In this report , we show that NF-kappaB activation by LMP1 or by each of its effector sites is mediated by a pathway that includes NIK , IKKalpha , and IKKbeta .

In this report , we show that <protein>NF-kappaB</protein> activation by <protein>LMP1</protein> or by each of its <protein>effector sites</protein> is mediated by a pathway that includes <protein>NIK</protein> , <protein>IKKalpha</protein> , and <protein>IKKbeta</protein> .


Dominant negative mutants of NIK , IKKalpha , or IKKbeta substantially inhibited NF-kappaB activation by LMP1 or by each of its effector sites .

<protein>Dominant negative mutants</protein> of <protein>NIK</protein> , <protein>IKKalpha</protein> , or <protein>IKKbeta</protein> substantially inhibited <protein>NF-kappaB</protein> activation by <protein>LMP1</protein> or by each of its <protein>effector sites</protein> .


Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function .

Targeted disruption of the <dna>MyD88 gene</dna> results in loss of IL-1- and IL-18-mediated function .


MyD88 , originally isolated as a myeloid differentiation primary response gene , is shown to act as an adaptor in interleukin-1 ( IL-1 ) signaling by interacting with both the IL-1 receptor complex and IL-1 receptor-associated kinase ( IRAK ) .

<protein>MyD88</protein> , originally isolated as a myeloid differentiation <dna>primary response gene</dna> , is shown to act as an adaptor in <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) signaling by interacting with both the <protein>IL-1 receptor complex</protein> and <protein>IL-1 receptor-associated kinase</protein> ( <protein>IRAK</protein> ) .


Mice generated by gene targeting to lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins and cytokines in response to IL-1 .

Mice generated by gene targeting to lack <protein>MyD88</protein> have defects in T cell proliferation as well as induction of acute phase proteins and <protein>cytokines</protein> in response to <protein>IL-1</protein> .


Increases in interferon-gamma production and natural killer cell activity in response to IL-18 are abrogated .

Increases in <protein>interferon-gamma</protein> production and natural killer cell activity in response to <protein>IL-18</protein> are abrogated .


In vivo Th1 response is also impaired .


Furthermore , IL-18 -induced activation of NF-kappaB and c-Jun N-terminal kinase ( JNK ) is blocked in MyD88-/- Th1-developing cells .

Furthermore , <protein>IL-18</protein> -induced activation of <protein>NF-kappaB</protein> and <protein>c-Jun N-terminal kinase</protein> ( <protein>JNK</protein> ) is blocked in <cell_line>MyD88-/- Th1-developing cells</cell_line> .


Taken together , these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor .

Taken together , these results demonstrate that <protein>MyD88</protein> is a critical component in the signaling cascade that is mediated by <protein>IL-1 receptor</protein> as well as <protein>IL-18 receptor</protein> .


Ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes .

Ciprofloxacin induces an immunomodulatory stress response in <cell_type>human T lymphocytes</cell_type> .


Exposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of specific genes .

Exposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of <dna>specific genes</dna> .


The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate interleukin-2 ( IL-2 ) gene induction .

The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) gene induction .


In the present investigation , the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early ( < 2 h ) gene expression in primary human peripheral blood lymphocytes was studied with Northern blots .

In the present investigation , the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early ( < 2 h ) gene expression in <cell_type>primary human peripheral blood lymphocytes</cell_type> was studied with Northern blots .


In addition , transcriptional activity of IL-2 and metallothionein enhancer and promoter regions and transcription factors AP-1 , NF-kappaB , and NF-AT were analyzed by chloramphenicol acetyltransferase ( CAT ) and electrophoretic mobility shift assays , respectively .

In addition , transcriptional activity of <protein>IL-2</protein> and <dna>metallothionein enhancer and promoter regions</dna> and <protein>transcription factors</protein> <protein>AP-1</protein> , <protein>NF-kappaB</protein> , and <protein>NF-AT</protein> were analyzed by <protein>chloramphenicol acetyltransferase</protein> ( <protein>CAT</protein> ) and electrophoretic mobility shift assays , respectively .


The concentration of c-fos , c-jun , c-myc , junB , and fra-1 mRNAs was increased in activated peripheral blood lymphocytes incubated with ciprofloxacin compared to that in untreated controls .

The concentration of <rna>c-fos , c-jun , c-myc , junB , and fra-1 mRNAs</rna> was increased in activated <cell_type>peripheral blood lymphocytes</cell_type> incubated with ciprofloxacin compared to that in untreated controls .


Ciprofloxacin increased CAT activity in stimulated lymphocytes transfected with plasmids containing either the IL-2 or metallothionein enhancer .

Ciprofloxacin increased <protein>CAT</protein> activity in stimulated lymphocytes transfected with <cell_type>plasmids</cell_type> containing either the <protein>IL-2</protein> or <dna>metallothionein enhancer</dna> .


Furthermore , among the transcription factors tested , AP-1 activity was increased in stimulated purified T helper lymphocytes incubated with ciprofloxacin compared to drug-free controls .

Furthermore , among the <protein>transcription factors</protein> tested , <protein>AP-1</protein> activity was increased in <cell_type>stimulated purified T helper lymphocytes</cell_type> incubated with ciprofloxacin compared to <cell_type>drug-free controls</cell_type> .


Taken together , ciprofloxacin increased the levels of immediate-early transcripts , enhanced IL-2 and metallothionein promoter induction , and upregulated AP-1 concentrations in primary lymphocytes , reflecting a program commonly observed in mammalian stress responses .

Taken together , ciprofloxacin increased the levels of <rna>immediate-early transcripts</rna> , enhanced <protein>IL-2</protein> and <protein>metallothionein</protein> promoter induction , and upregulated <protein>AP-1</protein> concentrations in <cell_type>primary lymphocytes</cell_type> , reflecting a program commonly observed in mammalian stress responses .


A novel retinoic acid receptor ( RAR ) -selective antagonist inhibits differentiation and apoptosis of HL-60 cells : implications of RARalpha -mediated signals in myeloid leukemic cells .

A novel <protein>retinoic acid receptor</protein> ( <protein>RAR</protein> ) -selective antagonist inhibits differentiation and apoptosis of <cell_line>HL-60 cells</cell_line> : implications of <protein>RARalpha</protein> -mediated signals in <cell_type>myeloid leukemic cells</cell_type> .


Retinoic acid ( RA ) induces HL-60 cells to differentiate terminally into mature granulocytes , which subsequently die by apoptosis .

Retinoic acid ( RA ) induces <cell_line>HL-60 cells</cell_line> to differentiate terminally into <cell_type>mature granulocytes</cell_type> , which subsequently die by apoptosis .


The biological effects of RA are mediated by two distinct families of transcription factors : retinoic acid receptors ( RARs ) and retinoid X receptors ( RXRs ) .

The biological effects of RA are mediated by two distinct families of <protein>transcription factors</protein> : <protein>retinoic acid receptors</protein> ( <protein>RARs</protein> ) and <protein>retinoid X receptors</protein> ( <protein>RXRs</protein> ) .


RARs and RXRs form heterodimers and regulate retinoid-mediated gene expression .

<protein>RARs</protein> and <protein>RXRs</protein> form <protein>heterodimers</protein> and regulate retinoid-mediated gene expression .


We have recently developed a novel RAR -selective antagonist ( ER27191 ) which prevents RAR activation by retinoids .

We have recently developed a novel <protein>RAR</protein> -selective antagonist ( ER27191 ) which prevents <protein>RAR</protein> activation by retinoids .


Using this RAR-selective antagonist , and RXR and RAR agonist , we demonstrate the RAR -mediated signaling pathway is important for differentiation and apoptosis of myeloid leukemic cells .

Using this RAR-selective antagonist , and <protein>RXR</protein> and <protein>RAR</protein> agonist , we demonstrate the <protein>RAR</protein> -mediated signaling pathway is important for differentiation and apoptosis of <cell_type>myeloid leukemic cells</cell_type> .


Simple activation of RXRs is not sufficient to induce apoptosis of the cells .

Simple activation of <protein>RXRs</protein> is not sufficient to induce apoptosis of the cells .


Interestingly , the combination of the RAR-selective antagonist and 9-cis RA resulted in partial differentiation and apoptosis of HL-60 and NB4 cells , whereas the RAR antagonist completely blocked all-trans RA-induced differentiation and apoptosis of the cells .

Interestingly , the combination of the RAR-selective antagonist and 9-cis RA resulted in partial differentiation and apoptosis of <cell_line>HL-60 and NB4 cells</cell_line> , whereas the <protein>RAR</protein> antagonist completely blocked all-trans RA-induced differentiation and apoptosis of the cells .


Additional experiments showed that levels of BCL-2 protein decreased during differentiation of myeloid leukemic cells .

Additional experiments showed that levels of <protein>BCL-2 protein</protein> decreased during differentiation of <cell_type>myeloid leukemic cells</cell_type> .


Furthermore , HL-60 cells transduced with a bcl-2 expression vector showed the same differentiation response to retinoids as did parental HL-60 cells even though apoptosis was inhibited in these bcl-2-transduced cells , suggesting that differentiation and apoptosis are regulated independently in myeloid leukemic cells .

Furthermore , <cell_line>HL-60 cells</cell_line> transduced with a <dna>bcl-2 expression vector</dna> showed the same differentiation response to retinoids as did <cell_line>parental HL-60 cells</cell_line> even though apoptosis was inhibited in these <cell_line>bcl-2-transduced cells</cell_line> , suggesting that differentiation and apoptosis are regulated independently in <cell_type>myeloid leukemic cells</cell_type> .


Thrombopoietin supports in vitro erythroid differentiation via its specific receptor c-Mpl in a human leukemia cell line .

<protein>Thrombopoietin</protein> supports in vitro erythroid differentiation via its specific receptor <protein>c-Mpl</protein> in a <cell_line>human leukemia cell line</cell_line> .


Thrombopoietin ( TPO ) acts on megakaryopoiesis and erythropoiesis in vitro and in vivo .

<protein>Thrombopoietin</protein> ( <protein>TPO</protein> ) acts on megakaryopoiesis and erythropoiesis in vitro and in vivo .


We isolated a novel subline , UT-7/GMT , from the human leukemia cell line UT-7/GM ( N. Komatsu , et al. , Blood , 89 : 4021-4033 , 1997 ) .

We isolated a novel subline , <cell_line>UT-7/GMT</cell_line> , from the <cell_line>human leukemia cell line UT-7/GM</cell_line> ( N. Komatsu , et al. , Blood , 89 : 4021-4033 , 1997 ) .


A small population of UT-7/GM cells positively stained for hemoglobin ( Hb ) after a 7-day exposure to TPO .

A small population of <cell_line>UT-7/GM cells</cell_line> positively stained for <protein>hemoglobin</protein> ( <protein>Hb</protein> ) after a 7-day exposure to <protein>TPO</protein> .


More than 50 % of TPO-treated UT-7/GMT cells positively stained for Hb .

More than 50 % of <cell_line>TPO-treated UT-7/GMT cells</cell_line> positively stained for <protein>Hb</protein> .


