Despite the dual specificity of HTLV-1 Tax for IkappaBalpha and IkappaBbeta at the protein level , Tax selectively stimulates NF-kappaB -directed transcription of the IkappaBalpha gene .

Despite the dual specificity of HTLV-1 <protein>Tax</protein> for <protein>IkappaBalpha</protein> and <protein>IkappaBbeta</protein> at the protein level , <protein>Tax</protein> selectively stimulates <protein>NF-kappaB</protein> -directed transcription of the <dna>IkappaBalpha gene</dna> .


Consequently , IkappaBbeta protein expression is chronically downregulated in HTLV-1-infected T lymphocytes .

Consequently , <protein>IkappaBbeta</protein> protein expression is chronically downregulated in <cell_type>HTLV-1-infected T lymphocytes</cell_type> .


These findings with IkappaBbeta provide a potential mechanism for the constitutive activation of NF-kappaB in Tax-expressing cells .

These findings with <protein>IkappaBbeta</protein> provide a potential mechanism for the constitutive activation of <protein>NF-kappaB</protein> in <cell_line>Tax-expressing cells</cell_line> .


The role of p16 in the E2F-dependent thymidine kinase regulation .

The role of <protein>p16</protein> in the <protein>E2F-dependent thymidine kinase</protein> regulation .


The role of alterations of the MTS1 tumor suppressor gene on chromosome 9p21 , which encodes p16 , the inhibitor of cyclin-dependent-kinase-4 and 6 , in tumorigenesis is not yet clear .

The role of alterations of the <dna>MTS1 tumor suppressor gene</dna> on <dna>chromosome 9p21</dna> , which encodes <protein>p16</protein> , the inhibitor of <protein>cyclin-dependent-kinase-4 and 6</protein> , in tumorigenesis is not yet clear .


Phosphorylation of the retinoblastoma protein by cyclin-dependent kinases 4 and 6 prevents its interaction with the transcription factor E2F , which subsequently promotes the expression of S phase regulated genes , such as thymidine kinase .

Phosphorylation of the <protein>retinoblastoma protein</protein> by <protein>cyclin-dependent kinases 4 and 6</protein> prevents its interaction with the <protein>transcription factor</protein> <protein>E2F</protein> , which subsequently promotes the expression of <dna>S phase regulated genes</dna> , such as <protein>thymidine kinase</protein> .


Although a role of p16 in this regulation has been presumed , there is no proof so far that loss of this tumor suppressor gene really affects E2F -mediated regulations .

Although a role of <protein>p16</protein> in this regulation has been presumed , there is no proof so far that loss of this <dna>tumor suppressor gene</dna> really affects <protein>E2F</protein> -mediated regulations .


We investigated the regulation of thymidine kinase in phytohemagglutinin-stimulated normal human lymphocytes and in the p16-negative human acute lymphoblastic leukemia cell lines , MOLT-4 and CEM .

We investigated the regulation of <protein>thymidine kinase</protein> in <cell_line>phytohemagglutinin-stimulated normal human lymphocytes</cell_line> and in the <cell_line>p16-negative human acute lymphoblastic leukemia cell lines</cell_line> , <cell_line>MOLT-4</cell_line> and <cell_line>CEM</cell_line> .


Compared to normal lymphocytes , MOLT-4 and CEM cells exhibited an altered cell cycle regulation of thymidine kinase , a much higher intracellular activity of this enzyme , and higher thymidine kinase mRNA expression .

Compared to <cell_type>normal lymphocytes</cell_type> , <cell_line>MOLT-4 and CEM cells</cell_line> exhibited an altered cell cycle regulation of <protein>thymidine kinase</protein> , a much higher intracellular activity of this <protein>enzyme</protein> , and higher <rna>thymidine kinase mRNA</rna> expression .


Transient expression of p16 in normal human lymphocytes caused arrest in G1 , but was without effect on the cell growth of MOLT-4 and CEM cells , although all of them express functional retinoblastoma protein .

Transient expression of <protein>p16</protein> in normal human lymphocytes caused arrest in G1 , but was without effect on the cell growth of <cell_line>MOLT-4 and CEM cells</cell_line> , although all of them express functional <protein>retinoblastoma protein</protein> .


Nevertheless , in the two leukemia cell lines transient overexpression of p16 reestablished the normal regulation of thymidine kinase , paralleled by an increase of the underphosphorylated form of retinoblastoma protein and decrease of free E2F bound to its motif in the thymidine kinase promoter .

Nevertheless , in the two <cell_line>leukemia cell lines</cell_line> transient overexpression of <protein>p16</protein> reestablished the normal regulation of <protein>thymidine kinase</protein> , paralleled by an increase of the underphosphorylated form of <protein>retinoblastoma protein</protein> and decrease of free <protein>E2F</protein> bound to its motif in the <dna>thymidine kinase promoter</dna> .


We demonstrate that loss of p16 causes upregulation of this DNA precursor pathway enzyme via activation of E2F by a mechanism involving retinoblastoma protein .

We demonstrate that loss of <protein>p16</protein> causes upregulation of this DNA precursor pathway <protein>enzyme</protein> via activation of <protein>E2F</protein> by a mechanism involving <protein>retinoblastoma protein</protein> .


Interactions of a transcriptional activator in the env gene of the mouse mammary tumor virus with activation-dependent , T cell-specific transacting factors .

Interactions of a <dna>transcriptional activator</dna> in the <dna>env gene</dna> of the mouse mammary tumor virus with <protein>activation-dependent , T cell-specific transacting factors</protein> .


The mouse mammary tumor virus env gene contains a transcriptional activator ( META ) that can control transcription of the adjacent long terminal repeat region .

The mouse mammary tumor virus <dna>env gene</dna> contains a <dna>transcriptional activator</dna> ( <dna>META</dna> ) that can control transcription of the adjacent <dna>long terminal repeat region</dna> .


Transcriptional control by META parallels that of several lymphokine genes , being specific to T cells , dependent on their activation , and inhibited by the immunosuppressive drug cyclosporine ( CsA ) .

Transcriptional control by <dna>META</dna> parallels that of several <dna>lymphokine genes</dna> , being specific to <cell_type>T cells</cell_type> , dependent on their activation , and inhibited by the immunosuppressive drug cyclosporine ( CsA ) .


DNase I footprinting indicated that nuclear factors from activated T lymphocytes bound a promoter-proximal site , META ( P ) , and a promoter-distal site , META ( D+ ) , within the 400-base pair META region .

<protein>DNase I</protein> footprinting indicated that <protein>nuclear factors</protein> from <cell_type>activated T lymphocytes</cell_type> bound a <dna>promoter-proximal site</dna> , <dna>META ( P )</dna> , and a <dna>promoter-distal site</dna> , <dna>META ( D+ )</dna> , within the <dna>400-base pair META region</dna> .


Nuclear factors from unstimulated , but not from activated cells , bound a site , META ( D- ) , adjacent to META ( D+ ) .

<protein>Nuclear factors</protein> from unstimulated , but not from activated cells , bound a site , <dna>META ( D- )</dna> , adjacent to <dna>META ( D+ )</dna> .


META ( D+ ) directed transcription of a linked luciferase gene , and gel shift analysis revealed binding of inducible , CsA-sensitive T cell factors , in parallel with transfection results .

<dna>META ( D+ )</dna> directed transcription of a linked <dna>luciferase gene</dna> , and gel shift analysis revealed binding of inducible , <protein>CsA-sensitive T cell factors</protein> , in parallel with transfection results .


Authentic NFAT and NF-kappaB targets did not compete for the META ( D+ ) binding factor ( s ) .

Authentic <dna>NFAT and NF-kappaB targets</dna> did not compete for the <protein>META ( D+ ) binding factor</protein> ( s ) .


The SV40 core sequence competed for META ( D+ ) binding factors , but META ( D+ ) failed to compete for the complexes obtained with the SV40 probe .

The <dna>SV40 core sequence</dna> competed for <protein>META ( D+ ) binding factors</protein> , but <dna>META ( D+ )</dna> failed to compete for the complexes obtained with the SV40 probe .


Our results , taken together , indicate that META ( D+ ) is a novel transcriptional enhancer element that is similar in its cell-type specificity , activation dependence , and CsA sensitivity to the NFAT element .

Our results , taken together , indicate that <dna>META ( D+ )</dna> is a novel <dna>transcriptional enhancer element</dna> that is similar in its cell-type specificity , activation dependence , and CsA sensitivity to the <dna>NFAT element</dna> .


It may be relevant to the role of MMTV in expression of Mls antigens or the induction of T cell lymphomas .

It may be relevant to the role of MMTV in expression of <protein>Mls antigens</protein> or the induction of T cell lymphomas .


A novel interferon regulatory factor family transcription factor , ICSAT/Pip/LSIRF , that negatively regulates the activity of interferon-regulated genes .

A novel <protein>interferon regulatory factor family transcription factor</protein> , <protein>ICSAT/Pip/LSIRF</protein> , that negatively regulates the activity of <dna>interferon-regulated genes</dna> .


We have isolated a novel cDNA clone encoding interferon ( IFN ) consensus sequence-binding protein in adult T-cell leukemia cell line or activated T cells ( ICSAT ) ; this protein is the human homolog of the recently cloned Pip/LSIRF .

We have isolated a <dna>novel cDNA clone</dna> encoding <protein>interferon ( IFN ) consensus sequence-binding protein</protein> in <cell_line>adult T-cell leukemia cell line</cell_line> or activated <cell_type>T cells</cell_type> ( <protein>ICSAT</protein> ) ; this protein is the human homolog of the recently cloned <protein>Pip/LSIRF</protein> .


ICSAT is structurally most closely related to the previously cloned ICSBP , a member of the IFN regulatory factor ( IRF ) family of proteins that binds to interferon consensus sequences ( ICSs ) found in many promoters of the IFN-regulated genes .

<protein>ICSAT</protein> is structurally most closely related to the previously cloned <protein>ICSBP</protein> , a member of the <protein>IFN regulatory factor ( IRF ) family</protein> of proteins that binds to <dna>interferon consensus sequences</dna> ( <dna>ICSs</dna> ) found in many promoters of the <dna>IFN-regulated genes</dna> .


Among T-cell lines investigated , ICSAT was abundantly expressed in human T-cell leukemia virus type 1 ( HTLV-1 ) -infected T cells .

Among <cell_line>T-cell lines</cell_line> investigated , <protein>ICSAT</protein> was abundantly expressed in <cell_line>human T-cell leukemia virus type 1 ( HTLV-1 ) -infected T cells</cell_line> .


When the HTLV-1 tax gene was expressed or phorbol myristake acetate-A23187 stimulation was used , ICSAT expression was induced in Jurkat cells which otherwise do not express ICSAT .

When the <dna>HTLV-1 tax gene</dna> was expressed or phorbol myristake acetate-A23187 stimulation was used , <protein>ICSAT</protein> expression was induced in <cell_line>Jurkat cells</cell_line> which otherwise do not express <protein>ICSAT</protein> .


When the binding of ICSAT to four different ICSs was tested , the relative differences in binding affinities for those ICSs were determined .

When the binding of <protein>ICSAT</protein> to four different <dna>ICSs</dna> was tested , the relative differences in binding affinities for those <dna>ICSs</dna> were determined .


To study the functional role of ICSAT , we performed cotransfection experiments with the human embryonal carcinoma cell line N-Tera2 .

To study the functional role of <protein>ICSAT</protein> , we performed cotransfection experiments with the <cell_line>human embryonal carcinoma cell line N-Tera2</cell_line> .


