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  • Cells, Cultured  (76)
  • American Association for the Advancement of Science (AAAS)  (76)
  • Annual Reviews
  • Cell Press
  • Copernicus
  • Springer Nature
  • 2005-2009
  • 1990-1994  (76)
  • 1980-1984
  • 1960-1964
  • 1993  (41)
  • 1990  (35)
Collection
Publisher
  • American Association for the Advancement of Science (AAAS)  (76)
  • Annual Reviews
  • Cell Press
  • Copernicus
  • Springer Nature
Years
  • 2005-2009
  • 1990-1994  (76)
  • 1980-1984
  • 1960-1964
Year
  • 1
    Publication Date: 1990-11-23
    Description: In Aplysia sensory and motor neurons in culture, the contributions of the major classes of calcium current can be selectively examined while transmitter release and its modulation are examined. A slowly inactivating, dihydropyridine-sensitive calcium current does not contribute either to normal synaptic transmission or to any of three different forms of plasticity: presynaptic inhibition, homosynaptic depression, and presynaptic facilitation. This current does contribute, however, to a fourth form of plasticity--modulation of transmitter release by tonic depolarization of the sensory neuron. By contrast, a second calcium current, which is rapidly inactivating and dihydropyridine-insensitive, contributes to release elicited by the transient depolarization of an action potential and to the other three forms of plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Edmonds, B -- Klein, M -- Dale, N -- Kandel, E R -- New York, N.Y. -- Science. 1990 Nov 23;250(4984):1142-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University College of London, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2174573" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Aplysia/*physiology ; Cadmium/pharmacology ; Calcium Channels/drug effects/*physiology ; Cells, Cultured ; Dihydropyridines/antagonists & inhibitors/pharmacology ; Electric Conductivity ; FMRFamide ; Motor Neurons/physiology ; Neuronal Plasticity/*physiology ; Neurons, Afferent/physiology ; Neuropeptides/pharmacology ; Nifedipine/pharmacology ; Serotonin/pharmacology ; Synapses/*physiology ; Synaptic Transmission/*physiology
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  • 2
    Publication Date: 1990-01-12
    Description: The murine white spotting locus (W) is allelic with the proto-oncogene c-kit, which encodes a transmembrane tyrosine protein kinase receptor for an unknown ligand. Mutations at the W locus affect various aspects of hematopoiesis and the proliferation and migration of primordial germ cells and melanoblasts during development to varying degrees of severity. The W42 mutation has a particularly severe effect in both the homozygous and the heterozygous states. The molecular basis of the W42 mutation was determined. The c-kit protein products in homozygous mutant mast cells were expressed normally but displayed a defective tyrosine kinase activity in vitro. Nucleotide sequence analysis of mutant complementary DNAs revealed a missense mutation that replaces aspartic acid with asparagine at position 790 in the c-kit protein product. Aspartic acid-790 is a conserved residue in all protein kinases. These results provide an explanation for the dominant nature of the W42 mutation and provide insight into the mechanism of c-kit-mediated signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, J C -- Nocka, K -- Ray, P -- Traktman, P -- Besmer, P -- P01-CA-16599/CA/NCI NIH HHS/ -- R01-CA-32926/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jan 12;247(4939):209-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1688471" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cells, Cultured ; DNA/genetics ; Gene Expression ; Homozygote ; Liver/analysis/cytology/embryology ; Mast Cells/metabolism ; Mice ; Molecular Sequence Data ; *Mutation ; *Phenotype ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases/*genetics ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins c-kit ; RNA/analysis ; Receptors, Cell Surface/genetics ; Signal Transduction
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  • 3
    Publication Date: 1990-09-28
    Description: Methodology has been developed that enables virtually complete purification and abundant recovery of early hematopoietic progenitors from normal human adult peripheral blood. A fraction of the pure progenitors is multipotent (generates mixed colonies) and exhibits self-renewal capacity (gives rise to blast cell colonies). This methodology provides a fundamental tool for basic and clinical studies on hematopoiesis. Optimal in vitro cloning of virtually pure progenitors requires not only the stimulatory effect of interleukin-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin, but also the permissive action of basic fibroblast growth factor. These findings suggest a regulatory role for this growth factor in early hematopoiesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gabbianelli, M -- Sargiacomo, M -- Pelosi, E -- Testa, U -- Isacchi, G -- Peschle, C -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1561-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Hematology and Oncology, Istituto Superiore di Sanita, Rome, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218497" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Antibodies, Monoclonal/immunology ; Cell Separation ; Cells, Cultured ; Clone Cells ; Erythropoietin/pharmacology ; Fibroblast Growth Factor 2/*pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Hematopoietic Stem Cells/*cytology/drug effects ; Humans ; Interleukin-3/pharmacology ; Monocytes/*cytology/drug effects ; Recombinant Proteins/pharmacology