Using UT-7/GMT cells , we examined how TPO promotes hemoglobinization .

Using <cell_line>UT-7/GMT cells</cell_line> , we examined how <protein>TPO</protein> promotes hemoglobinization .


TPO induced tyrosine phosphorylation of the TPO receptor but not the erythropoietin ( EPO ) receptor .

<protein>TPO</protein> induced tyrosine phosphorylation of the <protein>TPO</protein> receptor but not the <protein>erythropoietin ( EPO ) receptor</protein> .


There was no competition between TPO and EPO for binding to EPO receptor .

There was no competition between <protein>TPO</protein> and <protein>EPO</protein> for binding to <protein>EPO receptor</protein> .


These findings suggest that TPO has a direct effect on hemoglobinization via a specific receptor on UT-7/GMT cells .

These findings suggest that <protein>TPO</protein> has a direct effect on hemoglobinization via a specific receptor on <cell_line>UT-7/GMT cells</cell_line> .


Isoelectric focusing demonstrated that TPO induced fetal and adult Hb synthesis , whereas EPO induced embryonic , fetal , and adult Hb synthesis .

Isoelectric focusing demonstrated that <protein>TPO</protein> induced fetal and adult Hb synthesis , whereas <protein>EPO</protein> induced embryonic , fetal , and adult Hb synthesis .


Thus , our data suggest that TPO has a distinct action on erythropoiesis .

Thus , our data suggest that <protein>TPO</protein> has a distinct action on erythropoiesis .


Role of GATA-1 in proliferation and differentiation of definitive erythroid and megakaryocytic cells in vivo .

Role of <protein>GATA-1</protein> in proliferation and differentiation of definitive <cell_type>erythroid and megakaryocytic cells</cell_type> in vivo .


To elucidate the contributions of GATA-1 to definitive hematopoiesis in vivo , we have examined adult mice that were rendered genetically defective in GATA-1 synthesis ( Takahashi et al , J Biol Chem 272 : 12611 , 1997 ) .

To elucidate the contributions of <protein>GATA-1</protein> to definitive hematopoiesis in vivo , we have examined adult mice that were rendered genetically defective in <protein>GATA-1</protein> synthesis ( Takahashi et al , J Biol Chem 272 : 12611 , 1997 ) .


Because the GATA-1 gene is located on the X chromosome , which is randomly inactivated in every cell , heterozygous females can bear either an active wild-type or mutant ( referred to as GATA-1.05 ) GATA-1 allele , consequently leading to variable anemic severity .

Because the <dna>GATA-1 gene</dna> is located on the <dna>X chromosome</dna> , which is randomly inactivated in every cell , heterozygous females can bear either an active wild-type or mutant ( referred to as <dna>GATA-1.05</dna> ) <protein>GATA-1</protein> allele , consequently leading to variable anemic severity .


These heterozygous mutant mice usually developed normally , but they began to die after 5 months .


These affected animals displayed marked splenomegaly , anemia , and thrombocytopenia .


Proerythroblasts and megakaryocytes massively accumulated in the spleens of the heterozygotes , and we showed that the neomycin resistance gene ( which is the positive selection marker in ES cells ) was expressed profusely in the abnormally abundant cells generated in the GATA-1.05 mutant females .

<cell_type>Proerythroblasts</cell_type> and <cell_type>megakaryocytes</cell_type> massively accumulated in the spleens of the heterozygotes , and we showed that the <dna>neomycin resistance gene</dna> ( which is the positive selection marker in <cell_type>ES cells</cell_type> ) was expressed profusely in the abnormally abundant cells generated in the <protein>GATA-1.05</protein> mutant females .


We also observed hematopoiesis outside of the bone marrow in the affected mutant mice .


These data suggest that a small number of GATA-1.05 mutant hematopoietic progenitor cells begin to proliferate vigorously during early adulthood , but because the cells are unable to terminally differentiate , this leads to progenitor proliferation in the spleen and consequently death .

These data suggest that a small number of <cell_line>GATA-1.05 mutant hematopoietic progenitor cells</cell_line> begin to proliferate vigorously during early adulthood , but because the cells are unable to terminally differentiate , this leads to progenitor proliferation in the spleen and consequently death .


Thus , GATA-1 plays important in vivo roles for directing definitive hematopoietic progenitors to differentiate along both the erythroid and megakaryocytic pathways .

Thus , <protein>GATA-1</protein> plays important in vivo roles for directing definitive <cell_type>hematopoietic progenitors</cell_type> to differentiate along both the erythroid and megakaryocytic pathways .


The GATA-1 heterozygous mutant mouse shows a phenotype that is analogous to human myelodysplastic syndrome and thus may serve as a useful model for this disorder .

The <protein>GATA-1</protein> heterozygous mutant mouse shows a phenotype that is analogous to human myelodysplastic syndrome and thus may serve as a useful model for this disorder .


Differential regulation of the Janus kinase -STAT pathway and biologic function of IL-13 in primary human NK and T cells : a comparative study with IL-4 .

Differential regulation of the <protein>Janus kinase</protein> <protein>-STAT</protein> pathway and biologic function of <protein>IL-13</protein> in <cell_type>primary human NK and T cells</cell_type> : a comparative study with <protein>IL-4</protein> .


IL-13 , a cytokine similar to IL-4 , is a regulator of human B cell and monocyte functions .

<protein>IL-13</protein> , a cytokine similar to <protein>IL-4</protein> , is a regulator of human B cell and monocyte functions .


Biologic effects of IL-13 on primary human NK and T cells have not been well defined .

Biologic effects of <protein>IL-13</protein> on <cell_type>primary human NK and T cells</cell_type> have not been well defined .


We demonstrate that , in primary NK cells , IL-13 , but not IL-4 , may induce low levels of IFN-gamma secretion .

We demonstrate that , in <cell_type>primary NK cells</cell_type> , <protein>IL-13</protein> , but not <protein>IL-4</protein> , may induce low levels of <protein>IFN-gamma</protein> secretion .


When NK cells were costimulated with IL-13 and IL-2 , IL-13 generally resulted in two types of reactivity : IL-13 synergized with IL-2 to stimulate IFN-gamma production or it modestly inhibited IL-2 -mediated IFN-gamma production .

When <cell_type>NK cells</cell_type> were costimulated with <protein>IL-13</protein> and <protein>IL-2</protein> , <protein>IL-13</protein> generally resulted in two types of reactivity : <protein>IL-13</protein> synergized with <protein>IL-2</protein> to stimulate <protein>IFN-gamma</protein> production or it modestly inhibited <protein>IL-2</protein> -mediated <protein>IFN-gamma</protein> production .


In both types of donors , the effect of IL-13 on IL-2 -induced IFN-gamma production was in marked contrast to the strong inhibition seen with IL-4 in NK cells .

In both types of donors , the effect of <protein>IL-13</protein> on <protein>IL-2</protein> -induced <protein>IFN-gamma</protein> production was in marked contrast to the strong inhibition seen with <protein>IL-4</protein> in <cell_type>NK cells</cell_type> .


Additionally , IL-13 suppresses IL-2-induced NK cytolytic and proliferative activities although less efficiently than IL-4 .

Additionally , <protein>IL-13</protein> suppresses IL-2-induced NK cytolytic and proliferative activities although less efficiently than <protein>IL-4</protein> .


In T cells , IL-13 inhibits anti-CD3 mAb/IL-2- or PHA-mediated IFN-gamma production and enhances cytolytic potential .

In <cell_type>T cells</cell_type> , <protein>IL-13</protein> inhibits anti-CD3 mAb/IL-2- or PHA-mediated IFN-gamma production and enhances cytolytic potential .


Furthermore , we demonstrate that IL-13 , like IL-4 , induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 ( JAK3 ) in NK and T cells .

Furthermore , we demonstrate that <protein>IL-13</protein> , like <protein>IL-4</protein> , induces distinct <protein>STAT6-DNA binding complexes</protein> and tyrosine phosphorylation of <protein>STAT6</protein> and <protein>Janus kinase 3</protein> ( <protein>JAK3</protein> ) in NK and <cell_type>T cells</cell_type> .


We observed that Abs directed against unique domains of STAT6 have differential effects on complexes in T cells but not in NK cells , suggesting different STAT6 isoforms .

We observed that Abs directed against unique domains of <protein>STAT6</protein> have differential effects on complexes in <cell_type>T cells</cell_type> but not in <cell_type>NK cells</cell_type> , suggesting different <protein>STAT6 isoforms</protein> .


These findings show that IL-13 and IL-4 have the ability to regulate NK and T cell activation and that IL-13 is a potent regulator of STAT6 and JAK3 in these cell types .

These findings show that <protein>IL-13</protein> and <protein>IL-4</protein> have the ability to regulate NK and T cell activation and that <protein>IL-13</protein> is a potent regulator of <protein>STAT6</protein> and <protein>JAK3</protein> in these cell types .


The human toll signaling pathway : divergence of nuclear factor kappaB and JNK /SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 ( TRAF6 ) .

The human toll signaling pathway : divergence of <protein>nuclear factor kappaB</protein> and <protein>JNK</protein> <protein>/SAPK</protein> activation upstream of <protein>tumor necrosis factor receptor-associated factor 6</protein> ( <protein>TRAF6</protein> ) .


The human homologue of Drosophila Toll ( hToll ) is a recently cloned receptor of the interleukin 1 receptor ( IL-1R ) superfamily , and has been implicated in the activation of adaptive immunity .

The human homologue of <protein>Drosophila Toll</protein> ( <protein>hToll</protein> ) is a recently cloned receptor of the <protein>interleukin 1 receptor ( IL-1R ) superfamily</protein> , and has been implicated in the activation of adaptive immunity .


Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated kinase .

Signaling by <protein>hToll</protein> is shown to occur through sequential recruitment of the <protein>adapter molecule</protein> <protein>MyD88</protein> and the <protein>IL-1R-associated kinase</protein> .


Tumor necrosis factor receptor-activated factor 6 ( TRAF6 ) and the nuclear factor kappaB ( NF-kappaB ) -inducing kinase ( NIK ) are both involved in subsequent steps of NF-kappaB activation .

<protein>Tumor necrosis factor receptor-activated factor 6</protein> ( <protein>TRAF6</protein> ) and the <protein>nuclear factor kappaB ( NF-kappaB ) -inducing kinase</protein> ( <protein>NIK</protein> ) are both involved in subsequent steps of <protein>NF-kappaB</protein> activation .


Conversely , a dominant negative version of TRAF6 failed to block hToll -induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases , thus suggesting an early divergence of the two pathways .

Conversely , a dominant negative version of <protein>TRAF6</protein> failed to block <protein>hToll</protein> -induced activation of <protein>stress-activated protein kinase/c-Jun NH2-terminal kinases</protein> , thus suggesting an early divergence of the two pathways .


Inhibition of nuclear factor kappaB activation attenuates apoptosis resistance in lymphoid cells .

Inhibition of <protein>nuclear factor kappaB</protein> activation attenuates apoptosis resistance in <cell_type>lymphoid cells</cell_type> .