ICSAT was demonstrated to possess repressive function over the gene activation induced by IFN stimulation or by IRF-1 cotransfection .

<protein>ICSAT</protein> was demonstrated to possess repressive function over the gene activation induced by <protein>IFN</protein> stimulation or by <protein>IRF-1</protein> cotransfection .


Such repressive function is similar to that seen in IRF-2 or ICSBP .

Such repressive function is similar to that seen in <protein>IRF-2</protein> or <protein>ICSBP</protein> .


However , we have found that ICSAT has a different repressive effect from that of IRF-2 or ICSBP in some IFN-responsive reporter constructs .

However , we have found that <protein>ICSAT</protein> has a different repressive effect from that of <protein>IRF-2</protein> or <protein>ICSBP</protein> in some <dna>IFN-responsive reporter constructs</dna> .


These results suggest that a novel mechanism of gene regulation by `` differential repression '' is used by multiple members of repressor proteins with different repressive effects on the IFN-responsive genes .

These results suggest that a novel mechanism of gene regulation by `` differential repression '' is used by multiple members of <protein>repressor proteins</protein> with different repressive effects on the <dna>IFN-responsive genes</dna> .


Regulation of [ Ca2+ ] i rise activated by doxepin-sensitive H1-histamine receptors in Jurkat cells , cloned human T lymphocytes .

Regulation of [ Ca2+ ] i rise activated by <protein>doxepin-sensitive H1-histamine receptors</protein> in <cell_line>Jurkat cells</cell_line> , <cell_line>cloned human T lymphocytes</cell_line> .


To clarify the presence of histamine receptor and its transmembrane mechanism in human T lymphocytes , we investigated the effects of agonists or antagonists of histamine receptor subtypes and bacterial toxins on intracellular concentration of Ca2+ [ Ca2+ ] i ) , [ 3H ] pyrilamine binding and c-fos mRNA expression in Jurkat cells , cloned human T lymphocytes .

To clarify the presence of <protein>histamine receptor</protein> and its transmembrane mechanism in <cell_type>human T lymphocytes</cell_type> , we investigated the effects of agonists or antagonists of <protein>histamine receptor</protein> subtypes and bacterial toxins on intracellular concentration of Ca2+ [ Ca2+ ] i ) , [ 3H ] pyrilamine binding and <rna>c-fos mRNA</rna> expression in <cell_line>Jurkat cells</cell_line> , cloned <cell_type>human T lymphocytes</cell_type> .


H1-agonists ( histamine and 2-methylhistamine ) caused a transient rise of [ Ca2+ ] , and H1-antagonists ( pyrilamine and doxepin ) inhibited the histamine-induced [ Ca2+ ] i rise more potently than the H2-antagonist ( cimetidine ) on the H3-antagonist ( impromidine ) .


Binding parameters of [ 3H ] pyrilamine binding were Kd = 5.53 nM and Bmax = 2 , 647 sites/cell .


Pretreatment with B.pertussis , V.cholera. or C.botulinum toxin did not influence histamine-induced [ Ca2+ ] i rise .


Western Blot analysis using antibodies against subunits of GTP-binding proteins indicated that Gq/G11 richly existed in Jurkat cells .

Western Blot analysis using antibodies against subunits of <protein>GTP-binding proteins</protein> indicated that <protein>Gq/G11</protein> richly existed in <cell_line>Jurkat cells</cell_line> .


Histamine induced mRNA expression of an immediate early gene c-fos .

Histamine induced <rna>mRNA</rna> expression of an <dna>immediate early gene</dna> <dna>c-fos</dna> .


Pretreatment with a protein kinase C activator , phorbol 12-myristate 13-acetate , caused almost complete inhibition of histamine-induced [ Ca2+ ] i rise , but did not do so by activators of cAMP- and cGMP-dependent protein kinases .

Pretreatment with a <protein>protein kinase C</protein> activator , phorbol 12-myristate 13-acetate , caused almost complete inhibition of histamine-induced [ Ca2+ ] i rise , but did not do so by activators of <protein>cAMP- and cGMP-dependent protein kinases</protein> .


STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients .

STAT-related <protein>transcription factors</protein> are constitutively activated in <cell_type>peripheral blood cells</cell_type> from acute leukemia patients .


A signal transduction pathway activated by many cytokines has recently been elaborated .

A signal transduction pathway activated by many <protein>cytokines</protein> has recently been elaborated .


The JAK kinases and the signal transducers and activators of transcription ( STAT ) factors have been found to be essential components .

The <protein>JAK kinases</protein> and the <protein>signal transducers and activators of transcription ( STAT ) factors</protein> have been found to be essential components .


In this report , we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia .

In this report , we describe the presence of constitutively activated <protein>STAT factors</protein> in <cell_type>peripheral blood cells</cell_type> from patients with acute leukemia .


We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays .

We used oligonucleotide probes from the <dna>beta-casein and IRF-1 gene promoters</dna> and the ISRE probe to detect <protein>STAT proteins</protein> in nuclear extracts from <cell_type>acute leukemia cells</cell_type> in bandshift assays .


Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters , but not with the ISRE oligonucleotide probe , when cell extracts from acute lymphoblastic leukemia ( ALL ) and acute myeloid leukemia ( AML ) were investigated .

Specific DNA <protein>protein complex</protein> formation was observed with the probes from the beta-casein and <dna>IRF-1 gene promoters</dna> , but not with the ISRE oligonucleotide probe , when cell extracts from acute lymphoblastic leukemia ( ALL ) and acute myeloid leukemia ( AML ) were investigated .


We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation .


Specific antibodies directed against the individual STAT proteins were used in supershift experiments .

Specific <protein>antibodies</protein> directed against the individual <protein>STAT proteins</protein> were used in supershift experiments .


STAT5- and STAT1-related factors were detected in ALL and STAT1- , STAT3- , and STAT5-related proteins were present in nuclear cell extracts from AML .

<protein>STAT5- and STAT1-related factors</protein> were detected in ALL and <protein>STAT1- , STAT3- , and STAT5-related proteins</protein> were present in nuclear cell extracts from AML .


Since the cells were not treated with cytokines before the nuclear proteins were extracted , we conclude that these factors are constitutively activated in vivo .

Since the cells were not treated with <protein>cytokines</protein> before the <protein>nuclear proteins</protein> were extracted , we conclude that these factors are constitutively activated in vivo .


It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis .

It is likely that the constitutive activation of <protein>STAT proteins</protein> is a part of the events of leukemogenesis .


An element upstream from the human delta-globin-encoding gene specifically enhances beta-globin reporter gene expression in murine erythroleukemia cells .

An <dna>element</dna> upstream from the <dna>human delta-globin-encoding gene</dna> specifically enhances <dna>beta-globin reporter gene</dna> expression in <cell_type>murine erythroleukemia cells</cell_type> .


We have previously shown that a DNA-binding factor specific to adult hematopoietic cells ( polypryrimidine-binding factor , PYBF ) binds to a pyrimidine-rich region 1 kb upstream from the human delta-globin-encoding gene ( HBD ) .

We have previously shown that a <protein>DNA-binding factor</protein> specific to <cell_type>adult hematopoietic cells</cell_type> ( <protein>polypryrimidine-binding factor</protein> , <protein>PYBF</protein> ) binds to a <dna>pyrimidine-rich region</dna> <dna>1 kb upstream</dna> from the <dna>human delta-globin-encoding gene</dna> ( <dna>HBD</dna> ) .


The developmental stage-specificity of PYBF and the location of its binding site between the fetal and adult beta-globin ( HBB ) -like genes suggest that PBYF and its binding site may function in fetal-to-adult globin gene switching .

The developmental stage-specificity of <protein>PYBF</protein> and the location of its binding site between the <dna>fetal and adult beta-globin ( HBB ) -like genes</dna> suggest that <protein>PBYF</protein> and its binding site may function in fetal-to-adult <dna>globin gene</dna> switching .


Here , we describe the effect of 383-bp ( delta383 ) and 99-bp ( delta99 ) sequences containing the PYBF-binding site on transcription from various globin and non-globin promoters , using a transient assay with the cat reporter gene in murine erythroleukemia ( MEL ) cells , a cell line with abundant PYBF activity .

Here , we describe the effect of <dna>383-bp ( delta383 ) and 99-bp ( delta99 ) sequences</dna> containing the <dna>PYBF-binding site</dna> on transcription from various globin and non-globin promoters , using a transient assay with the <dna>cat reporter gene</dna> in <cell_line>murine erythroleukemia ( MEL ) cells</cell_line> , a cell line with abundant <protein>PYBF</protein> activity .


We show that both delta383 and delta99 specifically enhance expression of cat for plasmids containing a human adult globin ( HBB ) promoter , whereas expression of similar constructs using human fetal ( A gamma- ) globin ( HBG1 ) or simian virus 40 ( SV40 ) promoters is not enhanced .

We show that both <dna>delta383</dna> and <dna>delta99</dna> specifically enhance expression of <protein>cat</protein> for <dna>plasmids</dna> containing a <dna>human adult globin ( HBB ) promoter</dna> , whereas expression of similar constructs using <dna>human fetal ( A gamma- ) globin ( HBG1 ) or simian virus 40 ( SV40 ) promoters</dna> is not enhanced .


The results suggest that PYBF and the pyrimidine-rich region upstream from HBD can specifically enhance HBB transcription in adult erythroid cells .

The results suggest that <protein>PYBF</protein> and the <dna>pyrimidine-rich region</dna> upstream from <dna>HBD</dna> can specifically enhance <dna>HBB</dna> transcription in <cell_type>adult erythroid cells</cell_type> .


Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9 .

<dna>Translocation breakpoints</dna> in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from <dna>SOX9</dna> .


Campomelic dysplasia ( CMPD1 ) and autosomal XY sex reversal ( SRA1 ) are caused by mutations in the SRY-related gene SOX9 on 17q .

Campomelic dysplasia ( CMPD1 ) and autosomal XY sex reversal ( SRA1 ) are caused by mutations in the <dna>SRY-related gene</dna> <dna>SOX9</dna> on <dna>17q</dna> .


Unexpectedly , the 17q breakpoints in four CMPD1 translocation cases previously analyzed by us and others map 50 kb or more from SOX9 .

Unexpectedly , the <dna>17q breakpoints</dna> in four CMPD1 translocation cases previously analyzed by us and others map 50 kb or more from <dna>SOX9</dna> .


Here , we present clinical , cytogenetic , and molecular data from a new CMPD1/SRA1 patient with t ( 6 ; 17 ) ( q14 ; q24 ) .

Here , we present clinical , cytogenetic , and molecular data from a new CMPD1/SRA1 patient with <dna>t ( 6 ; 17 ) ( q14 ; q24 )</dna> .


Fluorescence in situ hybridization has shown that the 17q breakpoint in this case maps to the same region as the breakpoints in the other translocation cases , at least 130 kb from SOX9 .

Fluorescence in situ hybridization has shown that the <dna>17q breakpoint</dna> in this case maps to the same region as the breakpoints in the other translocation cases , at least 130 kb from <dna>SOX9</dna> .


Likewise , the breakpoints in two of the previously described cases also map more than 130 kb and , as shown by pulsed field gel electrophoresis analysis , at most 400 kb or 690 kb from SOX9 .

Likewise , the breakpoints in two of the previously described cases also map more than 130 kb and , as shown by pulsed field gel electrophoresis analysis , at most 400 kb or 690 kb from <dna>SOX9</dna> .


