Conversely , RS cells of virtually all HIV-HD express the EBV-encoded latent membrane protein 1 ( LMP1 ) , which , being functionally homologous to CD40 , may contribute , at least in part , to the modulation of the HIV-HD phenotype .

Conversely , <cell_line>RS cells</cell_line> of virtually all HIV-HD express the <protein>EBV-encoded latent membrane protein 1</protein> ( <protein>LMP1</protein> ) , which , being functionally homologous to <protein>CD40</protein> , may contribute , at least in part , to the modulation of the HIV-HD phenotype .


MDS1/EVI1 enhances TGF-beta1 signaling and strengthens its growth-inhibitory effect but the leukemia-associated fusion protein AML1/MDS1/EVI1 , product of the t ( 3 ; 21 ) , abrogates growth-inhibition in response to TGF-beta1 .

<dna>MDS1/EVI1</dna> enhances <protein>TGF-beta1</protein> signaling and strengthens its growth-inhibitory effect but the <protein>leukemia-associated fusion protein</protein> <protein>AML1/MDS1/EVI1</protein> , product of the t ( 3 ; 21 ) , abrogates growth-inhibition in response to <protein>TGF-beta1</protein> .


MDS1/EVI1 , located on chromosome 3 band q26 , encodes a zinc-finger DNA-binding transcription activator not detected in normal hematopoietic cells but expressed in several normal tissues .

<dna>MDS1/EVI1</dna> , located on <dna>chromosome 3 band q26</dna> , encodes a <protein>zinc-finger DNA-binding transcription activator</protein> not detected in <cell_type>normal hematopoietic cells</cell_type> but expressed in several normal tissues .


MDS1/EVI1 is inappropriately activated in myeloid leukemias following chromosomal rearrangements involving band 3q26 .

<dna>MDS1/EVI1</dna> is inappropriately activated in <cell_type>myeloid leukemias</cell_type> following chromosomal rearrangements involving <protein>band 3q26</protein> .


The rearrangements lead either to gene truncation , and to expression of the transcription repressor EVI1 , as seen in the t ( 3 ; 3 ) ( q21 ; q26 ) and inv ( 3 ) ( q21q26 ) , or to gene fusion , as seen in the t ( 3 ; 21 ) ( q26 ; q22 ) which results in the fusion protein AML1/MDS1/EVI1 .

The rearrangements lead either to gene truncation , and to expression of the <protein>transcription repressor EVI1</protein> , as seen in the <dna>t ( 3 ; 3 ) ( q21 ; q26 )</dna> and <dna>inv ( 3 ) ( q21q26 )</dna> , or to gene fusion , as seen in the <dna>t ( 3 ; 21 ) ( q26 ; q22 )</dna> which results in the fusion protein <protein>AML1/MDS1/EVI1</protein> .


This fusion protein contains the DNA-binding domain of the transcription factor AML1 fused in-frame to the entire MDS1/EVI1 with the exclusion of its first 12 amino acids .

This fusion protein contains the <protein>DNA-binding domain</protein> of the <protein>transcription factor</protein> <protein>AML1</protein> fused in-frame to the entire <dna>MDS1/EVI1</dna> with the exclusion of its first 12 amino acids .


In this report , we have analyzed the response of the hematopoietic precursor cell line 32Dcl3 , expressing either the normal protein MDS1/EVI1 or the fusion protein AML1/MDS1/EVI1 , to factors that control cell differentiation or cell replication .

In this report , we have analyzed the response of the <cell_line>hematopoietic precursor cell line 32Dcl3</cell_line> , expressing either the <protein>normal protein MDS1/EVI1</protein> or the <protein>fusion protein AML1/MDS1/EVI1</protein> , to factors that control cell differentiation or cell replication .


The 32Dcl3 cells are IL-3 -dependent for growth and they differentiate into granulocytes when exposed to G-CSF .

The <cell_line>32Dcl3 cells</cell_line> are <protein>IL-3</protein> -dependent for growth and they differentiate into granulocytes when exposed to <protein>G-CSF</protein> .


They are growth-inhibited by TGF-beta1 .

They are growth-inhibited by <protein>TGF-beta1</protein> .


We show that whereas the expression of MDS1/EVI1 has no effect on granulocytic differentiation induced by G-CSF , expression of AML1/MDS1/EVI1 blocks differentiation resulting in cell death .

We show that whereas the expression of <dna>MDS1/EVI1</dna> has no effect on granulocytic differentiation induced by <protein>G-CSF</protein> , expression of <protein>AML1/MDS1/EVI1</protein> blocks differentiation resulting in cell death .


This effect is similar to that previously described by others for 32Dcl3 cells that express transgenic Evil .

This effect is similar to that previously described by others for <cell_line>32Dcl3 cells</cell_line> that express <protein>transgenic Evil</protein> .


Furthermore , we show that whereas the expression of the fusion protein AML1/MDS1/EVI1 completely abrogates the growth-inhibitory effect of TGF-beta1 and allows 32Dcl3 cells to proliferate , expression of the normal protein MDS1/EVI1 has the opposite effect , and it strengthens the response of cells to the growth-inhibitory effect of TGF-beta1 .

Furthermore , we show that whereas the expression of the fusion protein <protein>AML1/MDS1/EVI1</protein> completely abrogates the growth-inhibitory effect of <protein>TGF-beta1</protein> and allows <cell_line>32Dcl3 cells</cell_line> to proliferate , expression of the normal protein <dna>MDS1/EVI1</dna> has the opposite effect , and it strengthens the response of cells to the growth-inhibitory effect of <protein>TGF-beta1</protein> .


By using the yeast two-hybrid system , we also show that EVI1 ( contained in its entirety in MDS1/EVI1 and AML1/MDS1/EVI1 ) physically interacts with SMAD3 , which is an intracellular mediator of TGF-beta1 signaling .

By using the yeast two-hybrid system , we also show that <protein>EVI1</protein> ( contained in its entirety in <dna>MDS1/EVI1</dna> and <protein>AML1/MDS1/EVI1</protein> ) physically interacts with <protein>SMAD3</protein> , which is an intracellular mediator of <protein>TGF-beta1</protein> signaling .


Finally , we have correlated the response of the cells to G-CSF or TGF-beta1 with the ability of the normal and fusion proteins to activate or repress promoters which they can directly regulate by binding to the promoter site .

Finally , we have correlated the response of the cells to <protein>G-CSF</protein> or <protein>TGF-beta1</protein> with the ability of the normal and <protein>fusion proteins</protein> to activate or repress promoters which they can directly regulate by binding to the <dna>promoter site</dna> .


We propose that mutations of MDS1/EVI1 either by gene truncation resulting in the transcription repressor EVI1 or by gene fusion to AML1 lead to an altered cellular response to growth and differentiation factors that could result in leukemic transformation .

We propose that mutations of <dna>MDS1/EVI1</dna> either by gene truncation resulting in the <protein>transcription repressor EVI1</protein> or by gene fusion to <protein>AML1</protein> lead to an altered cellular response to growth and <protein>differentiation factors</protein> that could result in leukemic transformation .


The different response of myeloid cells ectopically expressing the normal or the fusion protein to G-CSF and TGF-beta1 could depend on the different transactivation properties of these proteins resulting in divergent expression of downstream genes regulated by the two proteins .

The different response of myeloid cells ectopically expressing the normal or the <protein>fusion protein</protein> to <protein>G-CSF</protein> and <protein>TGF-beta1</protein> could depend on the different transactivation properties of these proteins resulting in divergent expression of <dna>downstream genes</dna> regulated by the two proteins .


Abnormalities of cyclic adenosine monophosphate signaling in platelets from untreated patients with bipolar disorder .

Abnormalities of cyclic adenosine monophosphate signaling in <cell_type>platelets</cell_type> from untreated patients with bipolar disorder .


BACKGROUND : Abnormalities in the cyclic adenosine monophosphate ( cAMP ) -dependent phosphorylation system have been recently reported in patients with bipolar disorder .


We evaluated the immunoreactivity of the regulatory and catalytic subunits of cAMP-dependent protein kinase ( protein kinase A ) and 1 of its substrates , Rap1 , in platelets from untreated euthymic , manic , and depressed patients with bipolar disorder and healthy subjects .

We evaluated the immunoreactivity of the <protein>regulatory and catalytic subunits</protein> of <protein>cAMP-dependent protein kinase</protein> ( <protein>protein kinase A</protein> ) and 1 of its substrates , <protein>Rap1</protein> , in <cell_type>platelets</cell_type> from untreated euthymic , manic , and depressed patients with bipolar disorder and healthy subjects .


METHODS : Platelets were collected from 112 drug-free patients with bipolar disorder ( 52 euthymic , 29 depressed , and 31 manic ) and 62 healthy subjects .

METHODS : <cell_type>Platelets</cell_type> were collected from 112 drug-free patients with bipolar disorder ( 52 euthymic , 29 depressed , and 31 manic ) and 62 healthy subjects .


The levels of cAMP-dependent protein kinase and Rap1 were assessed by Western blot analysis , immunostaining , and computer-assisted imaging .

The levels of <protein>cAMP-dependent protein kinase</protein> and <protein>Rap1</protein> were assessed by Western blot analysis , immunostaining , and computer-assisted imaging .


RESULTS : The immunolabeling of the catalytic subunit of cAMP-dependent protein kinase was significantly different among groups ( P < .001 ) , with higher values in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects .

RESULTS : The immunolabeling of the <protein>catalytic subunit</protein> of <protein>cAMP-dependent protein kinase</protein> was significantly different among groups ( P < .001 ) , with higher values in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects .


No significant differences were found in the immunolabeling of the regulatory subunits ( type I and type II ) of cAMP-dependent protein kinase .

No significant differences were found in the immunolabeling of the <protein>regulatory subunits</protein> ( type I and type II ) of <protein>cAMP-dependent protein kinase</protein> .


The immunolabeling of Rap1 was significantly higher ( P < .001 ) in untreated euthymic , depressed , and manic patients than in healthy persons .

The immunolabeling of <protein>Rap1</protein> was significantly higher ( P < .001 ) in untreated euthymic , depressed , and manic patients than in healthy persons .


CONCLUSIONS : Levels of Rap1 and the catalytic subunit of cAMP-dependent protein kinase are altered in the platelets of bipolar patients .

CONCLUSIONS : Levels of <protein>Rap1</protein> and the <protein>catalytic subunit</protein> of <protein>cAMP-dependent protein kinase</protein> are altered in the <cell_type>platelets</cell_type> of bipolar patients .


These findings may provide clues toward understanding the involvement of cAMP signaling in the pathogenesis of bipolar disorder .


Molecular regulation of cytokine gene expression during the immune response .

Molecular regulation of <dna>cytokine gene</dna> expression during the immune response .


Cytokine expression by immune system cells plays an important role in the regulation of the immune response .

<protein>Cytokine</protein> expression by immune system cells plays an important role in the regulation of the immune response .


On first encounter with antigen , naive CD4+ T helper ( Th ) cells differentiate into cytokine-producing effector cells .

On first encounter with antigen , <cell_type>naive CD4+ T helper ( Th ) cells</cell_type> differentiate into <cell_line>cytokine-producing effector cells</cell_line> .


Two types of effector cells characterized by their distinct expression of cytokine profiles have been described .

Two types of effector cells characterized by their distinct expression of <protein>cytokine</protein> profiles have been described .


Th1 cells produce IL-2 and IFN-gamma , whereas Th2 cells produce IL-4 , IL-5 , IL-6 , IL-10 , and IL-13 .

Th1 cells produce <protein>IL-2</protein> and <protein>IFN-gamma</protein> , whereas <cell_line>Th2 cells</cell_line> produce <protein>IL-4</protein> , <protein>IL-5</protein> , <protein>IL-6</protein> , <protein>IL-10</protein> , and <protein>IL-13</protein> .