Death-inducing ligands ( DILs ) such as tumor necrosis factor alpha ( TNFalpha ) or the cytotoxic drug doxorubicin have been shown to activate a nuclear factor kappaB ( NFkappaB ) -dependent program that may rescue cells from apoptosis induction .

<protein>Death-inducing ligands</protein> ( <protein>DILs</protein> ) such as <protein>tumor necrosis factor alpha</protein> ( <protein>TNFalpha</protein> ) or the cytotoxic drug doxorubicin have been shown to activate a <protein>nuclear factor kappaB</protein> ( <protein>NFkappaB</protein> ) -dependent program that may rescue cells from apoptosis induction .


We demonstrate here that TRAIL ( TNF-related apoptosis-inducing ligand ) , a recently identified DIL , also activates NFkappaB in lymphoid cell lines in a kinetic similar to TNFalpha .

We demonstrate here that <protein>TRAIL</protein> ( <protein>TNF-related apoptosis-inducing ligand</protein> ) , a recently identified <protein>DIL</protein> , also activates <protein>NFkappaB</protein> in lymphoid cell lines in a kinetic similar to <protein>TNFalpha</protein> .


NFkappaB activity is independent from FADD , caspases , and apoptosis induction .

<protein>NFkappaB</protein> activity is independent from <protein>FADD</protein> , <protein>caspases</protein> , and apoptosis induction .


To study the influence of NFkappaB activity on apoptosis mediated by TRAIL , CD95 , TNFalpha , or doxorubicin , NFkappaB activation was inhibited using the proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal or transient overexpression of mutant IkappaBalpha .

To study the influence of <protein>NFkappaB</protein> activity on apoptosis mediated by <protein>TRAIL</protein> , CD95 , <protein>TNFalpha</protein> , or doxorubicin , <protein>NFkappaB</protein> activation was inhibited using the <protein>proteasome</protein> inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal or transient overexpression of <protein>mutant IkappaBalpha</protein> .


Sensitivity for induction of apoptosis was markedly increased by these treatments in apoptosis sensitive cell lines .

Sensitivity for induction of apoptosis was markedly increased by these treatments in apoptosis sensitive <cell_line>cell lines</cell_line> .


Moreover , both in cell lines and in primary leukemia cells that are resistant towards induction of apoptosis by DILs and doxorubicin , antagonization of NFkappaB activity partially restored apoptosis sensitivity .

Moreover , both in cell lines and in primary leukemia cells that are resistant towards induction of apoptosis by <protein>DILs</protein> and doxorubicin , antagonization of <protein>NFkappaB</protein> activity partially restored apoptosis sensitivity .


These data suggest that inhibition of NFkappaB activation may provide a molecular approach to increase apoptosis sensitivity in anticancer treatment .

These data suggest that inhibition of <protein>NFkappaB</protein> activation may provide a molecular approach to increase apoptosis sensitivity in anticancer treatment .


Loss- and gain-of-function mutations reveal an important role of BSAP ( Pax-5 ) at the start and end of B cell differentiation .

Loss- and gain-of-function mutations reveal an important role of <protein>BSAP</protein> ( <protein>Pax-5</protein> ) at the start and end of B cell differentiation .


Pax-5 codes for the transcription factor BSAP which is expressed throughout B cell development except in terminally differentiated plasma cells .

<protein>Pax-5</protein> codes for the <protein>transcription factor</protein> <protein>BSAP</protein> which is expressed throughout B cell development except in <cell_type>terminally differentiated plasma cells</cell_type> .


Gene targeting experiments in the mouse revealed a differential dependency of fetal and adult B-lymphopoiesis on this transcription factor .

Gene targeting experiments in the mouse revealed a differential dependency of fetal and adult B-lymphopoiesis on this <protein>transcription factor</protein> .


BSAP is required for B-lineage commitment in the fetal liver and for progression beyond an early pro-B cell stage in adult bone marrow .

<protein>BSAP</protein> is required for B-lineage commitment in the fetal liver and for progression beyond an early pro-B cell stage in adult bone marrow .


The characterization of Pax-5-deficient pro-B cells demonstrated an important role of BSAP in the regulation of the CD19 , mb-1 ( Ig alpha ) and N-myc genes as well as in the developmental pathway controlling VH-to-DHJH recombination at the immunoglobulin heavy-chain ( IgH ) locus .

The characterization of <cell_type>Pax-5-deficient pro-B cells</cell_type> demonstrated an important role of <protein>BSAP</protein> in the regulation of the <protein>CD19</protein> , <protein>mb-1</protein> ( <protein>Ig alpha</protein> ) and <dna>N-myc genes</dna> as well as in the developmental pathway controlling VH-to-DHJH recombination at the <protein>immunoglobulin heavy-chain ( IgH ) locus</protein> .


The human PAX-5 gene was recently shown to participate together with the IgH locus in the chromosomal translocation t ( 9 ; 14 ) ( p13 ; q32 ) .

The <dna>human PAX-5 gene</dna> was recently shown to participate together with the <dna>IgH locus</dna> in the chromosomal translocation <dna>t ( 9 ; 14 ) ( p13 ; q32 )</dna> .


This translocation is characteristic of a small subset of non-Hodgkin lymphomas exhibiting plasmacytoid differentiation .


The translocated PAX-5 gene is deregulated by the insertion of IgH regulatory elements into its 5 ' region , which may contribute to tumorigenesis by interfering with the shut-down of PAX-5 transcription and thus with the completion of plasma cell differentiation

The <dna>translocated PAX-5 gene</dna> is deregulated by the insertion of <dna>IgH regulatory elements</dna> into its <dna>5 ' region</dna> , which may contribute to tumorigenesis by interfering with the shut-down of <protein>PAX-5</protein> transcription and thus with the completion of <cell_type>plasma cell</cell_type> differentiation


Acetylation and modulation of erythroid Kruppel-like factor ( EKLF ) activity by interaction with histone acetyltransferases .

Acetylation and modulation of <protein>erythroid Kruppel-like factor</protein> ( <protein>EKLF</protein> ) activity by interaction with <protein>histone acetyltransferases</protein> .


Erythroid Kruppel-like factor ( EKLF ) is a red cell-specific transcriptional activator that is crucial for consolidating the switch to high levels of adult beta-globin expression during erythroid ontogeny .

<protein>Erythroid Kruppel-like factor</protein> ( <protein>EKLF</protein> ) is a <protein>red cell-specific transcriptional activator</protein> that is crucial for consolidating the switch to high levels of adult <protein>beta-globin</protein> expression during erythroid ontogeny .


EKLF is required for integrity of the chromatin structure at the beta-like globin locus , and it interacts with a positive-acting factor in vivo .

<protein>EKLF</protein> is required for integrity of the chromatin structure at the <dna>beta-like globin locus</dna> , and it interacts with a <protein>positive-acting factor</protein> in vivo .


We find that EKLF is an acetylated transcription factor , and that it interacts in vivo with CBP , p300 , and P/CAF .

We find that <protein>EKLF</protein> is an <protein>acetylated transcription factor</protein> , and that it interacts in vivo with <protein>CBP</protein> , <protein>p300</protein> , and <protein>P/CAF</protein> .


However , its interactions with these histone acetyltransferases are not equivalent , as CBP and p300 , but not P/CAF , utilize EKLF as a substrate for in vitro acetylation within its trans- activation region .

However , its interactions with these <protein>histone acetyltransferases</protein> are not equivalent , as <protein>CBP</protein> and <protein>p300</protein> , but not <protein>P/CAF</protein> , utilize <protein>EKLF</protein> as a substrate for in vitro acetylation within its trans- <protein>activation region</protein> .


The functional effects of these interactions are that CBP and p300 , but not P/CAF , enhance EKLF 's transcriptional activation of the beta-globin promoter in erythroid cells .

The functional effects of these interactions are that <protein>CBP</protein> and <protein>p300</protein> , but not <protein>P/CAF</protein> , enhance <protein>EKLF</protein> 's transcriptional activation of the <dna>beta-globin promoter</dna> in <cell_type>erythroid cells</cell_type> .


These results establish EKLF as a tissue-specific transcription factor that undergoes post-translational acetylation and suggest a mechanism by which EKLF is able to alter chromatin structure and induce beta-globin expression within the beta-like globin cluster .

These results establish <protein>EKLF</protein> as a <protein>tissue-specific transcription factor</protein> that undergoes post-translational acetylation and suggest a mechanism by which <protein>EKLF</protein> is able to alter <dna>chromatin</dna> structure and induce <protein>beta-globin</protein> expression within the <dna>beta-like globin cluster</dna> .


Recognition of herpes simplex virus type 2 tegument proteins by CD4 T cells infiltrating human genital herpes lesions .

Recognition of <protein>herpes simplex virus type 2 tegument proteins</protein> by <cell_type>CD4 T cells</cell_type> infiltrating human genital herpes lesions .


The local cellular immune response to herpes simplex virus ( HSV ) is important in the control of recurrent HSV infection .


The antiviral functions of infiltrating CD4-bearing T cells may include cytotoxicity , inhibition of viral growth , lymphokine secretion , and support of humoral and CD8 responses .

The antiviral functions of <cell_type>infiltrating CD4-bearing T cells</cell_type> may include cytotoxicity , inhibition of viral growth , <protein>lymphokine</protein> secretion , and support of humoral and CD8 responses .


The antigens recognized by many HSV-specific CD4 T cells localizing to genital HSV-2 lesions are unknown .

The antigens recognized by many <cell_type>HSV-specific CD4 T cells</cell_type> localizing to genital HSV-2 lesions are unknown .


T cells recognizing antigens encoded within map units 0.67 to 0.73 of HSV DNA are frequently recovered from herpetic lesions .

<cell_type>T cells</cell_type> recognizing antigens encoded within map units 0.67 to 0.73 of <dna>HSV DNA</dna> are frequently recovered from herpetic lesions .


Expression cloning with this region of DNA now shows that tegument protein VP22 and the viral dUTPase , encoded by genes UL49 and UL50 , respectively , are T-cell antigens .

Expression cloning with this region of DNA now shows that <protein>tegument protein</protein> <protein>VP22</protein> and the <protein>viral dUTPase</protein> , encoded by <dna>genes UL49 and UL50</dna> , respectively , are <protein>T-cell antigens</protein> .


Separate epitopes in VP22 were defined for T-cell clones from each of three patients .

Separate <protein>epitopes</protein> in <protein>VP22</protein> were defined for <cell_line>T-cell clones</cell_line> from each of three patients .


Reactivity with the tegument protein encoded by UL21 was identified for an additional patient .

Reactivity with the <protein>tegument protein</protein> encoded by <dna>UL21</dna> was identified for an additional patient .


Three new epitopes were identified in VP16 , a tegument protein associated with VP22 .

Three new epitopes were identified in <protein>VP16</protein> , a <protein>tegument protein</protein> associated with <protein>VP22</protein> .


Some tegument-specific CD4 T-cell clones exhibited cytotoxic activity against HSV-infected cells .