By using a SOX9 coding sequence polymorphism , expression of both SOX9 alleles has been demonstrated by the reverse transcriptase polymerase chain reaction in lymphoblastoid cells from one of the translocation cases .

By using a <dna>SOX9 coding sequence polymorphism</dna> , expression of both <dna>SOX9</dna> alleles has been demonstrated by the <protein>reverse transcriptase</protein> polymerase chain reaction in <cell_type>lymphoblastoid cells</cell_type> from one of the translocation cases .


An alternatively spliced isoform of the Spi-B transcription factor .

An alternatively spliced isoform of the <protein>Spi-B</protein> <protein>transcription factor</protein> .


Spi-B is an Ets transcription factor related to the oncoprotein Spi-1/PU.1 and highly expressed in B lymphoid cells .

<protein>Spi-B</protein> is an <protein>Ets transcription factor</protein> related to the <protein>oncoprotein</protein> <protein>Spi-1/PU.1</protein> and highly expressed in <cell_type>B lymphoid cells</cell_type> .


The Ets proteins share a conserved Ets domain that mediates specific DNA binding .

The <protein>Ets proteins</protein> share a conserved <protein>Ets domain</protein> that mediates specific DNA binding .


Spi-B binds DNA sequences containing a core 5'-GGAA-3 ' and activates transcription through this motif .

<protein>Spi-B</protein> binds <dna>DNA sequences</dna> containing a core 5'-GGAA-3 ' and activates transcription through this motif .


Up to date , the biological function of Spi-B remains unknown .

Up to date , the biological function of <protein>Spi-B</protein> remains unknown .


Here , we describe the characterization of an alternatively spliced variant of Spi-B , named deltaSpi-B , which has lost the Ets domain .

Here , we describe the characterization of an alternatively spliced variant of <protein>Spi-B</protein> , named <protein>deltaSpi-B</protein> , which has lost the <protein>Ets domain</protein> .


In B lymphoid cells , deltaspi-B and spi-B mRNAs were present simultaneously in a ratio of around 10 % .

In <cell_type>B lymphoid cells</cell_type> , <rna>deltaspi-B and spi-B mRNAs</rna> were present simultaneously in a ratio of around 10 % .


DeltaSpi-B product was not able to bind DNA and was recovered in cytoplasmic cellular extracts .

<protein>DeltaSpi-B</protein> product was not able to bind DNA and was recovered in cytoplasmic cellular extracts .


We raise the hypothesis that delta Spi-B might affect Spi-B function by recruiting factors involved in Spi-B activity .

We raise the hypothesis that <protein>delta Spi-B</protein> might affect <protein>Spi-B</protein> function by recruiting factors involved in <protein>Spi-B</protein> activity .


Binding and cooperative interactions between two B cell-specific transcriptional coactivators .

Binding and cooperative interactions between two <protein>B cell-specific transcriptional coactivators</protein> .


The class II transactivator ( CIITA ) and B cell octamer-binding protein 1/octamer-binding factor 1/Oct coactivator from B cells ( Bob1/OBF-1/OCA-B ) represent two B cell-specific transcriptional coactivators .

The <protein>class II transactivator</protein> ( <protein>CIITA</protein> ) and <protein>B cell octamer-binding protein 1/octamer-binding factor 1/Oct coactivator</protein> from <cell_type>B cells</cell_type> ( <protein>Bob1/OBF-1/OCA-B</protein> ) represent two <protein>B cell-specific transcriptional coactivators</protein> .


CIITA and Bob1 interact with proteins that bind to conserved upstream sequences in promoters of class II major histocompatibility genes and octamer-binding transcription factors Oct-1 and Oct-2 , respectively .

<protein>CIITA</protein> and <protein>Bob1</protein> interact with proteins that bind to <dna>conserved upstream sequences</dna> in <dna>promoters</dna> of <dna>class II major histocompatibility genes</dna> and <protein>octamer-binding transcription factors</protein> <protein>Oct-1</protein> and <protein>Oct-2</protein> , respectively .


Both CIITA and Bob1 increase the expression from the DRA promoter , which is a prototypic class II promoter .

Both <protein>CIITA</protein> and <protein>Bob1</protein> increase the expression from the <dna>DRA promoter</dna> , which is a prototypic <dna>class II promoter</dna> .


Moreover , in the presence of CIITA , interactions between class II promoters and Bob1 are independent of the octamer-binding site .

Moreover , in the presence of <protein>CIITA</protein> , interactions between <dna>class II promoters</dna> and <protein>Bob1</protein> are independent of the <rna>octamer-binding site</rna> .


Using in vivo and in vitro binding assays , we confirm that Bob1 binds to CIITA .

Using in vivo and in vitro binding assays , we confirm that <protein>Bob1</protein> binds to <protein>CIITA</protein> .


Thus , CIITA not only activates the expression of class II genes but recruits another B cell-specific coactivator to increase transcriptional activity of class II promoters in B cells .

Thus , <protein>CIITA</protein> not only activates the expression of <dna>class II genes</dna> but recruits another B cell-specific coactivator to increase transcriptional activity of <dna>class II promoters</dna> in <cell_type>B cells</cell_type> .


Efficient transcription and replication of simian immunodeficiency virus in the absence of NF-kappaB and Sp1 binding elements .

Efficient transcription and replication of simian immunodeficiency virus in the absence of <dna>NF-kappaB and Sp1 binding elements</dna> .


Ten mutants of the simian immunodeficiency virus ( SIV ) SIVmac239 bearing deletions ( delta ) or substitutions ( subst ) in the NF-kappaB and/or Sp1 binding elements were created , and the replicative capacities of the mutants were analyzed .

Ten mutants of the simian immunodeficiency virus ( SIV ) SIVmac239 bearing deletions ( delta ) or substitutions ( subst ) in the <dna>NF-kappaB</dna> and/or <dna>Sp1 binding elements</dna> were created , and the replicative capacities of the mutants were analyzed .


All mutants , including one extensively mutagenized strain entirely missing the NF-kappaB and four Spl binding elements , replicated with wild-type kinetics and to a wild-type level in peripheral blood mononuclear cell cultures in 50 to 100 % of the experiments .

All mutants , including one extensively mutagenized strain entirely missing the <dna>NF-kappaB and four Spl binding elements</dna> , replicated with wild-type kinetics and to a wild-type level in <cell_line>peripheral blood mononuclear cell cultures</cell_line> in 50 to 100 % of the experiments .


One group of mutants replicated very similarly to SIVmac239 in kinetics and yield in CEMxl74 cells ( 2x NFKappaB > or = SlVmac239 approximately deltaNFkappaB approximately deltaSpl234 approximately substNFkappaB approximately substSpl2 approximately substSp23 ) , while a second group replicated with delayed or slightly delayed kinetics in CEMxl74 cells ( SIVmac239 > substSp34 > deltaNFkappaBdeltaSpl234 approximately deltaNFkappaBdeltaSp1 > substSpl234 ) .

One group of mutants replicated very similarly to SIVmac239 in kinetics and yield in <cell_line>CEMxl74 cells</cell_line> ( 2x <protein>NFKappaB</protein> > or = <protein>SlVmac239</protein> approximately <protein>deltaNFkappaB</protein> approximately <protein>deltaSpl234</protein> approximately <protein>substNFkappaB</protein> approximately <protein>substSpl2</protein> approximately <protein>substSp23</protein> ) , while a second group replicated with delayed or slightly delayed kinetics in <cell_line>CEMxl74 cells</cell_line> ( SIVmac239 > <protein>substSp34</protein> > <protein>deltaNFkappaBdeltaSpl234</protein> approximately <protein>deltaNFkappaBdeltaSp1</protein> > <protein>substSpl234</protein> ) .


Reversions or additional mutations were not detected in the U3 and R regions of proviral DNA from CEMxl74 cells infected with the SIVmac239 mutants .

Reversions or additional mutations were not detected in the <dna>U3 and R regions</dna> of <dna>proviral DNA</dna> from <cell_line>CEMxl74 cells</cell_line> infected with the SIVmac239 mutants .


Similar results were obtained when mutants of SIVmacMER ( a macrophage-competent derivative of SIVmac239 ) were tested in peripheral blood mononuclear cell and CEMx174 cultures .

Similar results were obtained when mutants of SIVmacMER ( a macrophage-competent derivative of SIVmac239 ) were tested in <cell_type>peripheral blood mononuclear cell</cell_type> and <cell_line>CEMx174 cultures</cell_line> .


However , the growth of most mutated viruses was suppressed in primary rhesus monkey alveolar macrophages ( SIVmacMER approximately 2xNFkappaB approximately substNFkappaB > deltaNFkappaB > deltaNFkappaB deltaSpl234 approximately deltaNFkappaBdeltaSpl > deltaSpl234 approximately substSpl2 > substSp23 approximately substSp34 approximately substSpl234 > or = SIVmac239 ) .

However , the growth of most mutated viruses was suppressed in <cell_type>primary rhesus monkey alveolar macrophages</cell_type> ( SIVmacMER approximately <protein>2xNFkappaB</protein> approximately <protein>substNFkappaB</protein> > <protein>deltaNFkappaB</protein> > <protein>deltaNFkappaB</protein> <protein>deltaSpl234</protein> approximately <protein>deltaNFkappaBdeltaSpl</protein> > <protein>deltaSpl234</protein> approximately <protein>substSpl2</protein> > <protein>substSp23</protein> approximately <protein>substSp34</protein> approximately <protein>substSpl234</protein> > or = SIVmac239 ) .


Thus , changes in the Sp1 binding sites had the most dramatic effects on SIVmac replication in primary macrophage cultures .

Thus , changes in the <dna>Sp1 binding sites</dna> had the most dramatic effects on SIVmac replication in <cell_line>primary macrophage cultures</cell_line> .


Analysis of long terminal repeat -driven secreted alkaline phosphatase activity in transient assays showed that , unlike human immunodeficiency virus type 1 , the SIV long terminal repeat possesses an enhancer region just upstream of the NF-kappaB element which maintains significant levels of basal transcription in the absence of NF-kappaB and Sp1 sites .

Analysis of <dna>long terminal repeat</dna> -driven secreted <protein>alkaline phosphatase</protein> activity in transient assays showed that , unlike human immunodeficiency virus type 1 , the <dna>SIV long terminal repeat</dna> possesses an <dna>enhancer region</dna> just upstream of the <dna>NF-kappaB element</dna> which maintains significant levels of basal transcription in the absence of <dna>NF-kappaB and Sp1 sites</dna> .


This region is responsive to transactivation by Tat .

This region is responsive to transactivation by <protein>Tat</protein> .


In addition , the SIV TATA box was shown to be stronger than that of human immunodeficiency virus type 1 .

In addition , the <dna>SIV TATA box</dna> was shown to be stronger than that of human immunodeficiency virus type 1 .


Therefore , the surprisingly high replicative capacity of NF-kappaB and Sp1 binding site mutants of SIVmac is due to unique features or the enhancer/promoter region .

Therefore , the surprisingly high replicative capacity of NF-kappaB and Sp1 binding site mutants of SIVmac is due to unique features or the <dna>enhancer/promoter region</dna> .


cAMP inducibility of transcriptional repressor ICER in developing and mature human T lymphocytes [ published erratum appears in Proc Natl Acad Sci U S A 1996 Jul 23 ; 93 ( 15 ) : 8154 ]

cAMP inducibility of <protein>transcriptional repressor</protein> <protein>ICER</protein> in developing and <cell_type>mature human T lymphocytes</cell_type> [ published erratum appears in Proc Natl Acad Sci U S A 1996 Jul 23 ; 93 ( 15 ) : 8154 ]


Stimulation of the cAMP-dependent signaling pathway exerts an inhibitory effect on the proliferation and effector functions of T cells .