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  • 4
    Publication Date: 1990-09-28
    Description: Heparin-binding growth factor-1 (HBGF-1) is an angiogenic polypeptide mitogen for mesoderm- and neuroectoderm-derived cells in vitro and remains biologically active after truncation of the amino-terminal domain (HBGF-1 alpha) of the HBGF-1 beta precursor. Polymerase chain reaction mutagenesis and prokaryotic expression systems were used to prepare a mutant of HBGF-1 alpha lacking a putative nuclear translocation sequence (amino acid residues 21 to 27; HBGF-1U). Although HBGF-1U retains its ability to bind to heparin, HBGF-1U fails to induce DNA synthesis and cell proliferation at concentrations sufficient to induce intracellular receptor-mediated tyrosine phosphorylation and c-fos expression. Attachment of the nuclear translocation sequence from yeast histone 2B at the amino terminus of HBGF-1U yields a chimeric polypeptide (HBGF-1U2) with mitogenic activity in vitro and indicates that nuclear translocation is important for this biological response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Imamura, T -- Engleka, K -- Zhan, X -- Tokita, Y -- Forough, R -- Roeder, D -- Jackson, A -- Maier, J A -- Hla, T -- Maciag, T -- HL 32348/HL/NHLBI NIH HHS/ -- HL 35627/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1567-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD 20855.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1699274" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding, Competitive ; Cattle ; Cell Division/drug effects ; Cell Line ; Cell Nucleus/metabolism ; Cells, Cultured ; DNA Replication/drug effects ; Endothelium, Vascular/drug effects/metabolism ; Fibroblast Growth Factor 1/*genetics/metabolism/pharmacology ; Kinetics ; Mice ; Mitogens/pharmacology ; Molecular Sequence Data ; *Mutation ; Oligonucleotide Probes ; Receptors, Mitogen/metabolism ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Proteins/metabolism/pharmacology ; Transcription, Genetic/drug effects
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-11-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, A -- New York, N.Y. -- Science. 1990 Nov 2;250(4981):622-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237413" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*physiology ; Animals ; Cells, Cultured ; DNA Damage ; Free Radicals ; Humans ; Life Expectancy
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  • 6
    Publication Date: 1990-05-04
    Description: Platelet-derived growth factor (PDGF) stimulates phospholipase C (PLC) activity and the phosphorylation of the gamma isozyme of PLC (PLC-gamma) in vitro and in living cells. The role of PLC-gamma in the phosphoinositide signaling pathway was addressed by examining the effect of overexpression of PLC-gamma on cellular responses to PDGF. Overexpression of PLC-gamma correlated with PDGF-induced tyrosine phosphorylation of PLC-gamma and with PDGF-induced breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2). However, neither bradykinin- nor lysophosphatidic acid-induced phosphoinositide metabolism was enhanced in the transfected cells, suggesting that the G protein-coupled phosphoinositide responses to these ligands are mediated by other PLC isozymes. The enhanced PDGF-induced generation of inositol trisphosphate (IP3) did not enhance intracellular calcium signaling or influence PDGF-induced DNA synthesis. Thus, enzymes other than PLC-gamma may limit PDGF-induced calcium signaling and DNA synthesis. Alternatively, PDGF-induced calcium signaling and DNA synthesis may use biochemical pathways other than phosphoinositide metabolism for signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Margolis, B -- Zilberstein, A -- Franks, C -- Felder, S -- Kremer, S -- Ullrich, A -- Rhee, S G -- Skorecki, K -- Schlessinger, J -- New York, N.Y. -- Science. 1990 May 4;248(4955):607-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rorer Biotechnology, King of Prussia, PA 19406.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2333512" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/physiology ; Cattle ; Cell Division/*drug effects ; Cells, Cultured ; DNA Replication/drug effects ; Genetic Vectors ; Inositol Phosphates/metabolism ; Isoenzymes/biosynthesis/*genetics/metabolism ; Kinetics ; Mice ; Platelet-Derived Growth Factor/*pharmacology ; Second Messenger Systems/*drug effects ; Transfection ; Type C Phospholipases/biosynthesis/*genetics/metabolism
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  • 7
    Publication Date: 1990-03-16