Some <cell_line>tegument-specific CD4 T-cell clones</cell_line> exhibited cytotoxic activity against <cell_type>HSV-infected cells</cell_type> .


These results suggest that herpes simplex tegument proteins are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines .

These results suggest that <protein>herpes simplex tegument proteins</protein> are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines .


Fibrinogen activates NF-kappa B transcription factors in mononuclear phagocytes .

<protein>Fibrinogen</protein> activates <protein>NF-kappa B transcription factors</protein> in <cell_type>mononuclear phagocytes</cell_type> .


Adhesion to extracellular matrices is known to modulate leukocyte activation , although the mechanisms are not fully understood .


Mononuclear phagocytes are exposed to fibrinous provisional matrix throughout migration into inflammatory foci , so this study was undertaken to determine whether fibrinogen triggers activation of NF-kappa B transcription factors .

<cell_type>Mononuclear phagocytes</cell_type> are exposed to fibrinous provisional matrix throughout migration into inflammatory foci , so this study was undertaken to determine whether fibrinogen triggers activation of <protein>NF-kappa B transcription factors</protein> .


U937 cells differentiated with PMA in nonadherent culture were shown to express two fibrinogen-binding integrins , predominately CD11b/CD18 , and to a lesser extent , CD11c/CD18 .

<cell_line>U937 cells</cell_line> differentiated with PMA in <cell_line>nonadherent culture</cell_line> were shown to express two <protein>fibrinogen-binding integrins</protein> , predominately <protein>CD11b/CD18</protein> , and to a lesser extent , <protein>CD11c/CD18</protein> .


Cells stimulated with fibrinogen ( 10-100 microg/ml ) /Mn2+ ( 50 microM ) for 2 h were examined by electrophoretic mobility shift assay .

Cells stimulated with <protein>fibrinogen</protein> ( 10-100 microg/ml ) /Mn2+ ( 50 microM ) for 2 h were examined by electrophoretic mobility shift assay .


NF-kappa B activation , minimal in unstimulated cells , was substantially up-regulated by fibrinogen .

<protein>NF-kappa B</protein> activation , minimal in <cell_type>unstimulated cells</cell_type> , was substantially up-regulated by <protein>fibrinogen</protein> .


Fibrinogen also caused activation of AP-1 , but not SP1 or cAMP response element-binding protein ( CREB ) factors .

<protein>Fibrinogen</protein> also caused activation of <protein>AP-1</protein> , but not <protein>SP1</protein> or <protein>cAMP response element-binding protein ( CREB ) factors</protein> .


Blocking mAbs against CD18 and CD11b abrogated fibrinogen -induced NF-kappa B activation .

Blocking <protein>mAbs</protein> against <protein>CD18</protein> and <protein>CD11b</protein> abrogated <protein>fibrinogen</protein> -induced <protein>NF-kappa B</protein> activation .


To determine the effects on transcriptional regulation , U937 cells were transfected with a plasmid containing the HIV-1 enhancer ( bearing two NF-kappa B sites ) coupled to a chloramphenicol acetyltransferase ( CAT ) reporter .

To determine the effects on transcriptional regulation , <cell_line>U937 cells</cell_line> were transfected with a plasmid containing the <dna>HIV-1 enhancer</dna> ( bearing two <dna>NF-kappa B sites</dna> ) coupled to a <dna>chloramphenicol acetyltransferase ( CAT ) reporter</dna> .


Cells were subsequently stimulated with 1 ) PMA for 24 h , inducing CAT activity by 2.6-fold , 2 ) fibrinogen /Mn2+ for 2 h , inducing CAT activity by 3.2-fold , or 3 ) costimulation with fibrinogen and PMA , inducing 5.7-fold the CAT activity induced by PMA alone .

Cells were subsequently stimulated with 1 ) PMA for 24 h , inducing <protein>CAT</protein> activity by 2.6-fold , 2 ) <protein>fibrinogen</protein> /Mn2+ for 2 h , inducing <protein>CAT</protein> activity by 3.2-fold , or 3 ) costimulation with <protein>fibrinogen</protein> and PMA , inducing 5.7-fold the <protein>CAT</protein> activity induced by PMA alone .


We conclude that contact with fibrinogen-derived proteins may contribute to mononuclear phagocyte activation by signaling through CD11b/CD18 , resulting in selective activation of transcriptional regulatory factors , including NF-kappa B .

We conclude that contact with <protein>fibrinogen-derived proteins</protein> may contribute to mononuclear phagocyte activation by signaling through <protein>CD11b/CD18</protein> , resulting in selective activation of <protein>transcriptional regulatory factors</protein> , including <protein>NF-kappa B</protein> .


Peripheral blood T cells and monocytes and B cell lines derived from patients with lupus express estrogen receptor transcripts similar to those of normal cells .

<cell_type>Peripheral blood T cells</cell_type> and <cell_type>monocytes</cell_type> and <cell_line>B cell lines</cell_line> derived from patients with lupus express estrogen receptor transcripts similar to those of <cell_type>normal cells</cell_type> .


OBJECTIVE : To identify and characterize estrogen receptor ( ER ) transcripts expressed in immune cells of patients with systemic lupus erythematosus ( SLE ) and healthy donors .

OBJECTIVE : To identify and characterize <rna>estrogen receptor ( ER ) transcripts</rna> expressed in <cell_type>immune cells</cell_type> of patients with systemic lupus erythematosus ( SLE ) and healthy donors .


METHODS : Peripheral blood monocytes and T cells were prepared from patients with SLE ( n = 6 ) and healthy donors ( n = 8 ) .

METHODS : <cell_type>Peripheral blood monocytes</cell_type> and <cell_type>T cells</cell_type> were prepared from patients with SLE ( n = 6 ) and healthy donors ( n = 8 ) .


T cells were separated into CD4 and CD8 .

<cell_type>T cells</cell_type> were separated into <cell_type>CD4</cell_type> and <cell_type>CD8</cell_type> .


Some monocytes and T cells were stimulated with estradiol , PMA , and ionomycin .

Some <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> were stimulated with estradiol , PMA , and ionomycin .


Epstein-Barr virus-transformed B cell lines ( n = 7 ) and B cell hybridomas ( n = 2 ) established from patients with SLE and a healthy individual were used as a B cell source .

Epstein-Barr virus-transformed <cell_line>B cell lines</cell_line> ( n = 7 ) and <cell_line>B cell hybridomas</cell_line> ( n = 2 ) established from patients with SLE and a healthy individual were used as a B cell source .


These cells were examined for ER mRNA by reverse transcription nested polymerase chain reaction .

These cells were examined for <rna>ER mRNA</rna> by reverse transcription nested polymerase chain reaction .


Amplified cDNA were sequenced by standard methods .

Amplified <dna>cDNA</dna> were sequenced by standard methods .


RESULTS : In all cells tested , ER mRNA was expressed without prior in vitro stimulation .

RESULTS : In all cells tested , <rna>ER mRNA</rna> was expressed without prior in vitro stimulation .


Partial sequences from exons 1-8 were nearly identical to the published sequence of the human ER mRNA .

Partial sequences from <dna>exons 1-8</dna> were nearly identical to the published sequence of the <rna>human ER mRNA</rna> .


There were no notable differences in the ER transcripts between patients and healthy controls .

There were no notable differences in the <rna>ER transcripts</rna> between patients and healthy controls .


Variant receptor transcripts lacking exon 5 or exon 7 , which encodes the hormone binding domain , were identified in the majority of the cells .

Variant receptor transcripts lacking <dna>exon 5</dna> or <dna>exon 7</dna> , which encodes the hormone binding domain , were identified in the majority of the cells .


Precise deletion of the exons suggests that they are alternatively spliced transcripts .


Whether the detected transcripts are translated into functional receptor proteins remains to be determined .


In vitro stimulation did not affect ER mRNA expression .

In vitro stimulation did not affect <rna>ER mRNA</rna> expression .


The presence of variants did not correlate with disease activity or medication .


CONCLUSION : Monocytes , T cells , and B cells in patients express transcripts of the normal wild type ER and the hormone binding domain variants in vivo .

CONCLUSION : <cell_type>Monocytes</cell_type> , <cell_type>T cells</cell_type> , and <cell_type>B cells</cell_type> in patients express transcripts of the normal <protein>wild type ER</protein> and the <protein>hormone binding domain variants</protein> in vivo .


DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1 .

DNA damaging agents induce expression of <protein>Fas ligand</protein> and subsequent apoptosis in <cell_type>T lymphocytes</cell_type> via the activation of <protein>NF-kappa B</protein> and <protein>AP-1</protein> .


Apoptosis induced by DNA damage and other stresses can proceed via expression of Fas ligand ( FasL ) and ligation of its receptor , Fas ( CD95 ) .

Apoptosis induced by DNA damage and other stresses can proceed via expression of <protein>Fas ligand</protein> ( <protein>FasL</protein> ) and ligation of its receptor , Fas ( CD95 ) .


We report that activation of the two transcription factors NF-kappa B and AP-1 is crucially involved in FasL expression induced by etoposide , teniposide , and UV irradiation .

We report that activation of the two transcription factors NF-kappa B and <protein>AP-1</protein> is crucially involved in <protein>FasL</protein> expression induced by etoposide , teniposide , and UV irradiation .


A nondegradable mutant of I kappa B blocked both FasL expression and apoptosis induced by DNA damage but not Fas ligation .

A nondegradable mutant of <protein>I kappa B</protein> blocked both <protein>FasL</protein> expression and apoptosis induced by DNA damage but not <protein>Fas</protein> ligation .


These stimuli also induced the stress-activated kinase pathway ( SAPK /JNK ) , which was required for the maximal induction of apoptosis .

These stimuli also induced the stress-activated kinase pathway ( <protein>SAPK</protein> <protein>/JNK</protein> ) , which was required for the maximal induction of apoptosis .


A 1.2 kb FasL promoter responded to DNA damage , as well as coexpression with p65 Rel or Fos/Jun .

A 1.2 kb <dna>FasL promoter</dna> responded to DNA damage , as well as coexpression with <protein>p65 Rel</protein> or <protein>Fos/Jun</protein> .


Mutations in the relevant NF-kappa B and AP-1 binding sites eliminated these responses .

Mutations in the relevant <protein>NF-kappa B</protein> and <dna>AP-1 binding sites</dna> eliminated these responses .


Thus , activation of NF-kappa B and AP-1 contributes to stress-induced apoptosis via the expression of FasL .

Thus , activation of <protein>NF-kappa B</protein> and <protein>AP-1</protein> contributes to stress-induced apoptosis via the expression of <protein>FasL</protein> .


A small , nonpeptidyl mimic of granulocyte-colony-stimulating factor [ see commetns ]

A small , nonpeptidyl mimic of <protein>granulocyte-colony-stimulating factor</protein> [ see commetns ]


A nonpeptidyl small molecule SB 247464 , capable of activating granulocyte-colony-stimulating factor ( G-CSF ) signal transduction pathways , was identified in a high-throughput assay in cultured cells .