In many pathological situations , the balance between Th1 and Th2 immune responses determines the outcome of diverse immunologically mediated clinical syndromes including infectious , autoimmune , and allergic diseases .


However , the molecular basis for the tissue-specific expression of Th1/Th2-like cytokines has remained elusive .

However , the molecular basis for the tissue-specific expression of <protein>Th1/Th2-like cytokines</protein> has remained elusive .


In this review we evaluate the possible in vivo role of different transcription factors and transcriptional mechanisms in T cell differentiation and the immune response .


Tcf-1 -mediated transcription in T lymphocytes : differential role for glycogen synthase kinase-3 in fibroblasts and T cells .

<protein>Tcf-1</protein> -mediated transcription in <cell_type>T lymphocytes</cell_type> : differential role for <protein>glycogen synthase kinase-3</protein> in <cell_type>fibroblasts</cell_type> and <cell_type>T cells</cell_type> .


Beta-catenin is the vertebrate homolog of the Drosophila segment polarity gene Armadillo and plays roles in both cell-cell adhesion and transduction of the Wnt signaling cascade .

Beta-catenin is the vertebrate homolog of the <dna>Drosophila segment polarity gene</dna> <dna>Armadillo</dna> and plays roles in both cell-cell adhesion and transduction of the Wnt signaling cascade .


Recently , members of the Lef/Tcf transcription factor family have been identified as protein partners of beta-catenin , explaining how beta-catenin alters gene expression .

Recently , members of the <protein>Lef/Tcf transcription factor family</protein> have been identified as protein partners of <protein>beta-catenin</protein> , explaining how <protein>beta-catenin</protein> alters gene expression .


Here we report that in T cells , Tcf-1 also becomes transcriptionally active through interaction with beta-catenin , suggesting that the Wnt signal transduction pathway is operational in T lymphocytes as well .

Here we report that in <cell_type>T cells</cell_type> , <protein>Tcf-1</protein> also becomes transcriptionally active through interaction with <protein>beta-catenin</protein> , suggesting that the Wnt signal transduction pathway is operational in <cell_type>T lymphocytes</cell_type> as well .


However , although Wnt signals are known to inhibit the activity of the negative regulatory protein kinase glycogen synthase kinase-3beta ( GSK-3beta ) , resulting in increased levels of beta-catenin , we find no evidence for involvement of GSK-3beta in Tcf-mediated transcription in T cells .

However , although Wnt signals are known to inhibit the activity of the <protein>negative regulatory protein kinase</protein> <protein>glycogen synthase kinase-3beta</protein> ( <protein>GSK-3beta</protein> ) , resulting in increased levels of <protein>beta-catenin</protein> , we find no evidence for involvement of <protein>GSK-3beta</protein> in Tcf-mediated transcription in <cell_type>T cells</cell_type> .


That is , a dominant negative GSK-3beta does not specifically activate Tcf transcription and stimuli ( lithium or phytohemagglutinin ) that inhibit GSK-3beta activity also do not activate Tcf reporter genes .

That is , a <protein>dominant negative GSK-3beta</protein> does not specifically activate Tcf transcription and stimuli ( lithium or <protein>phytohemagglutinin</protein> ) that inhibit <protein>GSK-3beta</protein> activity also do not activate <dna>Tcf reporter genes</dna> .


Thus , inhibition of GSK-3beta is insufficient to activate Tcf-dependent transcription in T lymphocytes .

Thus , inhibition of <protein>GSK-3beta</protein> is insufficient to activate Tcf-dependent transcription in <cell_type>T lymphocytes</cell_type> .


In contrast , in C57MG fibroblast cells , lithium inactivates GSK-3beta and induces Tcf-controlled transcription .

In contrast , in <cell_line>C57MG fibroblast cells</cell_line> , lithium inactivates <protein>GSK-3beta</protein> and induces Tcf-controlled transcription .


This is the first demonstration that lithium can alter gene expression of Tcf-responsive genes , and points to a difference in regulation of Wnt signaling between fibroblasts and lymphocytes .

This is the first demonstration that lithium can alter gene expression of <dna>Tcf-responsive genes</dna> , and points to a difference in regulation of Wnt signaling between <cell_type>fibroblasts</cell_type> and <cell_type>lymphocytes</cell_type> .


SHP2-interacting transmembrane adaptor protein ( SIT ) , a novel disulfide-linked dimer regulating human T cell activation .

<protein>SHP2-interacting transmembrane adaptor protein</protein> ( <protein>SIT</protein> ) , a novel <protein>disulfide-linked dimer</protein> regulating human T cell activation .


T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology ( SH ) 2 domain-containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs .

<cell_type>T lymphocytes</cell_type> express several <protein>low molecular weight transmembrane adaptor proteins</protein> that recruit <protein>src homology ( SH ) 2 domain-containing intracellular molecules</protein> to the cell membrane via tyrosine-based signaling motifs .


We describe here a novel molecule of this group termed SIT ( SHP2 interacting transmembrane adaptor protein ) .

We describe here a novel molecule of this group termed <protein>SIT</protein> ( <protein>SHP2 interacting transmembrane adaptor protein</protein> ) .


SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes .

<protein>SIT</protein> is a <protein>disulfide-linked homodimeric glycoprotein</protein> that is expressed in <cell_type>lymphocytes</cell_type> .


After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain-containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif .

After tyrosine phosphorylation by <protein>src</protein> and possibly <protein>syk</protein> <protein>protein tyrosine kinases</protein> <protein>SIT</protein> recruits the <protein>SH2 domain-containing tyrosine phosphatase</protein> <protein>SHP2</protein> via an immunoreceptor tyrosine-based inhibition motif .


Overexpression of SIT in Jurkat cells downmodulates T cell receptor- and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells ( NF-AT ) by interfering with signaling processes that are probably located upstream of activation of phospholipase C .

Overexpression of <protein>SIT</protein> in <cell_line>Jurkat cells</cell_line> downmodulates T cell receptor- and phytohemagglutinin-mediated activation of the <protein>nuclear factor of activated T cells</protein> ( <protein>NF-AT</protein> ) by interfering with signaling processes that are probably located upstream of activation of <protein>phospholipase C</protein> .


However , binding of SHP2 to SIT is not required for inhibition of NF-AT induction , suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2 .

However , binding of <protein>SHP2</protein> to <protein>SIT</protein> is not required for inhibition of <protein>NF-AT</protein> induction , suggesting that <protein>SIT</protein> not only regulates <protein>NF-AT</protein> activity but also controls <protein>NF-AT</protein> unrelated pathways of T cell activation involving <protein>SHP2</protein> .


Extracellular-regulated kinase 1/2 , Jun N-terminal kinase , and c-Jun are involved in NF-kappa B -dependent IL-6 expression in human monocytes .

<protein>Extracellular-regulated kinase 1/2</protein> , <protein>Jun N-terminal kinase</protein> , and <protein>c-Jun</protein> are involved in <protein>NF-kappa B</protein> -dependent <protein>IL-6</protein> expression in human monocytes .


In the present study we investigated the possible involvement of the mitogen-activated protein kinase family members extracellular-regulated kinase 1/2 ( ERK1/2 ) and c- Jun N-terminal kinase ( JNK ) in mediating IL-6 gene expression in human monocytes , in particular their role in enhancing NF-kappa B activity .

In the present study we investigated the possible involvement of the <protein>mitogen-activated protein kinase family</protein> members <protein>extracellular-regulated kinase 1/2</protein> ( <protein>ERK1/2</protein> ) and c- <protein>Jun N-terminal kinase</protein> ( <protein>JNK</protein> ) in mediating <protein>IL-6</protein> gene expression in <cell_type>human monocytes</cell_type> , in particular their role in enhancing <protein>NF-kappa B</protein> activity .


Freshly isolated monocytes treated with the protein phosphatase inhibitor okadaic acid secreted high levels of IL-6 protein , which coincided with enhanced binding activity of NF-kappa B as well as with phosphorylation and activation of the ERK1/2 and JNK proteins .

Freshly isolated monocytes treated with the protein phosphatase inhibitor okadaic acid secreted high levels of <protein>IL-6 protein</protein> , which coincided with enhanced binding activity of <protein>NF-kappa B</protein> as well as with phosphorylation and activation of the <protein>ERK1/2 and JNK proteins</protein> .


The ERK pathway-specific inhibitor PD98059 inhibited IL-6 secretion from monocytes .

The ERK pathway-specific inhibitor PD98059 inhibited <protein>IL-6</protein> secretion from <cell_type>monocytes</cell_type> .


Transient overexpression of inactive mutants of either Raf-1 or JNK1 showed that both pathways were involved in kappa B-dependent IL-6 promoter activity .

Transient overexpression of inactive mutants of either <protein>Raf-1</protein> or <protein>JNK1</protein> showed that both pathways were involved in kappa B-dependent <protein>IL-6</protein> promoter activity .


By using PD98059 , we demonstrated that the Raf1/MEK1/ ERK1/2 pathway did not affect the DNA binding of NF-kappa B but , rather , acted at the level of transcriptional activity of NF-kappa B .

By using PD98059 , we demonstrated that the Raf1/MEK1/ <protein>ERK1/2</protein> pathway did not affect the DNA binding of <protein>NF-kappa B</protein> but , rather , acted at the level of transcriptional activity of <protein>NF-kappa B</protein> .


Interestingly , it was shown that NF-kappa B -mediated gene transcription , both in the context of the IL-6 promoter as well as on its own , was dependent on both serine kinase activity and interaction with c-Jun protein .

Interestingly , it was shown that <protein>NF-kappa B</protein> -mediated gene transcription , both in the context of the <dna>IL-6 promoter</dna> as well as on its own , was dependent on both serine kinase activity and interaction with <protein>c-Jun protein</protein> .


We conclude that okadaic acid-induced IL-6 gene expression is at least partly mediated through the ERK1/2 and JNK pathway-dependent activation of NF-kappa B transcriptional capacity .

We conclude that okadaic acid-induced <protein>IL-6</protein> gene expression is at least partly mediated through the <protein>ERK1/2</protein> and <protein>JNK</protein> pathway-dependent activation of <protein>NF-kappa B</protein> transcriptional capacity .


Our results suggest that the JNK pathway may regulate NF-kappa B -mediated gene transcription through its phosphorylation and activation of c-Jun .

Our results suggest that the <protein>JNK</protein> pathway may regulate <protein>NF-kappa B</protein> -mediated gene transcription through its phosphorylation and activation of <protein>c-Jun</protein> .


The Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) , a protein required for B lymphocyte immortalization , induces the synthesis of type I interferon in Burkitt 's lymphoma cell lines .

The <protein>Epstein-Barr virus nuclear antigen 2</protein> ( <protein>EBNA2</protein> ) , a protein required for <cell_type>B lymphocyte</cell_type> immortalization , induces the synthesis of <protein>type I interferon</protein> in <cell_line>Burkitt 's lymphoma cell lines</cell_line> .


Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) , a protein involved in cell transformation , interferes with the cellular response to type I interferons ( IFN-alpha/beta ) .

<protein>Epstein-Barr virus nuclear antigen 2</protein> ( <protein>EBNA2</protein> ) , a protein involved in cell transformation , interferes with the cellular response to <protein>type I interferons</protein> ( <protein>IFN-alpha/beta</protein> ) .


We investigated the function of conditionally expressed EBNA2 in the context of the IFN response in Burkitt 's lymphoma cell lines .

We investigated the function of conditionally expressed <protein>EBNA2</protein> in the context of the <protein>IFN</protein> response in <cell_line>Burkitt 's lymphoma cell lines</cell_line> .