Stimulation of the cAMP-dependent signaling pathway exerts an inhibitory effect on the proliferation and effector functions of <cell_type>T cells</cell_type> .


The ability of T cells to form high intracellular levels of cAMP is acquired during development in the human thymus and is retained by the majority of mature peripheral T lymphocytes .

The ability of <cell_type>T cells</cell_type> to form high intracellular levels of cAMP is acquired during development in the human thymus and is retained by the majority of mature <cell_type>peripheral T lymphocytes</cell_type> .


Here we show that elevated cAMP levels in T cells correlate with the expression of the potent transcriptional repressor ICER ( inducible cAMP early repressor ) previously described in the hypothalamic-pituitary-gonadal axis .

Here we show that elevated cAMP levels in <cell_type>T cells</cell_type> correlate with the expression of the <protein>potent transcriptional repressor</protein> <protein>ICER</protein> ( <protein>inducible cAMP early repressor</protein> ) previously described in the hypothalamic-pituitary-gonadal axis .


Further , in transcriptional assays in vivo , ICER inhibits calcineurin -mediated expression of the interleukin 2 promoter as well as Tax -mediated transactivation of the human T-lymphotropic virus type I ( HTLV-I ) promoter .

Further , in transcriptional assays in vivo , <protein>ICER</protein> inhibits <protein>calcineurin</protein> -mediated expression of the <dna>interleukin 2 promoter</dna> as well as <protein>Tax</protein> -mediated transactivation of the <dna>human T-lymphotropic virus type I ( HTLV-I ) promoter</dna> .


Thus , the induction of ICER in T cells may play an important role in the cAMP-induced quiescence and the persistent latency of HTLV-I .

Thus , the induction of <protein>ICER</protein> in <cell_type>T cells</cell_type> may play an important role in the cAMP-induced quiescence and the persistent latency of HTLV-I .


A hydrophobic domain of Ca2+-modulating cyclophilin ligand modulates calcium influx signaling in T lymphocytes .

A hydrophobic domain of <protein>Ca2+-modulating cyclophilin ligand</protein> modulates calcium influx signaling in T lymphocytes .


Ca2+-modulating cyclophilin ligand ( CAML ) was originally described as a cyclophilin B-binding protein whose overexpression in T cells causes a rise in intracellular calcium , thus activating transcription factors responsible for the early immune response .

<protein>Ca2+-modulating cyclophilin ligand</protein> ( <protein>CAML</protein> ) was originally described as a <protein>cyclophilin B-binding protein</protein> whose overexpression in <cell_type>T cells</cell_type> causes a rise in intracellular calcium , thus activating <protein>transcription factors</protein> responsible for the early immune response .


As reported here , structure-function analysis of the CAML gene in Jurkat T cells indicates that two of CAML 's putative membrane-spanning domains are necessary and sufficient for the modulation of intracellular calcium .

As reported here , structure-function analysis of the <dna>CAML gene</dna> in <cell_line>Jurkat T cells</cell_line> indicates that two of <protein>CAML</protein> 's <protein>putative membrane-spanning domains</protein> are necessary and sufficient for the modulation of intracellular calcium .


We propose that the hydrophobic C-terminal tail of CAML forms its effector domain , thus implicating the N-terminal hydrophilic domain in a regulatory role .

We propose that the <protein>hydrophobic C-terminal tail</protein> of <protein>CAML</protein> forms its effector domain , thus implicating the <protein>N-terminal hydrophilic domain</protein> in a regulatory role .


These findings define a novel protein motif that functions in intracellular calcium signaling .

These findings define a <protein>novel protein motif</protein> that functions in intracellular calcium signaling .


The Epstein-Barr virus-encoded nuclear antigen EBNA-5 accumulates in PML-containing bodies .

The <protein>Epstein-Barr virus-encoded nuclear antigen EBNA-5</protein> accumulates in PML-containing bodies .


EBNA-5 is one of the Epstein-Barr virus ( EBV ) -encoded nuclear proteins required for immortalization of human B lymphocytes .

<protein>EBNA-5</protein> is one of the <protein>Epstein-Barr virus ( EBV ) -encoded nuclear proteins</protein> required for immortalization of <cell_type>human B lymphocytes</cell_type> .


In the nuclei of EBV-transformed lymphoblastoid cell lines EBNA-5 is preferentially targetted to distinct nuclear foci .

In the nuclei of <cell_line>EBV-transformed lymphoblastoid cell lines</cell_line> <protein>EBNA-5</protein> is preferentially targetted to distinct nuclear foci .


Previously we have shown ( W.Q. Jiang , L.Szekely , V.Wendel-Hansen , N.Ringertz , G.Klein , and A. Rosen , Exp.Cell Res .


A new variant translocation in acute promyelocytic leukaemia : molecular characterization and clinical correlation .


Translocation t ( 15 ; 17 ) ( q22 ; q21 ) is an acquired clonal cytogenetic change present in almost all cases of acute promelocytic leukemia ( APL ) .

<dna>Translocation t ( 15 ; 17 ) ( q22 ; q21</dna> ) is an acquired clonal cytogenetic change present in almost all cases of acute promelocytic leukemia ( APL ) .


The molecular genetic basis of the translocation supports its integral role in pathogenesis .


We describe a patient with APL in whom the leukaemic clone was characterized by a true variant of the classical t ( 15 ; 17 ) .

We describe a patient with APL in whom the leukaemic clone was characterized by a true variant of the <dna>classical t ( 15 ; 17 )</dna> .


The patient whose disease had numerous atypical clinical features , had t ( 11 ; 17 ) ( q13 ; 121 ) .

The patient whose disease had numerous atypical clinical features , had <dna>t ( 11 ; 17 ) ( q13 ; 121 )</dna> .


The chromosome 17 breakpoint was localized to intron 2 of RARA by Southern blotting , and there was no evidence at the molecular level for rearrangement at PML locus .

The <dna>chromosome 17 breakpoint</dna> was localized to <dna>intron 2</dna> of <dna>RARA</dna> by Southern blotting , and there was no evidence at the molecular level for rearrangement at <dna>PML locus</dna> .


These data , along with previous reports of rare variant translocations in APL , indicate that while dysregulation of RARA by gene fusion may be essential for the APL phenotype , the particular fusion partner may determine clinicopathological aspects , including presentation , response to treatment with all-trans retinoic acid ( ATRA ) , and prognosis .

These data , along with previous reports of rare variant translocations in APL , indicate that while dysregulation of <dna>RARA</dna> by gene fusion may be essential for the APL phenotype , the particular fusion partner may determine clinicopathological aspects , including presentation , response to treatment with all-trans retinoic acid ( ATRA ) , and prognosis .


This heterogeneity suggests that the variant fusion partners of RARA in APL encode factors with properties both common to and distinct from those of PML .

This heterogeneity suggests that the variant <protein>fusion partners</protein> of <dna>RARA</dna> in APL encode <protein>factors</protein> with properties both common to and distinct from those of <cell_type>PML</cell_type> .


Investigation of these factors promises to shed light on the complex development pathways involved in the regulation of haematopoiesis .


A model of latent adenovirus 5 infection in the guinea pig ( Cavia porcellus ) .


A model of adenovirus 5 ( Ad5 ) infection was developed in guinea pigs to begin to study its role in the pathogenesis of peripheral lung inflammation .


Forty animals were inoculated intranasally with 10 ( 7.0 ) pfu of Ad5/animal , and 15 animals inoculated with sterile culture media served as controls .


Viral titres were 10 ( 4.4 ) , 10 ( 6.1 ) , 10 ( 5.2 ) , and 10 ( 2.9 ) pfu/animal , on days 1 , 3 , 4 , and 7 after infection , respectively .


In situ hybridization to viral DNA and immunocytochemistry for Ad5 E1A protein localized the virus to airway and alveolar epithelial cells .

In situ hybridization to <dna>viral DNA</dna> and immunocytochemistry for Ad5 <protein>E1A protein</protein> localized the virus to airway and <cell_type>alveolar epithelial cells</cell_type> .


Histologic examination showed an extensive inflammatory cell infiltration around the airways , with epithelial necrosis and an alveolar exudate that caused localized alveolar collapse in the infected areas .


Immunocytochemistry identified the cells in the infiltrate as cytotoxic T cells .

Immunocytochemistry identified the cells in the infiltrate as <cell_type>cytotoxic T cells</cell_type> .


Although all animals 20 and 47 days after infection had seroconverted to Ad5 , virus was not detected in these groups either by viral plaque assay or in situ hybridization .


Ad5 E1A DNA was detected by polymerase chain reaction in five of six animals 20 days after infection and in five of five animals 47 days after infection .

<dna>Ad5 E1A DNA</dna> was detected by polymerase chain reaction in five of six animals 20 days after infection and in five of five animals 47 days after infection .


In these same animals , E1A protein was detected 20 days after infection in two and 47 days after infection in one while persistent bronchiolitis was observed in four and three animals 20 and 47 days after infection , respectively .

In these same animals , <protein>E1A protein</protein> was detected 20 days after infection in two and 47 days after infection in one while persistent bronchiolitis was observed in four and three animals 20 and 47 days after infection , respectively .


These results demonstrate that the guinea pig provides a useful model to study the role of Ad5 infection in chronic airway inflammation .


Cyclic AMP -responsive element -dependent activation of Epstein-Barr virus zebra promoter by human herpesvirus 6 .

Cyclic AMP <dna>-responsive element</dna> -dependent activation of Epstein-Barr virus <dna>zebra promoter</dna> by human herpesvirus 6 .


We have recently shown that infection of Epstein-Barr virus ( EBV ) genome-positive B cells by human herpesvirus 6 ( HHV-6 ) results in the expression of the immediate-early EBV Zebra gene , followed by virus replication ( L.Flamand , I.Stefanescu , D.V.Ablashi , and J.Menezes , J.Virol.67 : 6768-6777 , 1993 ) .

We have recently shown that infection of <cell_line>Epstein-Barr virus ( EBV ) genome-positive B cells</cell_line> by human herpesvirus 6 ( HHV-6 ) results in the expression of the <dna>immediate-early EBV Zebra gene</dna> , followed by virus replication ( L.Flamand , I.Stefanescu , D.V.Ablashi , and J.Menezes , J.Virol.67 : 6768-6777 , 1993 ) .


Here we show that HHV-6 upregulates Zebra gene transcription through a cyclic AMP-responsive element ( CRE ) located within the Zebra promoter ( Zp ) .

Here we show that HHV-6 upregulates <dna>Zebra gene</dna> transcription through a <dna>cyclic AMP-responsive element</dna> ( <dna>CRE</dna> ) located within the <dna>Zebra promoter</dna> ( <dna>Zp</dna> ) .


Using human B- or T-cell lines transfected with ZpCat reporter gene constructs , we demonstrate that a region designated the ZII domain of Zp is the target of HHV-6 transactivation .

Using <cell_line>human B- or T-cell lines</cell_line> transfected with <dna>ZpCat reporter gene constructs</dna> , we demonstrate that a region designated the <dna>ZII domain</dna> of <dna>Zp</dna> is the target of HHV-6 transactivation .