    Description: Many proteins are initially synthesized as part of a large precursor. The role of the pro-region in the biosynthesis of transforming growth factor--beta 1 (TGF-beta 1) and activin A, two structurally related disulfide-linked homodimers synthesized as large precursors, was studied. Vectors that expressed either the pro-region or the mature regions of these molecules were used in complementation experiments, only when the pro-region was coexpressed with the mature region did intracellular dimerization and secretion of biologically active homodimers occur. The pro-regions of activin A and TGF-beta 1, therefore, aid the folding, disulfide bond formation, and export of their respective homodimers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gray, A M -- Mason, A J -- New York, N.Y. -- Science. 1990 Mar 16;247(4948):1328-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2315700" target="_blank"〉PubMed〈/a〉
    Keywords: Activins ; Amino Acid Sequence ; Cells, Cultured ; Genetic Complementation Test ; Humans ; Inhibins/*biosynthesis/ultrastructure ; Macromolecular Substances ; Molecular Sequence Data ; Protein Processing, Post-Translational ; Protein Sorting Signals/physiology ; Transfection ; Transforming Growth Factors/*biosynthesis
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-03-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witkowski, J A -- New York, N.Y. -- Science. 1990 Mar 23;247(4949 Pt 1):1385-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2181660" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Chick Embryo ; History, 20th Century ; United States
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  • 9
    Publication Date: 1990-04-27
    Description: The beta-amyloid protein (beta/A4), derived from a larger amyloid precursor protein (APP), is the principal component of senile plaques in Alzheimer's disease. APP is an integral membrane glycoprotein and is secreted as a carboxyl-terminal truncated molecule. APP cleavage, which is a membrane-associated event, occurred at a site located within the beta/A4 region. This suggests that an intact amyloidogenic beta/A4 fragment is not generated during normal APP catabolism. Therefore, an early event in amyloid formation may involve altered APP processing that results in the release and subsequent deposition of intact beta/A4.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sisodia, S S -- Koo, E H -- Beyreuther, K -- Unterbeck, A -- Price, D L -- AG 03359/AG/NIA NIH HHS/ -- AG 05146/AG/NIA NIH HHS/ -- AG 07914/AG/NIA NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1990 Apr 27;248(4954):492-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2181.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1691865" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Alzheimer Disease/*metabolism ; Amyloid/genetics/*metabolism ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Animals ; Cell Membrane ; Cells, Cultured ; Cloning, Molecular ; DNA, Recombinant ; Glycosylation ; Half-Life ; Humans ; Immunoblotting ; Molecular Weight ; Plasmids ; Protein Precursors/genetics/*metabolism ; *Protein Processing, Post-Translational ; Recombinant Fusion Proteins/metabolism ; Substance P/genetics ; Transfection
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  • 10
    Publication Date: 1990-04-20
    Description: Coat protein gp120 from the human immunodeficiency virus type-1 (HIV-1) increased intracellular free calcium and injured rodent retinal ganglion cells and hippocampal neurons in culture. Highly purified recombinant gp120 envelope protein produced these effects in a dose-dependent fashion at picomolar concentrations. Immunoprecipitation with antibody to gp120, but not with control immunoglobulin-containing serum, depleted solutions of the viral envelope protein and also prevented both the rise in intracellular calcium and neuronal toxicity. The gp120-induced increase in intracellular calcium was abrogated by transiently lowering extracellular calcium or by adding the dihydropyridine calcium channel antagonist nimodipine (100 nM). Calcium channel antagonists also prevented gp120-induced neuronal injury. In addition, intracellular stores appeared to contribute substantially to the increase in calcium elicited by gp120. Since increases in intracellular calcium have been associated with neurotoxicity, it is possible that an injurious effect of gp120 on neurons might be related to this mechanism and that treatment with calcium channel antagonists may prove useful in mitigating HIV-1-related neuronal injury.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dreyer, E B -- Kaiser, P K -- Offermann, J T -- Lipton, S A -- EY 05477/EY/NEI NIH HHS/ -- NS 01395/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 20;248(4953):364-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Children's Hospital, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2326646" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium Channel Blockers/*pharmacology ; Cells, Cultured ; HIV Envelope Protein gp120/administration & dosage/antagonists & ; inhibitors/*physiology ; HIV-1/*analysis ; Hippocampus/cytology ; Neurons/*drug effects/metabolism ; Nimodipine/pharmacology ; Rats ; Recombinant Proteins/pharmacology ; Retinal Ganglion Cells/drug effects/metabolism
