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  • 1
    Publication Date: 1994-11-11
    Description: Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russell, S M -- Johnston, J A -- Noguchi, M -- Kawamura, M -- Bacon, C M -- Friedmann, M -- Berg, M -- McVicar, D W -- Witthuhn, B A -- Silvennoinen, O -- P30 CA21765/CA/NCI NIH HHS/ -- R01 DK42932/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1994 Nov 11;266(5187):1042-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7973658" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Enzyme Activation ; Humans ; Interleukin-2/pharmacology ; Janus Kinase 1 ; Janus Kinase 3 ; Mutation ; Phosphorylation ; Point Mutation ; Protein-Tyrosine Kinases/genetics/*metabolism ; Receptors, Interleukin-2/genetics/*metabolism ; Severe Combined Immunodeficiency/genetics/*immunology/metabolism ; Transfection ; Tyrosine/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1994-07-08
    Description: Both interferon gamma (IFN-gamma) produced by T helper 1 (TH1) lymphocytes and interleukin-4 (IL-4) produced by TH2 lymphocytes were reduced in either bulk circulating mononuclear cells or mitogen-induced CD4+ T cell clones from the peripheral blood of individuals infected with human immunodeficiency virus (HIV). There was a preferential reduction in clones producing IL-4 and IL-5 in the advanced phases of infection. However, enhanced proportions of CD4+ T cell clones producing both TH1-type and TH2-type cytokines (TH0 clones) were generated from either skin-infiltrating T cells that had been activated in vivo or peripheral blood T cells stimulated by antigen in vitro when cells were isolated from HIV-infected individuals. All TH2 and most TH0 clones supported viral replication, although viral replication was not detected in any of the TH1 clones infected in vitro with HIV. These results suggest that HIV (i) does not induce a definite TH1 to TH2 switch, but can favor a shift to the TH0 phenotype in response to recall antigens, and (ii) preferentially replicates in CD4+ T cells producing TH2-type cytokines (TH2 and TH0).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maggi, E -- Mazzetti, M -- Ravina, A -- Annunziato, F -- de Carli, M -- Piccinni, M P -- Manetti, R -- Carbonari, M -- Pesce, A M -- del Prete, G -- New York, N.Y. -- Science. 1994 Jul 8;265(5169):244-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Clinical Immunology and Allergy, University of Florence, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8023142" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/immunology ; Cell Line ; Cells, Cultured ; HIV/*physiology ; HIV Infections/*immunology/microbiology ; HIV Seropositivity/immunology ; Humans ; Immunologic Memory ; Interferon-gamma/*biosynthesis ; Interleukin-4/biosynthesis ; Interleukin-5/biosynthesis ; Interleukins/*biosynthesis ; Lymphocyte Activation ; Phenotype ; T-Lymphocytes, Helper-Inducer/*immunology/microbiology ; Virus Replication
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 1991-10-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chipperfield, M -- Maidek, M -- Pearson, P -- Ashburner, M -- Glover, D M -- Saunders, R D -- Duncan, I -- Hartl, D -- Merriam, J -- Lee, G -- New York, N.Y. -- Science. 1991 Oct 11;254(5029):247-62.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1925580" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chromosome Mapping ; Chromosomes ; Drosophila melanogaster/*genetics ; Genes ; *Genome ; *Genome, Human ; Humans
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  • 4
    Publication Date: 1992-03-27
    Description: Cell surface receptors for echovirus, a common human pathogen, were identified with monoclonal antibodies that protected susceptible cells from infection with echovirus 1. These monoclonal antibodies, which prevented virus attachment to specific receptor sites, recognized the alpha and beta subunits of the integrin VLA-2 (alpha 2 beta 1), a receptor for collagen and laminin. RD rhabdomyosarcoma cells expressed little VLA-2, did not bind to 35S-labeled virus, and resisted infection until transfected with complementary DNA encoding the alpha 2 subunit of VLA-2. Thus, integrins, adhesion receptors important in interactions between cells and with the extracellular matrix, can mediate virus attachment and infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bergelson, J M -- Shepley, M P -- Chan, B M -- Hemler, M E -- Finberg, R W -- AI 20382/AI/NIAID NIH HHS/ -- GM 38903/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Mar 27;255(5052):1718-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1553561" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/immunology ; Cytopathogenic Effect, Viral ; Enterovirus B, Human/*metabolism ; HeLa Cells ; Humans ; In Vitro Techniques ; Molecular Weight ; Receptors, Very Late Antigen/*metabolism ; Receptors, Virus/chemistry/*metabolism
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  • 5
    Publication Date: 1992-08-21
