The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo .

The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of <dna>human alpha-like globin promoters</dna> is indeed modulated by stable binding of <protein>specific nuclear factors</protein> in vivo .


Nitric oxide-stimulated guanine nucleotide exchange on p21ras .

Nitric oxide-stimulated guanine nucleotide exchange on <protein>p21ras</protein> .


The protooncogene p21ras , a monomeric G protein family member , plays a critical role in converting extracellular signals into intracellular biochemical events .

The <dna>protooncogene p21ras</dna> , a <protein>monomeric G protein family member</protein> , plays a critical role in converting extracellular signals into intracellular biochemical events .


Here , we report that nitric oxide ( NO ) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras .

Here , we report that nitric oxide ( NO ) activates <dna>p21ras</dna> in <cell_type>human T cells</cell_type> as evidenced by an increase in <protein>GTP-bound p21ras</protein> .


In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible .

In vitro studies using <protein>pure recombinant p21ras</protein> demonstrate that the activation is direct and reversible .


Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange .

Circular dichroism analysis reveals that NO induces a profound conformational change in <dna>p21ras</dna> in association with GDP/GTP exchange .


The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange .


Furthermore , we demonstrate that p21ras is essential for NO-induced downstream signaling , such as NF-kappa B activation , and that endogenous NO can activate p21ras in the same cell .

Furthermore , we demonstrate that <protein>p21ras</protein> is essential for NO-induced downstream signaling , such as <protein>NF-kappa B</protein> activation , and that endogenous NO can activate <protein>p21ras</protein> in the same cell .


These studies identify p21ras as a target of the same cell .

These studies identify <dna>p21ras</dna> as a target of the same cell .


These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors .

These studies identify <dna>p21ras</dna> as a target of NO in <cell_type>T cells</cell_type> and suggest that NO activates <dna>p21ras</dna> by an action which mimics that of <protein>guanine nucleotide exchange factors</protein> .


Interleukin-2 promoter activity in Epstein-Barr virus-transformed B lymphocytes is controlled by nuclear factor-chi B .

<dna>Interleukin-2 promoter</dna> activity in <cell_line>Epstein-Barr virus-transformed B lymphocytes</cell_line> is controlled by <protein>nuclear factor-chi B</protein> .


The regulation of interleukin ( IL ) -2 gene expression has been investigated mainly in T lymphocytes , the predominant producers of IL-2 .

The regulation of <dna>interleukin ( IL ) -2 gene</dna> expression has been investigated mainly in <cell_type>T lymphocytes</cell_type> , the predominant producers of <protein>IL-2</protein> .


However , B cells can also synthesize IL-2 .

However , <cell_type>B cells</cell_type> can also synthesize <protein>IL-2</protein> .


In the present study we analyzed the control of IL-2 promoter activity in Epstein-Barr virus ( EBV ) -transformed B cell clones which are capable of secreting IL-2 at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin .

In the present study we analyzed the control of <dna>IL-2 promoter</dna> activity in <cell_line>Epstein-Barr virus ( EBV ) -transformed B cell clones</cell_line> which are capable of secreting <protein>IL-2</protein> at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin .


Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL-2 promoter [ distal nuclear factor ( NF ) -AT , proximal NF-AT , AP-1/Octamer ( UPS ) or NF-chi B ( TCEd ) sites ] were performed .

Transient transfections using <dna>reporter constructs</dna> with multiples of <dna>transcription factor binding sites</dna> from the <dna>IL-2 promoter</dna> [ <protein>distal nuclear factor ( NF ) -AT</protein> , <protein>proximal NF-AT</protein> , <protein>AP-1/Octamer</protein> ( <protein>UPS</protein> ) or <protein>NF-chi B</protein> ( <protein>TCEd</protein> ) sites ] were performed .


In EBV-transformed B clones , the chi B site exerted the strongest inducible activity ; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells .

In <cell_line>EBV-transformed B clones</cell_line> , the <dna>chi B site</dna> exerted the strongest inducible activity ; the <dna>NF-AT binding sites</dna> showed either no or only weak activity compared to <cell_line>Jurkat T cells</cell_line> .


An IL-2 promoter bearing a defective NF-chi B site was completely inactive in EBV-transformed B cells , while it still had activity in Jurkat T cells .

An <dna>IL-2 promoter</dna> bearing a defective <dna>NF-chi B site</dna> was completely inactive in <cell_line>EBV-transformed B cells</cell_line> , while it still had activity in <cell_line>Jurkat T cells</cell_line> .


In seven EBV-B cell clones or lines differing in their capacity to secrete IL-2 , the activity of the IL-2 promoter correlated well with the status of IL-2 secretion .

In seven <cell_line>EBV-B cell clones</cell_line> or lines differing in their capacity to secrete <protein>IL-2</protein> , the activity of the <dna>IL-2 promoter</dna> correlated well with the status of <protein>IL-2</protein> secretion .


Similarly , a human immunodeficiency virus promoter , whose activity is controlled through chi B factors , was found to be active in the IL-2 producing EBV-B cells , but inactive in the non-IL-2-producing cells .

Similarly , a <dna>human immunodeficiency virus promoter</dna> , whose activity is controlled through <protein>chi B factors</protein> , was found to be active in the <cell_line>IL-2 producing EBV-B cells</cell_line> , but inactive in the <cell_line>non-IL-2-producing cells</cell_line> .


Electrophoretic mobility shift assays using protein extracts from EBV-B cells and the IL-2 NF-chi B probe revealed the constitutive generation of chi B complexes in IL-2-secreting cells consisting mainly of heterodimeric p50/p65 complexes .

Electrophoretic mobility shift assays using protein extracts from <cell_line>EBV-B cells</cell_line> and the <protein>IL-2</protein> <protein>NF-chi B</protein> probe revealed the constitutive generation of <protein>chi B complexes</protein> in <cell_line>IL-2-secreting cells</cell_line> consisting mainly of <protein>heterodimeric p50/p65 complexes</protein> .


A weaker chi B complex formation and faster-migrating complexes were detected in non-IL-2-secreting cells .

A weaker <dna>chi B</dna> complex formation and faster-migrating complexes were detected in <cell_line>non-IL-2-secreting cells</cell_line> .


These results demonstrate that the IL-2 NF-chi B site is indispensable for the activity of the IL-2 promoter in EBV-transformed B cells , whereas other transcription factors appear to be less important for IL-2 expression in these cells .

These results demonstrate that the <dna>IL-2 NF-chi B site</dna> is indispensable for the activity of the <dna>IL-2 promoter</dna> in <cell_line>EBV-transformed B cells</cell_line> , whereas other <protein>transcription factors</protein> appear to be less important for <protein>IL-2</protein> expression in these cells .


Latent membrane protein-1 induces cyclin D2 expression , pRb hyperphosphorylation , and loss of TGF-beta 1 -mediated growth inhibition in EBV-positive B cells .

<protein>Latent membrane protein-1</protein> induces <protein>cyclin D2</protein> expression , <protein>pRb</protein> hyperphosphorylation , and loss of <protein>TGF-beta 1</protein> -mediated growth inhibition in <cell_type>EBV-positive B cells</cell_type> .


The normal cell cycle is regulated by several molecules , such as the tumor-suppressor protein pRb , the G1 cyclins , the cyclin-dependent kinases , and their inhibitors .

The normal cell cycle is regulated by several molecules , such as the <protein>tumor-suppressor protein pRb</protein> , the <protein>G1 cyclins</protein> , the <protein>cyclin-dependent kinases</protein> , and their inhibitors .


These regulators are targeted by negative growth regulatory signals , such as that provided by TGF-beta .

These regulators are targeted by negative growth regulatory signals , such as that provided by <protein>TGF-beta</protein> .


Here , we show that the presence of either wild-type EBV or its transforming latent membrane protein-1 ( LMP-1 ) results in the loss of TGF-beta 1 -mediated growth inhibition in human B cells .

Here , we show that the presence of either wild-type EBV or its <protein>transforming latent membrane protein-1</protein> ( <protein>LMP-1</protein> ) results in the loss of <protein>TGF-beta 1</protein> -mediated growth inhibition in <cell_type>human B cells</cell_type> .


Chemical cross-linking with 125I-labeled TGF-beta 1 showed an essentially normal TGF-beta receptor profile in EBV-positive and EBV-negative Burkitt 's lymphoma cell lines , and these receptors were shown to be functional in transducing signals , as evidenced by the TGF-beta 1 -mediated modulation of junB gene expression .

Chemical cross-linking with <protein>125I-labeled TGF-beta 1</protein> showed an essentially normal <protein>TGF-beta receptor</protein> profile in <cell_line>EBV-positive and EBV-negative Burkitt 's lymphoma cell lines</cell_line> , and these receptors were shown to be functional in transducing signals , as evidenced by the <protein>TGF-beta 1</protein> -mediated modulation of <dna>junB gene</dna> expression .


However , TGF-beta 1 did not induce dephosphorylation of pRb in EBV ( or LMP-1 ) -positive cells as opposed to EBV-negative cells , suggesting a dichotomy in the TGF-beta 1 signaling pathway leading to separable gene regulatory and growth inhibitory responses .

However , <protein>TGF-beta 1</protein> did not induce dephosphorylation of <protein>pRb</protein> in <cell_line>EBV ( or LMP-1 ) -positive cells</cell_line> as opposed to <cell_line>EBV-negative cells</cell_line> , suggesting a dichotomy in the <protein>TGF-beta 1</protein> signaling pathway leading to separable gene regulatory and growth inhibitory responses .


Furthermore , LMP-1 was found to induce the expression of cyclin D2 ; normal B cells or EBV-negative Burkitt 's lymphoma cells do not express D-type cyclins .

Furthermore , <protein>LMP-1</protein> was found to induce the expression of <protein>cyclin D2</protein> ; normal <cell_type>B cells</cell_type> or <cell_line>EBV-negative Burkitt 's lymphoma cells</cell_line> do not express <protein>D-type cyclins</protein> .


Taken together , these data point to a potential mechanism underlying EBV-mediated B cell transformation whereby constitutive induction of key cell cycle regulators by LMP-1 can lead to pRb hyperphosphorylation and uncontrolled cell proliferation .

Taken together , these data point to a potential mechanism underlying EBV-mediated B cell transformation whereby constitutive induction of <protein>key cell cycle regulators</protein> by <protein>LMP-1</protein> can lead to <protein>pRb</protein> hyperphosphorylation and uncontrolled cell proliferation .


Does thyroidectomy , radioactive iodine therapy , or antithyroid drug treatment alter reactivity of patients ' T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases ?