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-06-15
    Description: Systemically administered flunarizine enhanced neuronal survival in lumbar sensory ganglia in newborn rats after axotomy. Flunarizine-treated rats lost 71 percent fewer neurons than the untreated control rats at the end of 1 week. In cell culture, flunarizine at 30 to 40 microM also prevented neuronal death in nerve growth factor-dependent embryonic sensory and sympathetic neurons after the abrupt withdrawal of neurotrophic support. The drug may cause this effect by acting at an intracellular site, one distinct from its blockade of voltage-dependent calcium channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rich, K M -- Hollowell, J P -- HL20604/HL/NHLBI NIH HHS/ -- NS18071/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 15;248(4961):1419-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosurgery, Washington University School of Medicine, St. Louis, Mo 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2356470" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Cell Survival/drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Flunarizine/administration & dosage/*pharmacology ; Ganglia, Spinal/cytology/embryology ; Ganglia, Sympathetic/cytology/embryology ; Microscopy, Electron, Scanning ; Nerve Crush ; Nerve Growth Factors/administration & dosage/*pharmacology ; Neurons/*cytology/drug effects ; Rats ; Sciatic Nerve/physiology/surgery
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  • 12
    Publication Date: 1990-08-31
    Description: Human B lymphocytes localize and differentiate within the microenvironment of lymphoid germinal centers. A frozen section binding assay was developed for the identification of those molecules involved in the adhesive interactions between B cells and lymphoid follicles. Activated human B cells and B cell lines were found to selectively adhere to germinal centers. The VLA-4 molecule on the lymphocyte and the adhesion molecule INCAM-110, expressed on follicular dendritic cells, supported this interaction. This cellular interaction model can be used for the study of how B cells differentiate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freedman, A S -- Munro, J M -- Rice, G E -- Bevilacqua, M P -- Morimoto, C -- McIntyre, B W -- Rhynhart, K -- Pober, J S -- Nadler, L M -- 5T32HL07627-03/HL/NHLBI NIH HHS/ -- AR33713/AR/NIAMS NIH HHS/ -- CA40216/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1990 Aug 31;249(4972):1030-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Tumor Immunology, Dana-Farber Cancer Institute and Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1697696" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal ; Antigens, CD/analysis ; B-Lymphocytes/cytology/*immunology/ultrastructure ; Cell Adhesion ; Cell Adhesion Molecules/*immunology ; Cells, Cultured ; Humans ; Palatine Tonsil/cytology/immunology ; Receptors, Very Late Antigen/*immunology ; Spleen/immunology ; Vascular Cell Adhesion Molecule-1
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  • 13
    Publication Date: 1990-11-09
    Description: The product of the cdc2 gene, designated p34cdc2, is a serine-threonine protein kinase that controls entry of eukaryotic cells into mitosis. Freshly isolated human T lymphocytes (G0 phase) were found to have very low amounts of p34cdc2 and cdc2 messenger RNA. Expression of cdc2 increased 18 to 24 hours after exposure of T cells to phytohemagglutinin, coincident with the G1 to S transition. Antisense oligodeoxynucleotides could reduce the increase in cdc2 expression and inhibited DNA synthesis, but had no effect on several early and mid-G1 events, including blastogenesis and expression of interleukin-2 receptors, transferrin receptors, c-myb, and c-myc. Induction of cdc2 required prior induction of c-myb and c-myc. These results suggest that cdc2 induction is part of an orderly sequence of events that occurs at the G1 to S transition in T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Furukawa, Y -- Piwnica-Worms, H -- Ernst, T J -- Kanakura, Y -- Griffin, J D -- CA36167/CA/NCI NIH HHS/ -- CA47843/CA/NCI NIH HHS/ -- CA50767/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1990 Nov 9;250(4982):805-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237430" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Blotting, Northern ; CDC2 Protein Kinase/biosynthesis/*genetics ; Cells, Cultured ; DNA/biosynthesis/genetics ; Flow Cytometry ; *G1 Phase ; *Gene Expression Regulation ; Genes, Retinoblastoma ; Genes, myc ; Humans ; Lymphocyte Activation ; Molecular Sequence Data ; Phosphorylation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-myb ; RNA, Messenger/biosynthesis/genetics ; *S Phase ; T-Lymphocytes/*cytology/metabolism
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  • 14
    Publication Date: 1990-09-28
