosal inflammation

These data indicate a highly polarized functional architecture for antigen processing and presentation by <cell_type>intestinal epithelial cells</cell_type> , and suggest that the functional outcome of antigen processing by the intestinal epithelium is both dependent on the cellular surface at which the foreign antigen is internalized and by the underlying degree of mucosal inflammation


Tobacco smoke induces coordinate activation of HSF and inhibition of NFkappaB in human monocytes : effects on TNFalpha release .

Tobacco smoke induces coordinate activation of <protein>HSF</protein> and inhibition of <protein>NFkappaB</protein> in <cell_type>human monocytes</cell_type> : effects on <protein>TNFalpha</protein> release .


Tobacco smoke ( TS ) exposure is a major risk factor for human disease , and macrophages of healthy smokers have a depressed capacity to release cytokines , including tumor necrosis factor ( TNF ) alpha .

Tobacco smoke ( TS ) exposure is a major risk factor for human disease , and <cell_type>macrophages</cell_type> of healthy smokers have a depressed capacity to release <protein>cytokines</protein> , including <protein>tumor necrosis factor ( TNF ) alpha</protein> .


TS induces the synthesis of heat shock ( HS ) /stress proteins ( HSP ) , and , in particular , of Hsp70 .

TS induces the synthesis of <protein>heat shock ( HS ) /stress proteins</protein> ( <protein>HSP</protein> ) , and , in particular , of <protein>Hsp70</protein> .


We determined whether Hsp70 induction by TS was mediated by the activation of the HS transcription factor , HSF .

We determined whether <protein>Hsp70</protein> induction by TS was mediated by the activation of the <protein>HS transcription factor</protein> , <protein>HSF</protein> .


HSF activation has been shown to inhibit NFkappaB .

<protein>HSF</protein> activation has been shown to inhibit <protein>NFkappaB</protein> .


Thus , we also determined the effects of TS on NFkappaB .

Thus , we also determined the effects of TS on <protein>NFkappaB</protein> .


U937 cells and human peripheral blood monocytes were exposed to TS , binding activities of the respective transcription factors were analyzed , and Hsp70 expression and TNFalpha release were determined in parallel .

<cell_line>U937 cells</cell_line> and <cell_type>human peripheral blood monocytes</cell_type> were exposed to TS , binding activities of the respective <protein>transcription factors</protein> were analyzed , and <protein>Hsp70</protein> expression and <protein>TNFalpha</protein> release were determined in parallel .


TS activated HSF , which was associated with Hsp70 overexpression and inhibition of NFkappaB binding activity and TNFalpha release .

TS activated <protein>HSF</protein> , which was associated with <protein>Hsp70</protein> overexpression and inhibition of <protein>NFkappaB</protein> binding activity and <protein>TNFalpha</protein> release .


The altered cytokine profile observed in smokers may relate to an HSF / Hsp70 -mediated inhibition of NFkappaB activity .

The altered <protein>cytokine profile</protein> observed in smokers may relate to an <protein>HSF</protein> / <protein>Hsp70</protein> -mediated inhibition of <protein>NFkappaB</protein> activity .


Copyright 1998 Academic Press .


[ Molecular mechanism of cytokine gene expression in Th1 and Th2 ]

[ Molecular mechanism of <dna>cytokine gene</dna> expression in <cell_line>Th1</cell_line> and <cell_line>Th2</cell_line> ]


Upon activation by antigens , helper T cells differentiate into one of several subsets , characterized by their distinct cytokine -production patterns .

Upon activation by <protein>antigens</protein> , <cell_type>helper T cells</cell_type> differentiate into one of several subsets , characterized by their distinct <protein>cytokine</protein> -production patterns .


Among these subsets , Th1 cells are known to activate cellular immunity resulting in inflammatory response , whereas Th2 cells induce humoral and allergic responses and suppress inflammation .

Among these subsets , <cell_line>Th1 cells</cell_line> are known to activate cellular immunity resulting in inflammatory response , whereas <cell_line>Th2 cells</cell_line> induce humoral and allergic responses and suppress inflammation .


Th1 and Th2 effector functions and their development are attributable to their distinct cytokine expression patterns .

Th1 and Th2 effector functions and their development are attributable to their distinct <protein>cytokine</protein> expression patterns .


Recent reports have demonstrated that differential expression of cell surface molecules , such as adhesion molecule and chemokine receptor , is involved in their recruitment into target tissues .

Recent reports have demonstrated that differential expression of cell surface molecules , such as <protein>adhesion molecule</protein> and <protein>chemokine receptor</protein> , is involved in their recruitment into target tissues .


It is , therefore , suggested that clarification of the mechanisms of differential gene expression in Th1/Th2 should lead to rational strategies for manipulating pathological immune responses .

It is , therefore , suggested that clarification of the mechanisms of differential gene expression in <cell_line>Th1/Th2</cell_line> should lead to rational strategies for manipulating pathological immune responses .


Activation of helper T cells mediated by the T cell receptor induces a series of biochemical events .

Activation of <cell_type>helper T cells</cell_type> mediated by the T cell receptor induces a series of biochemical events .


Among them , both the activation of PKC/Ras- and CaM/CN-mediated pathways play a central role in the signal transduction of cytokine gene expression .

Among them , both the activation of PKC/Ras- and CaM/CN-mediated pathways play a central role in the signal transduction of <dna>cytokine gene</dna> expression .


Closer examination using non-transformed murine Th1 and Th2 clones suggested that a balance between the activities of the two signaling pathways contributes to cytokine gene expression .

Closer examination using <cell_line>non-transformed murine Th1 and Th2 clones</cell_line> suggested that a balance between the activities of the two signaling pathways contributes to <dna>cytokine gene</dna> expression .


We propose that one of the targets of PGE2 , whose effect distinguishes Th1 from Th2 , resides in the downstream PKC/Ras -mediated pathway .

We propose that one of the targets of PGE2 , whose effect distinguishes <cell_line>Th1</cell_line> from Th2 , resides in the downstream <protein>PKC/Ras</protein> -mediated pathway .


Signalling into the T-cell nucleus : NFAT regulation .

Signalling into the T-cell nucleus : <protein>NFAT</protein> regulation .


The nuclear factor of activated T cells ( NFAT ) plays an important role in T-cell biology .

The <protein>nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) plays an important role in T-cell biology .


Activation of T cells results in the rapid calcineurin -dependent translocation of NFAT transcription factors from the cytoplasm to the nucleus .

Activation of T cells results in the rapid <protein>calcineurin</protein> -dependent translocation of <protein>NFAT</protein> <protein>transcription factors</protein> from the cytoplasm to the nucleus .


This translocation process coupled to the subsequent active maintenance of NFAT in the nucleus compartment is critical for the induction of expression of several genes encoding cytokines and membrane proteins that modulate immune responses .