Expression of EBNA2 led to the transcriptional activation of both endogenous or transfected IFN-stimulated genes ( ISGs ) , genes which contain within their promoters either the interferon-stimulated response element ( ISRE ) or the gamma interferon activation site ( GAS ) .

Expression of <protein>EBNA2</protein> led to the transcriptional activation of both endogenous or transfected <dna>IFN-stimulated genes</dna> ( <dna>ISGs</dna> ) , genes which contain within their <dna>promoters</dna> either the <dna>interferon-stimulated response element</dna> ( <dna>ISRE</dna> ) or the <dna>gamma interferon activation site</dna> ( <dna>GAS</dna> ) .


In search of a molecular mechanism for the transcriptional induction of ISGs , we observed an EBNA2 -dependent synthesis of IFN-beta mRNA at low levels and the secretion of low amounts of IFN .

In search of a molecular mechanism for the transcriptional induction of <dna>ISGs</dna> , we observed an <protein>EBNA2</protein> -dependent synthesis of IFN-beta mRNA at low levels and the secretion of low amounts of IFN .


A transfected IFN-beta promoter responded to EBNA2 activation , and a sequence closely resembling a RBP-Jkappa binding site was pinpointed as a potential target of EBNA2 activity .

A transfected IFN-beta promoter responded to <protein>EBNA2</protein> activation , and a sequence closely resembling a <dna>RBP-Jkappa binding site</dna> was pinpointed as a potential target of <protein>EBNA2</protein> activity .


EBNA2 -dependent transcriptional induction of the IFN-beta promoter occurred in EBV-negative Burkitt 's lymphoma cells , indicating that other EBV genes were not required for the induction of IFN-beta synthesis .

<protein>EBNA2</protein> -dependent transcriptional induction of the <dna>IFN-beta promoter</dna> occurred in <cell_line>EBV-negative Burkitt 's lymphoma cells</cell_line> , indicating that other <dna>EBV genes</dna> were not required for the induction of <protein>IFN-beta</protein> synthesis .


PGG-glucan , a soluble beta- ( 1 , 3 ) -glucan , enhances the oxidative burst response , microbicidal activity , and activates an NF-kappa B-like factor in human PMN : evidence for a glycosphingolipid beta- ( 1 , 3 ) -glucan receptor .

PGG-glucan , a soluble beta- ( 1 , 3 ) -glucan , enhances the oxidative burst response , microbicidal activity , and activates an <protein>NF-kappa B-like factor</protein> in <cell_type>human PMN</cell_type> : evidence for a <protein>glycosphingolipid beta- ( 1 , 3 ) -glucan receptor</protein> .


PGG-Glucan , a soluble beta- ( 1 , 6 ) -branched beta- ( 1 , 3 ) -linked glucose homopolymer derived from the cell wall of the yeast Saccharomyces cerevisiae , is an immunomodulator which enhances leukocyte anti-infective activity and enhances myeloid and megakaryocyte progenitor proliferation .


Incubation of human whole blood with PGG-Glucan significantly enhanced the oxidative burst response of subsequently isolated blood leukocytes to both soluble and particulate activators in a dose-dependent manner , and increased leukocyte microbicidal activity .

Incubation of human whole blood with PGG-Glucan significantly enhanced the oxidative burst response of <cell_type>subsequently isolated blood leukocytes</cell_type> to both soluble and particulate activators in a dose-dependent manner , and increased leukocyte microbicidal activity .


No evidence for inflammatory cytokine production was obtained under these conditions .

No evidence for inflammatory <protein>cytokine</protein> production was obtained under these conditions .


Electrophoretic mobility shift assays demonstrated that PGG-Glucan induced the activation of an NF-kappaB-like nuclear transcription factor in purified human neutrophils .

Electrophoretic mobility shift assays demonstrated that PGG-Glucan induced the activation of an <protein>NF-kappaB-like nuclear transcription factor</protein> in <cell_type>purified human neutrophils</cell_type> .


The binding of 3H-PGG-Glucan to human leukocyte membranes was specific , concentration-dependent , saturable , and high affinity ( Kd approximately 6 nM ) .


A monoclonal antibody specific to the glycosphingolipid lactosylceramide was able to inhibit activation of the NF-kappaB-like factor by PGG-Glucan , and ligand binding data , including polysaccharide specificity , suggested that the PGG-Glucan binding moiety was lactosylceramide .

A <protein>monoclonal antibody</protein> specific to the glycosphingolipid lactosylceramide was able to inhibit activation of the <protein>NF-kappaB-like factor</protein> by PGG-Glucan , and ligand binding data , including polysaccharide specificity , suggested that the PGG-Glucan binding moiety was lactosylceramide .


These results indicate that PGG-Glucan enhances neutrophil anti-microbial functions and that interaction between this beta-glucan and human neutrophils is mediated by the glycosphingolipid lactosylceramide present at the cell surface .

These results indicate that PGG-Glucan enhances neutrophil anti-microbial functions and that interaction between this beta-glucan and <cell_type>human neutrophils</cell_type> is mediated by the glycosphingolipid lactosylceramide present at the cell surface .


Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes .

Glucocorticoids promote nonphlogistic phagocytosis of <cell_type>apoptotic leukocytes</cell_type> .


Phagocyte recognition , uptake , and nonphlogistic degradation of neutrophils and other leukocytes undergoing apoptosis promote the resolution of inflammation .

Phagocyte recognition , uptake , and nonphlogistic degradation of <cell_type>neutrophils</cell_type> and other <cell_type>leukocytes</cell_type> undergoing apoptosis promote the resolution of inflammation .


This study assessed the effects of anti-inflammatory glucocorticoids on this leukocyte clearance mechanism .


Pretreatment of `` semimature '' 5-day human monocyte-derived macrophages ( M phi ) for 24 h with methylprednisolone , dexamethasone , and hydrocortisone , but not the nonglucocorticoid steroids aldosterone , estradiol , and progesterone , potentiated phagocytosis of apoptotic neutrophils .

Pretreatment of `` semimature '' 5-day <cell_type>human monocyte-derived macrophages</cell_type> ( M phi ) for 24 h with methylprednisolone , dexamethasone , and hydrocortisone , but not the nonglucocorticoid steroids aldosterone , estradiol , and progesterone , potentiated phagocytosis of <cell_type>apoptotic neutrophils</cell_type> .


These effects were specific in that the potentiated phagocytosis of apoptotic neutrophils was completely blocked by the glucocorticoid receptor antagonist RU38486 , and glucocorticoids did not promote 5-day M phi ingestion of opsonized erythrocytes .

These effects were specific in that the potentiated phagocytosis of <cell_type>apoptotic neutrophils</cell_type> was completely blocked by the <protein>glucocorticoid receptor</protein> antagonist RU38486 , and glucocorticoids did not promote 5-day M phi ingestion of <cell_type>opsonized erythrocytes</cell_type> .


Similar glucocorticoid-mediated potentiation was observed with 5-day M phi uptake of alternative apoptotic `` targets '' ( eosinophils and Jurkat T cells ) and in uptake of apoptotic neutrophils by alternative phagocytes ( human glomerular mesangial cells and murine M phi elicited into the peritoneum or derived from bone marrow ) .

Similar glucocorticoid-mediated potentiation was observed with 5-day M phi uptake of alternative apoptotic `` targets '' ( <cell_type>eosinophils</cell_type> and <cell_line>Jurkat T cells</cell_line> ) and in uptake of <cell_type>apoptotic neutrophils</cell_type> by alternative <cell_type>phagocytes</cell_type> ( <cell_type>human glomerular mesangial cells</cell_type> and <cell_line>murine M phi</cell_line> elicited into the peritoneum or derived from bone marrow ) .


Importantly , methylprednisolone-mediated enhancement of the uptake of apoptotic neutrophils did not trigger the release of the chemokines IL-8 and monocyte chemoattractant protein-1 .

Importantly , methylprednisolone-mediated enhancement of the uptake of <cell_type>apoptotic neutrophils</cell_type> did not trigger the release of the <protein>chemokines</protein> <protein>IL-8</protein> and <protein>monocyte chemoattractant protein-1</protein> .


Furthermore , longer-term potentiation by methylprednisolone was observed in maturing human monocyte-derived M phi , with greater increases in 5-day M phi uptake of apoptotic cells being observed the earlier glucocorticoids were added during monocyte maturation into M phi .

Furthermore , longer-term potentiation by methylprednisolone was observed in <cell_line>maturing human monocyte-derived M phi</cell_line> , with greater increases in 5-day <cell_line>M phi</cell_line> uptake of <cell_type>apoptotic cells</cell_type> being observed the earlier glucocorticoids were added during monocyte maturation into <cell_line>M phi</cell_line> .


We conclude that potentiation of nonphlogistic clearance of apoptotic leukocytes by phagocytes is a hitherto unrecognized property of glucocorticoids that has potential implications for therapies aimed at promoting the resolution of inflammatory diseases .

We conclude that potentiation of nonphlogistic clearance of <cell_type>apoptotic leukocytes</cell_type> by <cell_type>phagocytes</cell_type> is a hitherto unrecognized property of glucocorticoids that has potential implications for therapies aimed at promoting the resolution of inflammatory diseases .


1 , 25-Dihydroxyvitamin D3 induces differentiation of a retinoic acid-resistant acute promyelocytic leukemia cell line ( UF-1 ) associated with expression of p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) .

1 , 25-Dihydroxyvitamin D3 induces differentiation of a <cell_line>retinoic acid-resistant acute promyelocytic leukemia cell line</cell_line> ( <cell_line>UF-1</cell_line> ) associated with expression of <protein>p21 ( WAF1/CIP1 )</protein> and <protein>p27 ( KIP1 )</protein> .


Retinoic acid ( RA ) resistance is a serious problem for patients with acute promyelocytic leukemia ( APL ) who are receiving all-trans RA .


However , the mechanisms and strategies to overcome RA resistance by APL cells are still unclear .

However , the mechanisms and strategies to overcome RA resistance by <cell_type>APL cells</cell_type> are still unclear .


The biologic effects of RA are mediated by two distinct families of transcriptional factors : RA receptors ( RARs ) and retinoid X receptors ( RXRs ) .

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


RXRs heterodimerize with 1 , 25-dihydroxyvitamin D3 [ 1 , 25 ( OH ) 2D3 ] receptor ( VDR ) , enabling their efficient transcriptional activation .

<protein>RXRs</protein> heterodimerize with <protein>1 , 25-dihydroxyvitamin D3 [ 1 , 25 ( OH ) 2D3 ] receptor</protein> ( <protein>VDR</protein> ) , enabling their efficient transcriptional activation .


The cyclin-dependent kinase ( cdk ) inhibitor p21 ( WAF1/CIP1 ) has a vitamin D3-responsive element ( VDRE ) in its promoter , and 1 , 25 ( OH ) 2D3 enhances the expression of p21 ( WAF1/CIP1 ) and induces differentiation of selected myeloid leukemic cell lines .

The <protein>cyclin-dependent kinase ( cdk ) inhibitor</protein> <protein>p21 ( WAF1/CIP1 )</protein> has a <dna>vitamin D3-responsive element</dna> ( <dna>VDRE</dna> ) in its <dna>promoter</dna> , and 1 , 25 ( OH ) 2D3 enhances the expression of <protein>p21 ( WAF1/CIP1 )</protein> and induces differentiation of selected <cell_line>myeloid leukemic cell lines</cell_line> .


We have recently established a novel APL cell line ( UF-1 ) with features of RA resistance .

We have recently established a novel <cell_line>APL cell line</cell_line> ( <cell_line>UF-1</cell_line> ) with features of RA resistance .


1 , 25 ( OH ) 2D3 can induce growth inhibition and G1 arrest of UF-1 cells , resulting in differentiation of these cells toward granulocytes .

