The implication of EBV in the skin lesions was determined by the presence of EBV-DNA , EBV-encoded nuclear RNA ( EBER ) and a clonality of EBV-DNA fragments containing the terminal repeats .

The implication of EBV in the skin lesions was determined by the presence of <dna>EBV-DNA</dna> , <rna>EBV-encoded nuclear RNA</rna> ( <rna>EBER</rna> ) and a clonality of <dna>EBV-DNA fragments</dna> containing the <dna>terminal repeats</dna> .


Transcripts of EBV-encoded genes were screened by reverse transcription- polymerase chain reaction ( RT-PCR ) , and confirmed by Southern blot hybridization .

Transcripts of <dna>EBV-encoded genes</dna> were screened by reverse transcription- polymerase chain reaction ( RT-PCR ) , and confirmed by Southern blot hybridization .


The expression of EBV-related antigens was examined by immunostaining using paraffin-embedded tissue sections and cell pellets of EBV-positive cell lines .

The expression of <protein>EBV-related antigens</protein> was examined by immunostaining using paraffin-embedded tissue sections and cell pellets of <cell_line>EBV-positive cell lines</cell_line> .


Our study demonstrated that all samples from the patients contained EBV nuclear antigen ( EBNA ) -1 mRNA which was transcribed using the Q promoter , whereas both the Q promoter and another upstream promoter ( Cp/Wp ) were used in EBV-positive cell lines , B95.8 , Raji and Jiyoye .

Our study demonstrated that all samples from the patients contained <rna>EBV nuclear antigen ( EBNA ) -1 mRNA</rna> which was transcribed using the <dna>Q promoter</dna> , whereas both the <dna>Q promoter</dna> and another <dna>upstream promoter</dna> ( <dna>Cp/Wp</dna> ) were used in <cell_line>EBV-positive cell lines</cell_line> , <cell_line>B95.8</cell_line> , <cell_line>Raji</cell_line> and <cell_line>Jiyoye</cell_line> .


Latent membrane protein-1 ( LMP-1 ) mRNA was detected in seven of eight patients and all cell lines , whereas EBNA-2 transcripts were found only in the cell lines .

<rna>Latent membrane protein-1 ( LMP-1 ) mRNA</rna> was detected in seven of eight patients and all <cell_line>cell lines</cell_line> , whereas <rna>EBNA-2 transcripts</rna> were found only in the <cell_line>cell lines</cell_line> .


Immunostaining showed no LMP-1 , EBNA-2 or ZEBRA antigens in the paraffin-embedded tissue sections , although they were positive in the cell line cells .

Immunostaining showed no <protein>LMP-1 , EBNA-2 or ZEBRA antigens</protein> in the paraffin-embedded tissue sections , although they were positive in the <cell_line>cell line cells</cell_line> .


Latent BHRF1 transcripts encoding bcl-2 homologue and BCRF1 transcripts encoding viral interleukin ( vIL ) -10 were detected in one and two of eight patients , respectively .

<rna>Latent BHRF1 transcripts</rna> encoding <rna>bcl-2 homologue</rna> and <rna>BCRF1 transcripts</rna> encoding <protein>viral interleukin ( vIL ) -10</protein> were detected in one and two of eight patients , respectively .


A patient with NK-cell lymphoma expressing both transcripts died of rapid progression of the illness .


Our results indicate that the restricted expression of the latency-associated EBV genes and the production of vIL-10 and bcl-2 homologue may favour tumour growth , evading the host immune surveillance .

Our results indicate that the restricted expression of the <dna>latency-associated EBV genes</dna> and the production of <rna>vIL-10 and bcl-2 homologue</rna> may favour tumour growth , evading the host immune surveillance .


Copyright 2001 Cancer Research Campaign .


Oxidized alkyl phospholipids are specific , high affinity peroxisome proliferator-activated receptor gamma ligands and agonists .


Synthetic high affinity peroxisome proliferator-activated receptor ( PPAR ) agonists are known , but biologic ligands are of low affinity .


Oxidized low density lipoprotein ( oxLDL ) is inflammatory and signals through PPARs .

<protein>Oxidized low density lipoprotein</protein> ( <protein>oxLDL</protein> ) is inflammatory and signals through <protein>PPARs</protein> .


We showed , by phospholipase A ( 1 ) digestion , that PPARgamma agonists in oxLDL arise from the small pool of alkyl phosphatidylcholines in LDL .

We showed , by phospholipase A ( 1 ) digestion , that PPARgamma agonists in <protein>oxLDL</protein> arise from the small pool of alkyl phosphatidylcholines in <protein>LDL</protein> .


We identified an abundant oxidatively fragmented alkyl phospholipid in oxLDL , hexadecyl azelaoyl phosphatidylcholine ( azPC ) , as a high affinity ligand and agonist for PPARgamma .

We identified an abundant oxidatively fragmented alkyl phospholipid in <protein>oxLDL</protein> , hexadecyl azelaoyl phosphatidylcholine ( azPC ) , as a high affinity ligand and agonist for <protein>PPARgamma</protein> .


[ ( 3 ) H ] azPC bound recombinant PPARgamma with an affinity ( K ( d ) ( ( app ) ) approximately 40 nm ) that was equivalent to rosiglitazone ( BRL49653 ) , and competition with rosiglitazone showed that binding occurred in the ligand-binding pocket .

[ ( 3 ) H ] azPC bound <protein>recombinant PPARgamma</protein> with an affinity ( K ( d ) ( ( app ) ) approximately 40 nm ) that was equivalent to rosiglitazone ( BRL49653 ) , and competition with rosiglitazone showed that binding occurred in the <protein>ligand-binding pocket</protein> .


azPC induced PPRE reporter gene expression , as did rosiglitazone , with a half-maximal effect at 100 nm .


Overexpression of PPARalpha or PPARgamma revealed that azPC was a specific PPARgamma agonist .

Overexpression of <protein>PPARalpha</protein> or <protein>PPARgamma</protein> revealed that azPC was a specific PPARgamma agonist .


The scavenger receptor CD36 is encoded by a PPRE-responsive gene , and azPC enhanced expression of CD36 in primary human monocytes .

The <protein>scavenger receptor CD36</protein> is encoded by a <dna>PPRE-responsive gene</dna> , and azPC enhanced expression of <protein>CD36</protein> in <cell_type>primary human monocytes</cell_type> .


We found that anti-CD36 inhibited azPC uptake , and it inhibited PPRE reporter induction .

We found that <protein>anti-CD36</protein> inhibited azPC uptake , and it inhibited PPRE reporter induction .


Results with a small molecule phospholipid flippase mimetic suggest azPC acts intracellularly and that cellular azPC accumulation was efficient .

Results with a small molecule <protein>phospholipid flippase mimetic</protein> suggest azPC acts intracellularly and that cellular azPC accumulation was efficient .


Thus , certain alkyl phospholipid oxidation products in oxLDL are specific , high affinity extracellular ligands and agonists for PPARgamma that induce PPAR-responsive genes

Thus , certain alkyl phospholipid oxidation products in <protein>oxLDL</protein> are specific , high affinity extracellular ligands and agonists for <protein>PPARgamma</protein> that induce <dna>PPAR-responsive genes</dna>


Regulation of the human MAT2B gene encoding the regulatory beta subunit of methionine adenosyltransferase , MAT II .

Regulation of the <dna>human MAT2B gene</dna> encoding the <protein>regulatory beta subunit</protein> of <protein>methionine adenosyltransferase</protein> , <protein>MAT II</protein> .


Methionine adenosyltransferase ( MAT ) catalyzes the biosynthesis of S-adenosylmethionine ( AdoMet ) , a key molecule in transmethylation reactions and polyamine biosynthesis .

<protein>Methionine adenosyltransferase</protein> ( <protein>MAT</protein> ) catalyzes the biosynthesis of <protein>S-adenosylmethionine</protein> ( <protein>AdoMet</protein> ) , a key molecule in transmethylation reactions and polyamine biosynthesis .


The MAT II isozyme consists of a catalytic alpha2 and a regulatory beta subunit .

The <protein>MAT II isozyme</protein> consists of a <protein>catalytic alpha2 and a regulatory beta subunit</protein> .


Down-regulation of the MAT II beta subunit expression causes a 6-10-fold increase in intracellular AdoMet levels .

Down-regulation of the <protein>MAT II beta subunit</protein> expression causes a 6-10-fold increase in intracellular <protein>AdoMet</protein> levels .


To understand the mechanism by which the beta subunit expression is regulated , we cloned the MAT2B gene , determined its organization , characterized its 5'-flanking sequences , and elucidated the in vitro and in vivo regulation of its promoter .

To understand the mechanism by which the <protein>beta subunit</protein> expression is regulated , we cloned the <dna>MAT2B gene</dna> , determined its organization , characterized its <dna>5'-flanking sequences</dna> , and elucidated the in vitro and in vivo regulation of its <dna>promoter</dna> .


Transcription of the MAT2B gene initiates at position -203 relative to the translation start site .

Transcription of the <dna>MAT2B gene</dna> initiates at position -203 relative to the <dna>translation start site</dna> .


Promoter deletion analysis defined a minimal promoter between positions +52 and +93 base pairs , a GC-rich region .

<dna>Promoter deletion analysis</dna> defined a <dna>minimal promoter</dna> between <dna>positions +52 and +93</dna> base pairs , a <dna>GC-rich region</dna> .


Inclusion of the sequences between -4 and +52 enhanced promoter activity ; this was primarily because of an Sp1 recognition site at +9/+15 .

Inclusion of the sequences between -4 and +52 enhanced promoter activity ; this was primarily because of an <dna>Sp1 recognition site</dna> at +9/+15 .


The inclusion of sequences up to position -115 provided full activity ; this was attributed to a TATA at -32 .

The inclusion of sequences up to position -115 provided full activity ; this was attributed to a <dna>TATA</dna> at -32 .


The Sp1 site at position +9 was key for the formation of protein.DNA complexes .

The <dna>Sp1 site</dna> at position +9 was key for the formation of protein.DNA complexes .


Mutation of both the Sp1 site at +9 and the TATA at -32 reduced promoter activity to its minimal level .

Mutation of both the <dna>Sp1 site</dna> at +9 and the <dna>TATA</dna> at -32 reduced promoter activity to its minimal level .


Supershift assays showed no effect of the anti-Sp1 antibody on complex formation , whereas the anti-Sp3 antibody had a strong effect on protein.DNA complex formation , suggesting that Sp3 is one of the main factors binding to this Sp1 site .

Supershift assays showed no effect of the <protein>anti-Sp1 antibody</protein> on complex formation , whereas the <protein>anti-Sp3 antibody</protein> had a strong effect on protein.DNA complex formation , suggesting that <protein>Sp3</protein> is one of the main factors binding to this <dna>Sp1 site</dna> .


Chromatin immunoprecipitation assays supported the involvement of both Sp1 and Sp3 in complexes formed on the MAT2B promoter .

Chromatin immunoprecipitation assays supported the involvement of both <protein>Sp1</protein> and <protein>Sp3</protein> in complexes formed on the <dna>MAT2B promoter</dna> .


The data show that the 5'-untranslated sequences play an important role in regulating the MAT2B gene and identifies the Sp1 site at +9 as a potential target for modulating MAT2B expression , a process that can have a major effect on intracellular AdoMet levels .

The data show that the <dna>5'-untranslated sequences</dna> play an important role in regulating the <dna>MAT2B gene</dna> and identifies the <dna>Sp1 site</dna> at +9 as a potential target for modulating MAT2B expression , a process that can have a major effect on intracellular <protein>AdoMet</protein> levels .


Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression .

Molecular pathogenesis of influenza A virus infection and virus-induced regulation of <dna>cytokine gene</dna> expression .


Despite vaccines and antiviral substances influenza still causes significant morbidity and mortality world wide .


Better understanding of the molecular mechanisms of influenza virus replication , pathogenesis and host immune responses is required for the development of more efficient means of prevention and treatment of influenza .