This translocation process coupled to the subsequent active maintenance of <protein>NFAT</protein> in the nucleus compartment is critical for the induction of expression of several genes encoding <protein>cytokines</protein> and <protein>membrane proteins</protein> that modulate immune responses .


The molecular cloning of the NFAT family of transcription factors has facilitated rapid progress in the understanding of the signalling mechanisms that control the activity of NFAT .

The molecular cloning of the <protein>NFAT family</protein> of <protein>transcription factors</protein> has facilitated rapid progress in the understanding of the signalling mechanisms that control the activity of <protein>NFAT</protein> .


Differential RNA display identifies novel genes associated with decreased vitamin D receptor expression .

Differential RNA display identifies <dna>novel genes</dna> associated with decreased <protein>vitamin D receptor</protein> expression .


To characterize further the function of the intracellular vitamin D receptor ( VDR ) , we have developed stable transfectant variants of a vitamin D-responsive cell line ( U937 ) which express either decreased or increased numbers of VDR .

To characterize further the function of the <protein>intracellular vitamin D receptor</protein> ( <protein>VDR</protein> ) , we have developed <cell_line>stable transfectant variants</cell_line> of a <cell_line>vitamin D-responsive cell line</cell_line> ( <cell_line>U937</cell_line> ) which express either decreased or increased numbers of <protein>VDR</protein> .


In this study we have analyzed changes in gene expression associated with this variable VDR expression .

In this study we have analyzed changes in gene expression associated with this variable <protein>VDR</protein> expression .


Initial experiments indicated that a 50 % decrease in VDR levels was associated with a 2-fold increase in cell proliferation and a similar rise in c-myc mRNA expression .

Initial experiments indicated that a 50 % decrease in <protein>VDR</protein> levels was associated with a 2-fold increase in cell proliferation and a similar rise in <rna>c-myc mRNA</rna> expression .


Further studies were carried out using differential RNA display ( DD ) .


Sequence analysis of DD products revealed two cDNAs with identity to known gene products : the catalytic sub-unit of DNA-protein kinase ( DNA-PK ( CS ) ) , and the peroxisomal enzyme 17beta-hydroxysteroid dehydrogenase type IV ( 17beta-HSD IV ) .

Sequence analysis of <protein>DD products</protein> revealed two <dna>cDNAs</dna> with identity to <protein>known gene products</protein> : the <protein>catalytic sub-unit of DNA-protein kinase</protein> ( <protein>DNA-PK ( CS )</protein> ) , and the <protein>peroxisomal enzyme 17beta-hydroxysteroid dehydrogenase type IV</protein> ( <protein>17beta-HSD IV</protein> ) .


Northern analysis confirmed that expression of both mRNAs was reduced in cells with decreased numbers of VDR .

Northern analysis confirmed that expression of both <rna>mRNAs</rna> was reduced in cells with decreased numbers of <protein>VDR</protein> .


Down-regulation of 17beta-HSD IV mRNA expression was associated with enhanced estradiol inactivation by U937 cells , suggesting a link between estrogenic pathways and cell proliferation .

Down-regulation of <protein>17beta-HSD IV</protein> mRNA expression was associated with enhanced estradiol inactivation by <cell_line>U937 cells</cell_line> , suggesting a link between estrogenic pathways and cell proliferation .


Further Northern analyses indicated that there was no significant change in 17beta-HSD IV or DNA-PK ( CS ) mRNA levels following treatment with 1 , 25 ( OH ) 2D3 , although expression of both genes varied with changes in cell proliferation .

Further Northern analyses indicated that there was no significant change in <protein>17beta-HSD IV</protein> or <rna>DNA-PK ( CS ) mRNA</rna> levels following treatment with 1 , 25 ( OH ) 2D3 , although expression of both genes varied with changes in cell proliferation .


These data suggest that , in addition to its established role as a hormone-dependent trans-activator , VDR may influence gene expression by ligand-independent mechanisms .

These data suggest that , in addition to its established role as a <protein>hormone-dependent trans-activator</protein> , <protein>VDR</protein> may influence gene expression by ligand-independent mechanisms .


Prostaglandin E2 Up-regulates HIV-1 long terminal repeat -driven gene activity in T cells via NF-kappaB-dependent and -independent signaling pathways .

Prostaglandin E2 Up-regulates <dna>HIV-1 long terminal repeat</dna> -driven gene activity in <cell_type>T cells</cell_type> via NF-kappaB-dependent and -independent signaling pathways .


Replication of human immunodeficiency virus type-1 ( HIV-1 ) is highly dependent on the state of activation of the infected cells and is modulated by interactions between viral and host cellular factors .

Replication of human immunodeficiency virus type-1 ( HIV-1 ) is highly dependent on the state of activation of the <cell_type>infected cells</cell_type> and is modulated by interactions between <protein>viral and host cellular factors</protein> .


Prostaglandin E2 ( PGE2 ) , a pleiotropic immunomodulatory molecule , is observed at elevated levels during HIV-1 infection as well as during the course of other pathogenic infections .

Prostaglandin E2 ( PGE2 ) , a <protein>pleiotropic immunomodulatory molecule</protein> , is observed at elevated levels during HIV-1 infection as well as during the course of other pathogenic infections .


In 1G5 , a Jurkat-derived T cell line stably transfected with a luciferase gene driven by HIV-1 long terminal repeat ( LTR ) , we found that PGE2 markedly enhanced HIV-1 LTR -mediated reporter gene activity .

In <cell_line>1G5</cell_line> , a <cell_line>Jurkat-derived T cell line</cell_line> stably transfected with a <dna>luciferase gene</dna> driven by <dna>HIV-1 long terminal repeat</dna> ( <dna>LTR</dna> ) , we found that PGE2 markedly enhanced <dna>HIV-1 LTR</dna> -mediated <dna>reporter gene</dna> activity .


Experiments have been conducted to identify second messengers involved in this PGE2-dependent up-regulating effect on the regulatory element of HIV-1 .

Experiments have been conducted to identify <protein>second messengers</protein> involved in this PGE2-dependent up-regulating effect on the regulatory element of HIV-1 .


In this study , we present evidence indicating that signal transduction pathways induced by PGE2 necessitate the participation of cyclic AMP , protein kinase A , and Ca2+ .

In this study , we present evidence indicating that signal transduction pathways induced by PGE2 necessitate the participation of cyclic AMP , <protein>protein kinase A</protein> , and Ca2+ .


Experiments conducted with different HIV-1 LTR-based vectors suggested that PGE2-mediated activation effect on HIV-1 transcription was transduced via both NF-kappaB-dependent and -independent signaling pathways .

Experiments conducted with different <dna>HIV-1 LTR-based vectors</dna> suggested that PGE2-mediated activation effect on HIV-1 transcription was transduced via both NF-kappaB-dependent and -independent signaling pathways .