A nonpeptidyl small molecule SB 247464 , capable of activating <protein>granulocyte-colony-stimulating factor</protein> ( <protein>G-CSF</protein> ) signal transduction pathways , was identified in a high-throughput assay in <cell_type>cultured cells</cell_type> .


Like G-CSF , SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro .

Like <protein>G-CSF</protein> , SB 247464 induced tyrosine phosphorylation of <protein>multiple signaling proteins</protein> and stimulated <cell_type>primary murine bone marrow cells</cell_type> to form <cell_type>granulocytic colonies</cell_type> in vitro .


It also elevated peripheral blood neutrophil counts in mice .

It also elevated <cell_type>peripheral blood neutrophil</cell_type> counts in mice .


The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464 , suggesting that the compound acts by oligomerizing receptor chains .

The extracellular domain of the <protein>murine G-CSF receptor</protein> was required for the activity of SB 247464 , suggesting that the compound acts by <protein>oligomerizing receptor chains</protein> .


The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand .


Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in bone marrow .

Minimal residual disease in acute myelogenous leukemia with <rna>PML/RAR alpha or AML1/ETO mRNA</rna> and phenotypic analysis of <cell_type>possible T and natural killer cells</cell_type> in bone marrow .


Here we studied minimal residual disease ( MRD ) of patients with acute myeloid leukemia ( AML ) who have PML/RAR alpha or AML1/ETO as well as the phenotypic analysis of lymphocyte subsets involved in antitumor immunity .

Here we studied minimal residual disease ( MRD ) of patients with acute myeloid leukemia ( AML ) who have <protein>PML/RAR alpha</protein> or <protein>AML1/ETO</protein> as well as the phenotypic analysis of <cell_type>lymphocyte subsets</cell_type> involved in antitumor immunity .


Eight patients in long-term ( LT ; 3 to 15 years ) and 15 patients in short-term ( ST ; up to 3 years ) remission were studied .


Using the reverse transcription-polymerase chain reaction ( RT ) assay , the limit of detection was 10 ( -5 ) to 10 ( -6 ) for PML/RAR alpha transcript and 10 ( -4 ) to 10 ( -5 ) for the AML1/ETO transcript .

Using the reverse transcription-polymerase chain reaction ( RT ) assay , the limit of detection was 10 ( -5 ) to 10 ( -6 ) for <rna>PML/RAR alpha transcript</rna> and 10 ( -4 ) to 10 ( -5 ) for the <rna>AML1/ETO transcript</rna> .


Simultaneously , T lymphocyte subsets and NK cells from the peripheral blood ( PB ) and bone marrow ( BM ) were investigated by flow cytometric analysis .

Simultaneously , <cell_type>T lymphocyte subsets</cell_type> and <cell_type>NK cells</cell_type> from the peripheral blood ( PB ) and bone marrow ( BM ) were investigated by flow cytometric analysis .


Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD-positive .


Although all MRD-positive patients in LT remission are still until now event-free , 3 of the 7 MRD-positive ( MRD+ ) patients in ST remission soon relapsed .


The total populations of CD4 + , CD8 + and CD56 + [ possible T-cell and natural killer ( T/NK ) populations ] in the BM of ST patients and MRD+/LT patients were significantly ( p < .01 ) low .

The total populations of <protein>CD4</protein> + , <protein>CD8</protein> + and <protein>CD56</protein> + [ possible <cell_type>T-cell</cell_type> and <cell_type>natural killer</cell_type> ( <cell_type>T/NK</cell_type> ) populations ] in the BM of ST patients and MRD+/LT patients were significantly ( p < .01 ) low .


The CD8 + CD28 + population showed the same tendency ( p < .01-.02 ) .

The <protein>CD8</protein> + <protein>CD28</protein> + population showed the same tendency ( p < .01-.02 ) .


The T/NK subsets in the BM of MRD-negative ( MRD- ) LT ( MRD-/LT ) patients showed similar numbers of cells as normal volunteers .

The <cell_type>T/NK subsets</cell_type> in the BM of MRD-negative ( MRD- ) LT ( MRD-/LT ) patients showed similar numbers of cells as normal volunteers .


Basically , the total percentage of the CD4+ , CD8+ and CD56+ cell populations in the BM was increased and in the following order : MRD-/LT patients , normal volunteers , MRD+/LT patients and MRD+ or -/ST patients .

Basically , the total percentage of the <cell_type>CD4+ , CD8+ and CD56+ cell populations</cell_type> in the BM was increased and in the following order : MRD-/LT patients , normal volunteers , MRD+/LT patients and MRD+ or -/ST patients .


The percentages of the T/NK-cell subsets in the PB were not significantly different among these groups .

The percentages of the <cell_type>T/NK-cell subsets</cell_type> in the PB were not significantly different among these groups .


Thus , the difference of the possible T/NK-cell phenotype in the BM may strongly influence clinical and molecular remission .

Thus , the difference of the possible <cell_type>T/NK-cell</cell_type> phenotype in the BM may strongly influence clinical and molecular remission .


These results still remain to be confirmed by further studies of the functional anti-tumor immunity of T/NK cells of AML in remission .

These results still remain to be confirmed by further studies of the functional anti-tumor immunity of <cell_type>T/NK cells</cell_type> of AML in remission .


Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB -dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells .

Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce <protein>NF-kappaB</protein> -dependent activation of human immunodeficiency virus type 1 <dna>long terminal repeat</dna> in <cell_type>T cells</cell_type> .


Tuberculosis has emerged as an epidemic , extended by the large number of individuals infected with human immunodeficiency virus type 1 ( HIV-1 ) .


The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan ( ManLAM ) of Mycobacterium tuberculosis ( M. tuberculosis ) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system .

The major goal of this study was to determine whether the <cell_type>mycobacterial cell</cell_type> wall component mannose-capped lipoarabinomannan ( ManLAM ) of Mycobacterium tuberculosis ( M. tuberculosis ) could activate transcription of HIV-1 in <cell_type>T cells</cell_type> with the use of an in vitro cell culture system .


These experiments are of prime importance considering that CD4-expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals .

These experiments are of prime importance considering that <cell_type>CD4-expressing T lymphocytes</cell_type> represent the major virus reservoir in the peripheral blood of infected individuals .


Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR , it was first found that culture protein filtrates ( CFP ) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM .

Using the <cell_line>1G5 cell line</cell_line> harbouring the <dna>luciferase reporter gene</dna> under the control of the <dna>HIV-1 LTR</dna> , it was first found that culture protein filtrates ( CFP ) from M. tuberculosis or purified ManLAM could activate <dna>HIV-1 LTR-dependent gene</dna> expression unlike similarly prepared CFP extracts devoid of ManLAM .


The implication of protein tyrosine kinase ( s ) , protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7 .

The implication of <protein>protein tyrosine kinase ( s )</protein> , <protein>protein kinase A</protein> and/or <protein>protein kinase C</protein> was highlighted by the abrogation of the ManLAM-mediated activation of <dna>HIV-1 LTR-driven gene</dna> expression using herbimycin A and H7 .


It was also determined , using electrophoresis mobility shift assays , that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB .

It was also determined , using electrophoresis mobility shift assays , that M. tuberculosis ManLAM led to the nuclear translocation of the <protein>transcription factor NF-kappaB</protein> .


M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type , but not the kappaB-mutated , HIV-1 LTR region .

M. tuberculosis ManLAM resulted in clear induction of the <dna>luciferase gene</dna> placed under the control of the <dna>wild-type , but not the kappaB-mutated , HIV-1 LTR region</dna> .


Finally , the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha .

Finally , the ManLAM-mediated activation of <dna>HIV-1 LTR</dna> transcription was found to be independent of the autocrine or paracrine action of <protein>endogenous TNF-alpha</protein> .


The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection .

The results suggest that M. tuberculosis can upregulate HIV-1 expression in <cell_type>T cells</cell_type> and could thus have the potential to influence the pathogenesis of HIV-1 infection .


Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in basal transcription and nuclear factor recruitment in human glial cells and lymphocytes .

<dna>Human immunodeficiency virus type 1 long terminal repeat quasispecies</dna> differ in basal transcription and <protein>nuclear factor</protein> recruitment in <cell_type>human glial cells and lymphocytes</cell_type> .


The generation of genomic diversity during the course of infection has the potential to affect all aspects of HIV-1 replication , including expression of the proviral genome .

The generation of genomic diversity during the course of infection has the potential to affect all aspects of HIV-1 replication , including expression of the <dna>proviral genome</dna> .


To gain a better understanding of the impact of long terminal repeat ( LTR ) sequence diversity on LTR-directed gene expression in cells of the central nervous system ( CNS ) and immune system , we amplified and cloned LTRs from proviral DNA in HIV-1-infected peripheral blood .

To gain a better understanding of the impact of <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) sequence diversity on <dna>LTR-directed gene</dna> expression in cells of the central nervous system ( CNS ) and immune system , we amplified and cloned <dna>LTRs</dna> from <dna>proviral DNA</dna> in <cell_type>HIV-1-infected peripheral blood</cell_type> .


Sequence analysis of nineteen LTRs cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes ( with respect to the sequence of the LAI LTR ) within the 455-bp U3 region .

Sequence analysis of nineteen <dna>LTRs</dna> cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes ( with respect to the sequence of the <dna>LAI LTR</dna> ) within the <dna>455-bp U3 region</dna> .


Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these LTRs had activities which varied significantly from the LAI LTR in U-373 MG cells ( an astrocytoma cell line ) as well as in Jurkat cells ( a CD4-positive lymphocyte cell line ) .

Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these <dna>LTRs</dna> had activities which varied significantly from the <dna>LAI LTR</dna> in <cell_line>U-373 MG cells</cell_line> ( an <cell_line>astrocytoma cell line</cell_line> ) as well as in <cell_line>Jurkat cells</cell_line> ( a <cell_line>CD4-positive lymphocyte cell line</cell_line> ) .


While LTRs which demonstrated the highest activities in U-373 MG cells also yielded high activities in Jurkat cells , the LTRs were generally more active in Jurkat cells when compared to the LAI LTR .

While <dna>LTRs</dna> which demonstrated the highest activities in <cell_line>U-373 MG cells</cell_line> also yielded high activities in Jurkat cells , the <dna>LTRs</dna> were generally more active in <cell_line>Jurkat cells</cell_line> when compared to the <dna>LAI LTR</dna> .


Differences in LTR sequence also resulted in differences in transcription factor recruitment to cis-acting sites within the U3 region of the LTR , as demonstrated by electrophoretic mobility shift assays .

Differences in <dna>LTR sequence</dna> also resulted in differences in transcription factor recruitment to <dna>cis-acting sites</dna> within the <dna>U3 region</dna> of the <dna>LTR</dna> , as demonstrated by electrophoretic mobility shift assays .


In particular , naturally occurring sequence variation impacted transcription factor binding to an activating transcription factor/cAMP response element binding ( ATF/CREB ) binding site ( located between the LEF-1 and distal NF-kappaB transcription factor binding sites ) that we identified in previous studies of the HIV-1 LTR .