Influenza A virus , which replicates in epithelial cells and leukocytes , regulates host cell transcriptional and translational systems and activates , as well as downregulates apoptotic pathways .

Influenza A virus , which replicates in <cell_type>epithelial cells</cell_type> and <cell_type>leukocytes</cell_type> , regulates host cell transcriptional and translational systems and activates , as well as downregulates apoptotic pathways .


Influenza A virus infection results in the production of chemotactic ( RANTES , MIP-1 alpha , MCP-1 , MCP-3 , and IP-10 ) , pro-inflammatory ( IL-1 beta , IL-6 , IL-18 , and TNF-alpha ) , and antiviral ( IFN-alpha/beta ) cytokines .

Influenza A virus infection results in the production of chemotactic ( <protein>RANTES</protein> , <protein>MIP-1 alpha</protein> , <protein>MCP-1</protein> , <protein>MCP-3</protein> , and <protein>IP-10</protein> ) , pro-inflammatory ( <protein>IL-1 beta</protein> , <protein>IL-6</protein> , <protein>IL-18</protein> , and <protein>TNF-alpha</protein> ) , and <protein>antiviral ( IFN-alpha/beta ) cytokines</protein> .


Cytokine gene expression is associated with the activation of NF-kappa B , AP-1 , STAT and IRF signal transducing molecules in influenza A virus-infected cells .

Cytokine gene expression is associated with the activation of <protein>NF-kappa B</protein> , <protein>AP-1</protein> , <protein>STAT</protein> and <protein>IRF signal transducing molecules</protein> in influenza A virus-infected cells .


In addition of upregulating cytokine gene expression , influenza A virus infection activates caspase-1 enzyme , which is involved in the proteolytic processing of proIL-1 beta and proIL-18 into their biologically active forms .

In addition of upregulating <dna>cytokine gene</dna> expression , influenza A virus infection activates <protein>caspase-1 enzyme</protein> , which is involved in the proteolytic processing of <protein>proIL-1 beta</protein> and <protein>proIL-18</protein> into their biologically active forms .


Influenza A virus-induced IFN-alpha/beta is essential in host 's antiviral defence by activating the expression of antiviral Mx , PKR and oligoadenylate synthetase genes .

Influenza A virus-induced <protein>IFN-alpha/beta</protein> is essential in host 's antiviral defence by activating the expression of <dna>antiviral Mx</dna> , <dna>PKR and oligoadenylate synthetase genes</dna> .


IFN-alpha/beta also prolongs T cell survival , upregulates IL-12 and IL-18 receptor gene expression and together with IL-18 stimulates NK and T cell IFN-gamma production and the development of Th1-type immune response .

<protein>IFN-alpha/beta</protein> also prolongs T cell survival , upregulates IL-12 and IL-18 receptor gene expression and together with <protein>IL-18</protein> stimulates <cell_type>NK and T cell</cell_type> IFN-gamma production and the development of Th1-type immune response .


Comparison of hprt and lacI mutant frequency with DNA adduct formation in N-hydroxy-2-acetylaminofluorene-treated Big Blue rats .


N-Hydroxy-2-acetylaminofluorene ( N-OH-AAF ) is the proximate carcinogenic metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene .


In this study , transgenic Big Blue ( R ) rats were used to examine the relationship between in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver compared with that in nontarget tissues .


Male rats were given one , two , or four doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals , and groups of treated and control rats were euthanized up to 10 weeks after beginning the dosing .


Mutant frequencies were measured in the spleen lymphocyte hprt gene , and lacI mutant frequencies were determined in the liver and spleen lymphocytes .

Mutant frequencies were measured in the <dna>spleen lymphocyte hprt gene</dna> , and lacI mutant frequencies were determined in the liver and spleen <cell_type>lymphocytes</cell_type> .


At 6 weeks after beginning the dosing , the hprt mutant frequency in spleen lymphocytes from the four-dose group was 16.5 x 10 ( -6 ) compared with 3.2 x 10 ( -6 ) in control animals .

At 6 weeks after beginning the dosing , the hprt mutant frequency in <cell_type>spleen lymphocytes</cell_type> from the four-dose group was 16.5 x 10 ( -6 ) compared with 3.2 x 10 ( -6 ) in control animals .


Also at 6 weeks , rats given one , two , or four doses of N-OH-AAF had lacI mutant frequencies in the liver of 97.6 , 155.6 , and 406.8 x 10 ( -6 ) , respectively , compared with a control frequency of 25.7 x 10 ( -6 ) ; rats given four doses had lacI mutant frequencies in spleen lymphocytes of 55.8 x 10 ( -6 ) compared with a control frequency of 20.4 x 10 ( -6 ) .

Also at 6 weeks , rats given one , two , or four doses of N-OH-AAF had lacI mutant frequencies in the liver of 97.6 , 155.6 , and 406.8 x 10 ( -6 ) , respectively , compared with a control frequency of 25.7 x 10 ( -6 ) ; rats given four doses had lacI mutant frequencies in <cell_type>spleen lymphocytes</cell_type> of 55.8 x 10 ( -6 ) compared with a control frequency of 20.4 x 10 ( -6 ) .


Additional rats were evaluated for DNA adduct formation in the liver , spleen lymphocytes , and bone marrow by ( 32 ) P-postlabeling .

Additional rats were evaluated for DNA adduct formation in the liver , <cell_type>spleen lymphocytes</cell_type> , and bone marrow by ( 32 ) P-postlabeling .


Adduct analysis was conducted 1 day after one , two , and four treatments with N-OH-AAF , 5 days after one treatment , and 9 days after two treatments .


N- ( Deoxyguanosin-8-yl ) -2-aminofluorene was the major DNA adduct identified in all the tissues examined .


Adduct concentrations increased with total dose to maximum values in samples taken 1 day after two doses , and remained essentially the same after four doses .


In samples taken after four doses , adduct levels were 103 , 28 , and 7 fmol/microg of DNA in liver , spleen lymphocytes , and bone marrow , respectively .

In samples taken after four doses , adduct levels were 103 , 28 , and 7 fmol/microg of DNA in liver , <cell_type>spleen lymphocytes</cell_type> , and bone marrow , respectively .


The results indicate that the extent of both DNA adduct formation and mutant induction correlates with the organ specificity for N-OH-AAF carcinogenesis in the rat .


Environ. Mol. Mutagen. 37 : 195-202 , 2001 .


Published 2001 Wiley-Liss , Inc .


Expression of Mad1 in T cells leads to reduced thymic cellularity and impaired mitogen-induced proliferation .

Expression of <protein>Mad1</protein> in <cell_type>T cells</cell_type> leads to reduced thymic cellularity and impaired mitogen-induced proliferation .


To investigate Mad1 function in vivo , transgenic mice were generated that express a Mad1 transgene in T lineage cells under the control of the proximal lck promoter .

To investigate <protein>Mad1</protein> function in vivo , transgenic mice were generated that express a <dna>Mad1 transgene</dna> in <cell_type>T lineage cells</cell_type> under the control of the <dna>proximal lck promoter</dna> .


Thymus size in lck-Mad1 transgenic mice is drastically reduced although representation of the various thymocyte sub populations appears normal .

Thymus size in lck-Mad1 transgenic mice is drastically reduced although representation of the various <cell_type>thymocyte sub populations</cell_type> appears normal .


To investigate more closely any effects of Mad1 expression on thymocytes , we examined thymic selection using MHC class I-restricted H-Y-TCR transgenic mice .

To investigate more closely any effects of Mad1 expression on <cell_type>thymocytes</cell_type> , we examined thymic selection using MHC class I-restricted H-Y-TCR transgenic mice .


Mad1 expression in vivo reduces the efficiency of positive selection .


Furthermore , thymocytes and splenic T cells from lck-Mad1 transgenic mice display a profound proliferative defect in response to activation with either PMA/Ionomycin or immobilized anti-CD3/CD28 antibody .

Furthermore , <cell_type>thymocytes</cell_type> and <cell_type>splenic T cells</cell_type> from lck-Mad1 transgenic mice display a profound proliferative defect in response to activation with either PMA/Ionomycin or <protein>immobilized anti-CD3/CD28 antibody</protein> .


This proliferative defect is not reversed by addition of exogenous IL-2 and is p53-independent .

This proliferative defect is not reversed by addition of <protein>exogenous IL-2</protein> and is p53-independent .


The growth inhibition caused by Mad1 is overcome by expression of active c-Myc .

The growth inhibition caused by <protein>Mad1</protein> is overcome by expression of <protein>active c-Myc</protein> .


Differential requirement for the transcription factor PU.1 in the generation of natural killer cells versus B and T cells .

Differential requirement for the <protein>transcription factor PU.1</protein> in the generation of <cell_type>natural killer cells</cell_type> versus <cell_type>B and T cells</cell_type> .


PU.1 is a member of the Ets family of transcription factors required for the development of various lymphoid and myeloid cell lineages , but its role in natural killer ( NK ) cell development is not known .

<protein>PU.1</protein> is a member of the <protein>Ets family of transcription factors</protein> required for the development of various <cell_line>lymphoid and myeloid cell lineages</cell_line> , but its role in <cell_type>natural killer ( NK ) cell</cell_type> development is not known .


The study shows that PU.1 is expressed in NK cells and that , on cell transfer into alymphoid Rag2/gammac ( -/- ) mice , hematopoietic progenitors of PU.1 ( -/- ) fetal liver cells could generate functional NK cells but not B or T cells .

The study shows that <protein>PU.1</protein> is expressed in <cell_type>NK cells</cell_type> and that , on cell transfer into alymphoid Rag2/gammac ( -/- ) mice , <cell_type>hematopoietic progenitors</cell_type> of <cell_type>PU.1 ( -/- ) fetal liver cells</cell_type> could generate functional <cell_type>NK cells</cell_type> but not <cell_type>B or T cells</cell_type> .


Nevertheless , the numbers of bone marrow NK cell precursors and splenic mature NK cells were reduced compared to controls .

Nevertheless , the numbers of <cell_type>bone marrow NK cell precursors</cell_type> and <cell_type>splenic mature NK cells</cell_type> were reduced compared to controls .


Moreover , PU.1 ( -/- ) NK cells displayed reduced expression of the receptors for stem cell factor and interleukin ( IL ) -7 , suggesting a nonredundant role for PU.1 in regulating the expression of these cytokine receptor genes during NK cell development .

Moreover , <cell_type>PU.1 ( -/- ) NK cells</cell_type> displayed reduced expression of the receptors for <protein>stem cell factor</protein> and <protein>interleukin ( IL ) -7</protein> , suggesting a nonredundant role for <protein>PU.1</protein> in regulating the expression of these <dna>cytokine receptor genes</dna> during NK cell development .


PU.1 ( -/- ) NK cells also showed defective expression of inhibitory and activating members of the Ly49 family and failed to proliferate in response to IL-2 and IL-12 .

<cell_type>PU.1 ( -/- ) NK cells</cell_type> also showed defective expression of inhibitory and activating members of the <protein>Ly49 family</protein> and failed to proliferate in response to <protein>IL-2</protein> and <protein>IL-12</protein> .


Thus , despite the less stringent requirement for PU.1 in NK cell development compared to B and T cells , PU.1 regulates NK cell differentiation and homeostasis .

Thus , despite the less stringent requirement for <protein>PU.1</protein> in NK cell development compared to <cell_type>B and T cells</cell_type> , <protein>PU.1</protein> regulates NK cell differentiation and homeostasis .


Benzene-extracted components are important for the major activity of diesel exhaust particles : effect on interleukin-8 gene expression in human bronchial epithelial cells .

Benzene-extracted components are important for the major activity of diesel exhaust particles : effect on <dna>interleukin-8 gene</dna> expression in <cell_type>human bronchial epithelial cells</cell_type> .


Epidemiologic and experimental studies suggest that diesel exhaust particles ( DEPs ) may be related to increasing respiratory mortality and morbidity .


We have shown that DEPs augmented the production of inflammatory cytokines by human airway epithelial cells in vitro .