The involvement of NF-kappaB in the PGE2-dependent activating effect on HIV-1 transcription was further confirmed using a kappaB-regulated luciferase encoding vector and by electrophoretic mobility shift assays .

The involvement of <protein>NF-kappaB</protein> in the PGE2-dependent activating effect on HIV-1 transcription was further confirmed using a <dna>kappaB-regulated luciferase encoding vector</dna> and by electrophoretic mobility shift assays .


Results from Northern blot and flow cytometric analyses , as well as the use of a selective antagonist indicated that PGE2 modulation of HIV-1 LTR -driven reporter gene activity in studied T lymphoid cells is transduced via the EP4 receptor subtype .

Results from Northern blot and flow cytometric analyses , as well as the use of a selective antagonist indicated that PGE2 modulation of <dna>HIV-1 LTR</dna> -driven <dna>reporter gene</dna> activity in studied <cell_type>T lymphoid cells</cell_type> is transduced via the <protein>EP4 receptor subtype</protein> .


These results suggest that secretion of PGE2 by macrophages in response to infection or inflammatory activators could induce signaling events resulting in activation of proviral DNA present into T cells latently infected with HIV-1 .

These results suggest that secretion of PGE2 by <cell_type>macrophages</cell_type> in response to infection or inflammatory activators could induce signaling events resulting in activation of proviral DNA present into <cell_type>T cells</cell_type> latently infected with HIV-1 .


Activation of distinct transcription factors in neutrophils by bacterial LPS , interferon-gamma , and GM-CSF and the necessity to overcome the action of endogenous proteases .

Activation of distinct <protein>transcription factors</protein> in <cell_type>neutrophils</cell_type> by bacterial LPS , <protein>interferon-gamma</protein> , and <protein>GM-CSF</protein> and the necessity to overcome the action of <protein>endogenous proteases</protein> .


Human neutrophils can be induced to actively transcribe a number of early-response genes , in particular those encoding cytokines , chemokines , and the high-affinity surface receptor for IgG , FcgammaRI .

Human <cell_type>neutrophils</cell_type> can be induced to actively transcribe a number of <dna>early-response genes</dna> , in particular those encoding <protein>cytokines</protein> , <protein>chemokines</protein> , and the high-affinity surface receptor for <protein>IgG</protein> , <protein>FcgammaRI</protein> .


Although little is known to date about the regulation of gene transcription in neutrophils , several indications point to a role for distinct transcription factors , such as members of the NF-kappaB and STAT families .

Although little is known to date about the regulation of gene transcription in <cell_type>neutrophils</cell_type> , several indications point to a role for distinct <protein>transcription factors</protein> , such as members of the <protein>NF-kappaB</protein> and <protein>STAT families</protein> .


In this study , we investigated whether these transcription factors become activated under stimulatory conditions which are known to induce gene transcription in neutrophils .

In this study , we investigated whether these <protein>transcription factors</protein> become activated under stimulatory conditions which are known to induce gene transcription in <cell_type>neutrophils</cell_type> .


Unexpectedly , we found that conventional procedures employed to prepare cellular extracts cause the release of proteolytic activities that are normally stored in intracellular granules , resulting in the degradation of various NF-kappaB/Rel and STAT proteins .

Unexpectedly , we found that conventional procedures employed to prepare cellular extracts cause the release of proteolytic activities that are normally stored in intracellular granules , resulting in the degradation of various <protein>NF-kappaB/Rel</protein> and <protein>STAT proteins</protein> .


To circumvent this problem , we developed an alternative procedure which allowed us to show that in neutrophils , LPS and TNFalpha induce a NF-kappaB DNA-binding activity which essentially consists of p50/RelA dimers , and that IFNgamma promotes the binding of STAT1 homodimers to the IFNgamma response region of the FcgammaRI promoter .

To circumvent this problem , we developed an alternative procedure which allowed us to show that in <cell_type>neutrophils</cell_type> , LPS and <protein>TNFalpha</protein> induce a <protein>NF-kappaB</protein> DNA-binding activity which essentially consists of <protein>p50/RelA dimers</protein> , and that <protein>IFNgamma</protein> promotes the binding of <protein>STAT1 homodimers</protein> to the <dna>IFNgamma response region</dna> of the <dna>FcgammaRI promoter</dna> .


Moreover , we report that neutrophil stimulation with GM-CSF results in the formation of a STAT5 -containing DNA-binding activity .

Moreover , we report that neutrophil stimulation with <protein>GM-CSF</protein> results in the formation of a <protein>STAT5</protein> -containing DNA-binding activity .


Collectively , the current findings open new perspectives about mechanisms that are likely to regulate gene transcription in neutrophils .

Collectively , the current findings open new perspectives about mechanisms that are likely to regulate gene transcription in <cell_type>neutrophils</cell_type> .


In addition , the procedure described herein could prove useful in other cell types that express high levels of endogenous proteases .

In addition , the procedure described herein could prove useful in other cell types that express high levels of <protein>endogenous proteases</protein> .


Low CD3+CD28-induced interleukin-2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells .

Low CD3+CD28-induced <protein>interleukin-2</protein> production correlates with decreased reactive oxygen intermediate formation in <cell_type>neonatal T cells</cell_type> .


The capacity of neonatal T cells to secrete interleukin-2 ( IL-2 ) has been reported to be variable .

The capacity of <cell_type>neonatal T cells</cell_type> to secrete <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) has been reported to be variable .


We analysed IL-2 production in purified neonatal and adult T cells using polyclonal activator phorbol ester + calcium ionophore ( PDBu + iono ) or receptor-mediated anti-CD3 /anti-CD3+ anti-CD28 stimulation .

We analysed <protein>IL-2</protein> production in purified <cell_type>neonatal and adult T cells</cell_type> using polyclonal activator phorbol ester + calcium ionophore ( PDBu + iono ) or receptor-mediated <protein>anti-CD3</protein> /anti-CD3+ <protein>anti-CD28</protein> stimulation .


PDBu + iono induced equally high IL-2 levels in both groups and , when stimulated with plate-bound anti-CD3 monoclonal antibody ( mAb ) , the IL-2 secretion by neonatal cells was undetectable and adult cells produced low amounts of IL-2 ( mean 331 +/- 86 pg/ml ) .

PDBu + iono induced equally high <protein>IL-2</protein> levels in both groups and , when stimulated with plate-bound <protein>anti-CD3 monoclonal antibody</protein> ( <protein>mAb</protein> ) , the <protein>IL-2</protein> secretion by <cell_type>neonatal cells</cell_type> was undetectable and <cell_type>adult cells</cell_type> produced low amounts of <protein>IL-2</protein> ( mean 331 +/- 86 pg/ml ) .