    Description: The proliferative potential of human diploid endothelial cells is finite, and cellular senescence in vitro is accompanied by the failure of the endothelial cell to respond to exogenous growth factors. Senescent human endothelial cells were shown to contain high amounts of the transcript for the cytokine interleukin-1 alpha (IL-1 alpha), a potent inhibitor of endothelial cell proliferation in vitro. In contrast, transformed human endothelial cells did not contain detectable IL-1 alpha messenger RNA. Treatment of human endothelial cell populations with an antisense oligodeoxynucleotide to the human IL-1 alpha transcript prevented cell senescence and extended the proliferative life-span of the cells in vitro. Removal of the IL-1 alpha antisense oligomer resulted in the generation of the senescent phenotype and loss of proliferative potential. These data suggest that human endothelial cell senescence in vitro is a dynamic process regulated by the potential intracellular activity of IL-1 alpha.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maier, J A -- Voulalas, P -- Roeder, D -- Maciag, T -- AG07450/AG/NIA NIH HHS/ -- HL32348/HL/NHLBI NIH HHS/ -- HL35627/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1570-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, Jerome H. Holland, Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD 20855.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218499" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Division ; Cell Survival ; Cells, Cultured ; Endothelium, Vascular/*cytology/physiology ; Humans ; Interleukin-1/*genetics ; Kinetics ; Molecular Sequence Data ; Oligonucleotide Probes ; RNA, Antisense/*genetics
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-02-16
    Description: Activin, a member of the transforming growth factor beta protein family, was originally isolated from gonadal fluids and stimulates the release of pituitary follicle-stimulating hormone (FSH). Activin has numerous functions in both normal and neoplastic cells. Various cells synthesize activin and have a specific binding site for this peptide. However, the molecular basis for its actions is unknown. A binding protein for activin was purified from rat ovary and was identical to follistatin, a specific inhibitor of FSH release. It is likely that the binding protein participates in the diverse regulatory actions of activin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakamura, T -- Takio, K -- Eto, Y -- Shibai, H -- Titani, K -- Sugino, H -- New York, N.Y. -- Science. 1990 Feb 16;247(4944):836-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Frontier Research Program, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2106159" target="_blank"〉PubMed〈/a〉
    Keywords: Activins ; Animals ; *Carrier Proteins ; Cells, Cultured ; Female ; Follicle Stimulating Hormone/secretion ; Inhibins/isolation & purification/*metabolism/pharmacology ; Kinetics ; Molecular Weight ; Ovary/*metabolism ; Pituitary Gland/drug effects/secretion ; Protein Binding ; Rats
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  • 16
    Publication Date: 1990-09-28
    Description: Most immature CD4+CD8+ thymocytes express only a small number of T cell receptor (TCR) molecules on their surface, and the TCR molecules they do express are only marginally capable of transducing intracellular signals. TCR expression and function was not intrinsically low in immature CD4+CD8+ thymocytes, but was found to be actively inhibited by CD4-mediated signals. Indeed, release of CD4+CD8+ thymocytes from CD4-mediated signals resulted in significant increases in both TCR expression and signaling function. These results suggest that, in CD4+CD8+ cells developing in the thymus, increased TCR expression and function requires release from CD4-mediated inhibition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakayama, T -- June, C H -- Munitz, T I -- Sheard, M -- McCarthy, S A -- Sharrow, S O -- Samelson, L E -- Singer, A -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1558-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2120773" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Antigens, CD4/*immunology ; Antigens, CD8 ; Antigens, Differentiation, T-Lymphocyte/*immunology ; Cell Membrane/immunology ; Cells, Cultured ; Histocompatibility Antigens Class II/immunology ; Mice ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell/biosynthesis/*physiology ; T-Lymphocytes/*immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 17
    Publication Date: 1990-01-26
    Description: The finding that astrocytes possess glutamate-sensitive ion channels hinted at a previously unrecognized signaling role for these cells. Now it is reported that cultured hippocampal astrocytes can respond to glutamate with a prompt and oscillatory elevation of cytoplasmic free calcium, visible through use of the fluorescent calcium indicator fluo-3. Two types of glutamate receptor--one preferring quisqualate and releasing calcium from intracellular stores and the other preferring kainate and promoting surface-membrane calcium influx--appear to be involved. Moreover, glutamate-induced increases in cytoplasmic free calcium frequently propagate as waves within the cytoplasm of individual astrocytes and between adjacent astrocytes in confluent cultures. These propagating waves of calcium suggest that networks of astrocytes may constitute a long-range signaling system within the brain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cornell-Bell, A H -- Finkbeiner, S M -- Cooper, M S -- Smith, S J -- GM 07205/GM/NIGMS NIH HHS/ -- NS-12961-14/NS/NINDS NIH HHS/ -- NS16671-09/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Jan 26;247(4941):470-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Molecular Neurobiology, Howard Hughes Medical Institute, New Haven, CT.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1967852" target="_blank"〉PubMed〈/a〉