Does thyroidectomy , radioactive iodine therapy , or antithyroid drug treatment alter reactivity of patients ' <cell_type>T cells</cell_type> to epitopes of <protein>thyrotropin receptor</protein> in autoimmune thyroid diseases ?


The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves ' disease ( GD ) before and after thyroidectomy , 19 patients with GD before and after radioactive iodine ( RAI ) therapy , and 9 patients maintained euthyroid on antithyroid drugs ( ATD ) .


Twenty subjects matched for age and sex without known thyroid disease served as controls .


In GD patients , the responses of peripheral blood mononuclear cells ( PBMC ) and TSH receptor ( TSHR ) -specific T cell lines to recombinant human TSHR extracellular domain , thyroglobulin , and TSHR peptides were examined on the day of surgery or RAI therapy ( day 0 ) and also 6-8 weeks and 3-6 months thereafter .

In GD patients , the responses of <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) and <cell_line>TSH receptor ( TSHR ) -specific T cell lines</cell_line> to <protein>recombinant human TSHR extracellular domain</protein> , <protein>thyroglobulin</protein> , and <protein>TSHR</protein> peptides were examined on the day of surgery or RAI therapy ( day 0 ) and also 6-8 weeks and 3-6 months thereafter .


Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain .

Reactivity to <protein>TSHR</protein> peptides before surgery was heterogeneous and spanned the entire <protein>extracellular domain</protein> .


Six to 8 weeks after subtotal thyroidectomy , the number of patients ' PBMC responding to any peptide and the average number of recognized peptides decreased .

Six to 8 weeks after subtotal thyroidectomy , the number of patients ' <cell_type>PBMC</cell_type> responding to any peptide and the average number of recognized peptides decreased .


A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery .

A further decrease in the T cell reactivity to <protein>TSHR</protein> peptides was observed 3-6 months after surgery .


The responses of PBMC from Graves ' patients before RAI therapy were less than those in the presurgical group .

The responses of <cell_type>PBMC</cell_type> from Graves ' patients before RAI therapy were less than those in the presurgical group .


Six to 8 weeks after RAI therapy , the number of patients responding to any peptide and the average number of recognized peptides increased .


Three to 6 months after RAI , T cell responses to TSHR peptides were less than those 6-8 weeks after RAI therapy , but still higher than the values on day 0 .

Three to 6 months after RAI , T cell responses to <protein>TSHR</protein> peptides were less than those 6-8 weeks after RAI therapy , but still higher than the values on day 0 .


Responses of PBMC from patients with GD , maintained euthyroid on ATD , were lower than those before surgery or RAI therapy .

Responses of <cell_type>PBMC</cell_type> from patients with GD , maintained euthyroid on ATD , were lower than those before surgery or RAI therapy .


The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment .

The reactivity of <cell_line>T cell lines</cell_line> in different groups reflected a pattern similar to <cell_type>PBMC</cell_type> after treatment .


TSHR antibody and microsomal antibody levels decreased after surgery , but increased after RAI therapy .

<protein>TSHR antibody</protein> and <protein>microsomal antibody</protein> levels decreased after surgery , but increased after RAI therapy .


The difference in the number of recognized peptides by patients ' PBMC before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery .

The difference in the number of recognized peptides by patients ' <cell_type>PBMC</cell_type> before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery .


The decreased T cell reactivity to thyroid antigens after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer T cells .

The decreased T cell reactivity to <protein>thyroid antigens</protein> after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer <cell_type>T cells</cell_type> .


The increased T cell response after RAI therapy is probably epitope specific , rather than a response to the whole TSHR molecule .

The increased T cell response after RAI therapy is probably epitope specific , rather than a response to the whole <protein>TSHR</protein> molecule .


Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD , and the loss of recognition of one of these epitopes may be an early sign of immune remission and a predictor of euthyroidism .

Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD , and the loss of recognition of one of these <protein>epitopes</protein> may be an early sign of immune remission and a predictor of euthyroidism .


Circumvention of tolerance for the nuclear T cell protein TCF-1 by immunization of TCF-1 knock-out mice .

Circumvention of tolerance for the <protein>nuclear T cell protein</protein> <protein>TCF-1</protein> by immunization of <protein>TCF-1</protein> knock-out mice .


Molecular events that underlie the well-defined phenotypic changes of the differentiating thymocyte are poorly understood .

Molecular events that underlie the well-defined phenotypic changes of the <cell_type>differentiating thymocyte</cell_type> are poorly understood .


A candidate gene to control thymocyte differentiation , T cell factor-1 ( TCF-1 ) * encodes a DNA-binding protein .

A candidate gene to control <cell_type>thymocyte</cell_type> differentiation , <protein>T cell factor-1</protein> ( <protein>TCF-1</protein> ) * encodes a <protein>DNA-binding protein</protein> .


Its mRNA expression pattern is complex during embryogenesis , yet restricted to lymphocytes postnatally .

Its mRNA expression pattern is complex during embryogenesis , yet restricted to <cell_type>lymphocytes</cell_type> postnatally .


Expression studies on TCF-1 protein have been hampered by the difficulty to raise antibodies due to extreme evolutionary conservation .

Expression studies on <protein>TCF-1 protein</protein> have been hampered by the difficulty to raise <protein>antibodies</protein> due to extreme evolutionary conservation .


TCF-1 knock-out mice , generated recently in our laboratory , have strongly decreased numbers of thymocytes , but are otherwise normal .

<protein>TCF-1</protein> knock-out mice , generated recently in our laboratory , have strongly decreased numbers of <cell_type>thymocytes</cell_type> , but are otherwise normal .


We have used these mice to generate anti-TCF-1 antibodies .

We have used these mice to generate <protein>anti-TCF-1 antibodies</protein> .


By immunization with a recombinant fusion protein , we show that TCF-1 knock-out mice readily yield antiserum titers against human and mouse TCF-1 protein .

By immunization with a <protein>recombinant fusion protein</protein> , we show that <protein>TCF-1</protein> knock-out mice readily yield antiserum titers against human and mouse TCF-1 protein .


Wild-type littermates remain unresponsive to TCF-1 while they mount a high-titer antibody response to the fusion protein , Maltose Binding Protein ( MBP ) .

Wild-type littermates remain unresponsive to <protein>TCF-1</protein> while they mount a high-titer antibody response to the <protein>fusion protein</protein> , <protein>Maltose Binding Protein</protein> ( <protein>MBP</protein> ) .


Subsequently , TCF-1-specific hybridomas could be prepared from the spleens of immunized knock-out mice .

Subsequently , <cell_line>TCF-1-specific hybridomas</cell_line> could be prepared from the spleens of immunized knock-out mice .


This study illustrates the almost complete tolerance of mice for human TCF-1 and demonstrates that this tolerance is readily broken by gene knock-out .

This study illustrates the almost complete tolerance of mice for <protein>human TCF-1</protein> and demonstrates that this tolerance is readily broken by gene knock-out .


Furthermore , the usefulness of knock-out mice for the generation of monoclonal antibodies against the gene product of interest is underscored .

Furthermore , the usefulness of knock-out mice for the generation of <protein>monoclonal antibodies</protein> against the gene product of interest is underscored .


The transcription factor , Nm23H2 , binds to and activates the translocated c-myc allele in Burkitt 's lymphoma .

The <protein>transcription factor</protein> , <protein>Nm23H2</protein> , binds to and activates the translocated <dna>c-myc allele</dna> in Burkitt 's lymphoma .


We have identified an in vivo footprint over the PuF site on the translocated c-myc allele in Burkitt 's lymphoma cells .

We have identified an in vivo footprint over the <dna>PuF site</dna> on the translocated <dna>c-myc allele</dna> in Burkitt 's lymphoma cells .


The PuF site on the silent normal c-myc allele was unoccupied .

The <dna>PuF site</dna> on the <dna>silent normal c-myc allele</dna> was unoccupied .


We demonstrated by electrophoretic mobility shift assay , electrophoretic mobility shift assay with antibody , UV cross-linking followed by SDS-gel electrophoresis , and Western analysis that Nm23H2 in B cell nuclear extracts bound to the c-myc PuF site .

We demonstrated by electrophoretic mobility shift assay , electrophoretic mobility shift assay with antibody , UV cross-linking followed by SDS-gel electrophoresis , and Western analysis that <protein>Nm23H2</protein> in B cell nuclear extracts bound to the c-myc <dna>PuF site</dna> .


Transfection experiments with c-myc promoter constructs in both DHL-9 and Raji cells revealed that the PuF site functioned as a positive regulatory element in B cells with a drop in activity with mutation of this site .

Transfection experiments with <dna>c-myc promoter constructs</dna> in both <cell_line>DHL-9</cell_line> and <cell_line>Raji cells</cell_line> revealed that the <dna>PuF site</dna> functioned as a <dna>positive regulatory element</dna> in <cell_type>B cells</cell_type> with a drop in activity with mutation of this site .


Access to this site is blocked in the normal silent c-myc allele ; these data suggest that the Nm23H2 protein is involved in deregulation of the translocated c-myc allele in Burkitt 's lymphoma cells .

Access to this site is blocked in the <dna>normal silent c-myc allele</dna> ; these data suggest that the <protein>Nm23H2</protein> protein is involved in deregulation of the translocated <dna>c-myc allele</dna> in <cell_line>Burkitt 's lymphoma cells</cell_line> .


Identification of two novel regulatory elements within the 5'-untranslated region of the human A gamma-globin gene .

Identification of two novel <dna>regulatory elements</dna> within the <dna>5'-untranslated region</dna> of the <dna>human A gamma-globin gene</dna> .


Interaction between the stage selector element ( SSE ) in the proximal gamma-globin promoter and hypersensitivity site 2 in the locus control region partly mediates the competitive silencing of the beta-globin promoter in the fetal developmental stage .

Interaction between the <dna>stage selector element</dna> ( SSE ) in the <dna>proximal gamma-globin promoter</dna> and <dna>hypersensitivity site 2</dna> in the <dna>locus control region</dna> partly mediates the competitive silencing of the <dna>beta-globin promoter</dna> in the fetal developmental stage .


We have now demonstrated that a second SSE-like element in the 5'-untranslated region of the gamma-gene also contributes to this competitive silencing of the beta-gene .

We have now demonstrated that a second <dna>SSE-like element</dna> in the <dna>5'-untranslated region</dna> of the <dna>gamma-gene</dna> also contributes to this competitive silencing of the <dna>beta-gene</dna> .


Utilizing transient transfection assays in the fetal erythroid cell line , K562 , we have shown that the core enhancer of hypersensitivity site 2 can preferentially interact with the proximal gamma-promoter in the absence of the SSE , completely silencing a linked beta-promoter .