The addition of anti-CD28 mAb to anti-CD3-stimulated cells markedly increased IL-2 production in both cell types , but levels of IL-2 in neonatal T cells remained clearly lower than those of adult T cells ( respective mean values : 385 +/- 109 pg/ml and 4494 +/- 1199 pg/ml ) .

The addition of <protein>anti-CD28 mAb</protein> to <cell_line>anti-CD3-stimulated cells</cell_line> markedly increased <protein>IL-2</protein> production in both cell types , but levels of <protein>IL-2</protein> in <cell_type>neonatal T cells</cell_type> remained clearly lower than those of <cell_type>adult T cells</cell_type> ( respective mean values : 385 +/- 109 pg/ml and 4494 +/- 1199 pg/ml ) .


As NF-kappa B is a critical transcription factor in the control of IL-2 expression , we next analysed its nuclear translocation in neonatal and adult T cells using the electrophoretic mobility shift assay and , because induction of reactive oxygen intermediates ( ROI ) is required for the activation of NF-kappa B , we also analysed levels of intracellular ROI in these cells using the ROI-reactive fluorochrome DCFH-DA and flow cytometry .

As <protein>NF-kappa B</protein> is a critical <protein>transcription factor</protein> in the control of <protein>IL-2</protein> expression , we next analysed its nuclear translocation in <cell_type>neonatal and adult T cells</cell_type> using the electrophoretic mobility shift assay and , because induction of reactive oxygen intermediates ( ROI ) is required for the activation of <protein>NF-kappa B</protein> , we also analysed levels of intracellular ROI in these cells using the ROI-reactive fluorochrome DCFH-DA and flow cytometry .


In neonatal T cells NF-kappa B activation and ROI formation after anti-CD3 stimulation were low compared with adult T cells and , although addition of anti-CD28 mAb increased induction of NF-kappa B and ROI formation , levels similar to those of adults were not achieved .

In <cell_type>neonatal T cells</cell_type> <protein>NF-kappa B</protein> activation and ROI formation after <protein>anti-CD3</protein> stimulation were low compared with <cell_type>adult T cells</cell_type> and , although addition of <protein>anti-CD28 mAb</protein> increased induction of <protein>NF-kappa B</protein> and ROI formation , levels similar to those of adults were not achieved .


After PDBu + iono stimulation , the cells showed similar ROI formation and IL-2 secretion .

After PDBu + iono stimulation , the cells showed similar ROI formation and <protein>IL-2</protein> secretion .


Our results suggest that reduced IL-2 production by neonatal T cells is specific for anti-CD3 and anti-CD3 + anti-CD28 -mediated stimulation and that these activators can not effectively activate the ROI -NF-kappa B signalling pathway in neonatal T cells .

Our results suggest that reduced <protein>IL-2</protein> production by <cell_type>neonatal T cells</cell_type> is specific for <protein>anti-CD3</protein> and <protein>anti-CD3</protein> + <protein>anti-CD28</protein> -mediated stimulation and that these activators can not effectively activate the ROI <protein>-NF-kappa B</protein> signalling pathway in <cell_type>neonatal T cells</cell_type> .


CD30 is a CD40-inducible molecule that negatively regulates CD40-mediated immunoglobulin class switching in non-antigen-selected human B cells .

<protein>CD30</protein> is a <protein>CD40-inducible molecule</protein> that negatively regulates <protein>CD40-mediated immunoglobulin</protein> class switching in <cell_line>non-antigen-selected human B cells</cell_line> .


We used our monoclonal model of germinal center maturation , CL-01 B cells , to investigate the role of CD30 in human B cell differentiation .

We used our monoclonal model of germinal center maturation , <cell_type>CL-01 B cells</cell_type> , to investigate the role of <protein>CD30</protein> in human B cell differentiation .


CL-01 cells are IgM + IgD + CD30 + and switch to IgG , IgA , and IgE when exposed to CD40L and IL-4 .

<cell_line>CL-01 cells</cell_line> are <protein>IgM</protein> + <protein>IgD</protein> + <protein>CD30</protein> + and switch to <protein>IgG</protein> , <protein>IgA</protein> , and <protein>IgE</protein> when exposed to <protein>CD40L</protein> and <protein>IL-4</protein> .


Switching is hampered by CD30 coengagement , possibly through interference with the CD40 -mediated NF-kappaB -dependent transcriptional activation of downstream C ( H ) genes .

Switching is hampered by <protein>CD30</protein> coengagement , possibly through interference with the <protein>CD40</protein> -mediated <protein>NF-kappaB</protein> -dependent transcriptional activation of <dna>downstream C ( H ) genes</dna> .


The physiological relevance of this phenomenon is emphasized by similar CD30 -mediated effects in naive B cells .

The physiological relevance of this phenomenon is emphasized by similar <protein>CD30</protein> -mediated effects in <cell_type>naive B cells</cell_type> .


Expression of CD30 by these cells is induced by CD40L but is inhibited by B cell receptor coengagement and/or exposure to IL-6 and IL-12 .

Expression of <protein>CD30</protein> by these cells is induced by <protein>CD40L</protein> but is inhibited by B cell receptor coengagement and/or exposure to <protein>IL-6</protein> and <protein>IL-12</protein> .


Our data suggest that CD30 critically regulates the CD40 -mediated differentiation of non-antigen-selected human B cells .

Our data suggest that <protein>CD30</protein> critically regulates the <protein>CD40</protein> -mediated differentiation of <cell_line>non-antigen-selected human B cells</cell_line> .


Calcineurin and the biological effect of cyclosporine and tacrolimus .

<protein>Calcineurin</protein> and the biological effect of cyclosporine and tacrolimus .


The mechanism of the immunosuppressive effect of CyA and FK 506 can be monitored in vivo in humans .


The picture emerging is of a close relationship between drug concentrations and CN inhibition .


But many puzzles of the drugs remain .


What is the role of CyA in the activation of transforming growth factor-beta ( TGF-beta ) , particularly in relationship to nephrotoxicity and fibrogenesis ?

What is the role of CyA in the activation of <protein>transforming growth factor-beta</protein> ( <protein>TGF-beta</protein> ) , particularly in relationship to nephrotoxicity and fibrogenesis ?


How important are the anti-inflammatory ( non T ) effects of CyA , and which cells do they operate in ?


Are there effects of CyA and FK 506 all attributable to CN inhibition , and how much of them are mediated through the NFATC family of transcription factors ?

Are there effects of CyA and FK 506 all attributable to CN inhibition , and how much of them are mediated through the <protein>NFATC family</protein> of <protein>transcription factors</protein> ?


Finally , it would be useful to know what the inhibitory effects of CyA are on tolerance and negative regulatory events .


Stimulation of B and T cells activates expression of transcription and differentiation factors .