In particular , naturally occurring sequence variation impacted <protein>transcription factor</protein> binding to an <dna>activating transcription factor/cAMP response element binding ( ATF/CREB ) binding site</dna> ( located between the <dna>LEF-1 and distal NF-kappaB transcription factor binding sites</dna> ) that we identified in previous studies of the <dna>HIV-1 LTR</dna> .


These findings suggest that LTR sequence changes can significantly affect basal LTR function and transcription factor recruitment , which may , in turn , alter the course of viral replication in cells of CNS and immune system origin .

These findings suggest that <dna>LTR sequence</dna> changes can significantly affect basal <dna>LTR</dna> function and <protein>transcription factor</protein> recruitment , which may , in turn , alter the course of viral replication in cells of CNS and immune system origin .


HMG box containing transcription factors in lymphocyte differentiation .

<protein>HMG box</protein> containing <protein>transcription factors</protein> in <cell_type>lymphocyte</cell_type> differentiation .


The identification of the mammalian sex-determining gene Sry has led to the discovery of a large family of related ( ' HMG box ' ) transcription factors that control developmental events in yeast , C. elegans , Drosophila and vertebrates .

The identification of the <dna>mammalian sex-determining gene Sry</dna> has led to the discovery of a large family of related ( ' <protein>HMG box</protein> ' ) <protein>transcription factors</protein> that control developmental events in yeast , C. elegans , Drosophila and vertebrates .


In lymphocyte differentiation , several HMG box proteins play a decisive role .

In <cell_type>lymphocyte</cell_type> differentiation , several <protein>HMG box proteins</protein> play a decisive role .


Sox-4 is important for very early B-cell differentiation , while TCF-1/LEF-1 play a crucial role in early thymocyte development .

<protein>Sox-4</protein> is important for very early B-cell differentiation , while <protein>TCF-1/LEF-1</protein> play a crucial role in early thymocyte development .


TCF/LEF proteins have recently been found to constitute a downstream component of the Wingless/Wnt signal transduction pathway .

<protein>TCF/LEF proteins</protein> have recently been found to constitute a downstream component of the Wingless/Wnt signal transduction pathway .


In flies , this pathway controls segment polarity ; in Xenopus it controls the definition of the body axis .


Deregulation of the pathway occurs in several human tumors .


These insights in the molecular events that are involved in TCF/LEF function in these organisms may eventually lead to the understanding of the function of these HMG box proteins in lymphoid development

These insights in the molecular events that are involved in <protein>TCF/LEF</protein> function in these organisms may eventually lead to the understanding of the function of these <protein>HMG box proteins</protein> in lymphoid development


Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes : application for diagnosis , genetic counseling , and therapy .

Single strand conformation polymorphism analysis of <dna>androgen receptor gene</dna> mutations in patients with androgen insensitivity syndromes : application for diagnosis , genetic counseling , and therapy .


Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes , a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males .

Recent studies indicate that mutations in the <dna>androgen receptor gene</dna> are associated with androgen insensitivity syndromes , a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males .


In this report , we address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis , genetic counseling , and molecular subclassification of affected patients and their families .

In this report , we address the possibility of rapid mutational analysis of the <dna>androgen receptor gene</dna> for initial diagnosis , genetic counseling , and molecular subclassification of affected patients and their families .


DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied .

DNA from <cell_type>peripheral blood leukocytes</cell_type> of six patients from five families with various degrees of androgen insensitivity was studied .


Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing .

<dna>Exons 2 to 8</dna> of the <dna>androgen receptor gene</dna> were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing .


Female family members were also studied to identify heterozygote carriers .


Point mutations in the AR gene were identified in all six patients , and all mutations caused amino acid substitutions .

Point mutations in the <dna>AR gene</dna> were identified in all six patients , and all mutations caused amino acid substitutions .


One patient with incomplete androgen insensitivity was a mosaic for the mutation .


Four of the five mothers , as well as a young sister of one patient , were carriers of the mutation present in the affected child .


Our data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome .

Our data show that new mutations may occur in the <dna>androgen receptor gene</dna> leading to sporadic androgen insensitivity syndrome .


Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy , and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance .

Molecular genetic characterization of the <dna>variant allele</dna> can serve as a primary tool for diagnosis and subsequent therapy , and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance .


The identification of carriers is of substantial clinical importance for genetic counseling .


Proliferation index as a prognostic marker in breast cancer .


BACKGROUND .


The proliferative activity of tumors has been extensively investigated with different approaches , among which the use of the monoclonal antibody Ki-67 represents an easy and reliable means of assessing cell proliferation .

The proliferative activity of tumors has been extensively investigated with different approaches , among which the use of the <protein>monoclonal antibody Ki-67</protein> represents an easy and reliable means of assessing cell proliferation .


In this study , the proliferative activity of 129 primary breast cancers was investigated , and the results were related to prognosis .


METHODS .


Tumor samples , obtained from 129 patients who underwent surgery between January 1987 and December 1988 , were processed for staining by an immunohistochemical procedure ( avidin-biotin complex ) .

Tumor samples , obtained from 129 patients who underwent surgery between January 1987 and December 1988 , were processed for staining by an immunohistochemical procedure ( <protein>avidin-biotin complex</protein> ) .


The median time of observation was 42 months ( range , 31-55 months ) .


Life-table analysis ( Mantel-Cox ) was used to assess the probability of disease-free survival ( DFS ) and overall survival ( OS ) .


RESULTS .


Tumors with high Ki-67 proliferation indices ( > 20 % ) were associated with a higher 4-year probability of relapse of disease ( 55.3 % versus 79.1 % ; P = 0.003 ) and death ( 71 % versus 95.6 % ; P = 0.00005 ) when compared with tumors with low Ki-67 values .

Tumors with high <protein>Ki-67</protein> proliferation indices ( > 20 % ) were associated with a higher 4-year probability of relapse of disease ( 55.3 % versus 79.1 % ; P = 0.003 ) and death ( 71 % versus 95.6 % ; P = 0.00005 ) when compared with tumors with low <protein>Ki-67</protein> values .


In addition , this proliferative parameter maintained its prognostic significance when the patients were stratified according to lymph node involvement , menopausal status , and nuclear estrogen receptor content .

In addition , this proliferative parameter maintained its prognostic significance when the patients were stratified according to lymph node involvement , menopausal status , and <protein>nuclear estrogen receptor</protein> content .


CONCLUSIONS .


Tumor proliferative activity as evaluated by the monoclonal antibody Ki-67 seems to be an effective indicator of prognosis in breast cancer for DFS and OS .

Tumor proliferative activity as evaluated by the <protein>monoclonal antibody Ki-67</protein> seems to be an effective indicator of prognosis in breast cancer for DFS and OS .


Regulation of the Ets-related transcription factor Elf-1 by binding to the retinoblastoma protein .

Regulation of the <protein>Ets-related transcription factor</protein> <protein>Elf-1</protein> by binding to the <protein>retinoblastoma protein</protein> .


The retinoblastoma gene product ( Rb ) is a nuclear phosphoprotein that regulates cell cycle progression .

The <protein>retinoblastoma gene product</protein> ( <protein>Rb</protein> ) is a <protein>nuclear phosphoprotein</protein> that regulates cell cycle progression .


Elf-1 is a lymphoid-specific Ets transcription factor that regulates inducible gene expression during T cell activation .

<protein>Elf-1</protein> is a <protein>lymphoid-specific Ets transcription factor</protein> that regulates inducible gene expression during <cell_type>T cell</cell_type> activation .


In this report , it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo .

In this report , it is demonstrated that <protein>Elf-1</protein> contains a sequence motif that is highly related to the <protein>Rb binding sites</protein> of several viral <protein>oncoproteins</protein> and binds to the pocket region of <protein>Rb</protein> both in vitro and in vivo .


Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from patients with retinoblastoma .

<protein>Elf-1</protein> binds exclusively to the underphosphorylated form of <protein>Rb</protein> and fails to bind to <protein>Rb mutants</protein> derived from patients with retinoblastoma .


Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells .

Co-immunoprecipitation experiments demonstrated an association between <protein>Elf-1</protein> and <protein>Rb</protein> in <cell_type>resting normal human T cells</cell_type> .


After T cell activation , the phosphorylation of Rb results in the release of Elf-1 , which is correlated temporally with the activation of Elf-1 -mediated transcription .

After T cell activation , the phosphorylation of <protein>Rb</protein> results in the release of <protein>Elf-1</protein> , which is correlated temporally with the activation of <protein>Elf-1</protein> -mediated transcription .


Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1 -dependent transcription during T cell activation .

Overexpression of a phosphorylation-defective form of <protein>Rb</protein> inhibited <protein>Elf-1</protein> -dependent transcription during <cell_type>T cell</cell_type> activation .


These results demonstrate that Rb interacts specifically with a lineage-restricted Ets transcription factor .

These results demonstrate that <protein>Rb</protein> interacts specifically with a <protein>lineage-restricted Ets transcription factor</protein> .


This regulated interaction may be important for the coordination of lineage-specific effector functions such as lymphokine production with cell cycle progression in activated T cells .

This regulated interaction may be important for the coordination of lineage-specific effector functions such as <protein>lymphokine</protein> production with cell cycle progression in <cell_type>activated T cells</cell_type> .


Human CD3-CD16+ natural killer cells express the hGATA-3 T cell transcription factor and an unrearranged 2.3-kb TcR delta transcript .

<cell_line>Human CD3-CD16+ natural killer cells</cell_line> express the <protein>hGATA-3 T cell transcription factor</protein> and an unrearranged <protein>2.3-kb TcR delta transcript</protein> .


In this study we analyzed the T cell receptor ( TcR ) delta transcripts expressed by CD3-CD16+ cells and we investigated whether these cells expressed the hGATA-3 T cell transcription factor and the recombination-activating gene ( RAG ) -1 .

In this study we analyzed the <protein>T cell receptor ( TcR ) delta transcripts</protein> expressed by <cell_line>CD3-CD16+ cells</cell_line> and we investigated whether these cells expressed the <protein>hGATA-3 T cell transcription factor</protein> and the <dna>recombination-activating gene ( RAG ) -1</dna> .


Multiple TcR delta transcripts deriving from an unrearranged TcR delta gene were detected in both polyclonal and clonal CD3-CD16+ natural killer ( NK ) cell lines .

Multiple <protein>TcR delta transcripts</protein> deriving from an unrearranged <dna>TcR delta gene</dna> were detected in both <cell_line>polyclonal and clonal CD3-CD16+ natural killer ( NK ) cell lines</cell_line> .


Two unrearranged TcR delta transcripts had a size similar to that of the functional TcR delta mRNA ( 2.3 and 1.3 kb ) found in TcR gamma/delta+ T lymphocytes .

Two unrearranged <protein>TcR delta transcripts</protein> had a size similar to that of the functional <rna>TcR delta mRNA</rna> ( 2.3 and 1.3 kb ) found in <cell_line>TcR gamma/delta+ T lymphocytes</cell_line> .


Sequence analysis of nine different 2.3-kb cDNA clones obtained from NK-derived polyA+ RNA confirmed that they corresponded to an unrearranged TcR delta gene .