Utilizing transient transfection assays in the <cell_line>fetal erythroid cell line</cell_line> , <cell_line>K562</cell_line> , we have shown that the <dna>core enhancer</dna> of <dna>hypersensitivity site 2</dna> can preferentially interact with the <dna>proximal gamma-promoter</dna> in the absence of the <dna>SSE</dna> , completely silencing a <dna>linked beta-promoter</dna> .


Mutation of a 20-base pair sequence of the gamma-gene 5'-untranslated region ( UTR ) led to derepression of beta-promoter activity .

Mutation of a 20-base pair sequence of the <dna>gamma-gene 5'-untranslated region</dna> ( <dna>UTR</dna> ) led to derepression of <dna>beta-promoter</dna> activity .


A marked activation of gamma-promoter activity was also observed with this mutation , suggesting the presence of a repressor .

A marked activation of <dna>gamma-promoter</dna> activity was also observed with this mutation , suggesting the presence of a repressor .


Fine mutagenesis dissected these activities to different regions of the 5'-UTR .

Fine mutagenesis dissected these activities to different regions of the <dna>5'-UTR</dna> .


The stage selector activity was localized to a region centered on nucleotides +13 to +15 .

The stage selector activity was localized to a region centered on <dna>nucleotides +13 to +15</dna> .


Electromobility shift assays utilizing this sequence demonstrated binding of a fetal and erythroid-specific protein .

Electromobility shift assays utilizing this sequence demonstrated binding of a <protein>fetal and erythroid-specific protein</protein> .


The repressor activity of the 5'-UTR was localized to tandem GATA-like sites , which appear to bind a complex of two proteins , one of which is the erythroid transcription factor GATA-1 .

The repressor activity of the <dna>5'-UTR</dna> was localized to tandem <dna>GATA-like sites</dna> , which appear to bind a complex of two proteins , one of which is the <protein>erythroid transcription factor</protein> <protein>GATA-1</protein> .


These results indicate that the 5'-UTR of the gamma-gene contains sequences that may be important for its transcriptional and developmental regulation .

These results indicate that the <dna>5'-UTR</dna> of the <dna>gamma-gene</dna> contains sequences that may be important for its transcriptional and developmental regulation .


Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation .

Coupling of a <protein>signal response domain</protein> in <protein>I kappa B alpha</protein> to multiple pathways for <protein>NF-kappa B</protein> activation .


The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth .

The <protein>eukaryotic transcription factor</protein> <protein>NF-kappa B</protein> plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth .


The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha .

The nuclear activity of <protein>NF-kappa B</protein> is tightly regulated from the cytoplasmic compartment by an <protein>inhibitory subunit</protein> called <protein>I kappa B alpha</protein> .


This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents , including T-cell mitogens , proinflammatory cytokines , and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1 .

This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of <protein>NF-kappa B-inducing agents</protein> , including <protein>T-cell mitogens ,</protein> <protein>proinflammatory cytokines</protein> , and <protein>viral transactivators</protein> such as the <protein>Tax protein</protein> of human T-cell leukemia virus type 1 .


To explore these I kappa B alpha -dependent mechanisms for NF-kappa B induction , we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes .

To explore these <protein>I kappa B alpha</protein> -dependent mechanisms for <protein>NF-kappa B</protein> induction , we identified novel mutants of <protein>I kappa B alpha</protein> that uncouple its inhibitory and signal-transducing functions in <cell_type>human T lymphocytes</cell_type> .


Specifically , removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm .

Specifically , removal of the <protein>N-terminal 36 amino acids</protein> of <protein>I kappa B alpha</protein> failed to disrupt its ability to form latent complexes with <protein>NF-kappa B</protein> in the cytoplasm .


However , this deletion mutation prevented the induced phosphorylation , degradative loss , and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells .

However , this deletion mutation prevented the induced phosphorylation , degradative loss , and functional release of <protein>I kappa B alpha</protein> from <protein>NF-kappa B</protein> in <cell_line>Tax-expressing cells</cell_line> .


Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax -induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction , including those initiated from antigen and cytokine receptors .

Alanine substitutions introduced at two serine residues positioned within this <protein>N-terminal regulatory region</protein> of <protein>I kappa B alpha</protein> also yielded constitutive repressors that escaped from <protein>Tax</protein> -induced turnover and that potently inhibited immune activation pathways for <protein>NF-kappa B</protein> induction , including those initiated from <protein>antigen and cytokine receptors</protein> .


In contrast , introduction of a phosphoserine mimetic at these sites rectified this functional defect , a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor .

In contrast , introduction of a phosphoserine mimetic at these sites rectified this functional defect , a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this <protein>cytoplasmic inhibitor</protein> .


Together , these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli .

Together , these in vivo studies define a critical signal response domain in <protein>I kappa B alpha</protein> that coordinately controls the biologic activities of <protein>I kappa B alpha</protein> and <protein>NF-kappa B</protein> in response to viral and immune stimuli .


Growth regulation and cellular changes during differentiation of human prostatic cancer LNCaP cells as induced by T lymphocyte-conditioned medium .

Growth regulation and cellular changes during differentiation of <cell_line>human prostatic cancer LNCaP cells</cell_line> as induced by T lymphocyte-conditioned medium .


Human prostatic epithelial cells from an androgen-dependent LNCaP cell line were examined in response to conditioned medium ( CM ) derived from phytohemagglutinin ( PHA ) -stimulated lymphocytes .

<cell_line>Human prostatic epithelial cells</cell_line> from an <cell_line>androgen-dependent LNCaP cell line</cell_line> were examined in response to conditioned medium ( CM ) derived from <cell_line>phytohemagglutinin ( PHA ) -stimulated lymphocytes</cell_line> .


Addition of CM caused a greater than 70 % reduction of cell proliferation by cell counting and cell cycle .


These cells showed G1 phase arrest and the clonogenicity was reduced .


The growth-modulating effect was dose-dependent and not due to cell lysis or apoptosis .


The binding of androgen to androgen receptor on these cells showed approximately 50 % reduction , underlining a proliferation reduction mechanism .

The binding of androgen to <protein>androgen receptor</protein> on these cells showed approximately 50 % reduction , underlining a proliferation reduction mechanism .


The prostate-specific antigen ( PSA ) was downregulated to approximately 75 % during the process .

The <protein>prostate-specific antigen</protein> ( <protein>PSA</protein> ) was downregulated to approximately 75 % during the process .


Cell morphology showed dendritic processes extending from cytoplasm and other neuroendocrine cell characteristics .

Cell morphology showed dendritic processes extending from cytoplasm and other <cell_type>neuroendocrine cell</cell_type> characteristics .


The expression of several cytoskeleton and intracellular proteins increased as determined by immunostaining on slides and by ELISA procedures .

The expression of several <protein>cytoskeleton and intracellular proteins</protein> increased as determined by immunostaining on slides and by ELISA procedures .


These included vimentin , correlating to cell shape changes , cytokeratins 8 and 18 , associated with differentiated cell types of prostate epithelia , and neuron-specific enolase and serotonin , associated with neuroendocrine cells .

These included <protein>vimentin</protein> , correlating to cell shape changes , <protein>cytokeratins 8 and 18</protein> , associated with <cell_type>differentiated cell types</cell_type> of prostate epithelia , and <protein>neuron-specific enolase</protein> and serotonin , associated with <cell_type>neuroendocrine cells</cell_type> .


From these cellular changes , we can infer that the cell growth was modulated along with induction of terminal differentiation .


Activated T cells were demonstrated to be important in providing the modulating activity .

Activated <cell_type>T cells</cell_type> were demonstrated to be important in providing the modulating activity .


This growth modulator was semipurified and had an estimated molecular weight 13 , 000 to 24 , 000 Da .

This <protein>growth modulator</protein> was semipurified and had an estimated molecular weight 13 , 000 to 24 , 000 Da .


The activity was determined to be distinct from TGF , TNF , and some commonly known lymphokines .

The activity was determined to be distinct from <protein>TGF</protein> , <protein>TNF</protein> , and some commonly known <protein>lymphokines</protein> .


The interaction between lymphoid and prostatic cells in growth and development is described .

The interaction between <cell_type>lymphoid and prostatic cells</cell_type> in growth and development is described .


Platelet-activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes .

<protein>Platelet-activating factor</protein> stimulates transcription of the <protein>heparin-binding epidermal growth factor-like growth factor</protein> in <cell_type>monocytes</cell_type> .


Correlation with an increased kappa B binding activity .


Human peripheral blood monocytes responded to stimulation of platelet-activating factor ( PAF ) with up-regulation of the transcript for heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) , a potent mitogen for vascular smooth muscle cells .

Human peripheral blood <cell_type>monocytes</cell_type> responded to stimulation of <protein>platelet-activating factor</protein> ( <protein>PAF</protein> ) with up-regulation of the transcript for <protein>heparin-binding epidermal growth factor-like growth factor</protein> ( <protein>HB-EGF</protein> ) , a <protein>potent mitogen</protein> for <cell_type>vascular smooth muscle cells</cell_type> .


This function of PAF was observed at nanomolar concentrations of the ligand , starting at 30 min after stimulation .

This function of <protein>PAF</protein> was observed at nanomolar concentrations of the ligand , starting at 30 min after stimulation .


The PAF -induced up-regulation of HB-EGF mRNA was accompanied by an increase in kappa B binding activity .

The <protein>PAF</protein> -induced up-regulation of <rna>HB-EGF mRNA</rna> was accompanied by an increase in kappa B binding activity .


These functions of PAF appeared to be mediated through the cell surface PAF receptors , as two PAF receptor antagonists , WEB 2086 and L-659 , 989 , blocked both the up-regulation of HB-EGF mRNA and kappa B binding activity induced by PAF .

These functions of <protein>PAF</protein> appeared to be mediated through the <protein>cell surface PAF receptors</protein> , as two <protein>PAF</protein> receptor antagonists , WEB 2086 and L-659 , 989 , blocked both the up-regulation of <rna>HB-EGF mRNA</rna> and kappa B binding activity induced by <protein>PAF</protein> .


The antagonists , however , had no effect on phorbol ester-induced up-regulation of HB-EGF mRNA and kappa B binding activity .

The antagonists , however , had no effect on phorbol ester-induced up-regulation of <rna>HB-EGF mRNA</rna> and kappa B binding activity .


Pretreatment of monocytes with pertussis toxin inhibited these functions of PAF , whereas cholera toxin had no inhibitory effect .