1 , 25 ( OH ) 2D3 can induce growth inhibition and G1 arrest of <cell_line>UF-1 cells</cell_line> , resulting in differentiation of these cells toward <cell_type>granulocytes</cell_type> .


This 1 , 25 ( OH ) 2D3-induced G1 arrest is enhanced by all-trans RA .


Also , 1 , 25 ( OH ) 2D3 ( 10 ( -10 ) to 10 ( -7 ) mol/L ) in combination with RA markedly inhibits cellular proliferation in a dose- and time-dependent manner .


Associated with these findings , the levels of p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) mRNA and protein increased in these cells .

Associated with these findings , the levels of <protein>p21 ( WAF1/CIP1 )</protein> and <rna>p27 ( KIP1 ) mRNA</rna> and protein increased in these cells .


Northern blot analysis showed that p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) mRNA and protein increased in these cells .

Northern blot analysis showed that <rna>p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) mRNA</rna> and protein increased in these cells .


Northern blot analysis showed that p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) transcripts were induced after 6 hours ' exposure to 1 , 25 ( OH ) 2D3 and then decreased to basal levels over 48 hours .

Northern blot analysis showed that <protein>p21 ( WAF1/CIP1 )</protein> and <protein>p27 ( KIP1 )</protein> transcripts were induced after 6 hours ' exposure to 1 , 25 ( OH ) 2D3 and then decreased to basal levels over 48 hours .


Western blot experiments showed that p21 ( WAF1/CIP1 ) protein levels increased and became detectable after 12 hours of 1 , 25 ( OH ) 2D3 treatment and induction of p27 ( KIP1 ) protein was much more gradual and sustained in UF-1 cells .

Western blot experiments showed that <protein>p21 ( WAF1/CIP1 )</protein> protein levels increased and became detectable after 12 hours of 1 , 25 ( OH ) 2D3 treatment and induction of <protein>p27 ( KIP1 )</protein> protein was much more gradual and sustained in <cell_line>UF-1 cells</cell_line> .


Interestingly , the combination of 1 , 25 ( OH ) 2D3 and RA markedly enhanced the levels of p27 ( KIP1 ) transcript and protein as compared with levels induced by 1 , 25 ( OH ) 2D3 alone .

Interestingly , the combination of 1 , 25 ( OH ) 2D3 and RA markedly enhanced the levels of <protein>p27 ( KIP1 )</protein> transcript and protein as compared with levels induced by 1 , 25 ( OH ) 2D3 alone .


In addition , exogenous p27 ( KIP1 ) expression can enhance the level of CD11b antigen in myeloid leukemic cells .

In addition , exogenous <protein>p27 ( KIP1 )</protein> expression can enhance the level of <protein>CD11b antigen</protein> in <cell_type>myeloid leukemic cells</cell_type> .


In contrast , RA alone can induce G1 arrest of UF-1 cells ; however , it did not result in an increase of p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) transcript and protein expression in RA-resistant cells .

In contrast , RA alone can induce G1 arrest of <cell_line>UF-1 cells</cell_line> ; however , it did not result in an increase of <protein>p21 ( WAF1/CIP1 )</protein> and <protein>p27 ( KIP1 )</protein> transcript and protein expression in RA-resistant cells .


Taken together , we conclude that 1 , 25 ( OH ) 2D3 induces increased expression of cdk inhibitors , which mediates a G1 arrest , and this may be associated with differentiation of RA-resistant UF-1 cells toward mature granulocytes .

Taken together , we conclude that 1 , 25 ( OH ) 2D3 induces increased expression of <protein>cdk inhibitors</protein> , which mediates a G1 arrest , and this may be associated with differentiation of RA-resistant <cell_line>UF-1 cells</cell_line> toward mature <cell_type>granulocytes</cell_type> .


Molecular mechanisms of neutrophil-endothelial cell adhesion induced by redox imbalance .


Previous studies have implicated a role for intracellular thiols in the activation of nuclear factor-kappaB and transcriptional regulation of endothelial cell adhesion molecules .

Previous studies have implicated a role for intracellular thiols in the activation of <protein>nuclear factor-kappaB</protein> and transcriptional regulation of <protein>endothelial cell adhesion molecules</protein> .


This study was designed to determine whether changes in endothelial cell glutathione ( GSH ) or oxidized glutathione ( GSSG ) can alter neutrophil adhesivity and to define the molecular mechanism that underlies this GSSG/GSH-induced adhesion response .


Treatment of human umbilical vein endothelial cell ( HUVEC ) monolayers for 6 hours with 0.2 mmol/L diamide and 1 mmol/L buthionine sulfoximine ( BSO ) decreased GSH levels and increased the ratio of GSSG to GSH without cell toxicity .

Treatment of <cell_line>human umbilical vein endothelial cell ( HUVEC ) monolayers</cell_line> for 6 hours with 0.2 mmol/L diamide and 1 mmol/L buthionine sulfoximine ( BSO ) decreased GSH levels and increased the ratio of GSSG to GSH without cell toxicity .


These redox changes are similar to those observed with anoxia/reoxygenation .


Diamide plus BSO-induced thiol/disulfide imbalance was associated with a biphasic increase in neutrophil adhesion to HUVECs with peak responses observed at 15 minutes ( phase 1 ) and 240 minutes ( phase 2 ) .

Diamide plus BSO-induced thiol/disulfide imbalance was associated with a biphasic increase in <cell_type>neutrophil</cell_type> adhesion to <cell_line>HUVECs</cell_line> with peak responses observed at 15 minutes ( phase 1 ) and 240 minutes ( phase 2 ) .


N-Acetylcysteine treatment attenuated neutrophil adhesion in both phases , which indicated a role for GSH in the adhesion responses .

N-Acetylcysteine treatment attenuated <cell_type>neutrophil</cell_type> adhesion in both phases , which indicated a role for GSH in the adhesion responses .


Interestingly , phase 1 adhesion was inversely correlated with GSH levels but not with the GSSG/GSH ratio , whereas phase 2 neutrophil adhesion was positively correlated with GSSG/GSH ratio but not with GSH levels .

Interestingly , phase 1 adhesion was inversely correlated with GSH levels but not with the GSSG/GSH ratio , whereas phase 2 <cell_type>neutrophil</cell_type> adhesion was positively correlated with GSSG/GSH ratio but not with GSH levels .


Intercellular adhesion molecule-1 and P-selectin-specific monoclonal antibodies attenuated the increased neutrophil adhesion during both phases , whereas an anti-E-selectin monoclonal antibody also attenuated the phase 2 response .

<protein>Intercellular adhesion molecule-1</protein> and <protein>P-selectin-specific monoclonal antibodies</protein> attenuated the increased <cell_type>neutrophil</cell_type> adhesion during both phases , whereas an <protein>anti-E-selectin monoclonal antibody</protein> also attenuated the phase 2 response .


Pretreatment with actinomycin D and cycloheximide or with competing ds-oligonucleotides that contained nuclear factor-kappaB or activator protein-1 cognate DNA sequences significantly attenuated the phase 2 response , which implicated a role for de novo protein synthesis .

Pretreatment with actinomycin D and cycloheximide or with competing ds-oligonucleotides that contained <protein>nuclear factor-kappaB</protein> or <protein>activator protein-1</protein> cognate DNA sequences significantly attenuated the phase 2 response , which implicated a role for de novo protein synthesis .


Surface expression of intercellular adhesion molecule-1 , P-selectin , and E-selectin on HUVECs correlated with the phase 1 and 2 neutrophil adhesion responses .

Surface expression of <protein>intercellular adhesion molecule-1</protein> , <protein>P-selectin</protein> , and <protein>E-selectin</protein> on <cell_line>HUVECs</cell_line> correlated with the phase 1 and 2 <cell_type>neutrophil</cell_type> adhesion responses .


This study demonstrates that changes in endothelial cell GSSG/GSH cause transcription-independent and transcription-dependent surface expression of different endothelial cell adhesion molecules , which leads to a 2-phase neutrophil -endothelial adhesion response .

This study demonstrates that changes in endothelial cell GSSG/GSH cause transcription-independent and transcription-dependent surface expression of different <protein>endothelial cell adhesion molecules</protein> , which leads to a 2-phase <cell_type>neutrophil</cell_type> -endothelial adhesion response .


Glucocorticoid hormone suppression of human neutrophil -mediated tumor cell cytostasis .

Glucocorticoid hormone suppression of human <cell_type>neutrophil</cell_type> -mediated tumor cell cytostasis .


In the present study , we have investigated the effect of glucocorticoid hormones on neutrophil -mediated tumor cell cytostasis and found that hydrocortisone and a synthetic hormone , dexamethasone ( Dex ) , inhibited cytostasis in the presence or absence of tumor necrosis factor-alpha .

In the present study , we have investigated the effect of glucocorticoid hormones on <cell_type>neutrophil</cell_type> -mediated tumor cell cytostasis and found that hydrocortisone and a synthetic hormone , dexamethasone ( Dex ) , inhibited cytostasis in the presence or absence of <protein>tumor necrosis factor-alpha</protein> .


The effect of Dex was completely reversed by a glucocorticoid receptor antagonist , RU38486 .

The effect of Dex was completely reversed by a <protein>glucocorticoid receptor</protein> antagonist , RU38486 .


To clarify the underlying mechanisms , we examined effects of Dex on the binding avidity of beta2 integrin on the neutrophil surface and how these might in turn affect neutrophil -to-tumor cell binding .

To clarify the underlying mechanisms , we examined effects of Dex on the binding avidity of <protein>beta2 integrin</protein> on the <cell_type>neutrophil</cell_type> surface and how these might in turn affect <cell_type>neutrophil</cell_type> -to-tumor cell binding .


Dex was found to inhibit these neutrophil properties , and RU38486 completely suppressed both forms of Dex inhibition .

Dex was found to inhibit these <cell_type>neutrophil</cell_type> properties , and RU38486 completely suppressed both forms of Dex inhibition .


Taken together , our findings suggest that glucocorticoid hormone inhibition of neutrophil -mediated tumor cell cytostasis is at least partially due to a lowering of the ligand binding avidity of beta2 integrin on the neutrophil surface .

Taken together , our findings suggest that glucocorticoid hormone inhibition of <cell_type>neutrophil</cell_type> -mediated tumor cell cytostasis is at least partially due to a lowering of the ligand binding avidity of <protein>beta2 integrin</protein> on the <cell_type>neutrophil</cell_type> surface .


Constitutive activation of an epithelial signal transducer and activator of transcription ( STAT ) pathway in asthma .

Constitutive activation of an epithelial signal transducer and activator of transcription ( <protein>STAT</protein> ) pathway in asthma .


Cytokine effects on immunity and inflammation often depend on the transcription factors termed signal transducers and activators of transcription ( STATs ) , so STAT signaling pathways are candidates for influencing inflammatory disease .

<protein>Cytokine</protein> effects on immunity and inflammation often depend on the <protein>transcription factors</protein> termed <protein>signal transducers and activators of transcription</protein> ( <protein>STATs</protein> ) , so <protein>STAT</protein> signaling pathways are candidates for influencing inflammatory disease .


We reasoned that selective IFN responsiveness of the first STAT family member ( Stat1 ) and Stat1-dependent immune-response genes such as intercellular adhesion molecule-1 ( ICAM-1 ) , IFN regulatory factor-1 ( IRF-1 ) , and Stat1 itself in airway epithelial cells provides a basis for detecting cytokine signaling abnormalities in inflammatory airway disease .

We reasoned that selective <protein>IFN</protein> responsiveness of the first <protein>STAT family member</protein> ( <protein>Stat1</protein> ) and <dna>Stat1-dependent immune-response genes</dna> such as <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) , <protein>IFN regulatory factor-1</protein> ( <protein>IRF-1</protein> ) , and <protein>Stat1</protein> itself in <cell_type>airway epithelial cells</cell_type> provides a basis for detecting <protein>cytokine</protein> signaling abnormalities in inflammatory airway disease .