Mutation of the consensus AP-1/CRE site within ZII abolished the inducibility of Zp by HHV-6 , whereas positioning of the ZII domain upstream of the beta-globin minimal promoter conferred responsiveness following HHV-6 infection .

Mutation of the <dna>consensus AP-1/CRE site</dna> within <dna>ZII</dna> abolished the inducibility of <dna>Zp</dna> by HHV-6 , whereas positioning of the <dna>ZII domain</dna> upstream of the <dna>beta-globin minimal promoter</dna> conferred responsiveness following HHV-6 infection .


Binding of these factors to ZII was prevented by oligonucleotides containing CRE but not by AP-1 consensus sequences .

Binding of these factors to <dna>ZII</dna> was prevented by oligonucleotides containing <dna>CRE</dna> but not by <dna>AP-1 consensus sequences</dna> .


Antibodies against CRE-binding ( CREB ) protein but not against c-Fos or c-Jun were able to supershift the DNA-protein complex , identifying the nature of the transcription factor which binds to ZII as a member of the CREB family of proteins .

Antibodies against <protein>CRE-binding ( CREB ) protein</protein> but not against <protein>c-Fos</protein> or <protein>c-Jun</protein> were able to supershift the <protein>DNA-protein complex</protein> , identifying the nature of the <protein>transcription factor</protein> which binds to <dna>ZII</dna> as a member of the <protein>CREB family of proteins</protein> .


Finally , transfection of CREB protein and protein kinase A expression vectors were found to activate Zp in Jurkat cells , suggesting that phosphorylated form of CREB protein can play a determining role in the EBV reactivation process .

Finally , transfection of <protein>CREB protein</protein> and <dna>protein kinase A expression vectors</dna> were found to activate <dna>Zp</dna> in <cell_type>Jurkat cells</cell_type> , suggesting that phosphorylated form of <protein>CREB protein</protein> can play a determining role in the EBV reactivation process .


Regulation of the nuclear factor of activated T cells in stably transfected Jurkat cell clones .

Regulation of the <protein>nuclear factor of activated T cells</protein> in stably transfected <cell_line>Jurkat cell clones</cell_line> .


Two Jurkat cell clones have been stably transfected with a reporter vector for the nuclear factor of activated T cells ( NFAT ) .

Two <cell_line>Jurkat cell clones</cell_line> have been stably transfected with a <dna>reporter vector</dna> for the <protein>nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) .


Upon stimulation , they express high levels of secreted heat stable placental alkaline phosphatase .

Upon stimulation , they express high levels of secreted heat stable <protein>placental alkaline phosphatase</protein> .


With these clones , we demonstrated that NFAT activation induced by phorbol 12-myristate 13-acetate and ionomycin was inhibited by both cyclosporin A ( CsA ) ( IC50 = 8 nM ) and FK506 ( IC50 = 160 pM ) , presumably by inhibition of calcineurin activity .

With these clones , we demonstrated that <protein>NFAT</protein> activation induced by phorbol 12-myristate 13-acetate and ionomycin was inhibited by both cyclosporin A ( CsA ) ( IC50 = 8 nM ) and FK506 ( IC50 = 160 pM ) , presumably by inhibition of <protein>calcineurin</protein> activity .


Selective phosphatase inhibitors for protein phosphatase 1 ( PP1 ) and 2A ( PP2A ) that do not inhibit calcineurin , such as okadaic acid and calyculin A , also inhibited NFAT activation with IC50s of 87 nM and 4 nM , respectively , suggesting that okadaic acid and related inhibitors may block NFAT activation through the inhibition of PP1 , instead of PP2A .

Selective phosphatase inhibitors for <protein>protein phosphatase 1</protein> ( <protein>PP1</protein> ) and <protein>2A</protein> ( <protein>PP2A</protein> ) that do not inhibit <protein>calcineurin</protein> , such as okadaic acid and calyculin A , also inhibited <protein>NFAT</protein> activation with IC50s of 87 nM and 4 nM , respectively , suggesting that okadaic acid and related inhibitors may block <protein>NFAT</protein> activation through the inhibition of <protein>PP1</protein> , instead of <protein>PP2A</protein> .


NFAT activation was also inhibited by agents that increase cAMP concentrations such as dibutyryl cAMP , forskolin and prostaglandin E2 .

<protein>NFAT</protein> activation was also inhibited by agents that increase cAMP concentrations such as dibutyryl cAMP , forskolin and prostaglandin E2 .


These stable Jurkat cell clones provide a convenient and sensitive tool to study NFAT regulation .

These stable <cell_line>Jurkat cell clones</cell_line> provide a convenient and sensitive tool to study <protein>NFAT</protein> regulation .


Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma .

Glucocorticoids induced down-regulation of <protein>glucocorticoid receptor</protein> mRNA expression in asthma .


Although their precise mechanism of action remains to be elucidated , glucocorticoids represent the most effective therapy in the treatment of asthma .


Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes , including glucocorticoid receptor itself .

Interactions between the <protein>glucocorticoid receptor</protein> and the <protein>AP-1 complex</protein> have been shown to regulate the transcription of some genes , including <protein>glucocorticoid receptor</protein> itself .


The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid ( methyl prednisolone 120 mg/day ) for 10 days .

The aim of the present study was to compare the expression of <rna>mRNA</rna> for <protein>glucocorticoid receptor</protein> in <cell_type>human blood monocytes</cell_type> obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid ( methyl prednisolone 120 mg/day ) for 10 days .


mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase , by polymerase chain reaction using a semiquantitative competitive hybridization assay .

<rna>mRNA</rna> expression was identified after RNA extraction using RNAzol and analysed after <protein>reverse transcriptase</protein> , by polymerase chain reaction using a semiquantitative competitive hybridization assay .


All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment ( per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41 , P < 0.02 ) , and a significant decrease for glucocorticoid receptor mRNA expression ( P < 0.02 ) was observed in their monocytes .

All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment ( per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41 , P < 0.02 ) , and a significant decrease for <protein>glucocorticoid receptor</protein> <rna>mRNA</rna> expression ( P < 0.02 ) was observed in their monocytes .


This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression , following corticosteroid treatment .

This is the first report of an ex vivo down-regulation for the <protein>glucocorticoid receptor</protein> <rna>mRNA</rna> expression , following corticosteroid treatment .


Mapping of the transcriptional repression domain of the lymphoid-specific transcription factor oct-2A .

Mapping of the <protein>transcriptional repression domain</protein> of the <protein>lymphoid-specific transcription factor</protein> <protein>oct-2A</protein> .


The lymphoid-specific transcription factor Oct-2a is implicated in B cell-specific transcriptional activity via the octamer motif .

The <protein>lymphoid-specific transcription factor</protein> <protein>Oct-2a</protein> is implicated in B cell-specific transcriptional activity via the octamer motif .


Structure/function analysis of various Oct-2a effector regions in the context of the GAL4 DNA-binding domain revealed that Oct-2a contains two functionally different activation domains at the N and the C termini .

Structure/function analysis of various <protein>Oct-2a effector regions</protein> in the context of the <protein>GAL4 DNA-binding domain</protein> revealed that <protein>Oct-2a</protein> contains two functionally different <protein>activation domains</protein> at the <protein>N and the C termini</protein> .


The transcriptional activity of both domains is strongly potentiated by interactions with distinct B cell-specific coactivators .

The transcriptional activity of both domains is strongly potentiated by interactions with distinct <protein>B cell-specific coactivators</protein> .


Recently , we have identified a repression domain located within the N terminus of Oct-2a ( amino acids 2-99 ) .

Recently , we have identified a <protein>repression domain</protein> located within the <protein>N terminus</protein> of <protein>Oct-2a</protein> ( <protein>amino acids 2-99</protein> ) .


When this domain was transferred to a potent activator , transcription was strongly inhibited .


In this study we present a deletion analysis of the N-terminal region of Oct-2a to determine the minimal repression domain .

In this study we present a deletion analysis of the <protein>N-terminal region</protein> of <protein>Oct-2a</protein> to determine the <protein>minimal repression domain</protein> .


We identified a stretch of 23 amino acids , rich in serine and threonine residues , which was responsible for most of the repression activity .


We show that repression is strongly dependent on the type of enhancer present in the reporter plasmid as well as on the cell line tested .

We show that repression is strongly dependent on the type of <dna>enhancer</dna> present in the <dna>reporter plasmid</dna> as well as on the <cell_line>cell line</cell_line> tested .


The possibility that Oct-2a can act as an activator and/or a repressor may have important consequences for the function of Oct-2a in B cell differentiation and other developmental processes .

The possibility that <protein>Oct-2a</protein> can act as an activator and/or a repressor may have important consequences for the function of <protein>Oct-2a</protein> in B cell differentiation and other developmental processes .


Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes .

Opposing effects of glucocorticoids on the rate of apoptosis in <cell_type>neutrophilic and eosinophilic granulocytes</cell_type> .


Eosinophils and neutrophils are closely related , terminally differentiated cells that in vitro undergo constitutive cell death by apoptosis .

<cell_type>Eosinophils</cell_type> and <cell_type>neutrophils</cell_type> are closely related , <cell_type>terminally differentiated cells</cell_type> that in vitro undergo constitutive cell death by apoptosis .


The onset of apoptosis in both cell types can be delayed by hemopoietins and inflammatory mediators .

The onset of apoptosis in both cell types can be delayed by <protein>hemopoietins</protein> and <protein>inflammatory mediators</protein> .


Although there have been a number of reports demonstrating that glucocorticoids ( in particular dexamethasone ) antagonize the eosinophil life-prolonging effects of hemopoietins , direct effects of dexamethasone on eosinophil apoptosis have not been documented .

Although there have been a number of reports demonstrating that glucocorticoids ( in particular dexamethasone ) antagonize the eosinophil life-prolonging effects of <protein>hemopoietins</protein> , direct effects of dexamethasone on eosinophil apoptosis have not been documented .


In this study we examined the direct effects of glucocorticoids on eosinophil and neutrophil apoptosis in light of their common therapeutic use as anti-inflammatory and anti-allergic/hypereosinophilic agents .

In this study we examined the direct effects of glucocorticoids on <cell_type>eosinophil</cell_type> and <cell_type>neutrophil</cell_type> apoptosis in light of their common therapeutic use as anti-inflammatory and anti-allergic/hypereosinophilic agents .


We found that treatment with dexamethasone induced eosinophil apoptosis .

We found that treatment with dexamethasone induced <cell_type>eosinophil</cell_type> apoptosis .


In contrast , dexamethasone was a potent inhibitor of neutrophil apoptosis .

In contrast , dexamethasone was a potent inhibitor of <cell_type>neutrophil</cell_type> apoptosis .


The effect of dexamethasone on both cell types was mediated through the glucocorticoid receptor , i.e. , it was abolished by the glucocorticoid receptor antagonist RU38486 .

The effect of dexamethasone on both cell types was mediated through the <protein>glucocorticoid receptor</protein> , i.e. , it was abolished by the <protein>glucocorticoid receptor</protein> antagonist RU38486 .


This is the first description of an agent that promotes eosinophil apoptosis while inhibiting neutrophil apoptosis , and thus presents a novel approach to the study of control of apoptosis in these closely related cell types as well as increases our understanding of the clinical action of glucocorticoids in inflammation .

This is the first description of an agent that promotes <cell_type>eosinophil</cell_type> apoptosis while inhibiting <cell_type>neutrophil</cell_type> apoptosis , and thus presents a novel approach to the study of control of apoptosis in these closely related cell types as well as increases our understanding of the clinical action of glucocorticoids in inflammation .