Pretreatment of <cell_type>monocytes</cell_type> with pertussis toxin inhibited these functions of <protein>PAF</protein> , whereas cholera toxin had no inhibitory effect .


Pyrrolidine dithiocarbamate , an inhibitor for NF-kappa B activation , markedly reduced PAF -stimulated kappa B binding activity as well as up-regulation of HB-EGF mRNA .

Pyrrolidine dithiocarbamate , an inhibitor for <protein>NF-kappa B</protein> activation , markedly reduced <protein>PAF</protein> -stimulated kappa B binding activity as well as up-regulation of <rna>HB-EGF mRNA</rna> .


These results suggest a potential role of PAF in HB-EGF expression and provide evidence that this stimulation may occur through increased kappa B binding activity .

These results suggest a potential role of <protein>PAF</protein> in <protein>HB-EGF</protein> expression and provide evidence that this stimulation may occur through increased kappa B binding activity .


Mapping of the interaction site of the defective transcription factor in the class II major histocompatibility complex mutant cell line clone-13 to the divergent X2-box .

Mapping of the <protein>interaction site</protein> of the <protein>defective transcription factor</protein> in the <cell_line>class II major histocompatibility complex mutant cell line clone-13</cell_line> to the <dna>divergent X2-box</dna> .


We have previously described a mutant B lymphoblastoid cell line , Clone-13 , that expresses HLA-DQ in the absence of HLA-DR and -DP .

We have previously described a <cell_line>mutant B lymphoblastoid cell line</cell_line> , <cell_line>Clone-13 ,</cell_line> that expresses <protein>HLA-DQ</protein> in the absence of <protein>HLA-DR and -DP</protein> .


Several criteria indicated that the defect in this cell line influences the activity of an isotype-specific transcription factor .

Several criteria indicated that the defect in this cell line influences the activity of an <protein>isotype-specific transcription factor</protein> .


Indeed , transient transfection of HLA-DRA and DQB reporter constructs indicated that the affected factor operates via cis-elements located between -141 base pairs and the transcription initiation site .

Indeed , transient transfection of <dna>HLA-DRA and DQB reporter constructs</dna> indicated that the affected factor operates via <dna>cis-elements</dna> located between <dna>-141 base pairs</dna> and the <dna>transcription initiation site</dna> .


A series of hybrid DRA/DQB reporter constructs was generated to further map the relevant cis-elements in this system .

A series of <dna>hybrid DRA/DQB reporter constructs</dna> was generated to further map the relevant <dna>cis-elements</dna> in this system .


Insertion of oligonucleotides spanning the DQB X-box ( but not the DQB-W region or the DQB Y-box ) upstream of -141 in a DRA reporter plasmid rescued expression to nearly wild-type levels .

Insertion of oligonucleotides spanning the <dna>DQB X-box</dna> ( but not the <dna>DQB-W region</dna> or the <dna>DQB Y-box</dna> ) <dna>upstream of -141</dna> in a <dna>DRA reporter plasmid</dna> rescued expression to nearly wild-type levels .


Substitution promoters were then generated where the entire X-box , or only the X1- or X2-boxes of HLA-DRA were replaced with the analogous regions of HLA-DQB .

Substitution promoters were then generated where the entire <dna>X-box</dna> , or only the <dna>X1- or X2-boxes</dna> of <dna>HLA-DRA</dna> were replaced with the analogous regions of <dna>HLA-DQB</dna> .


The DQB X2-box was able to restore expression to the silent DRA reporter construct .

The <dna>DQB X2-box</dna> was able to restore expression to the <dna>silent DRA reporter construct</dna> .


Moreover , replacement of the DQB X2-box with the DRA X2-box markedly diminished the activity of the DQB promoter in the mutant cell .

Moreover , replacement of the <dna>DQB X2-box</dna> with the <dna>DRA X2-box</dna> markedly diminished the activity of the <dna>DQB promoter</dna> in the <cell_line>mutant cell</cell_line> .


of the hybrid reporter constructs were defective when transfected into the wild-type , HLA-DR/-DQ positive parental cell line , Jijoye .

of the <dna>hybrid reporter constructs</dna> were defective when transfected into the <protein>wild-type</protein> , <cell_line>HLA-DR/-DQ positive parental cell line</cell_line> , <cell_line>Jijoye</cell_line> .


These studies suggest that the divergent X2-box of the class II major histocompatibility complex promoters plays an important role in influencing differential expression of the human class II isotypes .

These studies suggest that the <dna>divergent X2-box</dna> of the <dna>class II major histocompatibility complex promoters</dna> plays an important role in influencing differential expression of the <dna>human class II isotypes</dna> .


Restoration of the Epstein-Barr virus ZEBRA protein 's capacity to disrupt latency by the addition of heterologous activation regions .

Restoration of the <protein>Epstein-Barr virus ZEBRA protein</protein> 's capacity to disrupt latency by the addition of <protein>heterologous activation regions</protein> .


The ZEBRA protein has a unique biological function among herpesviral proteins .

The <protein>ZEBRA protein</protein> has a unique biological function among <protein>herpesviral proteins</protein> .


It is responsible for the disruption of Epstein-Barr virus ( EBV ) latency and the induction of the lytic cycle .


ZEBRA is a bZIP transcriptional activator which binds as a dimer to 7-bp response elements within EBV promoters and is directly involved in the stimulation of virus replication at the EBV lytic origin .

<protein>ZEBRA</protein> is a <protein>bZIP transcriptional activator</protein> which binds as a dimer to <dna>7-bp response elements</dna> within <dna>EBV promoters</dna> and is directly involved in the stimulation of virus replication at the <dna>EBV lytic origin</dna> .


We have employed the ZEBRA /EBV biological system to test whether a heterologous activation domain can substitute for another activation domain ( the ZEBRA domain ) .

We have employed the <protein>ZEBRA</protein> /EBV biological system to test whether a <protein>heterologous activation domain</protein> can substitute for another activation domain ( the <protein>ZEBRA domain</protein> ) .


The ZEBRA activation region was replaced with the potent acid activation region from the herpes simplex virus VP16 protein or with the activation region of the EBV R protein .

The <protein>ZEBRA activation region</protein> was replaced with the potent <protein>acid activation region</protein> from the <protein>herpes simplex virus VP16 protein</protein> or with the <protein>activation region</protein> of the <protein>EBV R protein</protein> .


Both chimeras were found to transactivate model and native promoters at equivalent or better levels than ZEBRA itself .

Both chimeras were found to transactivate model and native promoters at equivalent or better levels than <protein>ZEBRA</protein> itself .


Activation was not target- or cell-type dependent , nor was it dependent on the presence of virus .


These activation domains restored ZEBRA 's ability to induce early antigen and to stimulate origin replication to levels that were equal to or greater than those of wild type .

These activation domains restored <protein>ZEBRA</protein> 's ability to induce <protein>early antigen</protein> and to stimulate origin replication to levels that were equal to or greater than those of wild type .


These studies suggest that the specificities of some of the known biological functions of ZEBRA are not dependent upon the nature of the activation domain present within ZEBRA .

These studies suggest that the specificities of some of the known biological functions of <protein>ZEBRA</protein> are not dependent upon the nature of the <protein>activation domain present</protein> within <protein>ZEBRA</protein> .


Interleukin 4 activates a signal transducer and activator of transcription ( Stat ) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line .

<protein>Interleukin 4</protein> activates a signal transducer and activator of <protein>transcription ( Stat ) protein</protein> which interacts with an <dna>interferon-gamma activation site-like sequence</dna> upstream of the <dna>I epsilon exon</dna> in a <cell_line>human B cell line</cell_line> .


Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat .

Evidence for the involvement of <protein>Janus kinase 3</protein> and <protein>interleukin-4 Stat</protein> .


Germ line C transcripts can be induced by IL-4 in the human B cell line , BL-2 .

<rna>Germ line C transcripts</rna> can be induced by <protein>IL-4</protein> in the <cell_line>human B cell line</cell_line> , <cell_line>BL-2</cell_line> .


Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon , we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells .

Utilizing a <dna>IFN-gamma activation site-like DNA sequence element</dna> located upstream of the <dna>I epsilon exon</dna> , we demonstrated by gel mobility shift assays that <protein>IL-4</protein> induced a binding activity in the cytosol and nucleus of <cell_line>BL-2 cells</cell_line> .


This factor was designated IL-4 NAF ( IL-4-induced nuclear-activating factors ) and was identified as a tyrosine phosphoprotein , which translocates from the cytosol to the nucleus upon IL-4 treatment .

This factor was designated <protein>IL-4 NAF</protein> ( <protein>IL-4-induced nuclear-activating factors</protein> ) and was identified as a <protein>tyrosine phosphoprotein</protein> , which translocates from the cytosol to the nucleus upon <protein>IL-4</protein> treatment .


Because these are the characteristics of a signal transducer and activator of transcription ( Stat ) protein , we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat , also known as Stat6 , but not antibodies to other Stat proteins , interfere with the formation of the IL-4 NAF complex .

Because these are the characteristics of a <protein>signal transducer and activator of transcription ( Stat ) protein</protein> , we determined whether <protein>antibodies to Stat proteins</protein> will interfere with gel mobility shift and found that <protein>antibodies to IL-4 Stat</protein> , also known as <protein>Stat6</protein> , but not <protein>antibodies</protein> to other <protein>Stat proteins</protein> , interfere with the formation of the <protein>IL-4 NAF complex</protein> .


Congruous with the involvement of a Stat protein , IL-4 induced robust Janus kinase 3 ( JAK3 ) activity in BL-2 cells .

Congruous with the involvement of a <protein>Stat protein</protein> , <protein>IL-4</protein> induced robust <protein>Janus kinase 3</protein> ( <protein>JAK3</protein> ) activity in <cell_line>BL-2 cells</cell_line> .


Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay .

Cotransfection of <protein>JAK3</protein> with <protein>IL-4 Stat</protein> into <cell_line>COS-7 cells</cell_line> produced an intracellular activity which bound the same <dna>IFN-gamma activation site-like sequence</dna> and comigrated with <protein>IL-4 NAF</protein> in electrophoretic mobility shift assay .


These results show that IL-4 NAF is IL-4 Stat , which is activated by JAK3 in response to IL-4 receptor engagement .

These results show that <protein>IL-4 NAF</protein> is <protein>IL-4 Stat</protein> , which is activated by <protein>JAK3</protein> in response to <protein>IL-4</protein> receptor engagement .


Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia ? A pediatric oncology group study .

Does activation of the <dna>TAL1 gene</dna> occur in a majority of patients with T-cell acute lymphoblastic leukemia ? A pediatric oncology group study .