On the basis of nuclear localization and phosphorylation , we found that epithelial Stat1 ( but not other control transcription factors ) was invariably activated in asthmatic compared with normal control or chronic bronchitis subjects .

On the basis of nuclear localization and phosphorylation , we found that <protein>epithelial Stat1</protein> ( but not other control <protein>transcription factors</protein> ) was invariably activated in asthmatic compared with normal control or chronic bronchitis subjects .


Furthermore , epithelial levels of activated Stat1 correlated with levels of expression for epithelial ICAM-1 , IRF-1 , and Stat1 , and in turn , ICAM-1 levels correlated with T-cell accumulation in tissue .

Furthermore , epithelial levels of activated <protein>Stat1</protein> correlated with levels of expression for <protein>epithelial ICAM-1</protein> , <protein>IRF-1</protein> , and <protein>Stat1</protein> , and in turn , <protein>ICAM-1</protein> levels correlated with T-cell accumulation in tissue .


However , only low levels of IFN-gamma or IFN-gamma-producing cells were detected in airway tissue in all subjects .

However , only low levels of <protein>IFN-gamma</protein> or <cell_type>IFN-gamma-producing cells</cell_type> were detected in airway tissue in all subjects .


The results therefore provide initial evidence linking abnormal behavior of STAT pathways for cytokine signaling to the development of an inflammatory disease .

The results therefore provide initial evidence linking abnormal behavior of <protein>STAT</protein> pathways for <protein>cytokine</protein> signaling to the development of an inflammatory disease .


In that context , the results also change the current scheme for asthma pathogenesis to one that must include a localized gain in transcriptional signal ordinarily used for a T helper 1-type cytokine ( IFN-gamma ) in combination with allergy-driven overproduction of T helper 2-type cytokines .

In that context , the results also change the current scheme for asthma pathogenesis to one that must include a localized gain in transcriptional signal ordinarily used for a <protein>T helper 1-type cytokine</protein> ( <protein>IFN-gamma</protein> ) in combination with allergy-driven overproduction of <protein>T helper 2-type cytokines</protein> .


Leukocyte populations , hormone receptors and apoptosis in eutopic and ectopic first trimester human pregnancies .

<cell_type>Leukocyte populations</cell_type> , <protein>hormone receptors</protein> and apoptosis in eutopic and ectopic first trimester human pregnancies .


The implantation of trophoblast cells at extrauterine sites still results in decidualization .

The implantation of <cell_type>trophoblast cells</cell_type> at extrauterine sites still results in decidualization .


The objective of the present study was to compare decidualization at eutopic and ectopic implantation sites .


Tissues from women undergoing elective termination of uterine pregnancy and from women with ectopic pregnancy were used to detect the presence of cells important for the maintenance of pregnancy , such as BCL-2+ , CD56+ , CD3+ , CD8+ and CD68+ cells , and the presence of oestrogen ( ER ) and progesterone receptors ( PR ) by immunohistochemistry .

Tissues from women undergoing elective termination of uterine pregnancy and from women with ectopic pregnancy were used to detect the presence of cells important for the maintenance of pregnancy , such as <cell_type>BCL-2+ , CD56+ , CD3+ , CD8+ and CD68+ cells</cell_type> , and the presence of <protein>oestrogen ( ER ) and progesterone receptors</protein> ( <protein>PR</protein> ) by immunohistochemistry .


In-situ detection of fragmented DNA was performed to identify apoptotic cells .

In-situ detection of fragmented DNA was performed to identify <cell_type>apoptotic cells</cell_type> .


The percentage of CD3+ cells among all immunocompetent cells in the tubal epithelium was 46.6 % ( 39.9 % of CD3+ were also CD8+ ) ; the other 53.4 % were CD68+ cells .

The percentage of <cell_type>CD3+ cells</cell_type> among all <cell_type>immunocompetent cells</cell_type> in the tubal epithelium was 46.6 % ( 39.9 % of <cell_type>CD3+</cell_type> were also <cell_type>CD8+</cell_type> ) ; the other 53.4 % were <cell_type>CD68+ cells</cell_type> .


CD56+ cells were undetectable in ectopic decidua at the feto-maternal interface in ectopic tissue .

<cell_type>CD56+ cells</cell_type> were undetectable in ectopic decidua at the feto-maternal interface in ectopic tissue .


In uterine decidua , we found 29.9 % CD3+ cells ( 2.2 % of CD3+ were CD8+ ) , 51.6 % CD56+ cells and 18.5 % CD68+ cells .

In uterine decidua , we found 29.9 % <cell_type>CD3+ cells</cell_type> ( 2.2 % of CD3+ were CD8+ ) , 51.6 % <cell_type>CD56+ cells</cell_type> and 18.5 % <cell_type>CD68+ cells</cell_type> .


The ratio of BCL2+ to CD3+ cells in ectopic pregnancy was 0.41 .

The ratio of <cell_type>BCL2+</cell_type> to <cell_type>CD3+ cells</cell_type> in ectopic pregnancy was 0.41 .


In uterine pregnancy , the ratio of BCL-2 to CD3 was 0.44 and 0.39 for CD56 .

In uterine pregnancy , the ratio of <protein>BCL-2</protein> to CD3 was 0.44 and 0.39 for CD56 .


Tissues from both ectopic and uterine pregnancies were positive for PR .

Tissues from both ectopic and uterine pregnancies were positive for <protein>PR</protein> .


Fewer apoptotic cell bodies were present in ectopic pregnancy .

Fewer <cell_type>apoptotic cell bodies</cell_type> were present in ectopic pregnancy .


The use of tissue obtained from ectopic pregnancy may become an excellent model to identify the mechanism of trophoblast invasion in eutopic pregnancies .


Angiotensin II activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes .

<protein>Angiotensin II</protein> activates the <protein>proinflammatory transcription factor</protein> <protein>nuclear factor-kappaB</protein> in <cell_type>human monocytes</cell_type> .


The renin -angiotensin system may contribute to the pathogenesis of atherosclerosis .

The <protein>renin</protein> -angiotensin system may contribute to the pathogenesis of atherosclerosis .


A common feature of all stages of atherosclerosis is inflammation of the vessel wall .


The transcription factor nuclear factor-kappaB ( NF-kappaB ) participates in most signaling pathways involved in inflammation .

The transcription factor <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) participates in most signaling pathways involved in inflammation .


This study therefore examined the effect of angiotensin ( ANG ) II on NF-kappaB activation in monocytic cells , a major cellular component of human atheroma , by electrophoretic mobility shift assay .

This study therefore examined the effect of <protein>angiotensin ( ANG ) II</protein> on <protein>NF-kappaB</protein> activation in <cell_type>monocytic cells</cell_type> , a major cellular component of human atheroma , by electrophoretic mobility shift assay .


ANG II , like TNFalpha , caused rapid activation of NF-kappaB in human mononuclear cells isolated from peripheral blood by Ficoll density gradient .

<protein>ANG II</protein> , like <protein>TNFalpha</protein> , caused rapid activation of <protein>NF-kappaB</protein> in <cell_type>human mononuclear cells</cell_type> isolated from peripheral blood by Ficoll density gradient .


This ANG II effect was blocked by the angiotensin AT1 receptor antagonist losartan .

This <protein>ANG II</protein> effect was blocked by the angiotensin AT1 receptor antagonist losartan .


Specificity of ANG II -induced NF-kappaB activation was ascertained by supershift and competition experiments .

Specificity of <protein>ANG II</protein> -induced <protein>NF-kappaB</protein> activation was ascertained by supershift and competition experiments .


Moreover , ANG II stimulated NF-kappaB activation in human monocytes , but not in lymphocytes from the same preparation .

Moreover , <protein>ANG II</protein> stimulated <protein>NF-kappaB</protein> activation in <cell_type>human monocytes</cell_type> , but not in <cell_type>lymphocytes</cell_type> from the same preparation .


Together , the data demonstrate the ability of the vasoactive peptide ANG II to activate inflammatory pathways in human monocytes .

Together , the data demonstrate the ability of the vasoactive peptide <protein>ANG II</protein> to activate inflammatory pathways in <cell_type>human monocytes</cell_type> .


Copyright 1999 Academic Press .


Signal transduction pathways activated in endothelial cells following infection with Chlamydia pneumoniae .

Signal transduction pathways activated in <cell_type>endothelial cells</cell_type> following infection with Chlamydia pneumoniae .


Chlamydia pneumoniae is an important respiratory pathogen .


Recently , its presence has been demonstrated in atherosclerotic lesions .


In this study , we characterized C. pneumoniae-mediated activation of endothelial cells and demonstrated an enhanced expression of endothelial adhesion molecules followed by subsequent rolling , adhesion , and transmigration of leukocytes ( monocytes , granulocytes ) .

In this study , we characterized C. pneumoniae-mediated activation of <cell_type>endothelial cells</cell_type> and demonstrated an enhanced expression of <protein>endothelial adhesion molecules</protein> followed by subsequent rolling , adhesion , and transmigration of <cell_type>leukocytes</cell_type> ( <cell_type>monocytes</cell_type> , <cell_type>granulocytes</cell_type> ) .


These effects were blocked by mAbs against endothelial and/or leukocyte adhesion molecules ( beta1 and beta2 integrins ) .

These effects were blocked by <protein>mAbs</protein> against <protein>endothelial and/or leukocyte adhesion molecules</protein> ( <protein>beta1 and beta2 integrins</protein> ) .


Additionally , activation of different signal transduction pathways in C. pneumoniae-infected endothelial cells was shown : protein tyrosine phosphorylation , up-regulation of phosphorylated p42/p44 mitogen-activated protein kinase , and NF-kappaB activation/translocation occurred within 10-15 min .

Additionally , activation of different signal transduction pathways in <cell_type>C. pneumoniae-infected endothelial cells</cell_type> was shown : protein tyrosine phosphorylation , up-regulation of phosphorylated <protein>p42/p44 mitogen-activated protein kinase</protein> , and <protein>NF-kappaB</protein> activation/translocation occurred within 10-15 min .


Increased mRNA and surface expression of E-selectin , ICAM-1 , and VCAM-1 were noted within hours .

Increased <rna>mRNA</rna> and surface expression of <protein>E-selectin</protein> , <protein>ICAM-1</protein> , and <protein>VCAM-1</protein> were noted within hours .


Thus , C. pneumoniae triggers a cascade of events that could lead to endothelial activation , inflammation , and thrombosis , which in turn may result in or may promote atherosclerosis .


Transient pseudo-hypoaldosteronism following resection of the ileum : normal level of lymphocytic aldosterone receptors outside the acute phase .

Transient pseudo-hypoaldosteronism following resection of the ileum : normal level of <protein>lymphocytic aldosterone receptors</protein> outside the acute phase .


Pseudo-hypoaldosteronism ( PHA ) is due to mineralocorticoid resistance and manifests as hyponatremia and hyperkalemia with increased plasma aldosterone levels .


It may be familial or secondary to abnormal renal sodium handling .


We report the case of a 54-year-old woman with multifocal cancer of the colon , who developed PHA after subtotal colectomy , ileal resection and jejunostomy .


She was treated with 6 g of salt daily to prevent dehydration , which she stopped herself because of reduced fecal losses .


One month later she was admitted with signs of acute adrenal failure , i.e. fatigue , severe nausea , blood pressure of 80/60 mmHg , extracellular dehydration , hyponatremia ( 118 mmol/l ) ; hyperkalemia ( 7.6 mmol/l ) , increased blood urea nitrogen ( BUN ) ( 200 mg/dl ) and creatininemia ( 2.5 mg/dl ) , and decreased plasma bicarbonates level ( HCO3- : 16 mmol/l ; N : 27-30 ) .