Sequence analysis of nine different 2.3-kb cDNA clones obtained from NK-derived polyA+ RNA confirmed that they corresponded to an unrearranged <dna>TcR delta gene</dna> .


These cDNA were 2343 bp long and their transcription initiation site was located 814 bp upstream from the J delta 1 segment .

These cDNA were 2343 bp long and their transcription initiation site was located <dna>814 bp upstream</dna> from the <dna>J delta 1 segment</dna> .


The sequence located upstream of the J delta 1 segment corresponded to the previously reported germ-line sequence .

The sequence located upstream of the <dna>J delta 1 segment</dna> corresponded to the previously reported germ-line sequence .


The J delta 1 segment was correctly spliced to C delta ; in addition the four C delta exons were found to be already assembled .

The <dna>J delta 1 segment</dna> was correctly spliced to <dna>C delta</dna> ; in addition the four C delta exons were found to be already assembled .


Two polyadenylation sites were present in the fourth C delta exon .

Two polyadenylation sites were present in the <dna>fourth C delta exon</dna> .


However , only that located at the 3 ' end appeared to be utilized in the 2.3-kb cDNA .

However , only that located at the 3 ' end appeared to be utilized in the <dna>2.3-kb cDNA</dna> .


The expression of hGATA-3 , a T cell-specific factor known to be involved in the regulation of the transcription of TcR delta locus , was analyzed by Northern blot , in cultured NK cell population and clones ( but not in freshly derived cell populations ) .

The expression of <protein>hGATA-3</protein> , a <protein>T cell-specific factor</protein> known to be involved in the regulation of the transcription of <dna>TcR delta locus</dna> , was analyzed by Northern blot , in cultured <cell_line>NK cell population</cell_line> and clones ( but not in freshly derived cell populations ) .


All NK clones and cell lines studied were found to express hGATA-3-specific mRNA , suggesting that hGATA-3 may be involved in the regulation of the unrearranged TcR delta gene expression in NK cells .

All <cell_line>NK clones</cell_line> and cell lines studied were found to express <rna>hGATA-3-specific mRNA</rna> , suggesting that <protein>hGATA-3</protein> may be involved in the regulation of the unrearranged <dna>TcR delta gene</dna> expression in <cell_type>NK cells</cell_type> .


Finally , no transcription of the RAG-1 gene could be detected in all NK cell lines or clones analyzed .

Finally , no transcription of the <dna>RAG-1 gene</dna> could be detected in all <cell_line>NK cell lines</cell_line> or clones analyzed .


Negative transcriptional regulation of human interleukin 2 ( IL-2 ) gene by glucocorticoids through interference with nuclear transcription factors AP-1 and NF-AT .

Negative transcriptional regulation of <dna>human interleukin 2 ( IL-2 ) gene</dna> by glucocorticoids through interference with <protein>nuclear transcription factors</protein> <protein>AP-1</protein> and <protein>NF-AT</protein> .


IL-2 gene transcription is affected by several nuclear proteins .

<dna>IL-2 gene</dna> transcription is affected by several <protein>nuclear proteins</protein> .


We asked whether dexamethasone ( Dex ) and cyclosporin A ( CsA ) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter .

We asked whether dexamethasone ( Dex ) and cyclosporin A ( CsA ) inhibit <dna>IL-2 gene</dna> transcription by interfering with the activity of <protein>nuclear proteins</protein> that bind to the IL-2 promoter .


Nuclear extracts from primary human T lymphocytes were analyzed by electrophoretic DNA mobility shift assays .

Nuclear extracts from <cell_type>primary human T lymphocytes</cell_type> were analyzed by electrophoretic DNA mobility shift assays .


Both Dex and CsA inhibited the binding of transcription factors AP-1 and NF-AT , but not of NF-kB and OCT-1/OAF , to their corresponding sites on the IL-2 gene promoter .

Both Dex and CsA inhibited the binding of transcription factors <protein>AP-1</protein> and <protein>NF-AT</protein> , but not of <protein>NF-kB</protein> and <protein>OCT-1/OAF</protein> , to their corresponding sites on the <dna>IL-2 gene promoter</dna> .


To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for IL-2 promoter repression , we used transient DNA transfections .

To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for <dna>IL-2 promoter</dna> repression , we used transient DNA transfections .


Jurkat cells were transfected with plasmids containing either the intact IL-2 promoter or its AP-1 , NF-AT , and NF-kB motifs .

<cell_line>Jurkat cells</cell_line> were transfected with <dna>plasmids</dna> containing either the intact <dna>IL-2 promoter</dna> or its <dna>AP-1 , NF-AT , and NF-kB motifs</dna> .


Dex inhibited the IL-2 promoter and the AP-1 , but not the NF-AT and NF-kB plasmids .

Dex inhibited the <dna>IL-2 promoter</dna> and the <dna>AP-1</dna> , but not the <dna>NF-AT</dna> and <dna>NF-kB plasmids</dna> .


In contrast , CsA inhibited the IL-2 promoter and the NF-AT , but not the AP-1 and NF-kB plasmids .

In contrast , CsA inhibited the <dna>IL-2 promoter</dna> and the <dna>NF-AT</dna> , but not the <dna>AP-1</dna> and <dna>NF-kB plasmids</dna> .


These results suggest that in human T lymphocytes both Dex and CsA inhibited IL-2 gene transcription through interference with transcription factors AP-1 and NF-AT .

These results suggest that in <cell_type>human T lymphocytes</cell_type> both Dex and CsA inhibited <dna>IL-2 gene</dna> transcription through interference with <protein>transcription factors</protein> <protein>AP-1</protein> and <protein>NF-AT</protein> .


We propose that , while maximum inhibition may involve interaction with both transcription factors , AP-1 is the primary target of Dex .

We propose that , while maximum inhibition may involve interaction with both <protein>transcription factors</protein> , <protein>AP-1</protein> is the primary target of Dex .


Nuclear factor kappa B , a mediator of lipopolysaccharide effects .

<protein>Nuclear factor kappa B</protein> , a mediator of lipopolysaccharide effects .


Exposure of certain cell types to bacterial lipopolysaccharide ( LPS ) leads to activation of nuclear factor kappa B ( NF-kappa B ) , an inducible transcription factor .

Exposure of certain cell types to bacterial lipopolysaccharide ( LPS ) leads to activation of <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) , an <protein>inducible transcription factor</protein> .


One of NF-kappa B 's unique properties is its posttranslational activation via release of an inhibitory subunit , called inhibitor of NF-kappa B ( I kappa B ) , from a sequestered cytoplasmic form .

One of <protein>NF-kappa B</protein> 's unique properties is its posttranslational activation via release of an <protein>inhibitory subunit</protein> , called <protein>inhibitor of NF-kappa B</protein> ( <protein>I kappa B</protein> ) , from a sequestered cytoplasmic form .


This event is also triggered under various other conditions of biomedical importance .


Other bacterial toxins , tumor necrosis factor-alpha ( TNF ) , interleukin-1 ( IL-1 ) , T cell mitogens , UV light , gamma rays and oxidative stress were reported to induce NF-kappa B .

Other bacterial toxins , <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF</protein> ) , <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) , <protein>T cell mitogens</protein> , UV light , gamma rays and oxidative stress were reported to induce <protein>NF-kappa B</protein> .


The activated form of NF-kappa B , which is rapidly taken up into nuclei , initiates transcription from immediate early genes in a wide variety of cell types .

The activated form of <protein>NF-kappa B</protein> , which is rapidly taken up into nuclei , initiates transcription from immediate early genes in a wide variety of cell types .


Most of the target genes for NF-kappa B are of relevance for the immune response and can be grouped into those encoding cytokines , cell surface receptors , acute phase proteins and viral genomes , such as that of human immunodeficiency virus type 1 ( HIV-1 ) .

Most of the target genes for <protein>NF-kappa B</protein> are of relevance for the immune response and can be grouped into those encoding <protein>cytokines</protein> , <protein>cell surface receptors</protein> , <protein>acute phase proteins</protein> and <dna>viral genomes</dna> , such as that of human immunodeficiency virus type 1 ( HIV-1 ) .


We will discuss recent experimental evidences suggesting that LPS might share a pathway of NF-kappa B activation with other inducers of the factor .

We will discuss recent experimental evidences suggesting that LPS might share a pathway of <protein>NF-kappa B</protein> activation with other inducers of the factor .


This common pathway may involve reactive oxygen intermediates ( ROI ) as messenger molecules .


[ The trend of molecular biology study on eosinophils ]

[ The trend of molecular biology study on <cell_type>eosinophils</cell_type> ]


Recently , many investigators have been interested in the study on eosinophil biology since genes association with eosinophils such as interleukin-5 or eosinophil granule proteins ( EPO , ECP , EDN , MBP , and CLC ) , were isolated .

Recently , many investigators have been interested in the study on <cell_type>eosinophil</cell_type> biology since genes association with <cell_type>eosinophils</cell_type> such as <protein>interleukin-5</protein> or <protein>eosinophil granule proteins</protein> ( <protein>EPO</protein> , <protein>ECP</protein> , <protein>EDN</protein> , <protein>MBP</protein> , and <protein>CLC</protein> ) , were isolated .


However , the molecular basis for the commitment of progenitors to the eosinophil lineage has not been determined .

However , the molecular basis for the commitment of progenitors to the <cell_type>eosinophil lineage</cell_type> has not been determined .


The mechanism by which eosinophil-specific genes encoding primary and secondary granule proteins ( e.g . ECP , EDN , EPO , MBP , and CLC ) are expressed and regulated during eosinophilopoiesis is also unknown .

The mechanism by which <dna>eosinophil-specific genes</dna> encoding primary and <protein>secondary granule proteins</protein> ( e.g . <protein>ECP</protein> , <protein>EDN</protein> , <protein>EPO</protein> , <protein>MBP</protein> , and <protein>CLC</protein> ) are expressed and regulated during eosinophilopoiesis is also unknown .


In this paper , I described the characterization of genes encoding eosinophil granule proteins and the mRNA expression of GATA-1 binding transcription factor during eosinophil differentiation .

In this paper , I described the characterization of genes encoding <protein>eosinophil granule proteins</protein> and the mRNA expression of <protein>GATA-1 binding transcription factor</protein> during eosinophil differentiation .


Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells ( NF-AT ) complex .

Characterization of the nuclear and cytoplasmic components of the <protein>lymphoid-specific nuclear factor</protein> of <cell_type>activated T cells</cell_type> ( <protein>NF-AT</protein> ) complex .


The lymphoid-specific transcription complex , NF-AT , is involved in early gene activation in T cells and is assembled from a pre-existing , T cell restricted cytoplasmic factor and an inducible ubiquitous nuclear component within 30 min after activation through the antigen receptor .

The <protein>lymphoid-specific transcription complex</protein> , <protein>NF-AT</protein> , is involved in early gene activation in <cell_type>T cells</cell_type> and is assembled from a pre-existing , <protein>T cell restricted cytoplasmic factor</protein> and an inducible <protein>ubiquitous</protein> <protein>nuclear component</protein> within 30 min after activation through the <protein>antigen receptor</protein> .