We have shown that DEPs augmented the production of <protein>inflammatory cytokines</protein> by <cell_type>human airway epithelial cells</cell_type> in vitro .


To better understand the mechanisms of their proinflammatory activities , we studied the effects of several components extracted from DEPs on interleukin ( IL ) -8 expression in human bronchial epithelial cell line BEAS-2B and normal human airway epithelial cells obtained from very peripheral airways by an ultrathin bronchoscope .

To better understand the mechanisms of their proinflammatory activities , we studied the effects of several components extracted from DEPs on interleukin ( IL ) -8 expression in <cell_line>human bronchial epithelial cell line BEAS-2B</cell_line> and <cell_type>normal human airway epithelial cells</cell_type> obtained from very peripheral airways by an ultrathin bronchoscope .


We used several agents active on signal transduction pathways in cytokine expression , such as the protein kinase C inhibitor staurosporin , antioxidant agents including N-acetyl cysteine ( NAC ) and pyrrolidine dithiocarbamate ( PDTC ) , and p38 mitogen-activated protein kinase ( MAPK ) inhibitor SB203580 .

We used several agents active on signal transduction pathways in cytokine expression , such as the protein kinase C inhibitor staurosporin , antioxidant agents including N-acetyl cysteine ( NAC ) and pyrrolidine dithiocarbamate ( PDTC ) , and <protein>p38 mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) inhibitor SB203580 .


Benzene-extracted components showed effects mimicking DEPs on IL-8 gene expression , release of several cytokines ( IL-8 ; granulocyte macrophage colony-stimulating factor ; and regulated on activation , normal T cells expressed and secreted ) and nuclear factor ( NF ) -kappa B activation .

Benzene-extracted components showed effects mimicking DEPs on IL-8 gene expression , release of several <protein>cytokines</protein> ( <protein>IL-8</protein> ; <protein>granulocyte macrophage colony-stimulating factor</protein> ; and regulated on activation , <cell_type>normal T cells</cell_type> expressed and secreted ) and nuclear factor ( NF ) -kappa B activation .


We also found that NAC , PDTC , and SB203580 suppressed the activities of DEPs and their benzene extracts , suggesting the roles of oxidants-mediated NF-kappa B activation and p38MAPK pathways .

We also found that NAC , PDTC , and SB203580 suppressed the activities of DEPs and their benzene extracts , suggesting the roles of oxidants-mediated NF-kappa B activation and <protein>p38MAPK</protein> pathways .


Finally , benzo [ a ] pyrene , one of the important compounds included in the benzene component , replicated the activities shown by DEPs .


The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis .

The <protein>nuclear receptor PPAR gamma</protein> is expressed by <cell_type>mouse T lymphocytes</cell_type> and PPAR gamma agonists induce apoptosis .


Peroxisome proliferator-activated receptor ( PPAR ) -gamma is a nuclear hormone receptor that serves as a trans factor to regulate lipid metabolism .

<protein>Peroxisome proliferator-activated receptor ( PPAR ) -gamma</protein> is a <protein>nuclear hormone receptor</protein> that serves as a trans factor to regulate lipid metabolism .


Intense interest is focused on PPAR-gamma and its ligands owing to its putative role in adipocyte differentiation .

Intense interest is focused on <protein>PPAR-gamma</protein> and its ligands owing to its putative role in adipocyte differentiation .


Little is known , however , about the functions of PPAR-gamma in the immune system , especially in T lymphocytes .

Little is known , however , about the functions of <protein>PPAR-gamma</protein> in the immune system , especially in <cell_type>T lymphocytes</cell_type> .


We demonstrate that both naive and activated ovalbumin-specific T cells from DO11.10-transgenic mice express PPAR-gamma mRNA and protein .

We demonstrate that both <cell_type>naive and activated ovalbumin-specific T cells</cell_type> from DO11.10-transgenic mice express <rna>PPAR-gamma</rna> mRNA and protein .


In order to determine the function of PPAR-gamma , T cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin or antigen and antigen-presenting cells .

In order to determine the function of <protein>PPAR-gamma</protein> , <cell_type>T cells</cell_type> were stimulated with phorbol 12-myristate 13-acetate and ionomycin or antigen and <cell_type>antigen-presenting cells</cell_type> .


Simultaneous exposure to PPAR-gamma ligands ( e.g. 15-deoxy-Delta ( 12 , 14 ) -prostaglandin J ( 2 ) , troglitazone ) showed drastic inhibition of proliferation and significant decreases in cell viability .


The decrease in cell viability was due to apoptosis of the T lymphocytes , and occurred only when cells were treated with PPAR-gamma , and not PPAR-alpha agonists , revealing specificity of this response for PPAR-gamma .

The decrease in cell viability was due to apoptosis of the <cell_type>T lymphocytes</cell_type> , and occurred only when cells were treated with <protein>PPAR-gamma</protein> , and not PPAR-alpha agonists , revealing specificity of this response for <protein>PPAR-gamma</protein> .


These observations suggest that PPAR-gamma agonists play an important role in regulating T cell-mediated immune responses by inducing apoptosis .


T cell death via PPAR-gamma ligation may act as a potent anti-inflammatory signal in the immune system , and ligands could possibly be used to control disorders in which excessive inflammation occurs .


Suppression of lung inflammation in rats by prevention of NF-kappaB activation in the liver .


Activation of NF-kappaB and production of NF-kappaB -dependent chemokines are thought to be involved in the pathogenesis of neutrophilic lung inflammation .

Activation of <protein>NF-kappaB</protein> and production of <protein>NF-kappaB</protein> -dependent <protein>chemokines</protein> are thought to be involved in the pathogenesis of neutrophilic lung inflammation .


Calpain-1 inhibitor ( CI-1 ) blocks activation of NF-kappaB by preventing proteolysis of the inhibitory protein IkappaB-alpha by the ubiquitin/proteasome pathway .

Calpain-1 inhibitor ( CI-1 ) blocks activation of <protein>NF-kappaB</protein> by preventing proteolysis of the inhibitory protein <protein>IkappaB-alpha</protein> by the ubiquitin/proteasome pathway .


We hypothesized that inhibition of proteasome function with CI-1 would block NF-kappaB activation in vivo after intraperitoneal ( i.p. ) treatment with bacterial lipopolysaccharide ( LPS ) , and that NF-kappaB inhibition would be associated with suppression of chemokine gene expression and attenuation of neutrophilic alveolitis .


We treated rats with a single i.p. injection of CI-1 ( 10 mg/kg ) two hours prior to i.p. LPS ( 7 mg/kg ) .


Treatment with Cl-1 prevented degradation of IkappaB-alpha and activation of NF-kappaB in the liver in response to LPS ; however , Cl-1 treatment had no detected effect on NF-kappaB activation in lung tissue .

Treatment with Cl-1 prevented degradation of <protein>IkappaB-alpha</protein> and activation of <protein>NF-kappaB</protein> in the liver in response to LPS ; however , Cl-1 treatment had no detected effect on NF-kappaB activation in lung tissue .


CI-1 treatment prior to LPS resulted in 40 % lower MIP-2 concentration in lung lavage fluid compared to rats treated with vehicle prior to LPS ( 502 +/- 112 pg/ml vs. 859 +/-144 pg/ml , P < 0.05 ) .


In addition , CI-1 treatment substantially inhibited LPS-induced neutrophilic alveolitis ( 2.7+ /- 1.2 x 10 ( 5 ) vs. 43.7 +/- 12.2 x 10 ( 5 ) lung lavage neutrophils , P < 0.01 ) .

In addition , CI-1 treatment substantially inhibited LPS-induced neutrophilic alveolitis ( 2.7+ /- 1.2 x 10 ( 5 ) vs. 43.7 +/- 12.2 x 10 ( 5 ) <cell_type>lung lavage neutrophils</cell_type> , P < 0.01 ) .


These data indicate that NF-kappaB inhibition in the liver can alter lung inflammation induced by systemic LPS treatment and suggest that a liver-lung interaction contributes to the inflammatory response of the lung .


Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength .

<protein>Notch1</protein> regulates maturation of <cell_type>CD4+ and CD8+ thymocytes</cell_type> by modulating TCR signal strength .


Notch signaling regulates cell fate decisions in multiple lineages .


We demonstrate in this report that retroviral expression of activated Notch1 in mouse thymocytes abrogates differentiation of immature CD4+CD8+ thymocytes into both CD4 and CD8 mature single-positive T cells .

We demonstrate in this report that retroviral expression of activated <protein>Notch1</protein> in <cell_type>mouse thymocytes</cell_type> abrogates differentiation of <cell_type>immature CD4+CD8+ thymocytes</cell_type> into both <cell_type>CD4 and CD8 mature single-positive T cells</cell_type> .


The ability of Notch1 to inhibit T cell development was observed in vitro and in vivo with both normal and TCR transgenic thymocytes .

The ability of <protein>Notch1</protein> to inhibit T cell development was observed in vitro and in vivo with both <cell_type>normal and TCR transgenic thymocytes</cell_type> .


Notch1 -mediated developmental arrest was dose dependent and was associated with impaired thymocyte responses to TCR stimulation .

<protein>Notch1</protein> -mediated developmental arrest was dose dependent and was associated with impaired thymocyte responses to TCR stimulation .


Notch1 also inhibited TCR-mediated signaling in Jurkat T cells .

<protein>Notch1</protein> also inhibited TCR-mediated signaling in <cell_line>Jurkat T cells</cell_line> .


These data indicate that constitutively active Notch1 abrogates CD4+ and CD8+ maturation by interfering with TCR signal strength and provide an explanation for the physiological regulation of Notch expression during thymocyte development .

These data indicate that constitutively active <protein>Notch1</protein> abrogates CD4+ and CD8+ maturation by interfering with TCR signal strength and provide an explanation for the physiological regulation of Notch expression during thymocyte development .


Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients .

Expression of <protein>SART3 antigen</protein> and induction of <cell_type>CTLs</cell_type> by SART3-derived peptides in breast cancer patients .


We recently reported the SART3 tumour-rejection antigen as possessing tumour epitopes capable of inducing HLA-class I-restricted cytotoxic T lymphocytes ( CTLs ) .

We recently reported the <protein>SART3 tumour-rejection antigen</protein> as possessing tumour epitopes capable of inducing <cell_type>HLA-class I-restricted cytotoxic T lymphocytes</cell_type> ( <cell_type>CTLs</cell_type> ) .


This study investigated expression of the SART3 antigen in breast cancer to explore an appropriate molecule for use in specific immunotherapy of breast cancer patients .

This study investigated expression of the <protein>SART3 antigen</protein> in breast cancer to explore an appropriate molecule for use in specific immunotherapy of breast cancer patients .


The SART3 antigen was detected in all of the breast cancer cell lines tested , 30 of 40 ( 75 % ) breast cancer tissue samples , and 0 of 3 non-tumourous breast tissue samples .

The <protein>SART3 antigen</protein> was detected in all of the <cell_line>breast cancer cell lines</cell_line> tested , 30 of 40 ( 75 % ) breast cancer tissue samples , and 0 of 3 non-tumourous breast tissue samples .


SART3 derived peptides at positions 109-118 and 315-323 induced HLA-A24 restricted CTLs that reacted to breast cancer cells from the peripheral blood mononuclear cells ( PBMCs ) of breast cancer patients .

SART3 derived peptides at <dna>positions 109-118 and 315-323</dna> induced HLA-A24 restricted <cell_type>CTLs</cell_type> that reacted to <cell_type>breast cancer cells</cell_type> from the <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) of breast cancer patients .


Therefore , the SART3 antigen and its peptides could be an appropriate molecule for use in specific immunotherapy of the majority of HLA-A24-positive breast cancer patients

Therefore , the <protein>SART3 antigen</protein> and its peptides could be an appropriate molecule for use in specific immunotherapy of the majority of HLA-A24-positive breast cancer patients


Autostimulation of the Epstein-Barr virus BRLF1 promoter is mediated through consensus Sp1 and Sp3 binding sites .