Permanent occupancy of the human immunodeficiency virus type 1 enhancer by NF-kappa B is needed for persistent viral replication in monocytes .

Permanent occupancy of the <dna>human immunodeficiency virus type 1 enhancer</dna> by <protein>NF-kappa B</protein> is needed for persistent viral replication in <cell_type>monocytes</cell_type> .


This work aimed to ascertain the role of kappaB-responsive elements of the human immunodeficiency virus type 1 ( HIV-1 ) enhancer not only in early initiation but also in long-term maintenance of proviral transcription in cells of the monocytic lineage .

This work aimed to ascertain the role of <dna>kappaB-responsive elements</dna> of the <dna>human immunodeficiency virus type 1 ( HIV-1 ) enhancer</dna> not only in early initiation but also in long-term maintenance of proviral transcription in cells of the <cell_type>monocytic lineage</cell_type> .


For this purpose , we used three main approaches .


The first was to abruptly terminate tumor necrosis factor-induced NF-kappaB binding to the enhancer sequences in U1 monocytic cells , using a short pulse of exogenous tumor necrosis factor .

The first was to abruptly terminate tumor necrosis factor-induced <protein>NF-kappaB</protein> binding to the enhancer sequences in U1 monocytic cells , using a short pulse of <protein>exogenous tumor necrosis factor</protein> .


This resulted in concomitant decrease in nuclear NF-kappaB DNA-binding activity and endogenous long terminal repeat transcriptional activity .

This resulted in concomitant decrease in nuclear <protein>NF-kappaB</protein> DNA-binding activity and <dna>endogenous long terminal repeat</dna> transcriptional activity .


The second was to suppress the permanent NF-kappaB translocation induced by HIV-1 replication itself in chronically infected U937 cells , using a specific proteasome inhibitor ( Z-LLL-H ) .

The second was to suppress the permanent <protein>NF-kappaB</protein> translocation induced by HIV-1 replication itself in <cell_line>chronically infected U937 cells</cell_line> , using a specific proteasome inhibitor ( Z-LLL-H ) .


As early as 2 h after addition of the inhibitor to the culture medium , there was an inhibition of both constitutive activation of NF-kappaB and HIV-1 genome expression .

As early as 2 h after addition of the inhibitor to the culture medium , there was an inhibition of both constitutive activation of <protein>NF-kappaB</protein> and HIV-1 genome expression .


The third approach was to monitor the replication competence in U937 cells of an infectious HIV-1 provirus carrying point mutations in the kappaB-responsive elements of both long terminal repeats .

The third approach was to monitor the replication competence in <cell_line>U937 cells</cell_line> of an infectious HIV-1 provirus carrying point mutations in the <dna>kappaB-responsive elements</dna> of both <dna>long terminal repeats</dna> .


Compared with its wild-type counterpart , this mutated provirus showed a profoundly decreased , Z-LLL-H-insensitive transcriptional and replicative activity in U937 monocytes .

Compared with its wild-type counterpart , this mutated provirus showed a profoundly decreased , Z-LLL-H-insensitive transcriptional and replicative activity in <cell_line>U937 monocytes</cell_line> .


Together , our results indicate that occupancy of the viral enhancer by NF-kappaB ( p50/p65 ) heterodimers is required for ongoing transcription of integrated HIV provirus in monocytes , even in cells chronically infected and permanently producing functional HIV Tat protein .

Together , our results indicate that occupancy of the <dna>viral enhancer</dna> by <protein>NF-kappaB ( p50/p65 ) heterodimers</protein> is required for ongoing transcription of integrated HIV provirus in <cell_type>monocytes</cell_type> , even in cells chronically infected and permanently producing functional <protein>HIV Tat protein</protein> .


Thus , the ability of HIV-1 replication to activate NF-kappaB is crucial to the intense self-perpetuated viral transcription observed in cells of the monocytic lineage .

Thus , the ability of HIV-1 replication to activate <protein>NF-kappaB</protein> is crucial to the intense self-perpetuated viral transcription observed in cells of the <cell_type>monocytic lineage</cell_type> .


Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor .

<cell_type>Rel-deficient T cells</cell_type> exhibit defects in production of <protein>interleukin 3</protein> and <protein>granulocyte-macrophage colony-stimulating factor</protein> .


The c-rel protooncogene encodes a subunit of the NF-kappa B-like family of transcription factors .

The <dna>c-rel protooncogene</dna> encodes a subunit of the <protein>NF-kappa B-like family of transcription factors</protein> .


Mice lacking Rel are defective in mitogenic activation of B and T lymphocytes and display impaired humoral immunity .

Mice lacking <protein>Rel</protein> are defective in mitogenic activation of <cell_type>B and T lymphocytes</cell_type> and display impaired humoral immunity .


In an attempt to identify changes in gene expression that accompany the T-cell stimulation defects associated with the loss of Rel , we have examined the expression of cell surface activation markers and cytokine production in mitogen-stimulated Rel-/- T cells .

In an attempt to identify changes in gene expression that accompany the T-cell stimulation defects associated with the loss of <protein>Rel</protein> , we have examined the expression of <protein>cell surface activation markers</protein> and cytokine production in mitogen-stimulated <cell_type>Rel-/- T cells</cell_type> .


The expression of cell surface markers including the interleukin 2 receptor alpha ( IL-2R alpha ) chain ( CD25 ) , CD69 and L-selectin ( CD62 ) is normal in mitogen-activated Rel-/- T cells , but cytokine production is impaired .

The expression of cell surface markers including the <protein>interleukin 2 receptor alpha ( IL-2R alpha ) chain</protein> ( <protein>CD25</protein> ) , <protein>CD69</protein> and <protein>L-selectin</protein> ( <protein>CD62</protein> ) is normal in <cell_line>mitogen-activated Rel-/- T cells</cell_line> , but <protein>cytokine</protein> production is impaired .


In Rel-/- splenic T cell cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin , the levels of IL-3 , IL-5 , granulocyte- macrophage colony-stimulating factor ( GM-CSF ) , tumor necrosis factor alpha ( TNF-alpha ) , and gamma interferon ( IFN-gamma ) were only 2- to 3-fold lower compared with normal T cells .

In <cell_line>Rel-/- splenic T cell cultures</cell_line> stimulated with phorbol 12-myristate 13-acetate and ionomycin , the levels of IL-3 , IL-5 , <protein>granulocyte- macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) , <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) , and <protein>gamma interferon</protein> ( <protein>IFN-gamma</protein> ) were only 2- to 3-fold lower compared with normal T cells .


In contrast , anti-CD3 and anti-CD28 stimulated Rel-/- T cells , which fail to proliferate , make little or no detectable cytokines .

In contrast , <protein>anti-CD3</protein> and <protein>anti-CD28</protein> stimulated <cell_line>Rel-/- T cells</cell_line> , which fail to proliferate , make little or no detectable <protein>cytokines</protein> .


Exogenous IL-2 , which restitutes the proliferative response of the anti-CD3- and anti-CD28-treated Rel-/- T cells , restores production of IL-5 , TNF-alpha , and IFN-gamma , but not IL-3 and GM-CSF expression to approximately normal levels .

Exogenous <protein>IL-2</protein> , which restitutes the proliferative response of the <cell_line>anti-CD3- and anti-CD28-treated Rel-/- T cells</cell_line> , restores production of IL-5 , <protein>TNF-alpha</protein> , and <protein>IFN-gamma</protein> , but not <protein>IL-3</protein> and <protein>GM-CSF</protein> expression to approximately normal levels .


In contrast to mitogen-activated Rel-/- T cells , lipopolysaccharide-stimulated Rel-/- macrophages produce higher than normal levels of GM-CSF .

In contrast to <cell_line>mitogen-activated Rel-/- T cells</cell_line> , lipopolysaccharide-stimulated <cell_line>Rel-/- macrophages</cell_line> produce higher than normal levels of <protein>GM-CSF</protein> .


These findings establish that Rel can function as an activator or repressor of gene expression and is required by T lymphocytes for production of IL-3 and GM-CSF .

These findings establish that <protein>Rel</protein> can function as an activator or repressor of gene expression and is required by <cell_type>T lymphocytes</cell_type> for production of <protein>IL-3</protein> and <protein>GM-CSF</protein> .


Nuclear appearance of a factor that binds the CD28 response element within the interleukin-2 enhancer correlates with interleukin-2 production .

Nuclear appearance of a factor that binds the <dna>CD28 response element</dna> within the <dna>interleukin-2 enhancer</dna> correlates with <protein>interleukin-2</protein> production .


Activation of T lymphocytes requires the combined signaling of the T cell receptor and costimulatory molecules such as CD28 .

Activation of <cell_type>T lymphocytes</cell_type> requires the combined signaling of the <protein>T cell receptor</protein> and <protein>costimulatory molecules</protein> such as <protein>CD28</protein> .


The ability of T cells to produce interleukin-2 ( IL-2 ) is a critical control point in T lymphocyte activation .

The ability of <cell_type>T cells</cell_type> to produce <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) is a critical control point in T lymphocyte activation .


The IL-2 enhancer contains a functional motif named CD28 response element ( CD28RE ) that serves a role as a target for mitogenic T cell activation signals .

The <protein>IL-2</protein> enhancer contains a functional motif named <dna>CD28 response element</dna> ( <dna>CD28RE</dna> ) that serves a role as a target for mitogenic T cell activation signals .


The CD28RE sequence reveals similarity to the consensus kappaB binding motif .

The <dna>CD28RE</dna> sequence reveals similarity to the <dna>consensus kappaB binding motif</dna> .


Here we demonstrate that CD28RE binds an inducible protein with a molecular mass of approximately 35 kDa called nuclear factor of mitogenic-activated T cells ( NF-MATp35 ) that is clearly different from the known NF- kappaB/Rel family members .

Here we demonstrate that <dna>CD28RE</dna> binds an inducible protein with a molecular mass of approximately 35 kDa called <protein>nuclear factor of mitogenic-activated T cells</protein> ( <protein>NF-MATp35</protein> ) that is clearly different from the known <protein>NF- kappaB/Rel family members</protein> .


Induction of NF-MATp35 was shown to depend on de novo protein synthesis and was restricted to T cells that received a mitogenic combination of T cell stimuli , not necessarily including CD28 signaling .

Induction of <protein>NF-MATp35</protein> was shown to depend on de novo protein synthesis and was restricted to <cell_type>T cells</cell_type> that received a mitogenic combination of T cell stimuli , not necessarily including <protein>CD28</protein> signaling .


Nonmitogenic T cell stimulation did not result in appearance of NF-MATp35 .

Nonmitogenic T cell stimulation did not result in appearance of <protein>NF-MATp35</protein> .


These results indicate that mitogenic combinations of T cell activation signals are integrated at the level of NF-MATp35 induction .

These results indicate that mitogenic combinations of T cell activation signals are integrated at the level of <protein>NF-MATp35</protein> induction .


Similar to its effect on IL-2 production , cyclosporin A inhibited the induction of NF-MATp35 .

Similar to its effect on <protein>IL-2</protein> production , cyclosporin A inhibited the induction of <protein>NF-MATp35</protein> .


Taken together , these data demonstrate that the nuclear appearance of NF-MATp35 shows excellent correlation with IL-2 production , which is a unique characteristic among nuclear factors implicated in the control of IL-2 gene expression .

