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  • 1
    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
    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: 1991-07-12
    Description: Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in the putative transmembrane domains were mutated. The sequence of anion selectivity of cAMP-regulated channels in cells containing either endogenous or recombinant CFTR was bromide greater than chloride greater than iodide greater than fluoride. Mutation of the lysines at positions 95 or 335 to acidic amino acids converted the selectivity sequence to iodide greater than bromide greater than chloride greater than fluoride. These data indicate that CFTR is a cAMP-regulated chloride channel and that lysines 95 and 335 determine anion selectivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, M P -- Gregory, R J -- Thompson, S -- Souza, D W -- Paul, S -- Mulligan, R C -- Smith, A E -- Welsh, M J -- New York, N.Y. -- Science. 1991 Jul 12;253(5016):202-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1712984" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Chloride Channels ; Chlorides/*physiology ; Cyclic AMP/physiology ; Cystic Fibrosis/physiopathology ; Cystic Fibrosis Transmembrane Conductance Regulator ; DNA Mutational Analysis ; Electric Conductivity ; HeLa Cells ; Humans ; In Vitro Techniques ; Ion Channels/genetics/*physiology ; Membrane Glycoproteins/genetics/physiology ; Membrane Potentials ; Membrane Proteins/genetics/*physiology ; Molecular Sequence Data ; Transfection
    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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  • 3
    Publication Date: 1990-11-09
    Description: Expression of the human T cell receptor (TCR) alpha gene is regulated by a T cell-specific transcriptional enhancer that is located 4.5 kilobases (kb) 3' to the C alpha gene segment. The core enhancer contains two nuclear protein binding sites, T alpha 1 and T alpha 2, which are essential for full enhancer activity. T alpha 1 contains a consensus cyclic adenosine monophosphate (cAMP) response element (CRE) and binds a set of ubiquitously expressed CRE binding proteins. In contrast, the transcription factors that interact with the T alpha 2 site have not been defined. In this report, a lambda gt11 expression protocol was used to isolate a complementary DNA (cDNA) that programs the expression of a T alpha 2 binding protein. DNA sequence analysis demonstrated that this clone encodes the human ets-1 proto-oncogene. Lysogen extracts produced with this cDNA clone contained a beta-galactosidase-Ets-1 fusion protein that bound specifically to a synthetic T alpha 2 oligonucleotide. The Ets-1 binding site was localized to a 17-base pair (bp) region from the 3' end of T alpha 2. Mutation of five nucleotides within this sequence abolished both Ets-1 binding and the activity of the TCR alpha enhancer in T cells. These results demonstrate that Ets-1 binds in a sequence-specific fashion to the human TCR alpha enhancer and suggest that this developmentally regulated proto-oncogene functions in regulating TCR alpha gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ho, I C -- Bhat, N K -- Gottschalk, L R -- Lindsten, T -- Thompson, C B -- Papas, T S -- Leiden, J M -- AI-29673/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 9;250(4982):814-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Ann Arbor, MI.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237431" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding, Competitive ; Cloning, Molecular ; DNA/genetics ; DNA Mutational Analysis ; *Enhancer Elements, Genetic ; Gene Expression Regulation ; Gene Rearrangement, T-Lymphocyte ; Humans ; Immunoblotting ; Molecular Sequence Data ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins c-ets ; *Proto-Oncogenes ; Receptors, Antigen, T-Cell/genetics/*metabolism ; Transcription Factors ; Transcription, Genetic
    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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  • 4
    Publication Date: 1991-06-07
    Description: The mechanism by which Ca2+ mediates gene induction in response to membrane depolarization was investigated. The adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) was shown to function as a Ca(2+)-regulated transcription factor and as a substrate for depolarization-activated Ca(2+)-calmodulin-dependent protein kinases (CaM kinases) I and II. CREB residue Ser133 was the major site of phosphorylation by the CaM kinases in vitro and of phosphorylation after membrane depolarization in vivo. Mutation of Ser133 impaired the ability of CREB to respond to Ca2+. These results suggest that CaM kinases may transduce electrical signals to the nucleus and that CREB functions to integrate Ca2+ and cAMP signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheng, M -- Thompson, M A -- Greenberg, M E -- R01 CA 43855/CA/NCI NIH HHS/ -- R01 NS 28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1991 Jun 7;252(5011):1427-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1646483" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases ; Chromosome Mapping ; Cloning, Molecular ; Cyclic AMP/physiology ; Cyclic AMP Response Element-Binding Protein ; DNA-Binding Proteins/*physiology ; Electrophoresis, Polyacrylamide Gel ; Fungal Proteins/pharmacology ; Gene Expression Regulation/*drug effects ; Genes, Regulator/physiology ; Humans ; In Vitro Techniques ; Phosphorylation ; Protein Kinases/pharmacology ; Rats ; Recombinant Fusion Proteins/pharmacology ; *Saccharomyces cerevisiae Proteins ; Serine/chemistry ; Signal Transduction ; TATA Box ; Transcription Factors/*physiology ; Transcription, Genetic/drug effects ; Transcriptional Activation