Autostimulation of the Epstein-Barr virus <dna>BRLF1 promoter</dna> is mediated through consensus <dna>Sp1 and Sp3 binding sites</dna> .


As an essential step in the lytic cascade , the Rta homologues of gammaherpesviruses all activate their own expression .


Consistent with this biologic function , the Epstein-Barr virus ( EBV ) Rta protein powerfully stimulates the promoter of its own gene , Rp , in EBV-positive B cells in transient-transfection reporter-based assays .

Consistent with this biologic function , the Epstein-Barr virus ( EBV ) <protein>Rta protein</protein> powerfully stimulates the <dna>promoter</dna> of its own gene , <dna>Rp</dna> , in <cell_type>EBV-positive B cells</cell_type> in transient-transfection reporter-based assays .


We analyzed the activity of RpCAT in response to Rta by deletional and site-directed mutagenesis .

We analyzed the activity of <dna>RpCAT</dna> in response to <protein>Rta</protein> by deletional and site-directed mutagenesis .


Two cognate Sp1 binding sites located at -279 and -45 relative to the transcriptional start site proved crucial for Rta-mediated activation .

Two <dna>cognate Sp1 binding sites</dna> located at -279 and -45 relative to the <dna>transcriptional start site</dna> proved crucial for Rta-mediated activation .


Previously described binding sites for the cellular transcription factor Zif268 and the viral transactivator ZEBRA were found to be dispensable for activation of RpCAT by Rta .

Previously described binding sites for the cellular <protein>transcription factor Zif268</protein> and the <protein>viral transactivator ZEBRA</protein> were found to be dispensable for activation of <dna>RpCAT</dna> by <protein>Rta</protein> .


Gel shift analysis , using extracts of B cells in latency or induced into the lytic cycle , identified Sp1 and Sp3 as the predominant cellular proteins bound to Rp near -45 .

Gel shift analysis , using extracts of <cell_type>B cells</cell_type> in latency or induced into the lytic cycle , identified <protein>Sp1</protein> and <protein>Sp3</protein> as the predominant <protein>cellular proteins</protein> bound to <dna>Rp</dna> near -45 .


During the lytic cycle , ZEBRA bound Rp near the Sp1/Sp3 site .

During the lytic cycle , <protein>ZEBRA</protein> bound <dna>Rp</dna> near the <dna>Sp1/Sp3 site</dna> .


The binding of Sp1 and Sp3 to Rp correlated with the reporter activities in the mutagenesis study , establishing a direct link between transcriptional activation of Rp by Rta and DNA binding by Sp1 and/or Sp3 .

The binding of <protein>Sp1</protein> and <protein>Sp3</protein> to <dna>Rp</dna> correlated with the reporter activities in the mutagenesis study , establishing a direct link between transcriptional activation of <dna>Rp</dna> by <protein>Rta</protein> and DNA binding by <protein>Sp1</protein> and/or <protein>Sp3</protein> .


The relative abundance or functional state of the cellular Sp1 and Sp3 transcription factors may be altered in response to stimuli that induce the BRLF1 promoter and thereby contribute to the activation of the viral lytic cycle .

The relative abundance or functional state of the cellular <protein>Sp1</protein> and <protein>Sp3</protein> <protein>transcription factors</protein> may be altered in response to stimuli that induce the <dna>BRLF1 promoter</dna> and thereby contribute to the activation of the viral lytic cycle .


Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the therapeutic efficacy of cancer immunotherapy .

Gene transfer of antisense <protein>hypoxia inducible factor-1 alpha</protein> enhances the therapeutic efficacy of cancer immunotherapy .


Solid tumors meet their demands for nascent blood vessels and increased glycolysis , to combat hypoxia , by activating multiple genes involved in angiogenesis and glucose metabolism .


Hypoxia inducible factor-1 ( HIF-1 ) is a constitutively expressed basic helix-loop-helix transcription factor , formed by the assembly of HIF-1alpha and HIF-1beta ( Arnt ) , that is stablized in response to hypoxia , and rapidly degraded under normoxic conditions .

<protein>Hypoxia inducible factor-1</protein> ( <protein>HIF-1</protein> ) is a constitutively expressed basic <protein>helix-loop-helix transcription factor</protein> , formed by the assembly of <protein>HIF-1alpha</protein> and <protein>HIF-1beta</protein> ( <protein>Arnt</protein> ) , that is stablized in response to hypoxia , and rapidly degraded under normoxic conditions .


It activates the transcription of genes important for maintaining oxygen homeostasis .


Here , we demonstrate that engineered down-regulation of HIF-1alpha by intratumoral gene transfer of an antisense HIF-1alpha plasmid leads to the down-regulation of VEGF , and decreased tumor microvessel density .

Here , we demonstrate that engineered down-regulation of <protein>HIF-1alpha</protein> by intratumoral gene transfer of an <dna>antisense HIF-1alpha plasmid</dna> leads to the down-regulation of <dna>VEGF</dna> , and decreased tumor microvessel density .


Antisense HIF-1alpha monotherapy resulted in the complete and permanent rejection of small ( 0.1 cm in diameter ) EL-4 tumors , which is unusual for an anti-angiogenic agent where transient suppression of tumor growth is the norm .


It induced NK cell -dependent rejection of tumors , but failed to stimulate systemic T cell -mediated anti-tumor immunity , and synergized with B7-1-mediated immunotherapy to cause the NK cell and CD8 T cell -dependent rejection of larger EL-4 tumors ( 0.4 cm in diameter ) that were refractory to monotherapies .

It induced <cell_type>NK cell</cell_type> -dependent rejection of tumors , but failed to stimulate systemic <cell_type>T cell</cell_type> -mediated anti-tumor immunity , and synergized with B7-1-mediated immunotherapy to cause the <cell_type>NK cell</cell_type> and <cell_type>CD8 T cell</cell_type> -dependent rejection of larger EL-4 tumors ( 0.4 cm in diameter ) that were refractory to monotherapies .


Mice cured of their tumors by combination therapy resisted a rechallenge with parental tumor cells , indicating systemic antitumor immunity had been achieved .

Mice cured of their tumors by combination therapy resisted a rechallenge with <cell_type>parental tumor cells</cell_type> , indicating systemic antitumor immunity had been achieved .


In summary , whilst intensive investigations are in progress to target the many HIF-1 effectors , the results herein indicate that blocking hypoxia-inducible pathways and enhancing NK-mediated antitumor immunity by targeting HIF-1 itself may be advantageous , especially when combined with cancer immunotherapy .

In summary , whilst intensive investigations are in progress to target the many <protein>HIF-1</protein> effectors , the results herein indicate that blocking hypoxia-inducible pathways and enhancing NK-mediated antitumor immunity by targeting <protein>HIF-1</protein> itself may be advantageous , especially when combined with cancer immunotherapy .


Runx2 : a novel oncogenic effector revealed by in vivo complementation and retroviral tagging .

<dna>Runx2</dna> : a novel oncogenic effector revealed by in vivo complementation and retroviral tagging .


The Runx2 ( Cbfa1 , Pebp2alphaA , Aml3 ) gene was previously identified as a frequent target for transcriptional activation by proviral insertion in T-cell lymphomas of CD2-MYC transgenic mice .

The <dna>Runx2</dna> ( <dna>Cbfa1</dna> , <dna>Pebp2alphaA</dna> , <dna>Aml3</dna> ) gene was previously identified as a frequent target for transcriptional activation by proviral insertion in T-cell lymphomas of CD2-MYC transgenic mice .


We have recently shown that over-expression of the full-length , most highly expressed Runx2 isoform in the thymus perturbs T-cell development , leads to development of spontaneous lymphomas at low frequency and is strongly synergistic with Myc .

We have recently shown that over-expression of the full-length , most highly expressed <dna>Runx2</dna> isoform in the thymus perturbs T-cell development , leads to development of spontaneous lymphomas at low frequency and is strongly synergistic with <protein>Myc</protein> .


To gain further insight into the relationship of Runx2 to other lymphomagenic pathways , we tested the effect of combining the CD2-Runx2 transgene either with a Pim1 transgene ( E ( mu ) -Pim1 ) or with the p53 null genotype , as each of these displays independent synergy with Myc .

To gain further insight into the relationship of <dna>Runx2</dna> to other lymphomagenic pathways , we tested the effect of combining the <dna>CD2-Runx2 transgene</dna> either with a <dna>Pim1 transgene</dna> ( <dna>E ( mu ) -Pim1</dna> ) or with the <dna>p53</dna> null genotype , as each of these displays independent synergy with <protein>Myc</protein> .


In both cases we observed synergistic tumour development .


However , Runx2 appeared to have a dominant effect on the tumour phenotype in each case , with most tumours conforming to the CD3 ( + ) , CD8 ( + ) , CD4 ( +/- ) phenotype seen in CD2-Runx2 mice .

However , <protein>Runx2</protein> appeared to have a dominant effect on the tumour phenotype in each case , with most tumours conforming to the CD3 ( + ) , CD8 ( + ) , CD4 ( +/- ) phenotype seen in CD2-Runx2 mice .


Neonatal infection of CD2-Runx2 mice with Moloney murine leukaemia virus ( Moloney MLV ) also led to a dramatic acceleration of tumour onset .


Analysis of known Moloney MLV target genes in these lymphomas showed a high frequency of rearrangement at c-Myc or N-Myc ( 82 % ) , and a significant number at Pim1 or Pim2 ( 23 % ) , and at Pal1/Gfi1 ( 18 % ) .

Analysis of known <dna>Moloney MLV target genes</dna> in these lymphomas showed a high frequency of rearrangement at <dna>c-Myc</dna> or <dna>N-Myc</dna> ( 82 % ) , and a significant number at <dna>Pim1</dna> or <dna>Pim2</dna> ( 23 % ) , and at <dna>Pal1/Gfi1</dna> ( 18 % ) .


These results indicate that Runx2 makes a distinct contribution to T-cell lymphoma development which does not coincide with any of the oncogene complementation groups previously identified by retroviral tagging .

These results indicate that <protein>Runx2</protein> makes a distinct contribution to T-cell lymphoma development which does not coincide with any of the oncogene complementation groups previously identified by retroviral tagging .


The involvement of TNF-alpha -related apoptosis-inducing ligand in the enhanced cytotoxicity of IFN-beta -stimulated human dendritic cells to tumor cells .

The involvement of <protein>TNF-alpha</protein> -related apoptosis-inducing ligand in the enhanced cytotoxicity of <protein>IFN-beta</protein> -stimulated <cell_type>human dendritic cells</cell_type> to <cell_type>tumor cells</cell_type> .


TNF-alpha -related apoptosis-inducing ligand ( TRAIL ) is characterized by its preferential induction of apoptosis of tumor cells but not normal cells .

<protein>TNF-alpha</protein> -related apoptosis-inducing ligand ( TRAIL ) is characterized by its preferential induction of apoptosis of <cell_type>tumor cells</cell_type> but not <cell_type>normal cells</cell_type> .


Dendritic cells ( DCs ) , besides their role as APCs , now have been demonstrated to exert cytotoxicity or cytostasis on some tumor cells .

<cell_type>Dendritic cells</cell_type> ( <cell_type>DCs</cell_type> ) , besides their role as APCs , now have been demonstrated to exert cytotoxicity or cytostasis on some <cell_type>tumor cells</cell_type> .


Here , we report that both human CD34 ( + ) stem cell -derived DCs ( CD34DCs ) and human CD14 ( + ) monocyte -derived DCs ( MoDCs ) express TRAIL and exhibit cytotoxicity to some types of tumor cells partially through TRAIL .

Here , we report that both <cell_type>human CD34 ( + ) stem cell</cell_type> -derived <cell_type>DCs</cell_type> ( <cell_type>CD34DCs</cell_type> ) and <cell_type>human CD14 ( + ) monocyte</cell_type> -derived <cell_type>DCs</cell_type> ( <cell_type>MoDCs</cell_type> ) express TRAIL and exhibit cytotoxicity to some types of <cell_type>tumor cells</cell_type> partially through TRAIL .