Almost 25 % of patients with T-cell acute lymphoblastic leukemia ( T-ALL ) have tumor-specific rearrangements of the TAL1 gene .

Almost 25 % of patients with T-cell acute lymphoblastic leukemia ( T-ALL ) have tumor-specific rearrangements of the <dna>TAL1 gene</dna> .


Although TAL1 expression has not been observed in normal lymphocytes , TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele .

Although <protein>TAL1</protein> expression has not been observed in <cell_type>normal lymphocytes</cell_type> , <protein>TAL1 gene products</protein> are readily detected in <cell_type>leukemic cells</cell_type> that harbor a <dna>rearranged TAL1 allele</dna> .


Hence , it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL .

Hence , it has been proposed that ectopic expression of <protein>TAL1</protein> promotes the development of T-ALL .


In this report , we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL , including many that do not display an apparent TAL1 gene alteration .

In this report , we show that <protein>TAL1</protein> is expressed in the <cell_type>leukemic cells</cell_type> of most patients with T-ALL , including many that do not display an apparent <dna>TAL1 gene</dna> alteration .


A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells .

A polymorphic dinucleotide repeat in the transcribed sequences of <protein>TAL1</protein> was used to determine the allele specificity of <protein>TAL1</protein> transcription in <cell_type>primary T-ALL cells</cell_type> .


Monoallelic expression of TAL1 was observed in the leukemic cells of all patients ( 8 of 8 ) bearing a TAL1 gene rearrangement .

Monoallelic expression of <protein>TAL1</protein> was observed in the <cell_type>leukemic cells</cell_type> of all patients ( 8 of 8 ) bearing a <dna>TAL1 gene</dna> rearrangement .


In the leukemic cells of patients without detectable TAL1 rearrangements , TAL1 transcription occurred in either a monoallelic ( 3 of 7 patients ) or a biallelic ( 4 of 7 patients ) fashion .

In the <cell_type>leukemic cells</cell_type> of patients without detectable <protein>TAL1</protein> rearrangements , <protein>TAL1</protein> transcription occurred in either a monoallelic ( 3 of 7 patients ) or a biallelic ( 4 of 7 patients ) fashion .


Thus , TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences ( affecting expression of a single TAL1 allele ) or changes in trans-acting factors that control TAL1 transcription ( affecting expression of both TAL1 alleles ) .

Thus , <protein>TAL1</protein> activation in these patients may result from subtle alterations in <dna>cis-acting regulatory sequences</dna> ( affecting expression of a <dna>single TAL1 allele</dna> ) or changes in trans-acting factors that control <protein>TAL1</protein> transcription ( affecting expression of both <dna>TAL1 alleles</dna> ) .


Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down 's syndrome .

Expression of <dna>erythroid-specific genes</dna> in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down 's syndrome .


Acute megakaryoblastic leukaemia ( M7 ) and transient myeloproliferative disorder in Down 's syndrome ( TMD ) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers .

Acute megakaryoblastic leukaemia ( M7 ) and transient myeloproliferative disorder in Down 's syndrome ( TMD ) are characterized by rapid growth of <cell_type>abnormal blast cells</cell_type> which express <protein>megakaryocytic markers</protein> .


To clarify properties of the blast cells in M7 and TMD cases , we examined erythroid markers expression in blasts from six cases with M7 and seven cases with TMD in this study .

To clarify properties of the <cell_type>blast cells</cell_type> in M7 and TMD cases , we examined erythroid markers expression in <cell_type>blasts</cell_type> from six cases with M7 and seven cases with TMD in this study .


Erythroid-specific mRNAs encoding gamma-globin and erythroid delta-aminolevulinate synthase were found to be expressed in blasts from most of these cases , indicating that majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes .

<rna>Erythroid-specific mRNAs</rna> encoding <protein>gamma-globin</protein> and <protein>erythroid delta-aminolevulinate synthase</protein> were found to be expressed in <cell_type>blasts</cell_type> from most of these cases , indicating that majorities of the <cell_type>blasts</cell_type> in M7 and TMD cases have erythroid and megakaryocytic phenotypes .


We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in all these cases .

We also found that <rna>mRNAs</rna> encoding <protein>GATA-1</protein> and <protein>GATA-2</protein> are expressed in all these cases .


These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells .

These results suggest that <cell_type>M7 blasts</cell_type> and <cell_type>TMD blasts</cell_type> correspond to the <cell_type>erythroid/megakaryocytic bipotential progenitor cells</cell_type> .


Expression of Ah receptor ( TCDD receptor ) during human monocytic differentiation .

Expression of <protein>Ah receptor</protein> ( <protein>TCDD receptor</protein> ) during human monocytic differentiation .


We have previously found a high expression of human Ah receptor ( TCDD receptor ) mRNA in peripheral blood cells of individuals .

We have previously found a high expression of <rna>human Ah receptor ( TCDD receptor ) mRNA</rna> in <cell_type>peripheral blood cells</cell_type> of individuals .


In this paper , the expression of this gene in blood cells was first investigated in fractions of nucleated cells , revealing predominant expression of the Ah receptor gene in the monocyte fraction .

In this paper , the expression of this gene in <cell_type>blood cells</cell_type> was first investigated in fractions of <cell_type>nucleated cells</cell_type> , revealing predominant expression of the <dna>Ah receptor gene</dna> in the <cell_type>monocyte fraction</cell_type> .


Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1 .

Then the expression levels of <rna>AhR mRNA</rna> in various <cell_line>hematopoietic cell lines</cell_line> were examined together with those of <protein>Arnt</protein> and <protein>P450IA1</protein> .


AhR was expressed at high levels in monocytoid U937 , THP1 , and HEL/S cells , and at moderate levels in promyelocytic HL60 cells and erythroblastic HEL cells .

<protein>AhR</protein> was expressed at high levels in <cell_line>monocytoid U937</cell_line> , <cell_line>THP1</cell_line> , and <cell_line>HEL/S cells</cell_line> , and at moderate levels in <cell_line>promyelocytic HL60 cells</cell_line> and <cell_line>erythroblastic HEL cells</cell_line> .


However , it was not detected in lymphoid cells MOLT4 ( T cell ) and BALL1 ( B cell ) , nor in K562 erythroblasts .

However , it was not detected in <cell_type>lymphoid cells</cell_type> <cell_line>MOLT4</cell_line> ( <cell_type>T cell</cell_type> ) and <cell_line>BALL1</cell_line> ( <cell_type>B cell</cell_type> ) , nor in <cell_line>K562 erythroblasts</cell_line> .


Furthermore , a specific induction of AhR during monocytic differentiation was investigated in HL60 and HEL cells .

Furthermore , a specific induction of <protein>AhR</protein> during monocytic differentiation was investigated in <cell_line>HL60</cell_line> and <cell_line>HEL cells</cell_line> .


HL60 cells were induced to differentiate toward monocytes-macrophages by incubation with phorbol ester , showing a 5- to 2-fold increase of AhR mRNA .

<cell_line>HL60 cells</cell_line> were induced to differentiate toward <cell_type>monocytes-macrophages</cell_type> by incubation with phorbol ester , showing a 5- to 2-fold increase of <rna>AhR mRNA</rna> .


The incubation with transforming growth factor beta 1 and 1 alpha , 25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of AhR mRNA .

The incubation with <protein>transforming growth factor beta 1</protein> and 1 alpha , 25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of <rna>AhR mRNA</rna> .


The HEL cells also exhibited a similar elevation of AhR mRNA level , when they had differentiated toward monocyte-macrophage cells by these combined inducers , but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types .

The <cell_line>HEL cells</cell_line> also exhibited a similar elevation of <rna>AhR mRNA</rna> level , when they had differentiated toward <cell_type>monocyte-macrophage cells</cell_type> by these combined inducers , but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types .


Treatment of the differentiated HL60 cells with 3-methylcholanthrene , a ligand of AhR , induced the expression of the P450IA1 gene .

Treatment of the <cell_line>differentiated HL60 cells</cell_line> with 3-methylcholanthrene , a ligand of <protein>AhR</protein> , induced the expression of the <protein>P450IA1</protein> gene .


These results indicated that expression of AhR mRNA was significantly induced during monocytic differentiation and that the differentiated cells were responsive to xenobiotics .

These results indicated that expression of <rna>AhR mRNA</rna> was significantly induced during monocytic differentiation and that the <cell_type>differentiated cells</cell_type> were responsive to xenobiotics .


Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens .

Our results suggest that <protein>AhR</protein> may play an important role in the function of <cell_type>monocytes</cell_type> and also in the eventual activation of environmental carcinogens .


Neutrophils and monocytes express high levels of PU.1 ( Spi-1 ) but not Spi-B .

<cell_type>Neutrophils</cell_type> and <cell_type>monocytes</cell_type> express high levels of <protein>PU.1</protein> ( <protein>Spi-1</protein> ) but not <protein>Spi-B</protein> .


PU.1 ( the Spi-1 oncogene ) and Spi-B are closely related members of the ets transcription factor family , sharing similar DNA binding specificities mediated by similar DNA binding domains .

<protein>PU.1</protein> ( the <dna>Spi-1 oncogene</dna> ) and <protein>Spi-B</protein> are closely related members of the <protein>ets transcription factor family</protein> , sharing similar DNA binding specificities mediated by similar <protein>DNA binding domains</protein> .


PU.1 and Spi-B have been previously described as being predominantly expressed coordinately in macrophages and B cells , but their expression in early hematopoietic stages and during the course of myeloid differentiation to monocytes and macrophages or to neutrophils has not been extensively investigated .

<protein>PU.1</protein> and <protein>Spi-B</protein> have been previously described as being predominantly expressed coordinately in <cell_type>macrophages</cell_type> and <cell_type>B cells</cell_type> , but their expression in early hematopoietic stages and during the course of myeloid differentiation to <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> or to <cell_type>neutrophils</cell_type> has not been extensively investigated .


Here , we report that PU.1 mRNA is upregulated during myeloid differentiation of human purified CD34+ cells and murine multipotential FDCP-mix A4 cells , suggesting that PU.1 is upregulated as an early event during differentiation of multipotential progenitor cells .

Here , we report that <rna>PU.1 mRNA</rna> is upregulated during myeloid differentiation of <cell_line>human purified CD34+ cells</cell_line> and <cell_line>murine multipotential FDCP-mix A4 cells</cell_line> , suggesting that <protein>PU.1</protein> is upregulated as an early event during differentiation of <cell_type>multipotential progenitor cells</cell_type> .