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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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  • 5
    Publication Date: 1991-08-16
    Description: The expression of the V(D)J [variable (diversity) joining elements] recombination activating genes, RAG-1 and RAG-2, has been examined during T cell development in the thymus. In situ hybridization to intact thymus and RNA blot analysis of isolated thymic subpopulations separated on the basis of T cell receptor (TCR) expression demonstrated that both TCR- and TCR+ cortical thymocytes express RAG-1 and RAG-2 messenger RNA's. Within the TCR+ population, RAG expression was observed in immature CD4+CD8+ (double positive) cells, but not in the more mature CD4+CD8- or CD4-CD8+ (single positive) subpopulations. Thus, although cortical thymocytes that bear TCR on their surface continue to express RAG-1 and RAG-2, it appears that the expression of both genes is normally terminated during subsequent thymic maturation. Since thymocyte maturation in vivo is thought to be regulated through the interaction of the TCR complex with self major histocompatibility complex (MHC) antigens, these data suggest that signals transduced by the TCR complex might result in the termination of RAG expression. Consistent with this hypothesis, thymocyte TCR cross-linking in vitro led to rapid termination of RAG-1 and RAG-2 expression, whereas cross-linking of other T cell surface antigens such as CD4, CD8, or HLA class I had no effect.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turka, L A -- Schatz, D G -- Oettinger, M A -- Chun, J J -- Gorka, C -- Lee, K -- McCormack, W T -- Thompson, C B -- DK-01899/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1991 Aug 16;253(5021):778-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, University of Michigan, Ann Arbor 48109.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1831564" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/physiology ; Antigens, CD3 ; Antigens, Differentiation, T-Lymphocyte/physiology ; Cell Differentiation ; Cell Survival ; DNA Nucleotidyltransferases/*genetics ; *DNA-Binding Proteins ; Gene Expression ; *Gene Rearrangement, T-Lymphocyte ; *Homeodomain Proteins ; Humans ; Mice ; Nuclear Proteins ; Nucleic Acid Hybridization ; Proteins/*genetics ; RNA, Messenger/genetics ; Receptor Aggregation ; Receptors, Antigen, T-Cell/*physiology ; Receptors, Interleukin-2/genetics ; T-Lymphocyte Subsets/enzymology/*physiology ; Thymus Gland/cytology/*enzymology ; VDJ Recombinases
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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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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, L -- New York, N.Y. -- Science. 1993 Jan 15;259(5093):303.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8419999" target="_blank"〉PubMed〈/a〉
    Keywords: *Genetic Therapy/history ; History, 20th Century ; Humans ; *National Institutes of Health (U.S.)/history ; *Research/history ; United States
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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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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, L -- New York, N.Y. -- Science. 1993 Jan 1;259(5091):22-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8418490" target="_blank"〉PubMed〈/a〉
    Keywords: Government Agencies ; Human Genome Project/*organization & administration ; Humans ; National Institutes of Health (U.S.) ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, L -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):452.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8424165" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; *Bioethics ; Brain Neoplasms/*therapy ; DNA, Recombinant ; Death ; *Ethical Review ; Federal Government ; Female ; *Genetic Therapy ; *Government Regulation ; Humans ; Middle Aged ; National Institutes of Health (U.S.) ; *Therapeutic Human Experimentation ; United States
    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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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, L -- New York, N.Y. -- Science. 1993 Jan 8;259(5092):172.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8421780" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; Ethical Review ; Federal Government ; Female ; Genetic Therapy/*legislation & jurisprudence ; *Government Regulation ; Humans ; Interleukin-2/*genetics ; Middle Aged ; National Institutes of Health (U.S.) ; Neoplasms/*therapy ; Patient Selection ; Research Subjects ; United States
    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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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-10-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, L -- New York, N.Y. -- Science. 1992 Oct 30;258(5083):744-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1472258" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/therapy ; Adenosine Deaminase/deficiency ; DNA, Viral/genetics ; Genetic Therapy/*trends ; Genetic Vectors ; HIV/genetics ; Humans ; Immunologic Deficiency Syndromes/therapy ; National Institutes of Health (U.S.) ; Neoplasms/therapy ; Retroviridae/genetics ; Transfection ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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