Moderate expression of TRAIL appeared on CD34DCs from the 8th day of culture and was also seen on freshly isolated monocytes .

Moderate expression of TRAIL appeared on <cell_type>CD34DCs</cell_type> from the 8th day of culture and was also seen on <cell_type>freshly isolated monocytes</cell_type> .


The level of TRAIL expression remained constant until DC maturation .


TRAIL expression on immature CD34DCs or MoDCs was greatly up-regulated after IFN-beta stimulation .

TRAIL expression on <cell_type>immature CD34DCs</cell_type> or <cell_type>MoDCs</cell_type> was greatly up-regulated after <protein>IFN-beta</protein> stimulation .


Moreover , IFN-beta could strikingly enhance the ability of CD34DCs or MoDCs to kill TRAIL-sensitive tumor cells , but LPS did not have such an effect .

Moreover , <protein>IFN-beta</protein> could strikingly enhance the ability of <cell_type>CD34DCs</cell_type> or <cell_type>MoDCs</cell_type> to kill TRAIL-sensitive <cell_type>tumor cells</cell_type> , but LPS did not have such an effect .


The up-regulation of TRAIL on IFN-beta -stimulated DCs partially contributed to the increased cytotoxicity of DCS : Pretreatment of TRAIL-sensitive tumor cells with caspase-3 inhibitor could significantly increase their resistance to the cytotoxicity of IFN-beta -stimulated DCS : In contrast , NF-kappaB inhibitor could significantly increase the sensitivity of tumor cells to the killing by nonstimulated or LPS-stimulated DCS : Our studies demonstrate that IFN-beta -stimulated DCs are functionally cytotoxic .

The up-regulation of TRAIL on <protein>IFN-beta</protein> -stimulated <cell_type>DCs</cell_type> partially contributed to the increased cytotoxicity of <cell_type>DCS</cell_type> : Pretreatment of TRAIL-sensitive <cell_type>tumor cells</cell_type> with caspase-3 inhibitor could significantly increase their resistance to the cytotoxicity of <protein>IFN-beta</protein> -stimulated <cell_type>DCS</cell_type> : In contrast , NF-kappaB inhibitor could significantly increase the sensitivity of <cell_type>tumor cells</cell_type> to the killing by nonstimulated or LPS-stimulated <cell_type>DCS</cell_type> : Our studies demonstrate that <protein>IFN-beta</protein> -stimulated <cell_type>DCs</cell_type> are functionally cytotoxic .


Thus , an innate mechanism of DC-mediated antitumor immunity might exist in vivo in which DCs act as effectors to directly kill tumor cells partially via TRAIL .

Thus , an innate mechanism of DC-mediated antitumor immunity might exist in vivo in which <cell_type>DCs</cell_type> act as effectors to directly kill <cell_type>tumor cells</cell_type> partially via TRAIL .


Subsequently , DCs act as APCs involved in the uptake , processing , and presentation of apoptotic tumor Ags to cross-prime CD8 ( + ) CTL cells .

Subsequently , <cell_type>DCs</cell_type> act as APCs involved in the uptake , processing , and presentation of <protein>apoptotic tumor Ags</protein> to cross-prime <cell_type>CD8 ( + ) CTL cells</cell_type> .


Tumor cells regulate the lytic activity of tumor-specific cytotoxic t lymphocytes by modulating the inhibitory natural killer receptor function .

<cell_type>Tumor cells</cell_type> regulate the lytic activity of <cell_type>tumor-specific cytotoxic t lymphocytes</cell_type> by modulating the inhibitory natural killer receptor function .


Tumor-infiltrating p58+ T cells from a renal tumor were specifically expanded in response to tumor cell stimulation and cloned .

<cell_type>Tumor-infiltrating p58+ T cells</cell_type> from a renal tumor were specifically expanded in response to tumor cell stimulation and cloned .


These p58+ T cells were found to express a memory phenotype and corresponded to clonal TCRBV3 T-cell expansion .

These <cell_type>p58+ T cells</cell_type> were found to express a <cell_type>memory phenotype</cell_type> and corresponded to clonal TCRBV3 T-cell expansion .


Functionally , p58 ( + ) CTLs displayed a low lytic activity for HLA-A2 tumor and normal cells .

Functionally , <cell_type>p58 ( + ) CTLs</cell_type> displayed a low lytic activity for <cell_type>HLA-A2 tumor and normal cells</cell_type> .


However , this lytic activity was significantly increased after blockade of p58 with specific monoclonal antibodies .

However , this lytic activity was significantly increased after blockade of <protein>p58</protein> with specific <protein>monoclonal antibodies</protein> .


Interestingly , we demonstrated that stimulation by tumor cells was required to trigger the inhibitory effect of p58 on the lytic activity of antigen-specific CTLs and that stimulation of the inhibitory function of p58 by tumor cells correlated with an inhibition of nuclear factor-kappaB activation in p58+ tumor-specific CTLS .

Interestingly , we demonstrated that stimulation by <cell_type>tumor cells</cell_type> was required to trigger the inhibitory effect of <protein>p58</protein> on the lytic activity of <cell_type>antigen-specific CTLs</cell_type> and that stimulation of the inhibitory function of <protein>p58</protein> by <cell_type>tumor cells</cell_type> correlated with an inhibition of nuclear factor-kappaB activation in <cell_type>p58+ tumor-specific CTLS</cell_type> .


T-cell factor-1 expression during human natural killer cell development and in circulating CD56 ( + ) bright natural killer cells .

<protein>T-cell factor-1</protein> expression during <cell_type>human natural killer cell</cell_type> development and in circulating <protein>CD56 ( + )</protein> bright <cell_type>natural killer cells</cell_type> .


Transcription factors are essential to govern differentiation along the lymphoid lineage from uncommitted hematopoietic stem cells .

<protein>Transcription factors</protein> are essential to govern differentiation along the <cell_type>lymphoid lineage</cell_type> from <cell_type>uncommitted hematopoietic stem cells</cell_type> .


Although many of these transcription factors have putative roles based on murine knockout experiments , their function in human lymphoid development is less known and was studied further .

Although many of these <protein>transcription factors</protein> have putative roles based on murine knockout experiments , their function in human lymphoid development is less known and was studied further .


Transcription factor expression in fresh and cultured adult human bone marrow and umbilical cord blood progenitors was evaluated .

Transcription factor expression in fresh and cultured <cell_type>adult human bone marrow and umbilical cord blood progenitors</cell_type> was evaluated .


We found that fresh CD34 ( + ) Lin ( - ) cells that are human leukocyte antigen ( HLA ) -DR ( - ) or CD38 ( - ) constitutively express GATA-3 but not T-cell factor-1 ( TCF-1 ) or Id-3 .

We found that <cell_type>fresh CD34 ( + ) Lin ( - ) cells</cell_type> that are human leukocyte antigen ( HLA ) -DR ( - ) or CD38 ( - ) constitutively express <protein>GATA-3</protein> but not <protein>T-cell factor-1</protein> ( <protein>TCF-1</protein> ) or <protein>Id-3</protein> .


Culture with the murine fetal liver cell line AFT024 and defined cytokines was capable of inducing TCF-1 mRNA .

Culture with the <cell_line>murine fetal liver cell line AFT024</cell_line> and defined <protein>cytokines</protein> was capable of inducing <rna>TCF-1 mRNA</rna> .


However , no T-cell receptor gene rearrangement was identified in cultured progeny .

However , no <dna>T-cell receptor gene</dna> rearrangement was identified in cultured progeny .


Id-3 , a basic helix loop helix factor with dominant negative function for T-cell differentiation transcription factors , also was upregulated and may explain unsuccessful T-cell maturation .

<protein>Id-3</protein> , a <protein>basic helix loop helix factor</protein> with dominant negative function for T-cell differentiation <protein>transcription factors</protein> , also was upregulated and may explain unsuccessful T-cell maturation .


To better understand the developmental link between natural killer ( NK ) cells derived from progenitors , we studied NK cell subsets circulating in blood .

To better understand the developmental link between <cell_type>natural killer ( NK ) cells</cell_type> derived from <cell_type>progenitors</cell_type> , we studied <cell_type>NK cell subsets</cell_type> circulating in blood .


CD56 ( +bright ) , but not CD56 ( +dim ) , NK cells constitutively express TCF-1 by reverse transcriptase polymerase chain reaction and Western blot analysis .

<cell_type>CD56 ( +bright )</cell_type> , but not <cell_type>CD56 ( +dim )</cell_type> , <cell_type>NK cells</cell_type> constitutively express <protein>TCF-1</protein> by reverse transcriptase polymerase chain reaction and Western blot analysis .


The TCF-1 isoform found in CD56 ( +bright ) cells , which express lectin but not immunoglobulin class I recognizing inhibitory receptors , was identical to that induced in NK cell differentiation culture and was distinctly different from isoforms in T cells .

The <protein>TCF-1 isoform</protein> found in <cell_type>CD56 ( +bright ) cells</cell_type> , which express <protein>lectin</protein> but not <protein>immunoglobulin class I</protein> recognizing <protein>inhibitory receptors</protein> , was identical to that induced in NK cell differentiation culture and was distinctly different from isoforms in <cell_type>T cells</cell_type> .


These results suggest that TCF-1 does not target human killer immunoglobulin receptor genes , TCF-1 is uniquely expressed in circulating CD56 ( +bright ) NK cells , and specific TCF-1 isoforms may play an important role in regulating NK differentiation from a common NK/T-cell progenitor .

These results suggest that <protein>TCF-1</protein> does not target <dna>human killer immunoglobulin receptor genes</dna> , <protein>TCF-1</protein> is uniquely expressed in circulating <cell_type>CD56 ( +bright ) NK cells</cell_type> , and specific <protein>TCF-1 isoforms</protein> may play an important role in regulating NK differentiation from a common <cell_type>NK/T-cell progenitor</cell_type> .


Transcriptional activation by a matrix associating region-binding protein .

Transcriptional activation by a <protein>matrix associating region-binding protein</protein> .


contextual requirements for the function of bright .

contextual requirements for the function of <protein>bright</protein> .


Bright ( B cell regulator of IgH transcription ) is a B cell -specific , matrix associating region-binding protein that transactivates gene expression from the IgH intronic enhancer ( E mu ) .

<protein>Bright</protein> ( <protein>B cell regulator of IgH transcription</protein> ) is a <cell_type>B cell</cell_type> -specific , <protein>matrix associating region-binding protein</protein> that transactivates gene expression from the <dna>IgH intronic enhancer</dna> ( <dna>E mu</dna> ) .


We show here that Bright has multiple contextual requirements to function as a transcriptional activator .

We show here that <protein>Bright</protein> has multiple contextual requirements to function as a <protein>transcriptional activator</protein> .


Bright can not transactivate via out of context , concatenated binding sites .

<protein>Bright</protein> can not transactivate via out of context , <protein>concatenated binding sites</protein> .


Transactivation is maximal on integrated substrates .


Two of the three previously identified binding sites in E mu are required for full Bright transactivation .

Two of the three previously identified <dna>binding sites</dna> in <dna>E mu</dna> are required for full <protein>Bright</protein> transactivation .


The Bright DNA binding domain defined a new family , which includes SWI1 , a component of the SWI.SNF complex shown to have high mobility group-like DNA binding characteristics .

The <protein>Bright DNA binding domain</protein> defined a new family , which includes <protein>SWI1</protein> , a component of the <protein>SWI.SNF complex</protein> shown to have high mobility group-like DNA binding characteristics .


Similar to one group of high mobility group box proteins , Bright distorts E mu binding site -containing DNA on binding , supporting the concept that it mediates E mu remodeling .

Similar to one group of <protein>high mobility group box proteins</protein> , <protein>Bright</protein> distorts <dna>E mu binding site</dna> -containing DNA on binding , supporting the concept that it mediates <dna>E mu</dna> remodeling .


Transfection studies further implicate Bright in facilitating spatially separated promoter-enhancer interactions in both transient and stable assays .