However , the plasma cortisol was high ( 66 microg/100 ml at 10 : 00 h ; N : 8-15 ) and the ACTH was normal ( 13 pg/ml , N : 10-60 ) ; there was a marked increase in plasma renin activity ( > 37 ng/ml/h ; N supine < 3 ) , active renin ( 869 pg/ml ; N supine : 1.120 ) , aldosterone ( > 2000 pg/ml ; N supine < 150 ) and plasma AVP ( 20 pmol/l ; N : 0.5-2.5 ) .


The plasma ANH level was 38 pmol/l ( N supine : 5-25 ) .


A urinary steroidogram resulted in highly elevated tetrahydrocortisol ( THF : 13.3 mg/24h ; N : 1.4+/-0.8 ) with no increase in tetrahydrocortisone ( THE : 3.16 mg/24h ; N : 2.7+/-2.0 ) excretion , and with low THE/THF ( 0.24 ; N : 1.87+/-0.36 ) and alpha THF/THF ( 0.35 ; N : 0.92+/-0.42 ) ratios .


The number of mineralocorticoid receptors in mononuclear leukocytes was in the lower normal range for age , while the number of glucocorticoid receptors was reduced .

The number of <protein>mineralocorticoid receptors</protein> in <cell_type>mononuclear leukocytes</cell_type> was in the lower normal range for age , while the number of <protein>glucocorticoid receptors</protein> was reduced .


Small-bowel resection in ileostomized patients causes excessive fecal sodium losses and results in chronic sodium depletion with contraction of the plasma volume and severe secondary hyperaldosteronism .


Nevertheless , this hyperaldosteronism may be associated with hyponatremia and hyperkalemia suggesting PHA related to the major importance of the colon for the absorption of sodium .


In conclusion , this case report emphasizes 1 ) the possibility of a syndrome of acquired PHA with severe hyperkalemia after resection of the ileum and colon responding to oral salt supplementation ; 2 ) the major increase in AVP and the small increase in ANH ; 3 ) the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios ; 4 ) the normal number of lymphocytic mineralocorticoid receptors outside the acute episode .

In conclusion , this case report emphasizes 1 ) the possibility of a syndrome of acquired PHA with severe hyperkalemia after resection of the ileum and colon responding to oral salt supplementation ; 2 ) the major increase in AVP and the small increase in ANH ; 3 ) the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios ; 4 ) the normal number of <protein>lymphocytic mineralocorticoid receptors</protein> outside the acute episode .


Modulation of the immune response by progesterone-induced lymphocyte factors .

Modulation of the immune response by <protein>progesterone-induced lymphocyte factors</protein> .


Rat spleen and peripheral blood lymphocytes express progesterone receptors whose concentration is increased greatly during the early phase of pregnancy .

Rat spleen and <cell_type>peripheral blood lymphocytes</cell_type> express <protein>progesterone receptors</protein> whose concentration is increased greatly during the early phase of pregnancy .


After stimulation of progesterone the expression of receptors was augmented 2-3 times .


When cells were cultured in the presence of progesterone they released a soluble factor that inhibited cellular immunoreactions ( MLR , CRC ) and cellular proliferation as measured by thymidine incorporation by spleen-cell culture .

When cells were cultured in the presence of progesterone they released a <protein>soluble factor</protein> that inhibited cellular immunoreactions ( MLR , CRC ) and cellular proliferation as measured by thymidine incorporation by <cell_line>spleen-cell culture</cell_line> .


This factor also inhibited the synthesis of anti-DNP antibodies by a mouse hybridoma and diminished the proportion of cells in phase S .

This factor also inhibited the synthesis of <protein>anti-DNP antibodies</protein> by a <cell_line>mouse hybridoma</cell_line> and diminished the proportion of cells in phase S .


However , the percentage of asymmetric molecules produced by the hybridoma remained unaltered .

However , the percentage of <protein>asymmetric molecules</protein> produced by the <cell_line>hybridoma</cell_line> remained unaltered .


These results support the hypothesis that soluble factors released by rat lymphocytes modulate the immune response of the mother and participate in the mechanism that protects the fetus against antipaternal antibodies .

These results support the hypothesis that <protein>soluble factors</protein> released by <cell_type>rat lymphocytes</cell_type> modulate the immune response of the mother and participate in the mechanism that protects the fetus against <protein>antipaternal antibodies</protein> .


Differential regulation of 4E-BP1 and 4E-BP2 , two repressors of translation initiation , during human myeloid cell differentiation .

Differential regulation of <protein>4E-BP1</protein> and <protein>4E-BP2</protein> , two repressors of translation initiation , during <cell_type>human myeloid cell</cell_type> differentiation .


Human myeloid differentiation is accompanied by a decrease in cell proliferation .


Because the translation rate is an important determinant of cell proliferation , we have investigated translation initiation during human myeloid cell differentiation using the HL-60 promyelocytic leukemia cell line and the U-937 monoblastic cell line .

Because the translation rate is an important determinant of cell proliferation , we have investigated translation initiation during <cell_type>human myeloid cell</cell_type> differentiation using the <cell_line>HL-60 promyelocytic leukemia cell line</cell_line> and the <cell_line>U-937 monoblastic cell line</cell_line> .


A decrease in the translation rate is observed when the cells are induced to differentiate along the monocytic/macrophage pathway or along the granulocytic pathway .


The inhibition in protein synthesis correlates with specific regulation of two repressors of translation initiation , 4E-BP1 and 4E-BP2 .

The inhibition in protein synthesis correlates with specific regulation of two repressors of translation initiation , <protein>4E-BP1</protein> and <protein>4E-BP2</protein> .


Induction of HL-60 and U-937 cell differentiation into monocytes/macrophages by IFN-gamma or PMA results in a dephosphorylation and consequent activation of 4E-BP1 .

Induction of <cell_line>HL-60</cell_line> and <cell_line>U-937</cell_line> cell differentiation into <cell_type>monocytes/macrophages</cell_type> by <protein>IFN-gamma</protein> or PMA results in a dephosphorylation and consequent activation of <protein>4E-BP1</protein> .


Dephosphorylation of 4E-BP1 was also observed when U-937 cells were induced to differentiate into monocytes/macrophages following treatment with retinoic acid or DMSO .

Dephosphorylation of <protein>4E-BP1</protein> was also observed when <cell_line>U-937 cells</cell_line> were induced to differentiate into <cell_type>monocytes/macrophages</cell_type> following treatment with retinoic acid or DMSO .


In contrast , treatment of HL-60 cells with retinoic acid or DMSO , which results in a granulocytic differentiation of these cells , decreases 4E-BP1 amount without affecting its phosphorylation and strongly increases 4E-BP2 amount .

In contrast , treatment of <cell_line>HL-60 cells</cell_line> with retinoic acid or DMSO , which results in a granulocytic differentiation of these cells , decreases <protein>4E-BP1</protein> amount without affecting its phosphorylation and strongly increases <protein>4E-BP2</protein> amount .


Taken together , these data provide evidence for differential regulation of the translational machinery during human myeloid differentiation , specific to the monocytic/macrophage pathway or to the granulocytic pathway .


Nonimmunoglobulin gene hypermutation in germinal center B cells .

Nonimmunoglobulin gene hypermutation in <cell_type>germinal center B cells</cell_type> .


Somatic hypermutation is the most critical mechanism underlying the diversification of Ig genes .

Somatic hypermutation is the most critical mechanism underlying the diversification of <dna>Ig genes</dna> .


Although mutation occurs specifically in B cells during the germinal center reaction , it remains a matter of debate whether the mutation machinery also targets non-Ig genes .

Although mutation occurs specifically in <cell_type>B cells</cell_type> during the germinal center reaction , it remains a matter of debate whether the mutation machinery also targets <dna>non-Ig genes</dna> .


We have studied mutations in the 5 ' noncoding region of the Bcl6 gene in different subtypes of lymphomas .

We have studied mutations in the <dna>5 ' noncoding region</dna> of the <dna>Bcl6 gene</dna> in different subtypes of lymphomas .


We found frequent hypermutation in follicular lymphoma ( 25 of 59 = 42 % ) ( germinal center cell origin ) and mucosa-associated lymphoid tissue ( MALT ) lymphoma ( 19 of 45 = 42 % ) ( postgerminal center ) , but only occasionally in mantle cell lymphoma ( 1 of 21 = 4.8 % ) ( pregerminal center ) .


Most mutations were outside the motifs potentially important for transcription , suggesting they were not important in lymphomagenesis but may , like Ig mutation , represent an inherent feature of the lymphoma precursor cells .

Most mutations were outside the motifs potentially important for transcription , suggesting they were not important in lymphomagenesis but may , like Ig mutation , represent an inherent feature of the <cell_type>lymphoma precursor cells</cell_type> .


Therefore , we investigated their normal cell counterparts microdissected from a reactive tonsil .


Bcl6 mutation was found in 13 of 24 ( 54 % ) clones from the germinal centre but only in 1 of 24 ( 4 % ) clones from the naive B cells of the mantle zone .

Bcl6 mutation was found in 13 of 24 ( 54 % ) clones from the germinal centre but only in 1 of 24 ( 4 % ) clones from the <cell_type>naive B cells</cell_type> of the mantle zone .


The frequency , distribution , and nature of these mutations were similar to those resulting from the Ig hypermutation process .


The results show unequivocal evidence of non- Ig gene hypermutation in germinal center B cells and provide fresh insights into the process of hypermutation and lymphomagenesis .

The results show unequivocal evidence of non- <dna>Ig gene</dna> hypermutation in <cell_type>germinal center B cells</cell_type> and provide fresh insights into the process of hypermutation and lymphomagenesis .


Impaired binding of a DQ2 and DQ8 -binding HSV VP16 peptide to a DQA1*0501/DQB1*0302 trans class II heterodimer .

Impaired binding of a <protein>DQ2</protein> and <protein>DQ8</protein> -binding HSV VP16 peptide to a <protein>DQA1*0501/DQB1*0302 trans class II heterodimer</protein> .


DQalpha and DQbeta trans heterodimeric HLA-DQ molecules form in individuals heterozygous for the DQ2 and DQ8 specificities .

<protein>DQalpha and DQbeta trans heterodimeric HLA-DQ molecules</protein> form in individuals heterozygous for the <protein>DQ2</protein> and <protein>DQ8</protein> specificities .


Unique functions and disease associations have been postulated for such trans-dimers , which may be different from cis-encoded DQ molecules encoded by the corresponding haplotypes .

Unique functions and disease associations have been postulated for such <protein>trans-dimers</protein> , which may be different from <protein>cis-encoded DQ molecules</protein> encoded by the corresponding haplotypes .


We analyzed the ability of the trans-dimer encoded by HLA-DQA1*0501/DQB1*0302 to bind a peptide antigen which interacts with DQ molecules encoded by both parental haplotypes .

We analyzed the ability of the trans-dimer encoded by <protein>HLA-DQA1*0501/DQB1*0302</protein> to bind a peptide antigen which interacts with <protein>DQ molecules</protein> encoded by both parental haplotypes .


Markedly impaired binding was observed , consistent with both the use of different anchor residues and with changes in levels of DQ cis- dimer availability for peptide binding interactions .

Markedly impaired binding was observed , consistent with both the use of different anchor residues and with changes in levels of DQ cis- <protein>dimer</protein> availability for peptide binding interactions .


Detection of intracellular phosphorylated STAT-1 by flow cytometry .

Detection of <protein>intracellular phosphorylated STAT-1</protein> by flow cytometry .


We have applied flow cytometry to the investigation of interferon-gamma activation of human monocytes .

We have applied flow cytometry to the investigation of <protein>interferon-gamma</protein> activation of <cell_type>human monocytes</cell_type> .