    Keywords: Aniline Compounds ; Astrocytes/drug effects/*metabolism ; Calcium/*metabolism ; Cells, Cultured ; Cytoplasm/metabolism ; Fluorescent Dyes ; Glutamates/*pharmacology ; Glutamic Acid ; Hippocampus/cytology ; Intercellular Junctions/metabolism ; Kainic Acid/metabolism/pharmacology ; Oxadiazoles/metabolism/pharmacology ; Periodicity ; Quisqualic Acid ; Receptors, Glutamate ; Receptors, Neurotransmitter/physiology ; Xanthenes
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  • 18
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-03-30
    Description: The ras proto-oncogene products appear to relay intracellular signals via the Ras guanosine triphosphatase (GTPase) activator protein, GAP. In dog epithelial cells expressing human platelet-derived growth factor (PDGF) receptors, binding of PDGF caused approximately one-tenth of the total GAP molecules to complex with the receptor. Studies with mutant PDGF receptors showed that maximum association required both receptor kinase activity and phosphorylatable tyrosine residues at both the identified sites of receptor autophosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kazlauskas, A -- Ellis, C -- Pawson, T -- Cooper, J A -- CA-28151/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 30;247(4950):1578-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fred Hutchinson Cancer Research Center, Seattle, WA 98104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2157284" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Electrophoresis, Gel, Two-Dimensional ; Electrophoresis, Polyacrylamide Gel ; GTP Phosphohydrolases/metabolism ; GTPase-Activating Proteins ; Humans ; Immunoblotting ; Oncogene Protein p21(ras)/metabolism ; Peptide Mapping ; Phosphopeptides/analysis ; Phosphorylation ; Platelet-Derived Growth Factor/*metabolism ; Precipitin Tests ; Protein Kinases/analysis ; Proteins/*metabolism ; Receptors, Cell Surface/*metabolism ; Receptors, Platelet-Derived Growth Factor ; Tyrosine/metabolism ; ras GTPase-Activating Proteins
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1990 Oct 12;250(4978):206-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Culture Techniques/methods ; Neurons/cytology/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-07-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):239.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2374922" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/*legislation & jurisprudence ; California ; Cells, Cultured ; Humans ; Informed Consent/*legislation & jurisprudence ; Research
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 21
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-11-30
    Description: Deep inflation of the lung stimulates surfactant secretion by unknown mechanisms. The hypothesis that mechanical distension directly stimulates type II cells to secrete surfactant was tested by stretching type II cells cultured on silastic membranes. The intracellular Ca2+ concentration was measured in single cells, before and after stretching. A single stretch of alveolar type II cells caused a transient (less than 60 seconds) increase in cytosolic Ca2+ followed by a sustained (15 to 30 minutes) stimulation of surfactant secretion. Both Ca2+ mobilization and exocytosis exhibited dose-dependence to the magnitude of the stretch-stimulus. Thus, mechanical factors can trigger complex cellular events in nonneuron, nonmuscle cells and may be involved in regulating normal lung functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wirtz, H R -- Dobbs, L G -- HL-24075/HL/NHLBI NIH HHS/ -- HL-34356/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 30;250(4985):1266-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Institute, University of California, San Francisco 94143-0130.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2173861" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Calcium/*metabolism ; Cells, Cultured ; Cyclic AMP/metabolism ; Epithelium/physiology ; *Exocytosis ; Kinetics ; Phosphatidylcholines/secretion ; Proteolipids/pharmacology ; Pulmonary Alveoli/*physiology ; Pulmonary Surfactant-Associated Proteins ; Pulmonary Surfactants/pharmacology/secretion ; Rats ; Surface Properties ; Tetradecanoylphorbol Acetate/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 22
    Publication Date: 1990-04-13