PU.1 expression is maintained at stable levels during differentiation of myeloid cell lines U937 and HL-60 to monocytic and neutrophilic cells .

<protein>PU.1</protein> expression is maintained at stable levels during differentiation of <cell_line>myeloid cell lines</cell_line> <cell_line>U937</cell_line> and <cell_line>HL-60</cell_line> to <cell_type>monocytic and neutrophilic cells</cell_type> .


PU.1 is expressed at highest levels in mature human monocytes and human peripheral blood neutrophils .

<protein>PU.1</protein> is expressed at highest levels in <cell_type>mature human monocytes</cell_type> and <cell_type>human peripheral blood neutrophils</cell_type> .


In contrast to PU.1 , significant levels of Spi-B mRNA and protein are found only in some B-cell lines and spleen but are not found in myeloid cell lines , neutrophils , or macrophages .

In contrast to <protein>PU.1</protein> , significant levels of <rna>Spi-B mRNA</rna> and protein are found only in some <cell_line>B-cell lines</cell_line> and spleen but are not found in <cell_line>myeloid cell lines</cell_line> , <cell_type>neutrophils</cell_type> , or <cell_type>macrophages</cell_type> .


In vitro translated Spi-B protein can bind to PU.1 binding sites in myeloid promoters and transactivate these promoters in nonmyeloid cells .

In vitro translated <protein>Spi-B protein</protein> can bind to <dna>PU.1 binding sites</dna> in <dna>myeloid promoters</dna> and transactivate these <dna>promoters</dna> in <cell_type>nonmyeloid cells</cell_type> .


Therefore , although PU.1 and Spi-B may bind to similar DNA control elements and have redundancy of transactivation function in vitro , the lack of significant levels of Spi-B in myeloid cells makes it unlikely that Spi-B plays a significant role in myeloid lineage development and gene expression .

Therefore , although <protein>PU.1</protein> and <protein>Spi-B</protein> may bind to similar DNA control elements and have redundancy of transactivation function in vitro , the lack of significant levels of <protein>Spi-B</protein> in <cell_type>myeloid cells</cell_type> makes it unlikely that <protein>Spi-B</protein> plays a significant role in myeloid lineage development and gene expression .


In contrast , PU.1 is expressed at high levels not only in monocytes and macrophages but also in neutrophils , indicating that PU.1 can activate gene expression in both major myeloid lineages .

In contrast , <protein>PU.1</protein> is expressed at high levels not only in <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> but also in <cell_type>neutrophils</cell_type> , indicating that <protein>PU.1</protein> can activate gene expression in both <cell_type>major myeloid lineages</cell_type> .


Identification of a major positive regulatory element located 5 ' to the human zeta-globin gene .

Identification of a major <dna>positive regulatory element</dna> located 5 ' to the <dna>human zeta-globin gene</dna> .


The function of the zeta-globin promoter was studied using a series of zeta-globin promoter deletion constructs to drive luciferase expression in transiently transfected human erythroleukemia cells .

The function of the <dna>zeta-globin promoter</dna> was studied using a series of <dna>zeta-globin promoter deletion constructs</dna> to drive <protein>luciferase</protein> expression in <cell_line>transiently transfected human erythroleukemia cells</cell_line> .


The promoters were used without enhancers , or with enhancers derived from the beta-globin locus control region and the alpha-globin HS-40 enhancer .

The <dna>promoters</dna> were used without <dna>enhancers</dna> , or with <dna>enhancers</dna> derived from the <dna>beta-globin locus control region</dna> and the <dna>alpha-globin HS-40 enhancer</dna> .


When transfected into K562 cells , which express zeta-globin , comparable amounts of activity were obtained from the -557 and -417 zeta-luciferase constructs and the alpha-luciferase constructs when no enhancers or the alpha-globin locus enhancers were used .

When transfected into <cell_line>K562 cells</cell_line> , which express <protein>zeta-globin</protein> , comparable amounts of activity were obtained from the <dna>-557 and -417 zeta-luciferase constructs</dna> and the <dna>alpha-luciferase constructs</dna> when no <dna>enhancers</dna> or the <dna>alpha-globin locus enhancers</dna> were used .


When the constructs were transfected into OCIM1 cells , which do not express zeta-globin , the zeta-globin promoters were at best 20 % as active as the alpha-globin promoters .

When the constructs were transfected into <cell_line>OCIM1 cells</cell_line> , which do not express <protein>zeta-globin</protein> , the <dna>zeta-globin promoters</dna> were at best 20 % as active as the <dna>alpha-globin promoters</dna> .


When sequences from -417 to -207 5 ' to the zeta-globin mRNA cap site were deleted , up to 95 % of the zeta-globin promoter activity was lost in K562 cells .

When <dna>sequences from -417 to -207 5 '</dna> to the <rna>zeta-globin mRNA cap site</rna> were deleted , up to 95 % of the <dna>zeta-globin promoter</dna> activity was lost in <cell_line>K562 cells</cell_line> .


Reinsertion of these sequences into zeta-luciferase constructs missing the -417 to -207 region showed that the sequences lack classical enhancer activity .

Reinsertion of these sequences into <dna>zeta-luciferase constructs</dna> missing the -417 to -207 region showed that the sequences lack classical enhancer activity .


Point mutation of a GATA-1 site at -230 reduced promoter activity by 37 % .

Point mutation of a <dna>GATA-1 site</dna> at -230 reduced promoter activity by 37 % .


Point mutation of a CCACC site at -240 had no effect .

Point mutation of a <dna>CCACC site</dna> at -240 had no effect .


Electrophoretic mobility shift assays indicated that the -230 GATA-1 site has a relatively low affinity for GATA-1 .

Electrophoretic mobility shift assays indicated that the <dna>-230 GATA-1 site</dna> has a relatively low affinity for <protein>GATA-1</protein> .


These experiments show the presence of a strong positive-acting element , located between -417 and -207 bp 5 ' to the zeta-globin mRNA cap site , is necessary for high-level promoter activity in K562 cells .

These experiments show the presence of a strong <dna>positive-acting element</dna> , located between <dna>-417 and -207 bp 5 '</dna> to the <dna>zeta-globin mRNA cap site</dna> , is necessary for high-level promoter activity in <cell_line>K562 cells</cell_line> .


This element requires GATA-1 and additional unknown factors for maximal activity .

This element requires <protein>GATA-1</protein> and <protein>additional unknown factors</protein> for maximal activity .


Analysis of the role of protein kinase C-alpha , -epsilon , and -zeta in T cell activation .

Analysis of the role of <protein>protein kinase C-alpha , -epsilon , and -zeta</protein> in T cell activation .


T cells express multiple isotypes of protein kinase C ( PKC ) and although it is well accepted that PKCs have an important role in T cell activation , little is known about the function of individual PKC isotypes .

<cell_type>T cells</cell_type> express multiple isotypes of <protein>protein kinase C</protein> ( <protein>PKC</protein> ) and although it is well accepted that <protein>PKCs</protein> have an important role in T cell activation , little is known about the function of individual <protein>PKC isotypes</protein> .


To address this issue , mutationally active PKC-alpha , -epsilon , or -zeta have been transfected into T cells and the consequences for T cell activation determined .

To address this issue , mutationally active <protein>PKC-alpha , -epsilon , or -zeta</protein> have been transfected into <cell_type>T cells</cell_type> and the consequences for T cell activation determined .


p21ras plays an essential role in T cell activation .

<protein>p21ras</protein> plays an essential role in T cell activation .


Accordingly , the effects of the constitutively active PKCs were compared to the effects of mutationally activated p21ras .

Accordingly , the effects of the <protein>constitutively active PKCs</protein> were compared to the effects of mutationally activated <protein>p21ras</protein> .


The data indicate that PKC-epsilon and , to a lesser extent PKC-alpha but not -zeta , can regulate the transcription factors AP-1 and nuclear factor of activated T cells ( NF-AT-1 ) .

The data indicate that <protein>PKC-epsilon</protein> and , to a lesser extent <protein>PKC-alpha</protein> but not <protein>-zeta</protein> , can regulate the <protein>transcription factors</protein> <protein>AP-1</protein> and nuclear <protein>factor of activated T cells</protein> ( <protein>NF-AT-1</protein> ) .


The ability of PKC-epsilon to induce transactivation of NF-AT-1 and AP-1 was similar to the stimulatory effect of a constitutively activated p21ras .

The ability of <protein>PKC-epsilon</protein> to induce transactivation of <protein>NF-AT-1</protein> and <protein>AP-1</protein> was similar to the stimulatory effect of a <protein>constitutively activated p21ras</protein> .


PKC-epsilon , but not PKC-alpha nor activated p21ras , was able to induce NF-KB activity .

<protein>PKC-epsilon</protein> , but not <protein>PKC-alpha</protein> nor activated <protein>p21ras</protein> , was able to induce <protein>NF-KB</protein> activity .


Phorbol esters induce expression of CD69 whereas none of the activated PKC isotypes tested were able to have this effect .

Phorbol esters induce expression of <protein>CD69</protein> whereas none of the <protein>activated PKC isotypes</protein> tested were able to have this effect .


Activated Src and p21ras were able to induce CD69 expression .

Activated <protein>Src</protein> and <protein>p21ras</protein> were able to induce <protein>CD69</protein> expression .


These results indicate selective functions for different PKC isotypes in T cells .

These results indicate selective functions for different <protein>PKC isotypes</protein> in <cell_type>T cells</cell_type> .


Moreover , the data comparing the effects of activated Ras and PKC mutants suggest that PKC-alpha , p21ras , and PKC-epsilon are not positioned linearly on a single signal transduction pathway .

Moreover , the data comparing the effects of <protein>activated Ras</protein> and <protein>PKC mutants</protein> suggest that <protein>PKC-alpha</protein> , <protein>p21ras</protein> , and <protein>PKC-epsilon</protein> are not positioned linearly on a single signal transduction pathway .


Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma .

Differences in binding of <protein>glucocorticoid receptor</protein> to DNA in steroid-resistant asthma .


Although glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases , a small proportion of patients are resistant to their therapeutic effects .


The molecular mechanism for this steroid resistance is unclear .


Steroid resistance can not be explained by pharmacokinetic mechanisms , by a defect in the binding of steroids to glucocorticoid receptors , nor by defective nuclear translocation of this receptor , thereby suggesting that the molecular abnormality lies distal to nuclear translocation .

Steroid resistance can not be explained by pharmacokinetic mechanisms , by a defect in the binding of steroids to <protein>glucocorticoid receptors</protein> , nor by defective nuclear translocation of this receptor , thereby suggesting that the molecular abnormality lies distal to nuclear translocation .