This approach uses monoclonal antibodies that distinguish between the native and phosphorylated forms of STAT-1 .

This approach uses <protein>monoclonal antibodies</protein> that distinguish between the native and phosphorylated forms of <protein>STAT-1</protein> .


It enables rapid and quantitative assessment of STAT-1 phosphorylation on a discrete cell basis and is both more sensitive and less time consuming than immunoblotting .

It enables rapid and quantitative assessment of <protein>STAT-1</protein> phosphorylation on a discrete cell basis and is both more sensitive and less time consuming than immunoblotting .


Furthermore , it allows for discrimination between a mixture of cells that differ in their response to interferon-gamma .

Furthermore , it allows for discrimination between a mixture of cells that differ in their response to <protein>interferon-gamma</protein> .


This approach should allow for the evaluation of different intracellular signaling pathways using a combination of monoclonal reagents that are specific for native and activation modified proteins .

This approach should allow for the evaluation of different intracellular signaling pathways using a combination of monoclonal reagents that are specific for native and <protein>activation modified proteins</protein> .


Application of this form of testing should prove valuable in screening for signaling defects in selected patients with recurrent infections .


In addition , this technique should permit dissection of a full range of cellular signaling pathways at the protein level .


Activation of nuclear factor-kappaB by lipopolysaccharide in mononuclear leukocytes is prevented by inhibitors of cytosolic phospholipase A2 .

Activation of <protein>nuclear factor-kappaB</protein> by lipopolysaccharide in <cell_type>mononuclear leukocytes</cell_type> is prevented by inhibitors of <protein>cytosolic phospholipase A2</protein> .


In monocytes , lipopolysaccharide induces synthesis and activity of the 85-kDa cytosolic phospholipase A2 .

In <cell_type>monocytes</cell_type> , lipopolysaccharide induces synthesis and activity of the 85-kDa <protein>cytosolic phospholipase A2</protein> .


This enzyme releases arachidonic acid and lyso-phospholipids from membranes which are metabolized to eicosanoids and platelet-activating-factor .


These lipid mediators increase activity of transcription factors and expression of cytokine genes indicating a function for cytosolic phospholipase A2 in signal transduction and inflammation .

These lipid mediators increase activity of <protein>transcription factors</protein> and expression of <dna>cytokine genes</dna> indicating a function for <protein>cytosolic phospholipase A2</protein> in signal transduction and inflammation .


We have shown previously that trifluoromethylketone inhibitors of cytosolic phospholipase A2 suppressed interleukin-1beta protein and steady-state mRNA levels in human lipopolysaccharide-stimulated peripheral blood mononuclear leukocytes .

We have shown previously that trifluoromethylketone inhibitors of <protein>cytosolic phospholipase A2</protein> suppressed interleukin-1beta protein and steady-state mRNA levels in human <cell_type>lipopolysaccharide-stimulated peripheral blood mononuclear leukocytes</cell_type> .


In this study , the subcellular mechanisms were analyzed by which trifluoromethylketones interfere with gene expression .


We found that they reduced the initial interleukin-1beta mRNA transcription rate through prevention of degradation of inhibitor-kappaB alpha .

We found that they reduced the initial <rna>interleukin-1beta mRNA</rna> transcription rate through prevention of degradation of <protein>inhibitor-kappaB alpha</protein> .


Consequently , cytosolic activation , nuclear translocation and DNA-binding of nuclear factor-kappaB were decreased .

Consequently , cytosolic activation , nuclear translocation and DNA-binding of <protein>nuclear factor-kappaB</protein> were decreased .


Trifluoromethylketones ameliorate chronic inflammation in vivo .


Thus , this therapeutic potency may reside in retention of inactive nuclear factor-kappaB in the cytosol thereby abrogating interleukin-1beta gene transcription .

Thus , this therapeutic potency may reside in retention of inactive <protein>nuclear factor-kappaB</protein> in the <cell_type>cytosol</cell_type> thereby abrogating <protein>interleukin-1beta</protein> gene transcription .


Cellular disposition of sulphamethoxazole and its metabolites : implications for hypersensitivity .


1. Bioactivation of sulphamethoxazole ( SMX ) to chemically-reactive metabolites and subsequent protein conjugation is thought to be involved in SMX hypersensitivity .


We have therefore examined the cellular metabolism , disposition and conjugation of SMX and its metabolites in vitro .


2. Flow cytometry revealed binding of N-hydroxy ( SMX-NHOH ) and nitroso ( SMX-NO ) metabolites of SMX , but not of SMX itself , to the surface of viable white blood cells .

2. Flow cytometry revealed binding of N-hydroxy ( SMX-NHOH ) and nitroso ( SMX-NO ) metabolites of SMX , but not of SMX itself , to the surface of viable <cell_type>white blood cells</cell_type> .


Cellular haptenation by SMX-NO was reduced by exogenous glutathione ( GSH ) .


3. SMX-NHOH and SMX-NO were rapidly reduced back to the parent compound by cysteine ( CYS ) , GSH , human peripheral blood cells and plasma , suggesting that this is an important and ubiquitous bioinactivation mechanism .

3. SMX-NHOH and SMX-NO were rapidly reduced back to the parent compound by cysteine ( CYS ) , GSH , <cell_type>human peripheral blood cells</cell_type> and plasma , suggesting that this is an important and <protein>ubiquitous</protein> bioinactivation mechanism .


4. Fluorescence HPLC showed that SMX-NHOH and SMX-NO depleted CYS and GSH in buffer , and to a lesser extent , in cells and plasma .


5. Neutrophil apoptosis and inhibition of neutrophil function were induced at lower concentrations of SMX-NHOH and SMX-NO than those inducing loss of membrane viability , with SMX having no effect .


Lymphocytes were significantly ( P < 0.05 ) more sensitive to the direct cytotoxic effects of SMX-NO than neutrophils .

<cell_type>Lymphocytes</cell_type> were significantly ( P < 0.05 ) more sensitive to the direct cytotoxic effects of SMX-NO than <cell_type>neutrophils</cell_type> .


6. Partitioning of SMX-NHOH into red blood cells was significantly ( P < 0.05 ) lower than with the hydroxylamine of dapsone .

6. Partitioning of SMX-NHOH into <cell_type>red blood cells</cell_type> was significantly ( P < 0.05 ) lower than with the hydroxylamine of dapsone .


7. Our results suggest that the balance between oxidation of SMX to its toxic metabolites and their reduction is an important protective cellular mechanism .


If an imbalance exists , haptenation of the toxic metabolites to bodily proteins including the surface of viable cells can occur , and may result in drug hypersensitivity .


Bcl-6 expression in reactive follicular hyperplasia , follicular lymphoma , and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers : heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma .

<protein>Bcl-6</protein> expression in reactive follicular hyperplasia , follicular lymphoma , and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers : heterogeneity of <cell_type>intrafollicular T-cells</cell_type> and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma .


BACKGROUND : The Bcl-6 gene product , a nuclear phosphoprotein , is expressed independently of Bcl-6 gene rearrangement .

BACKGROUND : The <protein>Bcl-6 gene product</protein> , a <protein>nuclear phosphoprotein</protein> , is expressed independently of <protein>Bcl-6</protein> gene rearrangement .


In lymph nodes , expression of Bcl-6 protein is restricted to germinal center ( GC ) B-cells and 10 % to 15 % of CD3/CD4+ intrafollicular T cells .

In lymph nodes , expression of <protein>Bcl-6</protein> protein is restricted to <cell_type>germinal center ( GC ) B-cells</cell_type> and 10 % to 15 % of <cell_type>CD3/CD4+ intrafollicular T cells</cell_type> .


Interfollicular cells are negative for Bcl-6 protein , except for rare CD3+/CD4+ T cells .

Interfollicular cells are negative for <protein>Bcl-6 protein</protein> , except for rare <cell_type>CD3+/CD4+ T cells</cell_type> .


Recently , we reported cases of angioimmunoblastic T-cell lymphoma ( AITL ) with hyperplastic GCs ( AITL/GC ) , and observed that borders of enlarged GCs were ill defined , with features suggestive of an outward migration of GC cells to surrounding interfollicular zones .

Recently , we reported cases of angioimmunoblastic T-cell lymphoma ( AITL ) with hyperplastic GCs ( AITL/GC ) , and observed that borders of enlarged GCs were ill defined , with features suggestive of an outward migration of <cell_type>GC cells</cell_type> to surrounding interfollicular zones .


This prompted a study of follicular borders with Bcl-6 staining in reactive follicular hyperplasias and follicular lymphomas to compare with AITL/GC .

This prompted a study of follicular borders with <protein>Bcl-6</protein> staining in reactive follicular hyperplasias and follicular lymphomas to compare with AITL/GC .


MATERIALS AND METHODS : Formalin-fixed paraffin sections were used for immunostaining of Bcl-6 .

MATERIALS AND METHODS : Formalin-fixed paraffin sections were used for immunostaining of <protein>Bcl-6</protein> .


Six cases of AITL/GC , 12 nonspecific reactive follicular hyperplasia ( FH ) , 7 HIV adenopathy , 10 follicular lymphoma ( FL ) , and 8 typical AITL ( ie , AITL without GC ) were studied .


Double staining for Bcl-6/CD20 , Bcl-6/CD3 , and Bcl-6/CD57 was performed in selected cases .

Double staining for <protein>Bcl-6/CD20</protein> , <protein>Bcl-6/CD3</protein> , and <protein>Bcl-6/CD57</protein> was performed in selected cases .


RESULTS : In FH and HIV adenopathy , staining for Bcl-6 revealed densely populated GCs with well-defined and regular GC borders , whereas Bcl-6+ cells were rare in the interfollicular areas .

RESULTS : In FH and HIV adenopathy , staining for <protein>Bcl-6</protein> revealed densely populated GCs with well-defined and regular GC borders , whereas <cell_type>Bcl-6+ cells</cell_type> were rare in the interfollicular areas .


An occasional GC with an ill-defined border was invariably surrounded by a broad mantle zone ; those with indistinct mantle zones had well-defined , regular borders .


In FL , follicles were densely populated , and their borders were irregular , with some Bcl-6+ cells in the interfollicular zones .

In FL , follicles were densely populated , and their borders were irregular , with some <cell_type>Bcl-6+ cells</cell_type> in the interfollicular zones .


In AITL/GC , GCs were less dense , GC borders were ill defined and irregular , and the number of interfollicular Bcl-6+ cells was markedly increased .

In AITL/GC , GCs were less dense , GC borders were ill defined and irregular , and the number of <cell_type>interfollicular Bcl-6+ cells</cell_type> was markedly increased .


Double staining revealed that these interfollicular Bcl-6+ cells in AITL/GC were Bcl6+/CD3+/CD20-/CD57- T cells .

Double staining revealed that these <cell_type>interfollicular Bcl-6+ cells</cell_type> in AITL/GC were <cell_type>Bcl6+/CD3+/CD20-/CD57- T cells</cell_type> .


Moreover , CD3+ intrafollicular T cells were depleted in AITL/GC , whereas they were abundant in FH .

Moreover , <cell_type>CD3+ intrafollicular T cells</cell_type> were depleted in AITL/GC , whereas they were abundant in FH .


Intrafollicular CD57+ cells did not stain for Bcl-6 , and were also depleted in AITL/GC .

Intrafollicular <cell_type>CD57+ cells</cell_type> did not stain for <protein>Bcl-6</protein> , and were also depleted in AITL/GC .


In typical AITL , some neoplastic cells were positive for Bcl-6 , showing variable degrees of staining .

In typical AITL , some neoplastic cells were positive for <protein>Bcl-6</protein> , showing variable degrees of staining .


CONCLUSIONS : ( 1 ) GCs of AITL/GC differed from those of other reactive follicular hyperplasias and follicular lymphomas , and staining for Bcl-6 was useful to discern them .