    Description: A point mutation in the POU-specific portion of the human gene that encodes the tissue-specific POU-domain transcription factor, Pit-1, results in hypopituitarism, with deficiencies of growth hormone, prolactin, and thyroid-stimulating hormone. In two unrelated Dutch families, a mutation in Pit-1 that altered an alanine in the first putative alpha helix of the POU-specific domain to proline was observed. This mutation generated a protein capable of binding to DNA response elements but unable to effectively activate its known target genes, growth hormone and prolactin. The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotrope, and thyrotrope cell types. Thus, a mutation in the POU-specific domain of Pit-1 has a selective effect on a subset of Pit-1 target genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pfaffle, R W -- DiMattia, G E -- Parks, J S -- Brown, M R -- Wit, J M -- Jansen, M -- Van der Nat, H -- Van den Brande, J L -- Rosenfeld, M G -- Ingraham, H A -- HD24960/HD/NICHD NIH HHS/ -- HD2697/HD/NICHD NIH HHS/ -- NIDDK 18477/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 21;257(5073):1118-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1509263" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Blotting, Northern ; DNA/chemistry/metabolism ; DNA-Binding Proteins/*genetics/metabolism ; Growth Hormone/deficiency ; Humans ; Hypopituitarism/*genetics/pathology ; Mice ; Molecular Sequence Data ; *Mutation ; Nucleic Acid Hybridization ; Pituitary Gland, Anterior/*pathology ; Pituitary Hormones/*deficiency ; Polymerase Chain Reaction ; Prolactin/deficiency ; Rats ; Sequence Homology, Nucleic Acid ; Thyrotropin/deficiency ; Transcription Factor Pit-1 ; Transcription Factors/*genetics/metabolism ; Transfection
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  • 6
    Publication Date: 1991-06-21
    Description: Automated partial DNA sequencing was conducted on more than 600 randomly selected human brain complementary DNA (cDNA) clones to generate expressed sequence tags (ESTs). ESTs have applications in the discovery of new human genes, mapping of the human genome, and identification of coding regions in genomic sequences. Of the sequences generated, 337 represent new genes, including 48 with significant similarity to genes from other organisms, such as a yeast RNA polymerase II subunit; Drosophila kinesin, Notch, and Enhancer of split; and a murine tyrosine kinase receptor. Forty-six ESTs were mapped to chromosomes after amplification by the polymerase chain reaction. This fast approach to cDNA characterization will facilitate the tagging of most human genes in a few years at a fraction of the cost of complete genomic sequencing, provide new genetic markers, and serve as a resource in diverse biological research fields.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adams, M D -- Kelley, J M -- Gocayne, J D -- Dubnick, M -- Polymeropoulos, M H -- Xiao, H -- Merril, C R -- Wu, A -- Olde, B -- Moreno, R F -- New York, N.Y. -- Science. 1991 Jun 21;252(5013):1651-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Receptor Biochemistry and Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2047873" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Automation ; *Base Sequence ; Brain/*physiology ; Chromosome Mapping ; DNA/*genetics ; Gene Expression ; *Gene Library ; *Human Genome Project ; Humans ; Molecular Sequence Data ; Multigene Family ; Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid
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  • 7
    Publication Date: 1991-12-20
    Description: The human immunodeficiency virus-1 (HIV-1) trans-activator Tat is an attractive target for the development of antiviral drugs because inhibition of Tat would arrest the virus at an early stage. The drug Ro 5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepine-2(H)-one], inhibited gene expression by HIV-1 at the level of transcriptional trans-activation by Tat. The compound did not inhibit the basal activity of the promoter. Both Tat and its target sequence TAR were required for the observed inhibitory activity. Ro 5-3335 reduced the amount of cell-associated viral RNA and antigen in acutely, as well as in chronically infected cells in vitro (median inhibition concentration 0.1 to 1 micromolar). Effective inhibition of viral replication was also observed 24 hours after cells were transfected with infectious recombinant HIV-1 DNA. The compound was active against both HIV-1 and HIV-2 and against 3'-azido-3'-deoxythymidine (AZT)-resistant clinical isolates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hsu, M C -- Schutt, A D -- Holly, M -- Slice, L W -- Sherman, M I -- Richman, D D -- Potash, M J -- Volsky, D J -- AI 27397/AI/NIAID NIH HHS/ -- AI 27670/AI/NIAID NIH HHS/ -- AI 29164/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1991 Dec 20;254(5039):1799-802.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Virology, Hoffmann-La Roche, Nutley, NJ 07110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1763331" target="_blank"〉PubMed〈/a〉
    Keywords: Antiviral Agents/*pharmacology ; Benzodiazepinones/*pharmacology ; Cell Line ; Gene Products, tat/*antagonists & inhibitors ; HIV Long Terminal Repeat/drug effects ; HIV-1/drug effects/genetics/*physiology ; HIV-2/drug effects/*physiology ; Humans ; Kinetics ; Promoter Regions, Genetic/drug effects ; Pyrroles/*pharmacology ; Virus Replication/*drug effects ; Zidovudine/pharmacology ; tat Gene Products, Human Immunodeficiency Virus