We examined the ability of nuclear translocated glucocorticoid receptors to bind to their DNA binding sites ( GRE ) using electrophoretic mobility shift assays in PBMC from patients with steroid-sensitive and steroid-resistant asthma .

We examined the ability of nuclear translocated <protein>glucocorticoid receptors</protein> to bind to their <dna>DNA binding sites</dna> ( <dna>GRE</dna> ) using electrophoretic mobility shift assays in <cell_type>PBMC</cell_type> from patients with steroid-sensitive and steroid-resistant asthma .


The binding of the glucocorticoid receptor to DNA in these patients was also studied using Scatchard analysis .

The binding of the <protein>glucocorticoid receptor</protein> to DNA in these patients was also studied using Scatchard analysis .


Dexamethasone induced a significant rapid and sustained twofold increase in GRE binding in PBMCs from steroid-sensitive asthmatic patients and nonasthmatic individuals , but this was markedly reduced in steroid-resistant asthmatic patients .

Dexamethasone induced a significant rapid and sustained twofold increase in <dna>GRE</dna> binding in <cell_type>PBMCs</cell_type> from steroid-sensitive asthmatic patients and nonasthmatic individuals , but this was markedly reduced in steroid-resistant asthmatic patients .


Scatchard analysis of glucocorticoid receptor - GRE binding showed no change in binding affinity but did show a reduced number of receptors available for DNA binding in the steroid-resistant patients .

Scatchard analysis of <protein>glucocorticoid receptor</protein> - <dna>GRE</dna> binding showed no change in binding affinity but did show a reduced number of <protein>receptors</protein> available for DNA binding in the steroid-resistant patients .


These results suggest that the ability of the glucocorticoid receptor to bind to GRE is impaired in steroid-resistant patients because of a reduced number of receptors available for binding to DNA .

These results suggest that the ability of the <protein>glucocorticoid receptor</protein> to bind to <dna>GRE</dna> is impaired in steroid-resistant patients because of a reduced number of <protein>receptors</protein> available for binding to DNA .


Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1 alpha .

<protein>Interleukin-5</protein> signaling in <cell_type>human eosinophils</cell_type> involves <protein>JAK2 tyrosine kinase</protein> and <protein>Stat1 alpha</protein> .


Signaling by a wide variety of cytokines , including interferons , interleukins , and growth factors , involves activation of JAK kinases and Stat ( Signal transducers and activators of transcription ) proteins .

Signaling by a wide variety of <protein>cytokines</protein> , including <protein>interferons</protein> , <protein>interleukins</protein> , and <protein>growth factors</protein> , involves activation of <protein>JAK kinases</protein> and <protein>Stat ( Signal transducers and activators of transcription ) proteins</protein> .


At present , not much is known about the molecular mechanisms by which interleukin-5 ( IL-5 ) exerts its diverse biologic effects .

At present , not much is known about the molecular mechanisms by which <protein>interleukin-5</protein> ( <protein>IL-5</protein> ) exerts its diverse biologic effects .


Human eosinophils are one of the most important target cells for IL-5 and were used here to study IL-5 signaling in a primary human cell .

<cell_type>Human eosinophils</cell_type> are one of the most important <cell_type>target cells</cell_type> for <protein>IL-5</protein> and were used here to study <protein>IL-5</protein> signaling in a <cell_type>primary human cell</cell_type> .


IL-5 induced rapid and transient tyrosine phosphorylation of JAK2 .

<protein>IL-5</protein> induced rapid and transient tyrosine phosphorylation of <protein>JAK2</protein> .


Moreover , IL-5 induced at least two DNA-binding complexes , using nuclear extracts from normal human eosinophils and the IL-6/interferon-gamma response element of the ICAM-1 promoter ( ICAM-1 pIRE ) in an electromobility shift assay .

Moreover , <protein>IL-5</protein> induced at least two <protein>DNA-binding complexes</protein> , using nuclear extracts from normal <cell_type>human eosinophils</cell_type> and the <dna>IL-6/interferon-gamma response element</dna> of the <dna>ICAM-1 promoter</dna> ( <dna>ICAM-1 pIRE</dna> ) in an electromobility shift assay .


From supershift experiments it was concluded that one DNA-binding complex contained Stat1 alpha , probably as a homodimer .

From supershift experiments it was concluded that one <protein>DNA-binding complex</protein> contained <protein>Stat1 alpha</protein> , probably as a homodimer .


Both DNA-binding complexes were inhibited by a phosphotyrosine antibody ( 4G10 ) , suggesting that tyrosine phosphorylation is required for complex formation .

Both <protein>DNA-binding complexes</protein> were inhibited by a <protein>phosphotyrosine antibody</protein> ( <protein>4G10</protein> ) , suggesting that tyrosine phosphorylation is required for complex formation .


IL-3 and granulocyte-macrophage colony-stimulating factor induced , similar to IL-5 , two DNA-binding complexes in human eosinophils , including Stat1 alpha .

<protein>IL-3</protein> and <protein>granulocyte-macrophage colony-stimulating factor</protein> induced , similar to <protein>IL-5</protein> , two <protein>DNA-binding complexes</protein> in <cell_type>human eosinophils</cell_type> , including <protein>Stat1 alpha</protein> .


These data show for the first time that molecular mechanisms of IL-5 signaling in human eosinophils involve members of the JAK kinase family as well as members of the Stat family .

These data show for the first time that molecular mechanisms of <protein>IL-5</protein> signaling in <cell_type>human eosinophils</cell_type> involve members of the <protein>JAK kinase family</protein> as well as members of the <protein>Stat family</protein> .


Infection and replication of Tat- human immunodeficiency viruses : genetic analyses of LTR and tat mutations in primary and long-term human lymphoid cells .

Infection and replication of Tat- human immunodeficiency viruses : genetic analyses of <dna>LTR</dna> and <protein>tat mutations</protein> in <cell_type>primary and long-term human lymphoid cells</cell_type> .


Tat is an essential regulatory protein for the replication of human immunodeficiency virus ( HIV ) .

<protein>Tat</protein> is an essential <protein>regulatory protein</protein> for the replication of human immunodeficiency virus ( HIV ) .


Mutations in the tat gene have been shown to block HIV replication in human T cells .

Mutations in the <dna>tat gene</dna> have been shown to block HIV replication in <cell_type>human T cells</cell_type> .


Several studies have established that Tat releases an elongation block to the transcription of HIV long terminal repeat ( LTR ) ; however , it is not known whether this mechanism alone is sufficient to explain the block to HIV replication in human T cells when Tat is absent .

Several studies have established that <protein>Tat</protein> releases an <protein>elongation block</protein> to the transcription of <dna>HIV long terminal repeat</dna> ( <dna>LTR</dna> ) ; however , it is not known whether this mechanism alone is sufficient to explain the block to HIV replication in <cell_type>human T cells</cell_type> when <protein>Tat</protein> is absent .


It is possible that Tat is also needed for other functions during HIV replication .

It is possible that <protein>Tat</protein> is also needed for other functions during HIV replication .


To test these hypotheses , we studied several tat mutants , including two stop codon mutants and one deletion mutant using replication-competent HIV-1 constructs carrying wild-type or mutant LTRs with modifications in the NF-kappa B and/or Sp1 binding sites .

To test these hypotheses , we studied several <protein>tat mutants</protein> , including two <protein>stop codon mutants</protein> and one <protein>deletion mutant</protein> using <dna>replication-competent HIV-1 constructs</dna> carrying <dna>wild-type or mutant LTRs</dna> with modifications in the <dna>NF-kappa B and/or Sp1 binding sites</dna> .


In this study , we show that Tat- HIV-1 with wild-type LTRs can replicate in HeLa cells , and the virus produced from HeLa cells can infect primary peripheral blood lymphocytes and macrophages .

In this study , we show that Tat- HIV-1 with <dna>wild-type LTRs</dna> can replicate in <cell_line>HeLa cells</cell_line> , and the virus produced from <cell_line>HeLa cells</cell_line> can infect primary <cell_type>peripheral blood lymphocytes</cell_type> and <cell_type>macrophages</cell_type> .


It was found that the propagation of the Tat mutants containing wild-type LTRs was less efficient than that of the LTR-modified Tat mutants .

It was found that the propagation of the <protein>Tat mutants</protein> containing <dna>wild-type LTRs</dna> was less efficient than that of the <protein>LTR-modified Tat mutants</protein> .


Large amounts of viral RNA and particles were synthesized in infections established using the tat mutants that contain modified LTRs .

Large amounts of <rna>viral RNA</rna> and particles were synthesized in infections established using the <protein>tat mutants</protein> that contain <dna>modified LTRs</dna> .


However , this efficient propagation of the LTR-modified tat mutants was restricted to some lymphoid cell lines that have been transformed with other viruses .

However , this efficient propagation of the <protein>LTR-modified tat mutants</protein> was restricted to some <cell_line>lymphoid cell lines</cell_line> that have been transformed with other viruses .


Thus , despite its essential role for releasing an elongation block , Tat is not otherwise absolutely required for synthesis of full-length HIV transcripts and assembly of virus particles .

Thus , despite its essential role for releasing an <protein>elongation block</protein> , <protein>Tat</protein> is not otherwise absolutely required for synthesis of <rna>full-length HIV transcripts</rna> and assembly of virus particles .


Direct sequencing of the viral genomes and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the Tat -virus .

Direct sequencing of the <dna>viral genomes</dna> and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the <protein>Tat</protein> -virus .


The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative Tat function are discussed .

The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative <protein>Tat</protein> function are discussed .


Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression .

Functional roles of the <protein>transcription factor Oct-2A</protein> and the <protein>high mobility group protein</protein> <protein>I/Y</protein> in <dna>HLA-DRA gene</dna> expression .


The class II major histocompatibility complex gene HLA-DRA is expressed in B cells , activated T lymphocytes , and in antigen-presenting cells .

The <dna>class II major histocompatibility complex gene</dna> <dna>HLA-DRA</dna> is expressed in <cell_type>B cells</cell_type> , activated <cell_type>T lymphocytes</cell_type> , and in <cell_type>antigen-presenting cells</cell_type> .


In addition , HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma ( IFN-gamma ) .

In addition , <dna>HLA-DRA gene</dna> expression is inducible in a variety of cell types by <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) .


Here we show that the lymphoid-specific transcription factor Oct-2A plays a critical role in HLA-DRA gene expression in class II-positive B cell lines , and that the high mobility group protein ( HMG ) I/Y binds to multiple sites within the DRA promoter , including the Oct-2A binding site .