Transfection studies further implicate <protein>Bright</protein> in facilitating spatially separated promoter-enhancer interactions in both transient and stable assays .


Finally , we show that overexpression of Bright leads to enhanced DNase I sensitivity of the endogenous E mu matrix associating regions .

Finally , we show that overexpression of <protein>Bright</protein> leads to enhanced DNase I sensitivity of the endogenous <dna>E mu</dna> matrix associating regions .


These data further suggest that Bright may contribute to increased gene expression by remodeling the immunoglobulin locus during B cell development .

These data further suggest that <protein>Bright</protein> may contribute to increased gene expression by remodeling the <dna>immunoglobulin locus</dna> during <cell_type>B cell</cell_type> development .


Analysis of BCL-6 mutations in classic Hodgkin disease of the B- and T-cell type .

Analysis of BCL-6 mutations in classic Hodgkin disease of the <cell_type>B- and T-cell type</cell_type> .


BCL-6 is essential for germinal center formation and thus for affinity maturation of immunoglobulin ( Ig ) genes by somatic mutations .

<dna>BCL-6</dna> is essential for germinal center formation and thus for affinity maturation of <dna>immunoglobulin ( Ig ) genes</dna> by somatic mutations .


The 5'-noncoding region of the BCL-6 gene is even a target for the mutation machinery .

The <dna>5'-noncoding region</dna> of the <dna>BCL-6 gene</dna> is even a target for the mutation machinery .


Translocations of the BCL-6 gene to heterologous promoters and mutations of its 5'-noncoding regulatory region were reported to be potential mechanisms for deregulating BCL-6 expression and for playing a role in the genesis of non-Hodgkin lymphoma .

Translocations of the <dna>BCL-6 gene</dna> to <dna>heterologous promoters</dna> and mutations of its <dna>5'-noncoding regulatory region</dna> were reported to be potential mechanisms for deregulating <dna>BCL-6</dna> expression and for playing a role in the genesis of non-Hodgkin lymphoma .


In line with this hypothesis is the observation that B-cell lymphoma with somatic mutations , such as diffuse large B-cell lymphoma and follicular lymphoma , also carry BCL-6 mutations , some of which are recurrently detectable .


Classic Hodgkin disease ( cHD ) is also derived from B cells with high loads of somatic mutations and thus a further candidate for BCL-6 mutations .

Classic Hodgkin disease ( cHD ) is also derived from <cell_type>B cells</cell_type> with high loads of somatic mutations and thus a further candidate for BCL-6 mutations .


To determine the presence and potential role of BCL-6 mutations in cHD , the 5'-noncoding BCL-6 proportion of single Hodgkin and Reed-Sternberg ( HRS ) cells from 6 cases of cHD and 6 cases of HD-derived cell lines was analyzed .

To determine the presence and potential role of BCL-6 mutations in cHD , the <dna>5'-noncoding BCL-6</dna> proportion of <cell_type>single Hodgkin and Reed-Sternberg ( HRS ) cells</cell_type> from 6 cases of cHD and 6 cases of <cell_line>HD-derived cell lines</cell_line> was analyzed .


All B-cell-derived HD cases and cell lines harbored BCL-6 mutations .


In contrast , both T-cell-derived HD cases and cell lines were devoid of BCL-6 mutations .


With only one exception , there were no lymphoma-specific recurrent BCL-6 mutations detected , and BCL-6 protein was absent from the HRS cells of most cases .

With only one exception , there were no lymphoma-specific recurrent BCL-6 mutations detected , and <protein>BCL-6 protein</protein> was absent from the <cell_type>HRS cells</cell_type> of most cases .


In conclusion , ( 1 ) somatic BCL-6 mutations are restricted to cHD cases of B-cell origin , and ( 2 ) the BCL-6 mutations represent mostly irrelevant somatic base substitutions without consequences for BCL-6 protein expression and the pathogenesis of cHD .

In conclusion , ( 1 ) somatic BCL-6 mutations are restricted to cHD cases of <cell_type>B-cell</cell_type> origin , and ( 2 ) the BCL-6 mutations represent mostly irrelevant somatic base substitutions without consequences for <protein>BCL-6 protein</protein> expression and the pathogenesis of cHD .


Gadd45gamma is dispensable for normal mouse development and T-cell proliferation .

<dna>Gadd45gamma</dna> is dispensable for normal mouse development and T-cell proliferation .


Gadd45gamma , a family member of the growth arrest and DNA damage-inducible gene family 45 ( Gadd45 ) , is strongly induced by interleukin-2 ( IL-2 ) in peripheral T cells .

<dna>Gadd45gamma</dna> , a family member of the <dna>growth arrest and DNA damage-inducible gene family 45</dna> ( <dna>Gadd45</dna> ) , is strongly induced by <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) in <cell_type>peripheral T cells</cell_type> .


While in most tissues all Gadd45 family members are expressed , Gadd45gamma is the only member that is induced by IL-2 .

While in most tissues all <dna>Gadd45 family members</dna> are expressed , <dna>Gadd45gamma</dna> is the only member that is induced by <protein>IL-2</protein> .


Here we show that the IL-2 -induced expression of Gadd45gamma is dependent on a signaling pathway mediated by the tyrosine kinase Jak3 and the transcription factors Stat5a and Stat5b ( signal transducer and activator of transcription ) .

Here we show that the <protein>IL-2</protein> -induced expression of <dna>Gadd45gamma</dna> is dependent on a signaling pathway mediated by the <protein>tyrosine kinase Jak3</protein> and the <protein>transcription factors</protein> <protein>Stat5a</protein> and <protein>Stat5b</protein> ( <protein>signal transducer and activator of transcription</protein> ) .


Previous studies with ectopically overexpressed Gadd45gamma in various cell lines implicated its function in negative growth control .

Previous studies with ectopically overexpressed <dna>Gadd45gamma</dna> in various cell lines implicated its function in negative growth control .


To analyze the physiological role of Gadd45gamma we used homologous recombination to generate mice lacking Gadd45gamma .

To analyze the physiological role of <dna>Gadd45gamma</dna> we used homologous recombination to generate mice lacking <dna>Gadd45gamma</dna> .


Gadd45gamma -deficient mice develop normally , are indistinguishable from their littermates , and are fertile .

<dna>Gadd45gamma</dna> -deficient mice develop normally , are indistinguishable from their littermates , and are fertile .


Furthermore , hematopoiesis in mice lacking Gadd45gamma is not impaired and Gadd45gamma -deficient T lymphocytes show normal responses to IL-2 .

Furthermore , hematopoiesis in mice lacking <dna>Gadd45gamma</dna> is not impaired and <dna>Gadd45gamma</dna> -deficient <cell_type>T lymphocytes</cell_type> show normal responses to <protein>IL-2</protein> .


These data demonstrate that Gadd45gamma is not essential for normal mouse development and hematopoiesis , possibly due to functional redundancy among the Gadd45 family members .

These data demonstrate that <dna>Gadd45gamma</dna> is not essential for normal mouse development and hematopoiesis , possibly due to functional redundancy among the <dna>Gadd45 family members</dna> .


Gadd45gamma is also dispensable for IL-2 -induced T-cell proliferation .

<dna>Gadd45gamma</dna> is also dispensable for <protein>IL-2</protein> -induced T-cell proliferation .


Decreased expression of c-myc family genes in thymuses from myasthenia gravis patients .

Decreased expression of <dna>c-myc family genes</dna> in thymuses from myasthenia gravis patients .


The thymus is a critical organ for the elimination of autoreactive T cells by apoptosis .

The thymus is a critical organ for the elimination of <cell_type>autoreactive T cells</cell_type> by apoptosis .


We studied the expression of apoptosis-associated genes , bcl-xL , bad , caspase-3 , and c-myc family genes in myasthenia gravis ( MG ) thymuses .

We studied the expression of apoptosis-associated genes , <dna>bcl-xL</dna> , <dna>bad</dna> , <dna>caspase-3</dna> , and <dna>c-myc family genes</dna> in myasthenia gravis ( MG ) thymuses .


We observed that the mRNA levels of myc family genes , c-myc and max , were markedly reduced in MG thymuses .

We observed that the mRNA levels of <dna>myc family genes</dna> , <dna>c-myc</dna> and <dna>max</dna> , were markedly reduced in MG thymuses .


These results indicate that c-myc -mediated signaling is abnormal in MG thymuses .

These results indicate that <dna>c-myc</dna> -mediated signaling is abnormal in MG thymuses .


The levels of molecules whose expressions are associated with myc , such as STAM , prothymosin-alpha , and NFkappaB

The levels of molecules whose expressions are associated with <dna>myc</dna> , such as <protein>STAM</protein> , <protein>prothymosin-alpha</protein> , and <protein>NFkappaB</protein>


Immunohistochemical detection of interferon-gamma-producing cells in dermatophytosis .

Immunohistochemical detection of <cell_type>interferon-gamma-producing cells</cell_type> in dermatophytosis .


Skin lesions of dermatophytosis are thought to be a result of a T cell -dependent inflammatory response that is mediated by various cytokines .

Skin lesions of dermatophytosis are thought to be a result of a <cell_type>T cell</cell_type> -dependent inflammatory response that is mediated by various <protein>cytokines</protein> .


We examined whether IFN-gamma-positive cells ( as expression of Th1 response ) were present in the skin lesions of dermatophytosis in situ by immunohistochemical techniques .

We examined whether <cell_type>IFN-gamma-positive cells</cell_type> ( as expression of <cell_type>Th1</cell_type> response ) were present in the skin lesions of dermatophytosis in situ by immunohistochemical techniques .


Mixtures of CD4-positive T cells and CD8-positive T cells were found to be present in the dermal infiltrates of the lesions .

Mixtures of <cell_type>CD4-positive T cells</cell_type> and <cell_type>CD8-positive T cells</cell_type> were found to be present in the dermal infiltrates of the lesions .


Considerable numbers of CD1a-positive cells were detected in the upper dermis and epidermis .

Considerable numbers of <cell_type>CD1a-positive cells</cell_type> were detected in the upper dermis and epidermis .


A marked accumulation of CD68-positive cells was found in the upper dermis .

A marked accumulation of <cell_type>CD68-positive cells</cell_type> was found in the upper dermis .


IFN-gamma-positive cells were present in the upper dermis of the lesions .

<cell_type>IFN-gamma-positive cells</cell_type> were present in the upper dermis of the lesions .


The pattern of IFN-gamma staining appeared to be intracellular in mononuclear lymphoid cells .

The pattern of <protein>IFN-gamma</protein> staining appeared to be intracellular in <cell_type>mononuclear lymphoid cells</cell_type> .


The staining was considered to be highly specific because it could be completely blocked by preabsorption with recombinant IFN-gamma .

The staining was considered to be highly specific because it could be completely blocked by preabsorption with <protein>recombinant IFN-gamma</protein> .


Our data support the hypothesis that the skin lesions of dermatophytosis may be associated with a Th1 response .

Our data support the hypothesis that the skin lesions of dermatophytosis may be associated with a <cell_type>Th1</cell_type> response .


Th1 response , which is characterized by IFN-gamma release , is thought to be involved in the host defense against dermatophytes and to reflect cutaneous reaction in dermatophytosis .

<cell_type>Th1</cell_type> response , which is characterized by <protein>IFN-gamma</protein> release , is thought to be involved in the host defense against dermatophytes and to reflect cutaneous reaction in dermatophytosis .


Regulation of the helix-loop-helix proteins , E2A and Id3 , by the Ras - ERK MAPK cascade .

Regulation of the <protein>helix-loop-helix proteins</protein> , <protein>E2A</protein> and <protein>Id3</protein> , by the <protein>Ras</protein> - <protein>ERK</protein> <protein>MAPK</protein> cascade .


Activation of mitogen-activated protein kinase ( MAPK ) pathways leads to cellular differentiation and/or proliferation in a wide variety of cell types , including developing thymocytes .