Stimulation of <cell_type>B and T cells</cell_type> activates expression of <protein>transcription and differentiation factors</protein> .


During B and T cell differentiation and proliferation many genes are induced or repressed while certain genes are constitutively expressed .


To investigate processes related to B and T cell activation , the gene expression of stimulated and nonstimulated Ramos and Jurkat cells was studied using cDNA microarray technology .

To investigate processes related to B and T cell activation , the gene expression of stimulated and <cell_line>nonstimulated Ramos and Jurkat cells</cell_line> was studied using cDNA microarray technology .


Simultaneous analysis of close to 600 genes indicated highest increase in the expression of certain transcription , differentiation and proliferation factors .

Simultaneous analysis of close to <dna>600 genes</dna> indicated highest increase in the expression of certain <protein>transcription , differentiation and proliferation factors</protein> .


Many of these genes have not previously been shown to funcion in the stimulated lymphocytes .

Many of these genes have not previously been shown to funcion in the <cell_type>stimulated lymphocytes</cell_type> .


Also genes encoding proteins involved in DNA replication , binding , transcription and translation were induced .


Large part of the activated genes were under very stringent regulation being expressed only after stimulation .

Large part of the <dna>activated genes</dna> were under very stringent regulation being expressed only after stimulation .


The mechanism and function of the expressed genes during lymphocyte differentiation and in disorders is discussed .

The mechanism and function of the <dna>expressed genes</dna> during lymphocyte differentiation and in disorders is discussed .


Interleukin 2 and 15 activate Stat3alpha in human T lymphocytes .

<protein>Interleukin 2 and 15</protein> activate <protein>Stat3alpha</protein> in <cell_type>human T lymphocytes</cell_type> .


Signal transducer and activator of transcription 3 ( Stat3 ) has recently been shown to exist in two alternatively spliced isoforms , a short form , Stat3beta , and a longer form , Stat3alpha , displaying differences in transcriptional activity .

<protein>Signal transducer and activator of transcription 3</protein> ( <protein>Stat3</protein> ) has recently been shown to exist in two alternatively spliced isoforms , a short form , <protein>Stat3beta</protein> , and a longer form , <protein>Stat3alpha</protein> , displaying differences in transcriptional activity .


It is unknown which Stat3 isoform ( s ) is activated in response to interleukin ( IL ) -2 and IL-15 .

It is unknown which <protein>Stat3 isoform</protein> ( s ) is activated in response to <protein>interleukin ( IL ) -2</protein> and <protein>IL-15</protein> .


Here , cytokine -induced activation of Stat3 in previously activated CD4 ( + ) human T cells was examined using Stat3 antibodies directed against different regions of Stat3 .

Here , <protein>cytokine</protein> -induced activation of <protein>Stat3</protein> in previously activated <cell_type>CD4 ( + ) human T cells</cell_type> was examined using <protein>Stat3</protein> antibodies directed against different regions of <protein>Stat3</protein> .


As determined by tyrosine phosphorylation , nuclear translocation and binding to an hSIE-oligonucleotide probe , IL-2 and IL-15 activated the slowly migrating isoform , Stat3alpha .

As determined by tyrosine phosphorylation , nuclear translocation and binding to an hSIE-oligonucleotide probe , <protein>IL-2</protein> and <protein>IL-15</protein> activated the slowly migrating isoform , <protein>Stat3alpha</protein> .


In contrast , minimal or no activation of Stat3beta was observed , suggesting that IL-2 and IL-15 predominantly activate Stat3alpha in human CD4 ( + ) T cells .

In contrast , minimal or no activation of <protein>Stat3beta</protein> was observed , suggesting that <protein>IL-2</protein> and <protein>IL-15</protein> predominantly activate <protein>Stat3alpha</protein> in <cell_type>human CD4 ( + ) T cells</cell_type> .


In this way , diversity in the expression and activation of Stat3 proteins may provide additional means of regulating cytokine -induced T cell responses .

In this way , diversity in the expression and activation of <protein>Stat3 proteins</protein> may provide additional means of regulating <protein>cytokine</protein> -induced T cell responses .


Copyright 1998 Academic Press .


Transcriptional regulation of lysosomal acid lipase in differentiating monocytes is mediated by transcription factors Sp1 and AP-2 .

Transcriptional regulation of <protein>lysosomal acid lipase</protein> in differentiating monocytes is mediated by <protein>transcription factors</protein> <protein>Sp1</protein> and <protein>AP-2</protein> .


Human lysosomal acid lipase ( LAL ) is a hydrolase required for the cleavage of cholesteryl esters and triglycerides derived from plasma lipoproteins .

Human <protein>lysosomal acid lipase</protein> ( <protein>LAL</protein> ) is a <protein>hydrolase</protein> required for the cleavage of cholesteryl esters and triglycerides derived from plasma lipoproteins .


It is shown here that during monocyte to macrophage differentiation , the expression of LAL-mRNA is induced .

It is shown here that during monocyte to macrophage differentiation , the expression of <rna>LAL-mRNA</rna> is induced .


This induction is dependent on protein kinase C activity and protein synthesis .

This induction is dependent on <protein>protein kinase C</protein> activity and protein synthesis .


The cell type-specific increase in LAL expression is further investigated in the THP-1 cell line with respect to transcriptional regulation .

The cell type-specific increase in <protein>LAL</protein> expression is further investigated in the <cell_line>THP-1 cell line</cell_line> with respect to transcriptional regulation .


The human monocytic leukemia cell line THP-1 differentiates into macrophage-like cells when treated with phorbol esters .

The <cell_line>human monocytic leukemia cell line</cell_line> <cell_line>THP-1</cell_line> differentiates into <cell_type>macrophage-like cells</cell_type> when treated with phorbol esters .


In order to determine the cis-acting elements necessary for both basal and phorbol 12-myristate-13 acetate ( PMA ) -enhanced promoter activity , we performed deletion analysis and reporter gene assays .

In order to determine the <dna>cis-acting elements</dna> necessary for both basal and phorbol 12-myristate-13 acetate ( PMA ) -enhanced promoter activity , we performed deletion analysis and <dna>reporter gene</dna> assays .


A PMA responsive element has been identified between -182 bp and -107 bp upstream of the major transcription start site .

A <dna>PMA responsive element</dna> has been identified between <dna>-182 bp</dna> and <dna>-107 bp</dna> upstream of the <dna>major transcription start site</dna> .


Gel mobility shift assays demonstrated that binding of Sp1 and AP-2 to the LAL promoter is increased by PMA in THP-1 cells .

Gel mobility shift assays demonstrated that binding of <protein>Sp1</protein> and <protein>AP-2</protein> to the <dna>LAL promoter</dna> is increased by PMA in <cell_line>THP-1 cells</cell_line> .