Here we show that the <protein>lymphoid-specific transcription factor Oct-2A</protein> plays a critical role in <dna>HLA-DRA gene</dna> expression in <cell_line>class II-positive B cell lines</cell_line> , and that the <protein>high mobility group protein</protein> ( <protein>HMG</protein> ) <protein>I/Y</protein> binds to multiple sites within the <dna>DRA promoter</dna> , including the <dna>Oct-2A binding site</dna> .


Coexpression of HMG I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene expression , and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct-2A binding to the HLA-DRA promoter .

Coexpression of <protein>HMG I/Y</protein> and <protein>Oct-2</protein> in <cell_line>cell lines</cell_line> lacking <protein>Oct-2</protein> results in high levels of <dna>HLA-DRA gene</dna> expression , and in vitro DNA-binding studies reveal that HMG <protein>I/Y</protein> stimulates <protein>Oct-2A</protein> binding to the <dna>HLA-DRA promoter</dna> .


Thus , Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells .

Thus , <protein>Oct-2A</protein> and <protein>HMG I/Y</protein> may synergize to activate <dna>HLA-DRA</dna> expression in <cell_type>B cells</cell_type> .


By contrast , Oct-2A is not involved in the IFN-gamma induction of the HLA-DRA gene in HeLa cells , but antisense HMG I/Y dramatically decreases the level of induction .

By contrast , <protein>Oct-2A</protein> is not involved in the <protein>IFN-gamma</protein> induction of the <dna>HLA-DRA gene</dna> in <cell_line>HeLa cells</cell_line> , but <dna>antisense HMG I/Y</dna> dramatically decreases the level of induction .


We conclude that distinct sets of transcription factors are involved in the two modes of HLA-DRA expression , and that HMG I/Y may be important for B cell-specific expression , and is essential for IFN-gamma induction .

We conclude that distinct sets of <protein>transcription factors</protein> are involved in the two modes of <dna>HLA-DRA</dna> expression , and that <protein>HMG I/Y</protein> may be important for B cell-specific expression , and is essential for <protein>IFN-gamma</protein> induction .


Heterogeneous expression of Epstein-Barr virus latent proteins in endemic Burkitt 's lymphoma .

Heterogeneous expression of <protein>Epstein-Barr virus latent proteins</protein> in endemic Burkitt 's lymphoma .


Epstein-Barr virus ( EBV ) -infected cells may sustain three distinct forms of virus latency .

<cell_type>Epstein-Barr virus ( EBV ) -infected cells</cell_type> may sustain three distinct forms of virus latency .


In lymphoblastoid cell lines , six EBV-encoded nuclear antigens ( EBNA1 , 2 , 3A , 3B , 3C , -LP ) , three latent membrane proteins ( LMP1 , 2A , 2B ) , and two nuclear RNAs ( EBERs ) are expressed .

In <cell_line>lymphoblastoid cell lines</cell_line> , six <protein>EBV-encoded nuclear antigens</protein> ( <protein>EBNA1 , 2 , 3A , 3B , 3C , -LP</protein> ) , three <protein>latent membrane proteins</protein> ( <protein>LMP1</protein> , <protein>2A</protein> , <protein>2B</protein> ) , and two <rna>nuclear RNAs</rna> ( <rna>EBERs</rna> ) are expressed .


This form of latency , termed latency III , is also encountered in some posttransplant lymphoproliferative disorders .


In EBV-positive cases of Hodgkin 's disease , the EBERs , EBNA1 , and the LMPs are expressed ( latency II ) , whereas in Burkitt 's lymphoma ( BL ) only the EBERs and EBNA1 have been detected ( latency I ) .

In EBV-positive cases of Hodgkin 's disease , the <rna>EBERs</rna> , <protein>EBNA1</protein> , and the <protein>LMPs</protein> are expressed ( latency II ) , whereas in Burkitt 's lymphoma ( BL ) only the <rna>EBERs</rna> and <protein>EBNA1</protein> have been detected ( latency I ) .


We have studied the expression of EBV proteins in 17 cases of EBV-positive endemic BL by immunohistology .

We have studied the expression of <protein>EBV proteins</protein> in 17 cases of EBV-positive endemic BL by immunohistology .


Expression of LMP1 was seen in variable proportions of tumor cells in two cases and EBNA2 was detected in some tumor cells in three other cases .

Expression of <protein>LMP1</protein> was seen in variable proportions of <cell_type>tumor cells</cell_type> in two cases and <protein>EBNA2</protein> was detected in some <cell_type>tumor cells</cell_type> in three other cases .


Also , the BZLF1 trans-activator protein was expressed in a few tumor cells in 6 cases , indicating entry into the lytic cycle .

Also , the <protein>BZLF1 trans-activator protein</protein> was expressed in a few <cell_type>tumor cells</cell_type> in 6 cases , indicating entry into the lytic cycle .


A phenotypic drift from latency I to latency III has been observed previously in some BL cell lines .

A phenotypic drift from latency I to latency III has been observed previously in some <cell_line>BL cell lines</cell_line> .


Our results suggest that a similar phenomenon may occur in BL in vivo and indicate that the operational definition of EBV latencies is not easily applied to human tumors .


The activation of the Jak -STAT 1 signaling pathway by IL-5 in eosinophils .

The activation of the <protein>Jak</protein> <protein>-STAT 1</protein> signaling pathway by <protein>IL-5</protein> in <cell_type>eosinophils</cell_type> .


The intracellular signal transduction of IL-5 in eosinophils is unknown .

The intracellular signal transduction of <protein>IL-5</protein> in <cell_type>eosinophils</cell_type> is unknown .


The objective of this study was to investigate the involvement of the newly discovered Jak -STAT pathway in the IL-5 signal transduction mechanism .

The objective of this study was to investigate the involvement of the newly discovered <protein>Jak</protein> <protein>-STAT</protein> pathway in the <protein>IL-5</protein> signal transduction mechanism .


Eosinophils were purified from peripheral blood by discontinuous Percoll gradients and stimulated with IL-5 .

<cell_type>Eosinophils</cell_type> were purified from peripheral blood by discontinuous Percoll gradients and stimulated with <protein>IL-5</protein> .


The involvement of Jak 2 was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation .

The involvement of <protein>Jak 2</protein> was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation .


The activation of Jak 2 was studied by autophosphorylation of the immunoprecipitated kinase .

The activation of <protein>Jak 2</protein> was studied by autophosphorylation of the <protein>immunoprecipitated kinase</protein> .


Jak 2 was tyrosine phosphorylated within 1 to 3 min after stimulation of eosinophils with IL-5 .

<protein>Jak 2</protein> was tyrosine phosphorylated within 1 to 3 min after stimulation of <cell_type>eosinophils</cell_type> with <protein>IL-5</protein> .


Further , the immunoprecipitated Jak 2 obtained from IL-5-stimulated cells underwent autophosphorylation .

Further , the <protein>immunoprecipitated Jak 2</protein> obtained from <cell_line>IL-5-stimulated cells</cell_line> underwent autophosphorylation .


Jak 2 coprecipitated with the beta-subunit of the IL-5 receptor , suggesting a physical association of the kinase with the receptor .

<protein>Jak 2</protein> coprecipitated with the beta-subunit of the <protein>IL-5 receptor</protein> , suggesting a physical association of the <protein>kinase</protein> with the receptor .


The nuclear factor STAT-1 ( p91 ) was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation .

The <protein>nuclear factor STAT-1</protein> ( <protein>p91</protein> ) was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation .


STAT-1 was tyrosine phosphorylated within 15 min of IL-5 stimulation .

<protein>STAT-1</protein> was tyrosine phosphorylated within 15 min of <protein>IL-5</protein> stimulation .


The presence of STAT-1 in the nuclear extract was studied by electrophoretic mobility shift assay .

The presence of <protein>STAT-1</protein> in the nuclear extract was studied by electrophoretic mobility shift assay .


IL-5 induced two proteins that bound to the gamma-activating sequence .

<protein>IL-5</protein> induced two proteins that bound to the <dna>gamma-activating sequence</dna> .


In the presence of an anti-STAT-1 Ab , the band was supershifted .

In the presence of an <protein>anti-STAT-1 Ab</protein> , the band was supershifted .


Thus , we demonstrated that IL-5 activated the Jak 2 -STAT 1 signaling pathway in eosinophils .

Thus , we demonstrated that <protein>IL-5</protein> activated the <protein>Jak 2</protein> <protein>-STAT 1</protein> signaling pathway in <cell_type>eosinophils</cell_type> .


We speculate that the Jak 2 -STAT 1 pathway may be involved in the activation of IL-5-inducible genes in eosinophils .

We speculate that the <protein>Jak 2</protein> <protein>-STAT 1</protein> pathway may be involved in the activation of <dna>IL-5-inducible genes</dna> in <cell_type>eosinophils</cell_type> .


Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer : a prospective longitudinal study .

Reduced mitogenic stimulation of <cell_type>peripheral blood mononuclear cells</cell_type> as a prognostic parameter for the course of breast cancer : a prospective longitudinal study .


Immunosuppression has been often associated with the course of malignant diseases .


In the present study , the proliferation of peripheral blood mononuclear cells ( PBMCs ) in response to mitogenic stimulation with phytohaemagglutinin ( PHA ) was assessed prospectively in 90 patients with stage I-III breast cancer .

In the present study , the proliferation of <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) in response to mitogenic stimulation with <protein>phytohaemagglutinin</protein> ( <protein>PHA</protein> ) was assessed prospectively in 90 patients with stage I-III breast cancer .


Whereas PHA -induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals ( P < 0.001 ) , the degree of the defect in PHA -induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement ( P < 0.003 in each case ) .

Whereas <protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals ( P < 0.001 ) , the degree of the defect in <protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement ( P < 0.003 in each case ) .


PHA -induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide , methotrexate and fluorouracil ( CMF ) after an observation period of 6 months ( P < 0.01 ) , but not in patients under adjuvant treatment with tamoxifen only .

<protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide , methotrexate and fluorouracil ( CMF ) after an observation period of 6 months ( P < 0.01 ) , but not in patients under adjuvant treatment with tamoxifen only .


After an additional 6 months ( i.e. 12 months after surgery ) , PHA -induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment ( P > 0.1 ) , but in all patients still significantly decreased as compared with healthy controls ( P < 0.001 ) .

After an additional 6 months ( i.e. 12 months after surgery ) , <protein>PHA</protein> -induced proliferation of <cell_type>PBMCs</cell_type> was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment ( P > 0.1 ) , but in all patients still significantly decreased as compared with healthy controls ( P < 0.001 ) .