Recent studies have implicated the family of AP1 factors as components of the murine NF-AT complex .

Recent studies have implicated the family of <protein>AP1 factors</protein> as components of the <protein>murine NF-AT complex</protein> .


Evidence is provided here that the nuclear component of human NF-AT contains the phorbol ester-inducible transcription factor AP1 ( Jun/Fos ) .

Evidence is provided here that the nuclear component of <protein>human NF-AT</protein> contains the <protein>phorbol ester-inducible transcription factor AP1</protein> ( <protein>Jun/Fos</protein> ) .


We further characterize which AP1 family members can assume this role .

We further characterize which <protein>AP1 family members</protein> can assume this role .


Antisera to Fos inhibits NF-AT DNA binding as does an oligonucleotide containing a binding site for AP1 .

Antisera to <protein>Fos</protein> inhibits <protein>NF-AT</protein> DNA binding as does an oligonucleotide containing a <dna>binding site for AP1</dna> .


Constitutive expression in vivo of Fos , and to a lesser extent Fra-1 , eliminates the requirement for phorbol 12-myristate 13-acetate ( PMA ) stimulation , leaving NF-AT -directed transcription responsive to calcium ionophore alone .

Constitutive expression in vivo of <protein>Fos</protein> , and to a lesser extent <protein>Fra-1</protein> , eliminates the requirement for phorbol 12-myristate 13-acetate ( PMA ) stimulation , leaving <protein>NF-AT</protein> -directed transcription responsive to calcium ionophore alone .


Overexpression of cJun or JunD , but not JunB , also eliminates the requirement for PMA , indicating that many but not all Jun- and Fos-related proteins functionally activate NF-AT -dependent transcription in the presence of the cytoplasmic component .

Overexpression of <protein>cJun</protein> or <protein>JunD</protein> , but not <protein>JunB</protein> , also eliminates the requirement for PMA , indicating that many but not all <protein>Jun- and Fos-related proteins</protein> functionally activate <protein>NF-AT</protein> -dependent transcription in the presence of the cytoplasmic component .


NF-AT DNA binding can be reconstituted in vitro using semi-purified AP1 proteins mixed with cytosol from T lymphocytes .

<protein>NF-AT</protein> DNA binding can be reconstituted in vitro using <protein>semi-purified AP1 proteins</protein> mixed with cytosol from <cell_type>T lymphocytes</cell_type> .


Fos proteins are not needed for this reconstitution , and although JunB is not functional , it can participate in the NF-AT DNA binding complex .

Fos proteins are not needed for this reconstitution , and although <protein>JunB</protein> is not functional , it can participate in the <protein>NF-AT DNA binding complex</protein> .


Finally , we have partially purified the cytoplasmic component of NF-AT and show by elution and renaturation from SDS-polyacrylamide gel electrophoresis gels that it has a molecular mass between 94 and 116 kDa and may have multiple differentially modified forms .


Glucocorticoid receptors in mononuclear cells of patients with sepsis .

<protein>Glucocorticoid receptors</protein> in <cell_type>mononuclear cells</cell_type> of patients with sepsis .


Glucocorticoid receptor ( GR ) hormone-binding activity was studied by a whole-cell method in mononuclear cells ( MNC ) from peripheral blood of 7 patients during the hemodynamic compensatory phase of sepsis .

<protein>Glucocorticoid receptor</protein> ( <protein>GR</protein> ) hormone-binding activity was studied by a whole-cell method in <cell_type>mononuclear cells</cell_type> ( <cell_type>MNC</cell_type> ) from peripheral blood of 7 patients during the hemodynamic compensatory phase of sepsis .


4 patients were receiving dopamine , which did not affect the GR count .

4 patients were receiving dopamine , which did not affect the <protein>GR</protein> count .


The patients ' plasma cortisol concentrations were normal or slightly elevated .


Despite a wide range , the mean GR count and affinity in MNC from septic patients did not differ from those in normal controls , suggesting that glucocorticoids could still be effective in the hemodynamic compensatory phase of sepsis .

Despite a wide range , the mean <protein>GR</protein> count and affinity in <cell_type>MNC</cell_type> from septic patients did not differ from those in normal controls , suggesting that glucocorticoids could still be effective in the hemodynamic compensatory phase of sepsis .


The impaired transcription factor AP-1 DNA binding activity in lymphocytes derived from subjects with some symptoms of premature aging .

The impaired <protein>transcription factor AP-1</protein> DNA binding activity in <cell_type>lymphocytes</cell_type> derived from subjects with some symptoms of premature aging .


The study of human disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence .


The main feature of cellular senescence in vitro is cessation of cell proliferation .


Down syndrome ( DS ) and neuronal ceroid-lypofuscinosis ( NCL ) are clinically characterized by the premature onset of numerous features normally associated with human aging .


Phytohemagglutinin stimulated lymphocytes derived from DS subjects showed a statistically significant diminished proliferation capacity in comparison with lymphocytes derived from NCL and healthy individuals .

<protein>Phytohemagglutinin</protein> stimulated <cell_type>lymphocytes</cell_type> derived from DS subjects showed a statistically significant diminished proliferation capacity in comparison with <cell_type>lymphocytes</cell_type> derived from NCL and healthy individuals .


We demonstrated , by applying the electrophoretic mobility shift assay , slightly impaired AP-1 DNA binding activity in NCL lymphocytes and strong in DS ones .

We demonstrated , by applying the electrophoretic mobility shift assay , slightly impaired <protein>AP-1</protein> DNA binding activity in <cell_type>NCL lymphocytes</cell_type> and strong in <cell_type>DS ones</cell_type> .


Our results showed that the same molecular mechanisms of proliferation cessation could exist in fibroblasts characterized by replicative senescence and in lymphocytes derived from individuals with premature aging syndromes ( Down

Our results showed that the same molecular mechanisms of proliferation cessation could exist in <cell_type>fibroblasts</cell_type> characterized by replicative senescence and in <cell_type>lymphocytes</cell_type> derived from individuals with premature aging syndromes ( Down


Differential contribution of herpes simplex virus type 1 gene products and cellular factors to the activation of human immunodeficiency virus type 1 provirus .

Differential contribution of <protein>herpes simplex virus type 1 gene products</protein> and <protein>cellular factors</protein> to the activation of human immunodeficiency virus type 1 provirus .


We have previously reported that infection with herpes simplex virus type 1 ( HSV-1 ) activates expression of the human immunodeficiency virus type 1 ( HIV-1 ) provirus in T cells .

We have previously reported that infection with herpes simplex virus type 1 ( HSV-1 ) activates expression of the human immunodeficiency virus type 1 ( HIV-1 ) provirus in <cell_type>T cells</cell_type> .


Activation of the HIV-1 provirus correlated with the activation of binding of 55- and 85-kDa proteins to the kappa B enhancer and binding of the 50-kDa HLP-1 protein to the LBP-1 sequences of the HIV-1 long terminal repeat .

Activation of the HIV-1 provirus correlated with the activation of binding of <protein>55- and 85-kDa proteins</protein> to the <dna>kappa B enhancer</dna> and binding of the <protein>50-kDa HLP-1 protein</protein> to the <dna>LBP-1 sequences</dna> of the <dna>HIV-1 long terminal repeat</dna> .


Further examination of this system has shown that the inhibition of HSV-1 replication by the antiviral drug acyclovir does not inhibit HSV-1-mediated induction of HIV-1 provirus .


Surprisingly , the NF-kappa B and HLP-1 binding activities were substantially inhibited in acyclovir-treated cells .

Surprisingly , the <protein>NF-kappa B</protein> and HLP-1 binding activities were substantially inhibited in <cell_line>acyclovir-treated cells</cell_line> .


In the transient-transfection assay , ICP0 , but not ICP4 , activated the HIV-1 long terminal repeat promoter region and the effect of ICP0 was greatly enhanced in the presence of the NF-kappa B binding proteins , suggesting that induction of the HIV-1 provirus involves cooperation between the HSV-1-activated cellular factor , NF-kappa B , and the virus-encoded transactivator , ICP0 .

In the transient-transfection assay , <protein>ICP0</protein> , but not <protein>ICP4</protein> , activated the <dna>HIV-1 long terminal repeat promoter region</dna> and the effect of <protein>ICP0</protein> was greatly enhanced in the presence of the <protein>NF-kappa B binding proteins</protein> , suggesting that induction of the HIV-1 provirus involves cooperation between the <protein>HSV-1-activated cellular factor</protein> , <protein>NF-kappa B</protein> , and the <protein>virus-encoded transactivator</protein> , <protein>ICP0</protein> .


Transcriptional activation of the macrophage colony-stimulating factor gene by IL-2 is associated with secretion of bioactive macrophage colony-stimulating factor protein by monocytes and involves activation of the transcription factor NF-kappa B .

Transcriptional activation of the <dna>macrophage colony-stimulating factor gene</dna> by <protein>IL-2</protein> is associated with secretion of bioactive <protein>macrophage colony-stimulating factor protein</protein> by <cell_type>monocytes</cell_type> and involves activation of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> .


Human peripheral blood monocytes ( Mo ) constitutively display the beta-chain of the receptor for IL-2 , whereas expression of the IL-2R alpha-chain is not constitutive but inducible with IL-2 .

<cell_type>Human peripheral blood monocytes</cell_type> ( <cell_type>Mo</cell_type> ) constitutively display the beta-chain of the receptor for <protein>IL-2</protein> , whereas expression of the <protein>IL-2R alpha-chain</protein> is not constitutive but inducible with <protein>IL-2</protein> .


Here we report that binding of human IL-2 to its binding site leads to transcriptional activation of the macrophage CSF ( M-CSF ) gene in Mo resulting in accumulation of M-CSF mRNA and subsequent release of bioactive M-CSF protein as demonstrated by ELISA and inhibition of IL-2 induced release of an activity-stimulating growth of monocyte-type colonies by a neutralizing anti-M-CSF antibody .

Here we report that binding of <protein>human IL-2</protein> to its binding site leads to transcriptional activation of the <dna>macrophage CSF ( M-CSF ) gene</dna> in <cell_type>Mo</cell_type> resulting in accumulation of <rna>M-CSF mRNA</rna> and subsequent release of bioactive <protein>M-CSF protein</protein> as demonstrated by ELISA and inhibition of <protein>IL-2</protein> induced release of an activity-stimulating growth of <cell_line>monocyte-type colonies</cell_line> by a neutralizing <protein>anti-M-CSF antibody</protein> .


Transcriptional activation of the M-CSF gene by IL-2 is preceded by enhanced binding activity of the transcription factor NF-kappa B to its recognition sequence in the 5 ' regulatory enhancer region of the M-CSF gene .

Transcriptional activation of the <dna>M-CSF gene</dna> by <protein>IL-2</protein> is preceded by enhanced binding activity of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> to its recognition sequence in the 5 ' regulatory enhancer region of the <dna>M-CSF gene</dna> .