CONCLUSIONS : ( 1 ) GCs of AITL/GC differed from those of other reactive follicular hyperplasias and follicular lymphomas , and staining for <protein>Bcl-6</protein> was useful to discern them .


( 2 ) Intrafollicular CD3+ T cells , many of which were also positive for Bcl-6 , were markedly depleted in AITL/GC , with increased interfollicular Bcl-6+/CD3+ cells , suggesting an outward migration of intrafollicular T cells in this condition .

( 2 ) <cell_type>Intrafollicular CD3+ T cells</cell_type> , many of which were also positive for <protein>Bcl-6</protein> , were markedly depleted in AITL/GC , with increased interfollicular <cell_type>Bcl-6+/CD3+ cells</cell_type> , suggesting an outward migration of <cell_type>intrafollicular T cells</cell_type> in this condition .


( 3 ) Interfollicular Bcl-6+/CD3+ cells in AITL/GC were too numerous to be accounted for by migration alone , suggesting local proliferation .

( 3 ) <cell_type>Interfollicular Bcl-6+/CD3+ cells</cell_type> in AITL/GC were too numerous to be accounted for by migration alone , suggesting local proliferation .


( 4 ) Intrafollicular CD57+ cells were negative for Bcl-6 , indicating heterogeneity of the intrafollicular T-cell population .

( 4 ) <cell_type>Intrafollicular CD57+ cells</cell_type> were negative for <protein>Bcl-6</protein> , indicating heterogeneity of the <cell_type>intrafollicular T-cell population</cell_type> .


( 5 ) Some neoplastic cells in AITL stained for Bcl-6 , suggesting up-regulation of Bcl-6 expression in this tumor .

( 5 ) Some neoplastic cells in AITL stained for <protein>Bcl-6</protein> , suggesting up-regulation of <protein>Bcl-6</protein> expression in this tumor .


Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression .

Human cytomegalovirus binding to <cell_type>human monocytes</cell_type> induces immunoregulatory gene expression .


To continue our investigation of the cellular events that occur following human CMV ( HCMV ) infection , we focused on the regulation of cellular activation following viral binding to human monocytes .

To continue our investigation of the cellular events that occur following human CMV ( HCMV ) infection , we focused on the regulation of cellular activation following viral binding to <cell_type>human monocytes</cell_type> .


First , we showed that viral binding induced a number of immunoregulatory genes ( IL-1beta , A20 , NF-kappaB-p105/p50 , and IkappaBalpha ) in unactivated monocytes and that neutralizing Abs to the major HCMV glycoproteins , gB ( UL55 ) and gH ( UL75 ) , inhibited the induction of these genes .

First , we showed that viral binding induced a number of <cell_type>immunoregulatory genes</cell_type> ( <protein>IL-1beta</protein> , <protein>A20</protein> , <protein>NF-kappaB-p105/p50</protein> , and <protein>IkappaBalpha</protein> ) in unactivated <cell_type>monocytes</cell_type> and that <protein>neutralizing Abs</protein> to the major <protein>HCMV glycoproteins</protein> , <protein>gB</protein> ( <protein>UL55</protein> ) and <protein>gH</protein> ( <protein>UL75</protein> ) , inhibited the induction of these genes .


Next , we demonstrated that these viral ligands directly up-regulated monocyte gene expression upon their binding to their appropriate cellular receptors .


We then investigated if HCMV binding also resulted in the translation and secretion of cytokines .

We then investigated if HCMV binding also resulted in the translation and secretion of <protein>cytokines</protein> .


Our results showed that HCMV binding to monocytes resulted in the production and release of IL-1beta protein .

Our results showed that HCMV binding to <cell_type>monocytes</cell_type> resulted in the production and release of <protein>IL-1beta protein</protein> .


Because these induced gene products have NF-kappaB sites in their promoter regions , we next examined whether there was an up-regulation of nuclear NF-kappaB levels .

Because these induced gene products have <dna>NF-kappaB sites</dna> in their <dna>promoter regions</dna> , we next examined whether there was an up-regulation of nuclear <protein>NF-kappaB</protein> levels .


These experiments showed that , in fact , NF-kappaB was translocated to the nucleus following viral binding or purified viral ligand binding .

These experiments showed that , in fact , <protein>NF-kappaB</protein> was translocated to the nucleus following viral binding or purified viral ligand binding .


Changes in IkappaBalpha levels correlated with the changes in NF-kappaB translocation .

Changes in <protein>IkappaBalpha</protein> levels correlated with the changes in <protein>NF-kappaB</protein> translocation .


Lastly , we demonstrated that p38 kinase activity played a central role in IL-1beta production and that it was rapidly up-regulated following infection .

Lastly , we demonstrated that <protein>p38</protein> kinase activity played a central role in <protein>IL-1beta</protein> production and that it was rapidly up-regulated following infection .


These results support our hypothesis that HCMV initiates a signal transduction pathway that leads to monocyte activation and pinpoints a potential mechanism whereby HCMV infection of monocytes can result in profound pathogenesis , especially in chronic inflammatory-type conditions .

These results support our hypothesis that HCMV initiates a signal transduction pathway that leads to monocyte activation and pinpoints a potential mechanism whereby HCMV infection of <cell_type>monocytes</cell_type> can result in profound pathogenesis , especially in chronic inflammatory-type conditions .


Regulation of the megakaryocytic glycoprotein IX promoter by the oncogenic Ets transcription factor Fli-1 .

Regulation of the <dna>megakaryocytic glycoprotein IX promoter</dna> by the <protein>oncogenic Ets transcription factor</protein> <protein>Fli-1</protein> .


Glycoprotein ( GP ) IX is a subunit of the von Willebrand receptor , GPIb-V-IX , which mediates adhesion of platelets to the subendothelium of damaged blood vessels .

<protein>Glycoprotein ( GP ) IX</protein> is a subunit of the <protein>von Willebrand receptor</protein> , <protein>GPIb-V-IX</protein> , which mediates adhesion of <cell_type>platelets</cell_type> to the subendothelium of damaged blood vessels .


Previous characterization of the GPIX promoter identified a functional Ets site that , when disrupted , reduced promoter activity .

Previous characterization of the <dna>GPIX promoter</dna> identified a functional Ets site that , when disrupted , reduced promoter activity .


However , the Ets protein ( s ) that regulated GPIX promoter expression was unknown .

However , the <protein>Ets protein</protein> ( s ) that regulated <dna>GPIX promoter</dna> expression was unknown .


In this study , transient cotransfection of several GPIX promoter/reporter constructs into 293T kidney fibroblasts with a Fli-1 expression vector shows that the oncogenic protein Fli-1 can transactivate the GPIX promoter when an intact GPIX Ets site is present .

In this study , transient cotransfection of several <dna>GPIX promoter/reporter constructs</dna> into <cell_line>293T kidney fibroblasts</cell_line> with a <dna>Fli-1 expression vector</dna> shows that the oncogenic protein <protein>Fli-1</protein> can transactivate the <dna>GPIX promoter</dna> when an intact <dna>GPIX Ets site</dna> is present .


In addition , Fli-1 binding of the GPIX Ets site was identified in antibody supershift experiments in nuclear extracts derived from hematopoietic human erythroleukemia cells .

In addition , <protein>Fli-1</protein> binding of the <dna>GPIX Ets site</dna> was identified in antibody supershift experiments in nuclear extracts derived from <cell_type>hematopoietic human erythroleukemia cells</cell_type> .


Comparative studies showed that Fli-1 was also able to transactivate the GPIbalpha and , to a lesser extent , the GPIIb promoter .

Comparative studies showed that <protein>Fli-1</protein> was also able to transactivate the <dna>GPIbalpha</dna> and , to a lesser extent , the <dna>GPIIb promoter</dna> .


Immunoblot analysis identified Fli-1 protein in lysates derived from platelets .

Immunoblot analysis identified <protein>Fli-1 protein</protein> in lysates derived from <cell_type>platelets</cell_type> .


In addition , expression of Fli-1 was identified immunohistochemically in megakaryocytes derived from CD34 ( + ) cells treated with the megakaryocyte differentiation and proliferation factor , thrombopoietin .

In addition , expression of <protein>Fli-1</protein> was identified immunohistochemically in <cell_type>megakaryocytes</cell_type> derived from <cell_type>CD34 ( + ) cells</cell_type> treated with the <protein>megakaryocyte differentiation and proliferation factor</protein> , <protein>thrombopoietin</protein> .


These results suggest that Fli-1 is likely to regulate lineage-specific genes during megakaryocytopoiesis .

These results suggest that <protein>Fli-1</protein> is likely to regulate <dna>lineage-specific genes</dna> during megakaryocytopoiesis .


Expression of IkappaBalpha in the nucleus of human peripheral blood T lymphocytes .

Expression of <protein>IkappaBalpha</protein> in the nucleus of <cell_type>human peripheral blood T lymphocytes</cell_type> .


According to current models the inhibitory capacity of I ( kappa ) B ( alpha ) would be mediated through the retention of Rel/NF-kappaB proteins in the cytosol .

According to current models the inhibitory capacity of <protein>I ( kappa ) B ( alpha )</protein> would be mediated through the retention of <protein>Rel/NF-kappaB proteins</protein> in the <cell_type>cytosol</cell_type> .


However , I ( kappa ) B ( alpha ) has also been detected in the nucleus of cell lines and when overexpressed by transient transfection .

However , <protein>I ( kappa ) B ( alpha )</protein> has also been detected in the nucleus of cell lines and when overexpressed by transient transfection .


To gain better insight into the potential role of nuclear I ( kappa ) B ( alpha ) in a physiological context we have analysed its presence in the nucleus of human peripheral blood T lymphocytes ( PBL ) .

To gain better insight into the potential role of <protein>nuclear I ( kappa ) B ( alpha )</protein> in a physiological context we have analysed its presence in the nucleus of <cell_type>human peripheral blood T lymphocytes</cell_type> ( <cell_type>PBL</cell_type> ) .


We demonstrate the nuclear localization of I ( kappa ) B ( alpha ) in PBL by different techniques : Western blot , indirect immunofluorescence and electron microscopy .

We demonstrate the nuclear localization of <protein>I ( kappa ) B ( alpha )</protein> in <cell_type>PBL</cell_type> by different techniques : Western blot , indirect immunofluorescence and electron microscopy .


Low levels of nuclear I ( kappa ) B ( alpha ) were detected in resting cells whereas a superinduction was obtained after PMA activation .

Low levels of nuclear <protein>I ( kappa ) B ( alpha )</protein> were detected in resting cells whereas a superinduction was obtained after PMA activation .


The nuclear pool of I ( kappa ) B ( alpha ) showed a higher stability than cytosolic I ( kappa ) B ( alpha ) and was partially independent of the resynthesis of the protein .

The nuclear pool of <protein>I ( kappa ) B ( alpha )</protein> showed a higher stability than cytosolic <protein>I ( kappa ) B ( alpha )</protein> and was partially independent of the resynthesis of the protein .


Unexpectedly , the presence of nuclear I ( kappa ) B ( alpha ) did not inhibit NF-kappaB binding to DNA and this phenomenon was not due to the presence of IkappaBbeta at the nuclear level .

Unexpectedly , the presence of <protein>nuclear I ( kappa ) B ( alpha )</protein> did not inhibit <protein>NF-kappaB</protein> binding to DNA and this phenomenon was not due to the presence of <protein>IkappaBbeta</protein> at the nuclear level .


Immunoprecipitation experiments failed to demonstrate an association between nuclear I ( kappa ) B ( alpha ) and NF-kappaB proteins .

Immunoprecipitation experiments failed to demonstrate an association between nuclear <protein>I ( kappa ) B ( alpha )</protein> and <protein>NF-kappaB</protein> proteins .