    Description: The product of the c-abl proto-oncogene (c-Abl) is phosphorylated on three sites during interphase and seven additional sites during mitosis. Two interphase and all mitotic c-Abl sites are phosphorylated by cdc2 kinase isolated from either interphase or mitotic cells, with the mitotic cdc2 having an 11-fold higher activity. Inhibition of phosphatases with okadaic acid in interphase cells leads to the phosphorylation of c-Abl mitotic sites, indicating that those sites are preferentially dephosphorylated during interphase. The differential phosphorylation of c-Abl in the cell cycle is therefore determined by an equilibrium between cdc2 kinase and protein phosphatase activities. Treatment of interphase cells with okadaic acid leads to a rounded morphology similar to that observed during mitosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kipreos, E T -- Wang, J Y -- CA43054/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 13;248(4952):217-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, San Diego, La Jolla 92093.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2183353" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; CDC2 Protein Kinase ; *Cell Cycle ; Cells, Cultured ; Ethers, Cyclic/pharmacology ; Interphase/drug effects ; Mice ; Mice, Inbred Strains ; Molecular Sequence Data ; Molecular Weight ; Okadaic Acid ; Peptide Fragments/isolation & purification ; Peptide Mapping ; Phosphoproteins/*metabolism ; Phosphorylation ; Protein-Tyrosine Kinases/*metabolism ; Proto-Oncogene Proteins/isolation & purification/*metabolism ; Proto-Oncogene Proteins c-abl
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  • 23
    Publication Date: 1990-07-06
    Description: Kinesin is a mechanochemical protein that converts the chemical energy in adenosine triphosphate into mechanical force for movement of cellular components along microtubules. The regions of the kinesin molecule responsible for generating movement were determined by studying the heavy chain of Drosophila kinesin, and its truncated forms, expressed in Escherichia coli. The results demonstrate that (i) kinesin heavy chain alone, without the light chains and other eukaryotic factors, is able to induce microtubule movement in vitro, and (ii) a fragment likely to contain only the kinesin head is also capable of inducing microtubule motility. Thus, the amino-terminal 450 amino acids of kinesin contain all the basic elements needed to convert chemical energy into mechanical force.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, J T -- Saxton, W M -- Stewart, R J -- Raff, E C -- Goldstein, L S -- GM35252/GM/NIGMS NIH HHS/ -- HD16739/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1990 Jul 6;249(4964):42-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2142332" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/biosynthesis/genetics/*physiology ; Amino Acid Sequence ; Animals ; Base Sequence ; Cells, Cultured ; Drosophila ; Escherichia coli/genetics/metabolism ; Kinesin ; Male ; Microtubule Proteins/biosynthesis/genetics/*physiology ; Microtubules/*physiology ; Molecular Sequence Data ; Movement ; Peptide Fragments/biosynthesis/genetics/*physiology ; Plasmids ; Recombinant Proteins/biosynthesis/genetics/physiology ; Sea Urchins ; Spermatozoa/physiology
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  • 24
    Publication Date: 1990-10-12
    Description: The amyloid beta protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid beta protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid beta protein caused dendritic and axonal retraction followed by neuronal death. A portion of the amyloid beta protein (amino acids 25 to 35) mediated both the trophic and toxic effects and was homologous to the tachykinin neuropeptide family. The effects of the amyloid beta protein were mimicked by tachykinin antagonists and completely reversed by specific tachykinin agonists. Thus, the amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yankner, B A -- Duffy, L K -- Kirschner, D A -- AG08572/AG/NIA NIH HHS/ -- NS01240/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Oct 12;250(4978):279-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218531" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amyloid beta-Peptides/antagonists & inhibitors/*pharmacology ; Animals ; Cells, Cultured ; Embryo, Mammalian ; Hippocampus/cytology ; Molecular Sequence Data ; Neurons/*cytology/drug effects ; *Neurotoxins ; Peptide Fragments/pharmacology ; Rats ; Tachykinins/*pharmacology
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  • 25
    Publication Date: 1990-10-12
    Description: Most rhythmic behaviors such as respiration, locomotion, and feeding are under the control of networks of neurons in the central nervous system known as central pattern generators (CPGs). The respiratory rhythm of the pond snail Lymnaea stagnalis is a relatively simple, CPG-based behavior for which the underlying neural elements have been identified. A three-neuron network capable of generating the respiratory rhythm of this air-breathing mollusk has been reconstructed in culture. The intrinsic and network properties of this neural ensemble have been studied, and the mechanism of postinhibitory rebound excitation was found to be important for the rhythm generation. This in vitro model system enables a better understanding of the neural basis of rhythm generation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Syed, N I -- Bulloch, A G -- Lukowiak, K -- New York, N.Y. -- Science. 1990 Oct 12;250(4978):282-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neuroscience Research Group, University of Calgary, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218532" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Dopamine/physiology ; Evoked Potentials ; Ganglia/cytology/physiology ; Interneurons/physiology ; Lymnaea/*physiology ; Membrane Potentials ; Models, Biological ; *Oxygen Consumption ; Synapses/physiology