Co-transfections with expression plasmids for Sp1 and AP-2 further emphasized the important role of these transcription factors in both basal and PMA-enhanced LAL expression .

Co-transfections with <dna>expression plasmids</dna> for <protein>Sp1</protein> and <protein>AP-2</protein> further emphasized the important role of these <protein>transcription factors</protein> in both basal and PMA-enhanced <protein>LAL</protein> expression .


Our data suggest that differentiation dependent increase of lysosomal acid lipase ( LAL ) expression in THP-1 cells is mediated by a concerted action of Sp1 and AP-2 .

Our data suggest that differentiation dependent increase of <protein>lysosomal acid lipase</protein> ( <protein>LAL</protein> ) expression in <cell_line>THP-1 cells</cell_line> is mediated by a concerted action of <protein>Sp1</protein> and <protein>AP-2</protein> .


Relationship between IkappaBalpha constitutive expression , TNFalpha synthesis , and apoptosis in EBV-infected lymphoblastoid cells .

Relationship between <protein>IkappaBalpha</protein> constitutive expression , <protein>TNFalpha</protein> synthesis , and apoptosis in <cell_type>EBV-infected lymphoblastoid cells</cell_type> .


In order to understand the role of NF-kappaB in EBV transformation we have established stably transfected IkappaBalpha into lymphoblastoid cells .

In order to understand the role of <protein>NF-kappaB</protein> in EBV transformation we have established stably transfected <protein>IkappaBalpha</protein> into <cell_type>lymphoblastoid cells</cell_type> .


Two clones were obtained in which the loss of NF-kappaB binding activity correlated with the constitutive expression of the transgenic IkappaBalpha .

Two clones were obtained in which the loss of <protein>NF-kappaB</protein> binding activity correlated with the constitutive expression of the transgenic <protein>IkappaBalpha</protein> .


Protein latency expression was determined by immunocytochemistry .


Expression of surface markers , intracytoplasmic content of cytokines cell cycle analysis after BrdU incorporation and DNA staining with propidium iodide were studied by flow cytometry .

Expression of surface markers , intracytoplasmic content of <protein>cytokines</protein> cell cycle analysis after <protein>BrdU</protein> incorporation and DNA staining with propidium iodide were studied by flow cytometry .


Percentage of apoptotic cells was determined by in-situ labelling of DNA strand breaks .

Percentage of <cell_type>apoptotic cells</cell_type> was determined by in-situ labelling of DNA strand breaks .


No significative changes in EBV latency nor in cell surface marker expression was found .


In contrast , intracytoplasmic TNFalpha levels were strongly reduced in transfected clones .

In contrast , intracytoplasmic <protein>TNFalpha</protein> levels were strongly reduced in <cell_line>transfected clones</cell_line> .


Furthermore , 30 % of IkappaBalpha transfected cells were apoptotic after 8 h of TNFalpha treatment .

Furthermore , 30 % of <cell_line>IkappaBalpha transfected cells</cell_line> were apoptotic after 8 h of <protein>TNFalpha</protein> treatment .


This correlated with a strong reduction of BrdU incorporation after 24 h of TNFalpha treatment .

This correlated with a strong reduction of BrdU incorporation after 24 h of <protein>TNFalpha</protein> treatment .


No effect was seen with non transfected cells or with cells transfected with a control plasmid .

No effect was seen with non <cell_line>transfected cells</cell_line> or with cells transfected with a control plasmid .


Our results suggest that the TNFalpha gene could be one of the targets of NF-kappaB in EBV infected cells and that NF-kappaB protects EBV-infected cells from apoptosis induced by TNFalpha , which may favour the proliferative effect of this cytokine .

Our results suggest that the <dna>TNFalpha gene</dna> could be one of the targets of <protein>NF-kappaB</protein> in EBV infected cells and that <cell_type>NF-kappaB protects EBV-infected cells</cell_type> from apoptosis induced by <protein>TNFalpha</protein> , which may favour the proliferative effect of this <protein>cytokine</protein> .


Seminoma in a postmenopausal woman with a Y ; 15 translocation in peripheral blood lymphocytes and a t ( Y ; 15 ) /45 , X Turner mosaic pattern in skin fibroblasts .

Seminoma in a postmenopausal woman with a <dna>Y ; 15 translocation</dna> in <cell_type>peripheral blood lymphocytes</cell_type> and a t ( Y ; 15 ) /45 , X Turner mosaic pattern in <cell_type>skin fibroblasts</cell_type> .


We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses .


The patient was a phenotypic female with late onset menarche ( 18 years of age ) , who was amenorrhoeic for the first year , followed by menses of one to three days ' slight flow with dysmenorrhoea , but an otherwise normal menstrual history .


A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass .


Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46 , X , -Y , t ( Y ; 15 ) ( q12 ; p13 ) .

Repeated karyotypic studies on <cell_type>peripheral blood lymphocyte cultures</cell_type> showed only 46 , X , -Y , t ( Y ; 15 ) ( q12 ; p13 ) .


Cytogenetic examination of the patient 's younger brother , who had fathered three healthy children , showed an identical karyotype .


Mosaicism of 46 , X , -Y , t ( Y ; 15 ) ( q12 ; p13 ) /45 , X cell lines was found in skin samples from the patient 's elbow and genital regions , although there were no clinical stigmata of Turner syndrome .

Mosaicism of <cell_line>46 , X , -Y , t ( Y ; 15 ) ( q12 ; p13 ) /45 , X cell lines</cell_line> was found in skin samples from the patient 's elbow and genital regions , although there were no clinical stigmata of Turner syndrome .


An androgen receptor binding assay of cultured genital skin fibroblasts was negative .

An androgen receptor binding assay of <cell_line>cultured genital skin fibroblasts</cell_line> was negative .


Molecular analysis using Southern blot hybridisation , PCR , and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences , including the SRY ( sex determining region of the Y chromosome ) gene sequence .

Molecular analysis using Southern blot hybridisation , PCR , and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences , including the <dna>SRY ( sex determining region of the Y chromosome ) gene sequence</dna> .


These findings suggest that Turner mosaicism of the 45 , X cell line may have contributed to this atypical presentation in an XY female , although we can not exclude abnormalities of other genes related to sex differentiation .

These findings suggest that Turner mosaicism of the <cell_line>45 , X cell line</cell_line> may have contributed to this atypical presentation in an XY female , although we can not exclude abnormalities of other genes related to sex differentiation .


Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid , cepharanthine , in chronically infected monocytic cells .

Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid , cepharanthine , in <cell_type>chronically infected monocytic cells</cell_type> .


Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory , antiallergic , and immunomodulatory activities in vivo .


As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection , we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha ( TNF-alpha ) - and phorbol 12-myristate 13-acetate ( PMA ) -induced HIV-1 replication in chronically infected cell lines .