Activation of <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) pathways leads to cellular differentiation and/or proliferation in a wide variety of cell types , including <cell_type>developing thymocytes</cell_type> .


The basic helix-loop-helix ( bHLH ) proteins E12 and E47 and an inhibitor HLH protein , Id3 , play key roles in thymocyte differentiation .

The <protein>basic helix-loop-helix ( bHLH ) proteins</protein> <protein>E12</protein> and <protein>E47</protein> and an <protein>inhibitor HLH protein</protein> , <protein>Id3</protein> , play key roles in thymocyte differentiation .


We show here that E2A DNA binding is lowered in primary immature thymocytes consequent to T cell receptor ( TCR ) -mediated ligation .

We show here that <protein>E2A</protein> DNA binding is lowered in <cell_type>primary immature thymocytes</cell_type> consequent to T cell receptor ( TCR ) -mediated ligation .


Whereas expression of E2A mRNA and protein are unaltered , Id3 transcripts are rapidly induced upon signaling from the TCR .

Whereas expression of E2A mRNA and protein are unaltered , <rna>Id3 transcripts</rna> are rapidly induced upon signaling from the <protein>TCR</protein> .


Activation of Id3 transcription is regulated in a dose-dependent manner by the extracellular signal-regulated kinase ( ERK ) MAPK module .

Activation of Id3 transcription is regulated in a dose-dependent manner by the extracellular signal-regulated kinase ( <protein>ERK</protein> ) <protein>MAPK</protein> module .


These observations directly connect the ERK MAPK cascade and HLH proteins in a linear pathway .

These observations directly connect the <protein>ERK</protein> <protein>MAPK</protein> cascade and <protein>HLH proteins</protein> in a linear pathway .


Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion -- evidence for retinoid signaling pathways in the mast cell lineage .

Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion -- evidence for retinoid signaling pathways in the <cell_type>mast cell lineage</cell_type> .


Investigation of mast cell responsiveness toward retinoic acid ( RA ) revealed selective promotion of ICAM-3 expression in the human mast cell line HMC-1 .

Investigation of mast cell responsiveness toward retinoic acid ( RA ) revealed selective promotion of <protein>ICAM-3</protein> expression in the <cell_line>human mast cell line HMC-1</cell_line> .


This process was dose- and time-dependent and detectable by flow cytometry , Western blot analysis , ELISA , and Northern blot analysis .


ICAM-3 modulation was found to be cell-type dependent , detectable also for HL-60 cells and monocytes but not U-937 and only weakly for KU812 cells .

<protein>ICAM-3</protein> modulation was found to be cell-type dependent , detectable also for <cell_line>HL-60 cells</cell_line> and <cell_type>monocytes</cell_type> but not <cell_line>U-937</cell_line> and only weakly for <cell_line>KU812 cells</cell_line> .


Terminally differentiated skin mast cells also failed to up-modulate their ICAM-3 , suggesting the requirement for some degree of immaturity for the process .

<cell_type>Terminally differentiated skin mast cells</cell_type> also failed to up-modulate their <protein>ICAM-3</protein> , suggesting the requirement for some degree of immaturity for the process .


RA-mediated effects on ICAM-1 expression , studied in parallel , were clearly distinct from those on ICAM-3 .

RA-mediated effects on <protein>ICAM-1</protein> expression , studied in parallel , were clearly distinct from those on <protein>ICAM-3</protein> .


Investigation of retinoid receptor expression , known to mediate intracellular RA signaling , revealed presence of RAR alpha , RAR gamma , RXR beta , and RXR gamma transcripts in all cell lines studied , and HMC-1 cells were the only line lacking RXR alpha .

Investigation of <protein>retinoid receptor</protein> expression , known to mediate intracellular RA signaling , revealed presence of <rna>RAR alpha , RAR gamma , RXR beta , and RXR gamma transcripts</rna> in all cell lines studied , and <cell_line>HMC-1 cells</cell_line> were the only line lacking <protein>RXR alpha</protein> .


RAR beta , not expressed at baseline , was induced by RA in a fashion obviously correlating with ICAM-3 up-regulation .

<protein>RAR beta</protein> , not expressed at baseline , was induced by RA in a fashion obviously correlating with <protein>ICAM-3</protein> up-regulation .


Increased ICAM-3 expression was of functional significance , such that processes stimulated or co-stimulated via ICAM-3 ( homotypic aggregation , IL-8 secretion ) were clearly enhanced upon RA pretreatment , suggesting that RA may contribute via hitherto unrecognized pathways to immune function and host defense .

Increased <protein>ICAM-3</protein> expression was of functional significance , such that processes stimulated or co-stimulated via <protein>ICAM-3</protein> ( homotypic aggregation , IL-8 secretion ) were clearly enhanced upon RA pretreatment , suggesting that RA may contribute via hitherto unrecognized pathways to immune function and host defense .


CD28 and T cell co-stimulation .

<protein>CD28</protein> and <cell_type>T cell</cell_type> co-stimulation .


Over the last decade the concept of T cell co-stimulation has emerged to take a central role in the process of T cell activation .

Over the last decade the concept of <cell_type>T cell</cell_type> co-stimulation has emerged to take a central role in the process of T cell activation .


However , the exact definition of co-stimulation is still unclear .


In this review , we re-examine the concept of co-stimulation .


We suggest that while co-stimulation is important , there is little evidence to link co-stimulation with T cell anergy .

We suggest that while co-stimulation is important , there is little evidence to link co-stimulation with <cell_type>T cell</cell_type> anergy .


We then suggest a framework for studying co-stimulation .


Focusing on recent advances in our understanding of CD28 , we discuss four areas of T cell activation where co-stimulation may play a role .

Focusing on recent advances in our understanding of <protein>CD28</protein> , we discuss four areas of <cell_type>T cell</cell_type> activation where co-stimulation may play a role .


Regulation of activator protein-1 and NF-kappa B in CD8+ T cells exposed to peripheral self-antigens .

Regulation of <protein>activator protein-1</protein> and <protein>NF-kappa B</protein> in <cell_type>CD8+ T cells</cell_type> exposed to <protein>peripheral self-antigens</protein> .


The transcriptional events that control T cell tolerance to peripheral self Ags are still unknown .

The transcriptional events that control <cell_type>T cell</cell_type> tolerance to <protein>peripheral self Ags</protein> are still unknown .


In this study , we analyzed the regulation of AP-1 - and NF-kappa B -mediated transcription during in vivo induction of tolerance to a self Ag expressed exclusively on hepatocytes .

In this study , we analyzed the regulation of <protein>AP-1</protein> - and <protein>NF-kappa B</protein> -mediated transcription during in vivo induction of tolerance to a <protein>self Ag</protein> expressed exclusively on <cell_type>hepatocytes</cell_type> .


Naive CD8 ( + ) Desire ( Des ) ( + ) T cells isolated from the Des TCR-transgenic mice that are specific for the H-2K ( b ) class I Ag were transferred into Alb-K ( b ) -transgenic mice that express the H-2K ( b ) Ag on hepatocytes only .

<cell_type>Naive CD8 ( + ) Desire ( Des ) ( + ) T cells</cell_type> isolated from the Des TCR-transgenic mice that are specific for the <protein>H-2K ( b ) class I Ag</protein> were transferred into Alb-K ( b ) -transgenic mice that express the <protein>H-2K ( b ) Ag</protein> on <cell_type>hepatocytes</cell_type> only .


Tolerance develops in these mice .


We found that the self-reactive CD8 ( + ) Des ( + ) T cells were transiently activated , then became unresponsive and were further deleted .

We found that the <cell_type>self-reactive CD8 ( + ) Des ( + ) T cells</cell_type> were transiently activated , then became unresponsive and were further deleted .


In contrast to CD8 ( + ) Des ( + ) T cells activated in vivo with APCs , which express high AP-1 and high NF-kappa B transcriptional activity , the unresponsive CD8 ( + ) Des ( + ) T cells expressed no AP-1 and only weak NF-kappa B transcriptional activity .

In contrast to <cell_type>CD8 ( + ) Des ( + ) T cells</cell_type> activated in vivo with APCs , which express high <protein>AP-1</protein> and high <protein>NF-kappa B</protein> transcriptional activity , the unresponsive <cell_type>CD8 ( + ) Des ( + ) T cells</cell_type> expressed no <protein>AP-1</protein> and only weak <protein>NF-kappa B</protein> transcriptional activity .


The differences in NF-kappa B transcriptional activity correlated with the generation of distinct NF-kappa B complexes .

The differences in <protein>NF-kappa B</protein> transcriptional activity correlated with the generation of distinct <protein>NF-kappa B complexes</protein> .


Indeed , in vivo primed T cells predominantly express p50/p50 and p65/p50 dimers , whereas these p50-containing complexes are barely detectable in tolerant T cells that express p65- and c-Rel-containing complexes .

Indeed , in vivo <cell_type>primed T cells</cell_type> predominantly express <protein>p50/p50 and p65/p50 dimers</protein> , whereas these <protein>p50-containing complexes</protein> are barely detectable in <cell_type>tolerant T cells</cell_type> that express <protein>p65- and c-Rel-containing complexes</protein> .


These observations suggest that fine regulation of NF-kappa B complex formation may determine T cell fate .

These observations suggest that fine regulation of <protein>NF-kappa B complex</protein> formation may determine <cell_type>T cell</cell_type> fate .


Transcriptional regulation in lymphocytes .

Transcriptional regulation in <cell_type>lymphocytes</cell_type> .


Lymphocytes have been used to investigate many cellular processes , including lineage commitment , differentiation , proliferation and apoptosis .

<cell_type>Lymphocytes</cell_type> have been used to investigate many cellular processes , including lineage commitment , differentiation , proliferation and apoptosis .


The transcription factors that mediate these processes are often expressed broadly in many cell types .

The <protein>transcription factors</protein> that mediate these processes are often expressed broadly in many cell types .


The emerging theme is one of cell-type-specific regulation , affecting not only the functional activation of transcription factors but also their access to appropriate regions of DNA .

The emerging theme is one of cell-type-specific regulation , affecting not only the functional activation of <protein>transcription factors</protein> but also their access to appropriate regions of DNA .


Existence of retinoic acid-receptor -independent retinoid X-receptor -dependent pathway in myeloid cell function .

Existence of <protein>retinoic acid-receptor</protein> -independent <protein>retinoid X-receptor</protein> -dependent pathway in <cell_type>myeloid cell</cell_type> function .


We previously reported that ER-27191 ( 4- [ 4 , 5 , 7 , 8 , 9 , 10-hexahydro-7 , 7 , 10 , 10-tetramethyl-1- ( 3-pyridylmethyl ) anthra [ 1 , 2-b ] pyrrol-3-yl ] benzoic acid ) is a potent antagonist of retinoic acid receptor ( RAR ) , and ER-35795 ( ( 2E , 4E , 6E ) -7- [ 1- ( 1-methylethyl ) -8-chloro-1 , 2 , 3 , 4-tetrahydroquinolin-6-yl ] -6-fluoro-3-methyl-2 , 4 , 6-nonatrienoic acid ) is a novel retinoid X receptor ( RXR ) -specific agonist .

We previously reported that ER-27191 ( 4- [ 4 , 5 , 7 , 8 , 9 , 10-hexahydro-7 , 7 , 10 , 10-tetramethyl-1- ( 3-pyridylmethyl ) anthra [ 1 , 2-b ] pyrrol-3-yl ] benzoic acid ) is a potent antagonist of <protein>retinoic acid receptor</protein> ( <protein>RAR</protein> ) , and ER-35795 ( ( 2E , 4E , 6E ) -7- [ 1- ( 1-methylethyl ) -8-chloro-1 , 2 , 3 , 4-tetrahydroquinolin-6-yl ] -6-fluoro-3-methyl-2 , 4 , 6-nonatrienoic acid ) is a novel <protein>retinoid X receptor</protein> ( <protein>RXR</protein> ) -specific agonist .


By using these compounds , we investigated whether distinct RAR -dependent and RXR -dependent pathways operate to mediate the diverse activities of retinoids , particularly , the effects of the RXR pathway on cellular function .