Taken together , these data demonstrate that the nuclear appearance of <protein>NF-MATp35</protein> shows excellent correlation with <protein>IL-2</protein> production , which is a unique characteristic among nuclear factors implicated in the control of <protein>IL-2</protein> gene expression .


Transcriptional basis for hyporesponsiveness of the human inducible nitric oxide synthase gene to lipopolysaccharide/interferon-gamma .

Transcriptional basis for hyporesponsiveness of the <dna>human inducible nitric oxide synthase gene</dna> to lipopolysaccharide/interferon-gamma .


The work reported here resolves , at the level of gene regulation , the controversy as to whether or not human monocytes/macrophages can produce nitric oxide ( NO ) when stimulated with lipopolysaccharide ( LPS ) , with or without co-stimulation by interferon-gamma ( IFN-gamma ) .

The work reported here resolves , at the level of gene regulation , the controversy as to whether or not <cell_type>human monocytes/macrophages</cell_type> can produce nitric oxide ( NO ) when stimulated with lipopolysaccharide ( LPS ) , with or without co-stimulation by interferon-gamma ( <protein>IFN-gamma</protein> ) .


Studies included structural comparison of the promoters for human and mouse inducible NO synthase ( iNOS ) genes , transfection and assay of human and mouse iNOS promoter regions in response to LPS +/- IFN-gamma , and electrophoretic mobility shift assays of kappa B response elements .

Studies included structural comparison of the promoters for human and mouse <dna>inducible NO synthase ( iNOS ) genes</dna> , transfection and assay of human and mouse <dna>iNOS promoter regions</dna> in response to LPS +/- <protein>IFN-gamma</protein> , and electrophoretic mobility shift assays of <dna>kappa B response elements</dna> .


Two explanations for hyporesponsiveness of the human iNOS promoter to LPS +/- IFN-gamma were found : ( 1 ) multiple inactivating nucleotide substitutions in the human counterpart of the enhancer element that has been shown to regulate LPS/ IFN-gamma induced expression of the mouse iNOS gene ; and ( 2 ) and absence of one or more nuclear factors in human macrophages ( e.g. , an LPS-inducible nuclear factor-kappa B/Rel complex ) , that is ( are ) required for maximal expression of the gene .

Two explanations for hyporesponsiveness of the <dna>human iNOS promoter</dna> to LPS +/- <protein>IFN-gamma</protein> were found : ( 1 ) multiple inactivating nucleotide substitutions in the human counterpart of the <dna>enhancer element</dna> that has been shown to regulate LPS/ <protein>IFN-gamma</protein> induced expression of the <dna>mouse iNOS gene</dna> ; and ( 2 ) and absence of one or more <protein>nuclear factors</protein> in <cell_type>human macrophages</cell_type> ( e.g. , an <protein>LPS-inducible nuclear factor-kappa B/Rel complex</protein> ) , that is ( are ) required for maximal expression of the gene .


The importance of resolution of this controversy is that future research in this area should be directed toward the understanding of alternative mechanisms that can result in the successful production of NO .


X inactivation analysis in a female with hypomelanosis of Ito associated with a balanced X ; 17 translocation : evidence for functional disomy of Xp .

X inactivation analysis in a female with hypomelanosis of Ito associated with a <dna>balanced X ; 17 translocation</dna> : evidence for functional disomy of Xp .


X inactivation analysis was performed on normal and hypopigmented skin samples obtained from a female with hypomelanosis of Ito associated with a balanced whole arm X ; 17 translocation .

X inactivation analysis was performed on normal and hypopigmented skin samples obtained from a female with hypomelanosis of Ito associated with a <dna>balanced whole arm X ; 17 translocation</dna> .


Severe skewing of X inactivation resulting in inactivity of the intact X was found in blood and cultures of both types of skin , but analysis of DNA prepared directly from hypopigmented skin showed significant inactivation of the translocated X , inconsistent with the usual mechanism of phenotypic expression in X ; autosome translocations .

Severe skewing of X inactivation resulting in inactivity of the intact <dna>X</dna> was found in blood and cultures of both types of skin , but analysis of DNA prepared directly from hypopigmented skin showed significant inactivation of the translocated <dna>X</dna> , inconsistent with the usual mechanism of phenotypic expression in <dna>X ; autosome translocations</dna> .


In addition , dual colour FISH analysis using centromere specific probes for chromosomes X and 17 showed that the breakpoints on both chromosomes lie within the alphoid arrays , making interruption of a locus on either chromosome unlikely .

In addition , dual colour FISH analysis using centromere specific probes for chromosomes <dna>X</dna> and <dna>17</dna> showed that the breakpoints on both <dna>chromosomes</dna> lie within the alphoid arrays , making interruption of a locus on either chromosome unlikely .


While partial variable monosomy of loci on chromosome 17p can not be excluded as contributing to the phenotype in this patient , it is argued that the major likely factor is partial functional disomy of sequences on Xp in cell lineages that have failed to inactivate the intact X chromosome .

While partial variable monosomy of loci on <dna>chromosome 17p</dna> can not be excluded as contributing to the phenotype in this patient , it is argued that the major likely factor is partial functional disomy of sequences on <dna>Xp</dna> in cell lineages that have failed to inactivate the intact <dna>X chromosome</dna> .


Identification of a herpesvirus Saimiri cis-acting DNA fragment that permits stable replication of episomes in transformed T cells .

Identification of a <dna>herpesvirus Saimiri cis-acting DNA fragment</dna> that permits stable replication of episomes in transformed <cell_type>T cells</cell_type> .


Herpesvirus saimiri is a lymphotropic herpesvirus capable of immortalizing and transforming T cells both in vitro and in vivo .

Herpesvirus saimiri is a lymphotropic herpesvirus capable of immortalizing and transforming <cell_type>T cells</cell_type> both in vitro and in vivo .


Immortalized and transformed T cells harbor several copies of the viral genome as a persisting genome .

Immortalized and transformed <cell_type>T cells</cell_type> harbor several copies of the <dna>viral genome</dna> as a <dna>persisting genome</dna> .


The mapping of the cis-acting genetic cis-acting segment ( oriP ) required for viral episomal maintenance is reported here .

The mapping of the <dna>cis-acting genetic cis-acting segment</dna> ( <dna>oriP</dna> ) required for viral episomal maintenance is reported here .


Viral DNA fragments that potentially contain oriP were cloned into a plasmid that contains the hygromycin resistance gene .

<dna>Viral DNA fragments</dna> that potentially contain <dna>oriP</dna> were cloned into a <dna>plasmid</dna> that contains the <dna>hygromycin resistance gene</dna> .


After several round of subcloning followed by transfection , oriP was mapped to a 1.955-kb viral segment .

After several round of subcloning followed by transfection , <dna>oriP</dna> was mapped to a <dna>1.955-kb viral segment</dna> .


This viral fragment permits stable plasmid replication without deletion or rearrangement as well as episomal maintenance without integration or recombination .

This viral fragment permits stable <dna>plasmid</dna> replication without deletion or rearrangement as well as episomal maintenance without integration or recombination .


The function of oriP depends on a trans-acting factor ( s ) encoded by the viral genome .

The function of <dna>oriP</dna> depends on a <protein>trans-acting factor</protein> ( s ) encoded by the <dna>viral genome</dna> .


The 1.955-kb viral segment includes a dyad symmetry region located between two small nuclear RNA genes and is located upstream of the dihydrofolate reductase gene homolog .

The <dna>1.955-kb viral segment</dna> includes a dyad symmetry region located between two <dna>small nuclear RNA genes</dna> and is located upstream of the <dna>dihydrofolate reductase gene homolog</dna> .


Therefore , this oriP contains novel elements distinct from those of other DNA viruses .

Therefore , this <dna>oriP</dna> contains novel elements distinct from those of other DNA viruses .


In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors .

In vivo <cell_line>anergized CD4+ T cells</cell_line> express perturbed AP-1 and <protein>NF-kappa B</protein> <protein>transcription factors</protein> .


Anergy is a major mechanism to ensure antigen-specific tolerance in T lymphocytes in the adult .

Anergy is a major mechanism to ensure antigen-specific tolerance in <cell_type>T lymphocytes</cell_type> in the adult .


In vivo , anergy has mainly been studied at the cellular level .


In this study , we used the T-cell-activating superantigen staphylococcal enterotoxin A ( SEA ) to investigate molecular mechanisms of T-lymphocyte anergy in vivo .

In this study , we used the <protein>T-cell-activating superantigen</protein> <protein>staphylococcal enterotoxin A</protein> ( <protein>SEA</protein> ) to investigate molecular mechanisms of T-lymphocyte anergy in vivo .


Injection of SEA to adult mice activates CD4+ T cells expressing certain T-cell receptor ( TCR ) variable region beta-chain families and induces strong and rapid production of interleukin 2 ( IL-2 ) .

Injection of <protein>SEA</protein> to adult mice activates <cell_type>CD4+ T cells</cell_type> expressing certain <protein>T-cell receptor ( TCR ) variable region beta-chain families</protein> and induces strong and rapid production of interleukin 2 ( <protein>IL-2</protein> ) .


In contrast , repeated injections of SEA cause CD4+ T-cell deletion and anergy in the remaining CD4+ T cells , characterized by reduced expression of IL-2 at mRNA and protein levels .

In contrast , repeated injections of <protein>SEA</protein> cause <cell_type>CD4+ T-cell</cell_type> deletion and anergy in the remaining CD4+ <cell_type>T cells</cell_type> , characterized by reduced expression of <protein>IL-2</protein> at mRNA and protein levels .


We analyzed expression of AP-1 , NF-kappa B , NF-AT , and octamer binding transcription factors , which are known to be involved in the regulation of IL-2 gene promoter activity .

We analyzed expression of <protein>AP-1</protein> , <protein>NF-kappa B</protein> , <protein>NF-AT</protein> , and <protein>octamer binding transcription factors</protein> , which are known to be involved in the regulation of <protein>IL-2</protein> gene promoter activity .


Large amounts of AP-1 and NF-kappa B and significant quantities of NF-AT were induced in SEA-activated CD4+ spleen T cells , whereas Oct-1 and Oct-2 DNA binding activity was similar in both resting and activated T cells .

Large amounts of <protein>AP-1</protein> and <protein>NF-kappa B</protein> and significant quantities of <protein>NF-AT</protein> were induced in <cell_line>SEA-activated CD4+ spleen T cells</cell_line> , whereas Oct-1 and Oct-2 DNA binding activity was similar in both resting and <cell_type>activated T cells</cell_type> .


In contrast , anergic CD4+ T cells contained severely reduced levels of AP-1 and Fos/Jun-containing NF-AT complexes but expressed significant amounts of NF-kappa B and Oct binding proteins after SEA stimulation .

In contrast , <cell_type>anergic CD4+ T cells</cell_type> contained severely reduced levels of <protein>AP-1</protein> and <protein>Fos/Jun-containing NF-AT complexes</protein> but expressed significant amounts of <protein>NF-kappa B</protein> and <protein>Oct binding proteins</protein> after <protein>SEA</protein> stimulation .


Resolution of the NF-kappa B complex demonstrated predominant expression of p50-p65 heterodimers in activated CD4+ T cells , while anergic cells mainly expressed the transcriptionally inactive p50 homodimer .

Resolution of the <protein>NF-kappa B complex</protein> demonstrated predominant expression of <protein>p50-p65 heterodimers</protein> in <cell_type>activated CD4+ T cells</cell_type> , while anergic cells mainly expressed the transcriptionally inactive <protein>p50 homodimer</protein> .