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  • 8
    Publication Date: 1993-06-18
    Description: Lymphocytes recognize antigens with highly variable heterodimeric surface receptors. Although four distinct antigen receptors could in principle be produced by any lymphocyte, only one functional combination of receptor chains has thus far been found expressed on their surface. Examination of human gamma delta T cells revealed a population that violated this rule by expressing on their surface two distinct functional gamma delta T cell receptors (TCRs) that used different TCR gamma gene alleles. Thus, current models for T cell clonal selection may need modification, and a possible escape mechanism for autoreactive TCRs is suggested.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davodeau, F -- Peyrat, M A -- Houde, I -- Hallet, M M -- De Libero, G -- Vie, H -- Bonneville, M -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1800-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM U211, Institut de Biologie, Nantes, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8390096" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Cell Line ; Cytotoxicity, Immunologic ; *Gene Expression ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Humans ; Molecular Sequence Data ; Receptors, Antigen, T-Cell, gamma-delta/analysis/*genetics/immunology ; T-Lymphocytes/*immunology ; T-Lymphocytes, Cytotoxic/*immunology
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  • 9
    Publication Date: 1994-11-25
    Description: GADD45 is a ubiquitously expressed mammalian gene that is induced by DNA damage and certain other stresses. Like another p53-regulated gene, p21WAF1/CIP1, whose product binds to cyclin-dependent kinases (Cdk's) and proliferating cell nuclear antigen (PCNA), GADD45 has been associated with growth suppression. Gadd45 was found to bind to PCNA, a normal component of Cdk complexes and a protein involved in DNA replication and repair. Gadd45 stimulated DNA excision repair in vitro and inhibited entry of cells into S phase. These results establish GADD45 as a link between the p53-dependent cell cycle checkpoint and DNA repair.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, M L -- Chen, I T -- Zhan, Q -- Bae, I -- Chen, C Y -- Gilmer, T M -- Kastan, M B -- O'Connor, P M -- Fornace, A J Jr -- ES05777/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1994 Nov 25;266(5189):1376-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7973727" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Division/drug effects ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/metabolism ; DNA/biosynthesis ; DNA Damage ; *DNA Repair ; *Genes, p53 ; Humans ; Intracellular Signaling Peptides and Proteins ; Proliferating Cell Nuclear Antigen/*metabolism ; Proteins/*metabolism/pharmacology ; Recombinant Proteins/metabolism/pharmacology ; S Phase/*drug effects ; Transfection ; Tumor Cells, Cultured
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  • 10
    Publication Date: 1990-06-29
    Description: In Rous sarcoma virus (RSV)-infected chickens, wounding leads to tumor formation with nearly 100% frequency in tissues that would otherwise remain tumor-free. Identifying molecular mediators of this phenomenon should yield important clues to the mechanisms involved in RSV tumorigenesis. Immunohistochemical staining showed that TGF-beta is present locally shortly after wounding, but not unwounded controls. In addition, subcutaneous administration of recombinant transforming growth factor-beta 1 (TGF-beta 1) could substitute completely for wounding in tumor induction. A treatment protocol of four doses of 800 nanograms of TGF-beta resulted in v-src-expressing tumors with 100% frequency; four doses of only 10 nanograms still led to tumor formation in 80% of the animals. This effect was specific, as other growth factors with suggested roles in wound healing did not elicit the same response. Epidermal growth factor (EGF) or TGF-alpha had no effect, and platelet-derived growth factor (PDGF) or insulin-like growth factor-1 (IGF-1) yielded only occasional tumors after longer latency. TGF-beta release during the wound-healing response may thus be a critical event that creates a conducive environment for RSV tumorigenesis and may act as a cofactor for transformation in this system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sieweke, M H -- Thompson, N L -- Sporn, M B -- Bissell, M J -- New York, N.Y. -- Science. 1990 Jun 29;248(4963):1656-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell and Molecular Biology Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2163544" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies ; Chickens ; Epidermal Growth Factor/pharmacology ; Humans ; Immunoenzyme Techniques ; Insulin-Like Growth Factor I/pharmacology ; Platelet-Derived Growth Factor/pharmacology ; Recombinant Proteins/pharmacology ; Sarcoma, Avian/complications/*pathology ; Swine ; Transforming Growth Factors/analysis/*pharmacology ; Wound Healing ; Wounds and Injuries/complications/*pathology
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