As several <protein>inflammatory cytokines</protein> and oxidative stresses are involved in the pathogenesis of HIV-1 infection , we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha ( <protein>TNF-alpha</protein> ) - and phorbol 12-myristate 13-acetate ( PMA ) -induced HIV-1 replication in <cell_line>chronically infected cell lines</cell_line> .


Two chronically HIV-1-infected cell lines , U1 ( monocytic ) and ACH-2 ( T lymphocytic ) , were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound .

Two <cell_line>chronically HIV-1-infected cell lines</cell_line> , <cell_line>U1</cell_line> ( monocytic ) and <cell_line>ACH-2</cell_line> ( T lymphocytic ) , were stimulated with <protein>TNF-alpha</protein> or PMA and cultured in the presence of various concentrations of the compound .


HIV-1 replication was determined by p24 antigen level .

HIV-1 replication was determined by <protein>p24 antigen</protein> level .


The inhibitory effects of cepharanthine on HIV-1 long terminal repeat ( LTR ) -driven gene expression and nuclear factor kappaB ( NF-kappaB ) activation were also examined .

The inhibitory effects of cepharanthine on <dna>HIV-1 long terminal repeat</dna> ( <dna>LTR</dna> ) -driven gene expression and <protein>nuclear factor kappaB</protein> ( <protein>NF-kappaB</protein> ) activation were also examined .


Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells .

Cepharanthine dose dependently inhibited HIV-1 replication in <cell_line>TNF-alpha- and PMA-stimulated U1 cells</cell_line> but not in <cell_line>ACH-2 cells</cell_line> .


Its 50 % effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells , respectively .

Its 50 % effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in <cell_line>PMA-stimulated U1 cells</cell_line> , respectively .


Cepharanthine was found to suppress HIV-1 LTR -driven gene expression through the inhibition of NF-kappaB activation .

Cepharanthine was found to suppress <dna>HIV-1 LTR</dna> -driven gene expression through the inhibition of <protein>NF-kappaB</protein> activation .


These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line .

These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a <cell_line>chronically infected monocytic cell line</cell_line> .


Since biscoclaurine alkaloids , containing cepharanthine as a major component , are widely used for the treatment of patients with various inflammatory diseases in Japan , cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1-infected patients .


NF-kappaB only partially mediates Epstein-Barr virus latent membrane protein 1 activation of B cells .

<protein>NF-kappaB</protein> only partially mediates <protein>Epstein-Barr virus latent membrane protein 1</protein> activation of B cells .


The latent membrane protein 1 ( LMP1 ) of Epstein-Barr virus ( EBV ) is required for EBV-induced immortalization of human B cells and causes tumorigenic transformation of cell lines .

The <protein>latent membrane protein 1</protein> ( <protein>LMP1</protein> ) of Epstein-Barr virus ( EBV ) is required for EBV-induced immortalization of <cell_type>human B cells</cell_type> and causes tumorigenic transformation of <cell_line>cell lines</cell_line> .


LMP1 expression induces phenotypic changes resembling B cell activation , such as cell size increase and up-regulation of cell surface activation markers .

<protein>LMP1</protein> expression induces phenotypic changes resembling B cell activation , such as cell size increase and up-regulation of <protein>cell surface activation markers</protein> .


LMP1 contains two domains that activate the transcription factor NF-kappaB , one through interactions with TRAF proteins and the other with the TRADD protein .

<protein>LMP1</protein> contains two domains that activate the <protein>transcription factor</protein> <protein>NF-kappaB</protein> , one through interactions with <protein>TRAF proteins</protein> and the other with the <protein>TRADD protein</protein> .


The purpose of the present study was to investigate the importance of NF-kappaB induction in the up-regulation of the B cell activation markers ICAM-1 and CD71 by LMP1 .

The purpose of the present study was to investigate the importance of <protein>NF-kappaB</protein> induction in the up-regulation of the B cell activation markers <protein>ICAM-1</protein> and <protein>CD71</protein> by <protein>LMP1</protein> .


This study shows that expression of LMP1 activates transcription from p50/p65- and c-Rel- responsive promoters , and that this activity can be completely inhibited by expression of a dominant inhibitory IkappaB mutant .

This study shows that expression of <protein>LMP1</protein> activates transcription from <dna>p50/p65- and c-Rel- responsive promoters</dna> , and that this activity can be completely inhibited by expression of a dominant <protein>inhibitory IkappaB mutant</protein> .


ICAM-1 and CD71 are nevertheless up-regulated by LMP1 in primary B cells and cell lines expressing the dominant IkappaB .

<protein>ICAM-1</protein> and <protein>CD71</protein> are nevertheless up-regulated by <protein>LMP1</protein> in <cell_type>primary B cells</cell_type> and cell lines expressing the <protein>dominant IkappaB</protein> .


Furthermore , LMP1 -induced cell size increase of primary B cells was unaffected by IkappaB expression .

Furthermore , <protein>LMP1</protein> -induced cell size increase of <cell_type>primary B cells</cell_type> was unaffected by <protein>IkappaB</protein> expression .


It was concluded that even when LMP1 is unable to activate NF-kappaB , it is still capable of inducing certain characteristics of activated B cells , strongly suggesting that LMP1 can also activate cells independently of NF-kappaB .

It was concluded that even when <protein>LMP1</protein> is unable to activate <protein>NF-kappaB</protein> , it is still capable of inducing certain characteristics of <cell_type>activated B cells</cell_type> , strongly suggesting that <protein>LMP1</protein> can also activate cells independently of <protein>NF-kappaB</protein> .


Models of lineage switching in hematopoietic development : a new myeloid-committed eosinophil cell line ( YJ ) demonstrates trilineage potential .

Models of lineage switching in hematopoietic development : a new <cell_line>myeloid-committed eosinophil cell line</cell_line> ( <cell_line>YJ</cell_line> ) demonstrates trilineage potential .


A new human leukemia cell line with an eosinophilic phenotype , designated YJ , was established from the peripheral blood cells of a patient with chronic myelomonocytic leukemia ( CMMoL ) with eosinophilia .

A new <cell_line>human leukemia cell line</cell_line> with an eosinophilic phenotype , designated <cell_line>YJ</cell_line> , was established from the <cell_type>peripheral blood cells</cell_type> of a patient with chronic myelomonocytic leukemia ( CMMoL ) with eosinophilia .


When cultured in RPMI 1640 medium containing 10 % fetal bovine serum , most YJ cells were myeloblastoid with a small number of the cells having eosinophilic granules .

When cultured in RPMI 1640 medium containing 10 % fetal bovine serum , most <cell_line>YJ cells</cell_line> were myeloblastoid with a small number of the cells having eosinophilic granules .


Cell surface markers in the YJ cells were positive for CD33 and were negative for CD34 , CD16 and CD23 .