These alterations of transcription factors are likely to be responsible for repression of IL-2 in anergic T cells .

These alterations of <protein>transcription factors</protein> are likely to be responsible for repression of <protein>IL-2</protein> in <cell_type>anergic T cells</cell_type> .


Fas ligation induces apoptosis and Jun kinase activation independently of CD45 and Lck in human T cells .

<protein>Fas</protein> ligation induces apoptosis and <protein>Jun kinase</protein> activation independently of <protein>CD45</protein> and <protein>Lck</protein> in <cell_type>human T cells</cell_type> .


Stimulation through the Fas/APO-1 receptor results in apoptosis through an incompletely characterized signaling pathway .

Stimulation through the <protein>Fas/APO-1 receptor</protein> results in apoptosis through an incompletely characterized signaling pathway .


More is known regarding signal transduction events that occur after ligation of the T-cell antigen receptor ( TCR ) .

More is known regarding signal transduction events that occur after ligation of the <protein>T-cell antigen receptor</protein> ( <protein>TCR</protein> ) .


It has been shown that TCR stimulation requires both the membrane tyrosine phosphatase , CD45 , and the Src-family kinase , Lck , to result in cellular activation .

It has been shown that <protein>TCR</protein> stimulation requires both the <protein>membrane tyrosine phosphatase</protein> , <protein>CD45</protein> , and the <protein>Src-family kinase</protein> , <protein>Lck</protein> , to result in cellular activation .


Although prior studies suggest a role for protein tyrosine kinases and phosphatases in Fas signaling , we report here that Fas ligation induces apoptosis in T cells deficient in either CD45 or Lck .

Although prior studies suggest a role for <protein>protein tyrosine kinases</protein> and phosphatases in <protein>Fas</protein> signaling , we report here that Fas ligation induces apoptosis in <cell_type>T cells</cell_type> deficient in either <protein>CD45</protein> or <protein>Lck</protein> .


Further , in normal and CD45- or Lck-deficient cell lines , Fas stimulation results in activation of Jun kinase ( JNK ) , a proposed mediator of stress activation pathways .

Further , in normal and <cell_line>CD45- or Lck-deficient cell lines</cell_line> , Fas stimulation results in activation of <protein>Jun kinase</protein> ( <protein>JNK</protein> ) , a proposed mediator of stress activation pathways .


Previous studies have also demonstrated a role for endogenous ceramide release in Fas-mediated apoptosis .


We show that stimulation with a synthetic ceramide analog results in JNK activation as well as apoptosis , suggesting ceramide release occurs proximal to JNK activation in Fas signaling .

We show that stimulation with a synthetic ceramide analog results in <protein>JNK</protein> activation as well as apoptosis , suggesting ceramide release occurs proximal to <protein>JNK</protein> activation in <protein>Fas</protein> signaling .


Our data suggest that although CD45 and Lck are not required for Fas signaling , JNK activation may play an important role transducing distal signals that lead to apoptosis after Fas ligation .

Our data suggest that although <protein>CD45</protein> and <protein>Lck</protein> are not required for <protein>Fas</protein> signaling , <protein>JNK</protein> activation may play an important role transducing distal signals that lead to apoptosis after <protein>Fas</protein> ligation .


Globin gene switching .


In vivo protein-DNA interactions of the human beta-globin locus in erythroid cells expressing the fetal or the adult globin gene program .

In vivo protein-DNA interactions of the <dna>human beta-globin locus</dna> in <cell_type>erythroid cells</cell_type> expressing the fetal or the adult <dna>globin gene</dna> program .


To characterize the protein-DNA interactions important for the developmental control of the human beta-globin locus , we analyzed by in vivo dimethyl sulfate footprinting erythroid cells expressing either the fetal or the adult globin developmental program .

To characterize the protein-DNA interactions important for the developmental control of the <dna>human beta-globin locus</dna> , we analyzed by in vivo dimethyl sulfate footprinting <cell_type>erythroid cells</cell_type> expressing either the fetal or the adult globin developmental program .


In the locus control region ( LCR ) of the beta-globin locus , in vivo footprints on NF-E2 ( or AP-1 ) and GATA-1 motifs remained the same regardless of whether the fetal or the adult globin genes are expressed .

In the <dna>locus control region</dna> ( <dna>LCR</dna> ) of the <dna>beta-globin locus</dna> , in vivo footprints on <protein>NF-E2</protein> ( or <protein>AP-1</protein> ) and <dna>GATA-1 motifs</dna> remained the same regardless of whether the fetal or the <dna>adult globin genes</dna> are expressed .


In contrast , in vivo footprints on GT ( CACCC ) motifs differed between the cells expressing the fetal or the adult globin program .

In contrast , in vivo footprints on <dna>GT ( CACCC ) motifs</dna> differed between the cells expressing the fetal or the adult globin program .


In promoter regions , the actively transcribed genes demonstrated extensive and consistent footprints over the canonical elements , such as CACCC and CCAAT motifs .

In <dna>promoter regions</dna> , the <dna>actively transcribed genes</dna> demonstrated extensive and consistent footprints over the canonical elements , such as <dna>CACCC and CCAAT motifs</dna> .


The adult globin expressing cells displayed more extensive footprints than the fetal globin expressing cells in the 3 ' regulatory sequences of both the Agamma- and the beta-globin genes , suggesting a role of these 3 ' elements in beta-globin gene expression .

The <cell_type>adult globin expressing cells</cell_type> displayed more extensive footprints than the <cell_type>fetal globin expressing cells</cell_type> in the <dna>3 ' regulatory sequences</dna> of both the <dna>Agamma- and the beta-globin genes</dna> , suggesting a role of these <dna>3 ' elements</dna> in <dna>beta-globin gene</dna> expression .


Our results suggest that the bulk of protein-DNA interactions that underlies the developmental control of globin genes takes place in the gamma- and beta-globin gene promoters , and that GT motifs of the beta-globin locus LCR may play a role in the developmental regulation of human beta-globin gene expression , perhaps by increasing the probability of interaction of the LCR holocomplex with the fetal or the adult globin gene .

Our results suggest that the bulk of protein-DNA interactions that underlies the developmental control of <dna>globin genes</dna> takes place in the <dna>gamma- and beta-globin gene promoters</dna> , and that <dna>GT motifs</dna> of the <dna>beta-globin locus</dna> <dna>LCR</dna> may play a role in the developmental regulation of human <dna>beta-globin gene</dna> expression , perhaps by increasing the probability of interaction of the <protein>LCR holocomplex</protein> with the <dna>fetal or the adult globin gene</dna> .


Antisense inhibition of vitamin D receptor expression induces apoptosis in monoblastoid U937 cells .

Antisense inhibition of <protein>vitamin D receptor</protein> expression induces apoptosis in <cell_line>monoblastoid U937 cells</cell_line> .


The active vitamin D3 metabolite 1 , 25-dihydroxycholecalciferol ( 1 , 25 ( OH ) 2D3 ) acts as an antiproliferative and differentiating agent for the monoblastoid cell line U937 and as an important immunologic mediator implicated particularly in the function of cells belonging to the monocyte/macrophage lineage .

The active vitamin D3 metabolite 1 , 25-dihydroxycholecalciferol ( 1 , 25 ( OH ) 2D3 ) acts as an antiproliferative and differentiating agent for the <cell_line>monoblastoid cell line U937</cell_line> and as an important immunologic mediator implicated particularly in the function of cells belonging to the <cell_type>monocyte/macrophage lineage</cell_type> .


These effects are controlled by the vitamin D receptor ( VDR ) , a member of the steroid hormone receptor family .

These effects are controlled by the <protein>vitamin D receptor</protein> ( <protein>VDR</protein> ) , a member of the <protein>steroid hormone receptor family</protein> .


The objective of this study was to develop U937 transfectants expressing antisense VDR mRNA , and to use these to examine the role of 1 , 25 ( OH ) 2D3 -VDR interaction in this lineage .

The objective of this study was to develop <cell_line>U937</cell_line> transfectants expressing antisense <rna>VDR mRNA</rna> , and to use these to examine the role of 1 , 25 ( OH ) 2D3 <protein>-VDR</protein> interaction in this lineage .


A 2-kb VDR cDNA insert ( including the complete VDR coding region ) was cloned in an antisense orientation into the EBV episomal vector pMEP4 under the control of an inducible promoter and transfected into U937 .

A <dna>2-kb VDR cDNA insert</dna> ( including the complete <dna>VDR coding region</dna> ) was cloned in an antisense orientation into the EBV episomal vector pMEP4 under the control of an <dna>inducible promoter</dna> and transfected into <cell_line>U937</cell_line> .


The resultant cell line , DH42 , was hygromycin resistant , contained VDR cDNA , expressed fewer VDRs than controls , and showed a substantial decrease in antiproliferative response to 1 , 25 ( OH ) 2D3 .

The <cell_line>resultant cell line</cell_line> , <cell_line>DH42</cell_line> , was hygromycin resistant , contained <dna>VDR cDNA</dna> , expressed fewer <protein>VDRs</protein> than controls , and showed a substantial decrease in antiproliferative response to 1 , 25 ( OH ) 2D3 .


However , 1 , 25 ( OH ) 2D3 increased the number of cells expressing macrophage cell surface Ags , including CD14 and CD11b .

However , 1 , 25 ( OH ) 2D3 increased the number of cells expressing <protein>macrophage cell surface Ags</protein> , including <protein>CD14</protein> and <protein>CD11b</protein> .


A subpopulation of smaller cells did not express the differentiation markers after cadmium stimulation .


Cell cycle analysis showed shifts in the distribution of cells from G1 to S phase , which were more pronounced after cadmium treatment .


A considerable proportion of cells were outside the cycle and DNA fragmentation confirmed apoptosis .


Thus , the functional outcome of the VDR antisense transfection suggests that in the myelomonocytic lineage , VDR expression may act as a protective mechanism against programmed cell death .

Thus , the functional outcome of the <protein>VDR</protein> antisense transfection suggests that in the <cell_type>myelomonocytic lineage</cell_type> , <protein>VDR</protein> expression may act as a protective mechanism against programmed cell death .


Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside-binding lectin , galectin-3 .

Human T lymphotropic virus-I infection of <cell_type>human T lymphocytes</cell_type> induces expression of the <protein>beta-galactoside-binding lectin</protein> , <protein>galectin-3</protein> .


Animal lectins play important roles in a variety of biological processes via their recognition of glycoconjugates .

Animal <protein>lectins</protein> play important roles in a variety of biological processes via their recognition of glycoconjugates .


Galectin-3 is a beta-galactoside-binding lectin previously designated as epsilon BP ( IgE-binding protein ) , CBP35 , Mac-2 , L-29 , and L-34 , and its expression has been associated with various physiological and pathological processes , including cell growth , tumor transformation , and metastasis .

Galectin-3 is a <protein>beta-galactoside-binding lectin</protein> previously designated as <protein>epsilon BP</protein> ( <protein>IgE-binding protein</protein> ) , <protein>CBP35</protein> , <protein>Mac-2</protein> , <protein>L-29</protein> , and <protein>L-34</protein> , and its expression has been associated with various physiological and pathological processes , including cell growth , tumor transformation , and metastasis .


Galectin-3 is widely distributed in various tissues and cell types and is expressed in many leukocytes , with the notable exception of B and T lymphocytes .

<protein>Galectin-3</protein> is widely distributed in various tissues and cell types and is expressed in many <cell_type>leukocytes</cell_type> , with the notable exception of <cell_type>B and T lymphocytes</cell_type> .