By using these compounds , we investigated whether distinct <protein>RAR</protein> -dependent and <protein>RXR</protein> -dependent pathways operate to mediate the diverse activities of retinoids , particularly , the effects of the <protein>RXR</protein> pathway on cellular function .


ER-27191 completely antagonized HL60 cell differentiation induced by all-trans-retinoic acid ( atRA ) .

ER-27191 completely antagonized <cell_line>HL60 cell</cell_line> differentiation induced by all-trans-retinoic acid ( atRA ) .


However , the differentiation induced by the ER-35795 was not antagonized at all by the RAR antagonist , but was inhibited by an RXR homodimer antagonist ( LGD100754 , ( 2E , 4E , 6Z ) -7- ( 3-n-propoxy-5 , 6 , 7 , 8-tetrahydro-5 , 5 , 8 , 8-tetramethylnaphthalen-2-yl ) -3-methylocta-2 , 4 , 6-trienoic acid ) .

However , the differentiation induced by the ER-35795 was not antagonized at all by the <protein>RAR</protein> antagonist , but was inhibited by an <protein>RXR homodimer</protein> antagonist ( LGD100754 , ( 2E , 4E , 6Z ) -7- ( 3-n-propoxy-5 , 6 , 7 , 8-tetrahydro-5 , 5 , 8 , 8-tetramethylnaphthalen-2-yl ) -3-methylocta-2 , 4 , 6-trienoic acid ) .


Its agonistic action on RXR/RAR heterodimer , on the other hand , was neutralized by the RAR antagonist .

Its agonistic action on <protein>RXR/RAR heterodimer</protein> , on the other hand , was neutralized by the <protein>RAR</protein> antagonist .


During HL60 cell differentiation , atRA induced RARbeta mRNA , while the RXR had no effect .

During <cell_line>HL60 cell</cell_line> differentiation , atRA induced <rna>RARbeta mRNA</rna> , while the <protein>RXR</protein> had no effect .


Interestingly , a functional RXR -pathway was also seen in lipopolysaccharide-induced inhibition of mouse splenocyte proliferation .

Interestingly , a functional <protein>RXR</protein> -pathway was also seen in lipopolysaccharide-induced inhibition of <cell_type>mouse splenocyte</cell_type> proliferation .


These results strongly suggest the existence of a pharmacological RXR -dependent pathway that is activated by a ligand that can bind to RXR .

These results strongly suggest the existence of a pharmacological <protein>RXR</protein> -dependent pathway that is activated by a ligand that can bind to <protein>RXR</protein> .


Targeting Src homology 2 domain-containing tyrosine phosphatase ( SHP-1 ) into lipid rafts inhibits CD3 -induced T cell activation .

Targeting <protein>Src homology 2 domain-containing tyrosine phosphatase</protein> ( <protein>SHP-1</protein> ) into lipid rafts inhibits <protein>CD3</protein> -induced <cell_type>T cell</cell_type> activation .


To study the mechanism by which protein tyrosine phosphatases ( PTPs ) regulate CD3 -induced tyrosine phosphorylation , we investigated the distribution of PTPs in subdomains of plasma membrane .

To study the mechanism by which <protein>protein tyrosine phosphatases</protein> ( <protein>PTPs</protein> ) regulate <protein>CD3</protein> -induced tyrosine phosphorylation , we investigated the distribution of <protein>PTPs</protein> in subdomains of plasma membrane .


We report here that the bulk PTP activity associated with T cell membrane is present outside the lipid rafts , as determined by sucrose density gradient sedimentation .

We report here that the bulk <protein>PTP</protein> activity associated with <cell_type>T cell</cell_type> membrane is present outside the lipid rafts , as determined by sucrose density gradient sedimentation .


In Jurkat T cells , approximately 5 -- 10 % of Src homology 2 domain-containing tyrosine phosphatase ( SHP-1 ) is constitutively associated with plasma membrane , and nearly 50 % of SHP-2 is translocated to plasma membrane after vanadate treatment .

In <cell_line>Jurkat T cells</cell_line> , approximately 5 -- 10 % of <protein>Src homology 2 domain-containing tyrosine phosphatase</protein> ( <protein>SHP-1</protein> ) is constitutively associated with plasma membrane , and nearly 50 % of <protein>SHP-2</protein> is translocated to plasma membrane after vanadate treatment .


Similar to transmembrane PTP , CD45 , the membrane-associated populations of SHP-1 and SHP-2 are essentially excluded from lipid rafts , where other signaling molecules such as Lck , linker for activation of T cells , and CD3 zeta are enriched .

Similar to <protein>transmembrane PTP</protein> , <protein>CD45</protein> , the membrane-associated populations of <protein>SHP-1</protein> and <protein>SHP-2</protein> are essentially excluded from lipid rafts , where other <protein>signaling molecules</protein> such as <protein>Lck , linker for activation of T cells</protein> , and <protein>CD3 zeta</protein> are enriched .


We further demonstrated that CD3 -induced tyrosine phosphorylation of these substrates is largely restricted to lipid rafts , unless PTPs are inhibited .

We further demonstrated that <protein>CD3</protein> -induced tyrosine phosphorylation of these substrates is largely restricted to lipid rafts , unless <protein>PTPs</protein> are inhibited .


It suggests that a restricted partition of PTPs among membrane subdomains may regulate protein tyrosine phosphorylation in T cell membrane .

It suggests that a restricted partition of <protein>PTPs</protein> among membrane subdomains may regulate protein tyrosine phosphorylation in <cell_type>T cell</cell_type> membrane .


To test this hypothesis , we targeted SHP-1 into lipid rafts by using the N-terminal region of Lck ( residues 1 -- 14 ) .

To test this hypothesis , we targeted <protein>SHP-1</protein> into lipid rafts by using the <protein>N-terminal region of Lck</protein> ( <protein>residues 1 -- 14</protein> ) .


The results indicate that the expression of Lck/SHP-1 chimera inside lipid rafts profoundly inhibits CD3 -induced tyrosine phosphorylation of CD3 zeta/epsilon , IL-2 generation , and nuclear mobilization of NF-AT .

The results indicate that the expression of <protein>Lck/SHP-1 chimera</protein> inside lipid rafts profoundly inhibits <protein>CD3</protein> -induced tyrosine phosphorylation of <protein>CD3 zeta/epsilon</protein> , IL-2 generation , and nuclear mobilization of <protein>NF-AT</protein> .


Collectively , these results suggest that the exclusion of PTPs from lipid rafts may be a mechanism that potentiates TCR / CD3 activation

Collectively , these results suggest that the exclusion of <protein>PTPs</protein> from lipid rafts may be a mechanism that potentiates <protein>TCR</protein> / <protein>CD3</protein> activation


An instructive component in T helper cell type 2 ( Th2 ) development mediated by GATA-3 .

An instructive component in <cell_type>T helper cell type 2</cell_type> ( <cell_type>Th2</cell_type> ) development mediated by <protein>GATA-3</protein> .


Although interleukin ( IL ) -12 and IL-4 polarize naive CD4 ( + ) T cells toward T helper cell type 1 ( Th1 ) or Th2 phenotypes , it is not known whether cytokines instruct the developmental fate in uncommitted progenitors or select for outgrowth of cells that have stochastically committed to a particular fate .

Although <protein>interleukin ( IL ) -12</protein> and <protein>IL-4</protein> polarize <cell_type>naive CD4 ( + ) T cells</cell_type> toward T helper cell type 1 ( Th1 ) or Th2 phenotypes , it is not known whether <protein>cytokines</protein> instruct the developmental fate in <cell_type>uncommitted progenitors</cell_type> or select for outgrowth of cells that have stochastically committed to a particular fate .


To distinguish these instructive and selective models , we used surface affinity matrix technology to isolate committed progenitors based on cytokine secretion phenotype and developed retroviral-based tagging approaches to directly monitor individual progenitor fate decisions at the clonal and population levels .

To distinguish these instructive and selective models , we used surface affinity matrix technology to isolate <cell_type>committed progenitors</cell_type> based on cytokine secretion phenotype and developed retroviral-based tagging approaches to directly monitor individual progenitor fate decisions at the clonal and population levels .


We observe IL-4 -dependent redirection of phenotype in cells that have already committed to a non-IL-4-producing fate , inconsistent with predictions of the selective model .

We observe <protein>IL-4</protein> -dependent redirection of phenotype in cells that have already committed to a non-IL-4-producing fate , inconsistent with predictions of the selective model .


Further , retroviral tagging of naive progenitors with the Th2-specific transcription factor GATA-3 provided direct evidence for instructive differentiation , and no evidence for the selective outgrowth of cells committed to either the Th1 or Th2 fate .

Further , retroviral tagging of <cell_type>naive progenitors</cell_type> with the <protein>Th2-specific transcription factor GATA-3</protein> provided direct evidence for instructive differentiation , and no evidence for the selective outgrowth of cells committed to either the Th1 or Th2 fate .


These data would seem to exclude selection as an exclusive mechanism in Th1 / Th2 differentiation , and support an instructive model of cytokine-driven transcriptional programming of cell fate decisions .

These data would seem to exclude selection as an exclusive mechanism in <cell_type>Th1</cell_type> / <cell_type>Th2</cell_type> differentiation , and support an instructive model of cytokine-driven transcriptional programming of cell fate decisions .


In vitro-activated human lupus T cells express normal estrogen receptor proteins which bind to the estrogen response element .

In vitro-activated <cell_type>human lupus T cells</cell_type> express normal <protein>estrogen receptor proteins</protein> which bind to the <protein>estrogen response element</protein> .


We have shown that estrogen receptor ( ERalpha , ERbeta ) transcripts are expressed in SLE and normal T cells .

We have shown that <protein>estrogen receptor</protein> ( <protein>ERalpha</protein> , <protein>ERbeta</protein> ) transcripts are expressed in <cell_type>SLE and normal T cells</cell_type> .


In this study , T cell nuclear extracts from female lupus patients and normal donors were tested for biologically active ER proteins capable of binding to the human estrogen response element ( hERE ) by electrophoretic mobility shift assays .

In this study , T cell nuclear extracts from female lupus patients and normal donors were tested for biologically active <protein>ER proteins</protein> capable of binding to the <dna>human estrogen response element</dna> ( <dna>hERE</dna> ) by electrophoretic mobility shift assays .


When peripheral blood T cells were stimulated with 17beta-estradiol ( E2 ) , PMA and ionomycin , two major retarded bands in T cell nuclear extracts exhibited a migration pattern similar to slow migrating protein-ERE complexes in human breast cancer cell extracts .

When <cell_type>peripheral blood T cells</cell_type> were stimulated with 17beta-estradiol ( E2 ) , PMA and ionomycin , two major retarded bands in T cell nuclear extracts exhibited a migration pattern similar to slow migrating <protein>protein-ERE complexes</protein> in human breast cancer cell extracts .


T cells cultured only with E2 did not have these complexes .

<cell_type>T cells</cell_type> cultured only with E2 did not have these complexes .


The formation of the complexes was inhibited by competition with the hERE cold oligonucleotide and partially with anti-ERalpha antibodies .

The formation of the complexes was inhibited by competition with the hERE cold oligonucleotide and partially with <protein>anti-ERalpha antibodies</protein> .


There was no notable difference in the migration pattern of ERE-binding proteins between the SLE and normal T cell extracts .

There was no notable difference in the migration pattern of <protein>ERE-binding proteins</protein> between the SLE and normal T cell extracts .


Together , these results suggest that activated human T cells , whether lupus-derived or normal-derived , contain biologically active ERalpha proteins .

Together , these results suggest that <cell_type>activated human T cells</cell_type> , whether lupus-derived or normal-derived , contain biologically active <protein>ERalpha proteins</protein> .


Other factors may be responsible for differential sensitivity of lupus T cells to estrogen .

Other factors may be responsible for differential sensitivity of <cell_type>lupus T cells</cell_type> to estrogen .