<protein>Cell surface markers</protein> in the <cell_line>YJ cells</cell_line> were positive for <protein>CD33</protein> and were negative for <protein>CD34</protein> , <protein>CD16</protein> and <protein>CD23</protein> .


The eosinophilic characteristics of YJ cells were confirmed by histochemical staining with Fast-Green/Neutral-Red and by the expression of mRNAs for eosinophil-associated granule proteins , eosinophil cationic protein ( ECP ) , eosinophil-derived neurotoxin ( EDN ) , eosinophil peroxidase ( EPO ) , and major basic protein ( MBP ) , and for the Charcot-Leyden crystal ( CLC ) protein .

The eosinophilic characteristics of <cell_line>YJ cells</cell_line> were confirmed by histochemical staining with Fast-Green/Neutral-Red and by the expression of <rna>mRNAs</rna> for <protein>eosinophil-associated granule proteins</protein> , <protein>eosinophil cationic protein</protein> ( <protein>ECP</protein> ) , <protein>eosinophil-derived neurotoxin</protein> ( <protein>EDN</protein> ) , <protein>eosinophil peroxidase</protein> ( <protein>EPO</protein> ) , and <protein>major basic protein</protein> ( <protein>MBP</protein> ) , and for the <protein>Charcot-Leyden crystal ( CLC ) protein</protein> .


The YJ cells could be induced towards monocytic differentiation by stimulation with phorbol 12-myristate 13-acetate ( PMA ) .

The <cell_line>YJ cells</cell_line> could be induced towards monocytic differentiation by stimulation with phorbol 12-myristate 13-acetate ( PMA ) .


The monocytic characteristics of YJ cells treated with PMA were confirmed by morphological analysis with alpha-naphthyl butyrate esterase staining , by CD14 expression , and by increased expression of Egr-1 mRNA .

The monocytic characteristics of <cell_line>YJ cells</cell_line> treated with PMA were confirmed by morphological analysis with alpha-naphthyl butyrate esterase staining , by <protein>CD14</protein> expression , and by increased expression of <rna>Egr-1 mRNA</rna> .


Furthermore , YJ cells could be differentiated towards the neutrophil lineage by stimulation with all-trans retinoic acid ( RA ) .

Furthermore , <cell_line>YJ cells</cell_line> could be differentiated towards the <cell_type>neutrophil lineage</cell_type> by stimulation with all-trans retinoic acid ( RA ) .


YJ cells treated in vitro with 2 microM RA differentiated into metamyelocytes and band neutrophils , and increased the number of nitroblue tetrazolium ( NBT ) -positive cells and increased gp91phox mRNA expression .

<cell_line>YJ cells</cell_line> treated in vitro with 2 microM RA differentiated into <cell_type>metamyelocytes</cell_type> and <cell_type>band neutrophils</cell_type> , and increased the number of <cell_line>nitroblue tetrazolium ( NBT ) -positive cells</cell_line> and increased <rna>gp91phox mRNA</rna> expression .


Thus , the YJ cell line exhibited eosinophilic characteristics , but was able to differentiate to the monocytic or neutrophilic lineages in response to PMA or RA , respectively .

Thus , the <cell_line>YJ cell line</cell_line> exhibited eosinophilic characteristics , but was able to differentiate to the <cell_type>monocytic or neutrophilic lineages</cell_type> in response to PMA or RA , respectively .


The expression of genes for transcription factors involved in myeloid differentiation was evaluated by Northern blot analysis .

The expression of genes for <protein>transcription factors</protein> involved in myeloid differentiation was evaluated by Northern blot analysis .


Increased expression of Egr-1 was observed with macrophage differentiation .

Increased expression of <protein>Egr-1</protein> was observed with macrophage differentiation .


In contrast , increased expressions of C/EBPbeta and MZF-1 mRNA occurred with neutrophilic differentiation .

In contrast , increased expressions of <protein>C/EBPbeta</protein> and <rna>MZF-1 mRNA</rna> occurred with neutrophilic differentiation .


The YJ cell line should be useful for elucidating the molecular mechanisms governing lineage switching from the eosinophil to monocytic or neutrophil lineages .

The <cell_line>YJ cell line</cell_line> should be useful for elucidating the molecular mechanisms governing lineage switching from the <cell_type>eosinophil</cell_type> to <cell_type>monocytic or neutrophil lineages</cell_type> .


Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury .

<protein>Interleukin-6</protein> production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury .


Hemorrhagic shock ( HS ) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils ( PMN ) and may progress to organ failure , inducing acute respiratory distress syndrome ( ARDS ) .

Hemorrhagic shock ( HS ) initiates an inflammatory cascade that includes the production of <protein>cytokines</protein> and recruitment of <cell_type>neutrophils</cell_type> ( <cell_type>PMN</cell_type> ) and may progress to organ failure , inducing acute respiratory distress syndrome ( ARDS ) .


To examine the hypothesis that interleukin-6 ( IL-6 ) contributes to PMN infiltration and lung damage in HS , we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of IL-6 and activation of Stat3 .

To examine the hypothesis that <protein>interleukin-6</protein> ( <protein>IL-6</protein> ) contributes to PMN infiltration and lung damage in HS , we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of <protein>IL-6</protein> and activation of <protein>Stat3</protein> .


Using semiquantitative RT-PCR , we found a striking increase in IL-6 mRNA levels only in resuscitated HS , with peak levels observed 1 h after initiation of resuscitation .

Using semiquantitative RT-PCR , we found a striking increase in <rna>IL-6 mRNA</rna> levels only in resuscitated HS , with peak levels observed 1 h after initiation of resuscitation .


Increased IL-6 protein expression was localized to bronchial and alveolar cells .

Increased <protein>IL-6</protein> protein expression was localized to <cell_type>bronchial and alveolar cells</cell_type> .


Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in Stat3 activation with kinetics similar to IL-6 mRNA .

Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in <protein>Stat3</protein> activation with kinetics similar to <rna>IL-6 mRNA</rna> .


In situ DNA binding assay determined Stat3 activation predominantly within alveoli .

In situ DNA binding assay determined <protein>Stat3</protein> activation predominantly within alveoli .


Intratracheal instillation of IL-6 alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli , marked elevation of bronchoalveolar lavage cellularity , and increased wet-to-dry ratio .

Intratracheal instillation of <protein>IL-6</protein> alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli , marked elevation of bronchoalveolar lavage cellularity , and increased wet-to-dry ratio .


These findings indicate that IL-6 production and Stat3 activation occur early in HS and may contribute to PMN-mediated lung injury , including ARDS after HS .

These findings indicate that <protein>IL-6</protein> production and <protein>Stat3</protein> activation occur early in HS and may contribute to PMN-mediated lung injury , including ARDS after HS .