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  • 26
    Publication Date: 1990-07-13
    Description: Human neutrophils can initiate the rapid degradation of extracellular matrix macromolecules by localizing the destructive process to sites of cell-substrate contact. Although plasma and its filtrates contain multiple proteinase inhibitors, these inhibitors did not prevent neutrophils from attacking either underlying fibronectin or elastin. However, subjacent substrates could be protected from neutrophils by recombinant secretory leukoprotease inhibitor, a structurally unique serine proteinase inhibitor whose natural counterpart is normally confined to human mucous secretions. The identification of this extravascular proteinase inhibitor as a potent regulator of subjacent proteolysis could lead to the development of a new class of anti-inflammatory therapeutics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, W G -- Weiss, S J -- AI 21301/AI/NIAID NIH HHS/ -- HL 28024/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jul 13;249(4965):178-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Simpson Memorial Research Institute, University of Michigan, Ann Arbor 48109.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2371565" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Adhesion ; Cells, Cultured ; Elastin/metabolism ; Extracellular Matrix/*metabolism ; Fibronectins/metabolism ; Humans ; Neutrophils/*metabolism ; Proteinase Inhibitory Proteins, Secretory ; *Proteins ; Recombinant Proteins/metabolism ; Serine Proteinase Inhibitors/*metabolism ; Solubility
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  • 27
    Publication Date: 1990-06-29
    Description: The presence of endothelin, a vasoconstrictor peptide, in the hypothalamus and posterior pituitary suggests that it also regulates neural and other nonvascular target cells. In pituitary gonadotrophs, low doses of endothelin evoked oscillations in the intracellular calcium concentration, and high doses induced a biphasic calcium response. Mobilization of intracellular calcium predominated during the spike phase of the calcium response to endothelin, whereas calcium entry through dihydropyridine-sensitive channels contributed to both the spike and plateau phases of the calcium response. Endothelin was a potent as hypothalamic gonadotropin-releasing hormone (GnRH) in stimulation of gonadotropin release in perifused pituitary cells. Endothelin bound specifically to pituitary cells with a dissociation constant of 70 picomolar, and induced rapid formation of inositol trisphosphate and diacyglycerol. Although intracellular calcium concentration and gonadotropin secretory responses to endothelin were independent to the GnRH receptor, endothelin and GnRH appeared to have a common signal transduction mechanism. These observations suggest that endothelin can act as a neuropeptide to regulate anterior pituitary function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stojilkovic, S S -- Merelli, F -- Iida, T -- Krsmanovic, L Z -- Catt, K J -- New York, N.Y. -- Science. 1990 Jun 29;248(4963):1663-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2163546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Cells, Cultured ; Cytosol/metabolism ; Endothelins ; Endothelium, Vascular ; Female ; Follicle Stimulating Hormone/*secretion ; Gonadotropin-Releasing Hormone/pharmacology ; Kinetics ; Luteinizing Hormone/*secretion ; Male ; Nifedipine/pharmacology ; Orchiectomy ; Peptides/metabolism/*pharmacology ; Pituitary Gland, Anterior/drug effects/*metabolism/secretion ; Rats ; Rats, Inbred Strains ; Receptors, Cell Surface/metabolism ; Receptors, Endothelin ; Reference Values
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  • 28
    Publication Date: 1990-06-29
    Description: Platelet-derived growth factor (PDGF) induction of DNA synthesis is believed to involve activation of phospholipase C (PLC) and subsequent accumulation of inositol 1,4,5-triphosphate [I(1,4,5)P3], increase in intracellular Ca2+, activation of protein kinase C (PKC), and receptor down regulation. Generation of these events is triggered by the tyrosine protein kinase (TPK) activity of the PDGF receptor. The TPK inhibitor genistein blocked PDGF induction of these events, including DNA synthesis, with the exception of receptor down regulation. PDGF-induced phosphotyrosine phosphorylations, including receptor autophosphorylation, were inhibited by genistein. Removal of genistein and PDGF resulted in DNA synthesis without the occurrence of PLC activation. These findings indicate that these early events, with the exception of receptor down regulation, are not necessary for PDGF-induced DNA synthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hill, T D -- Dean, N M -- Mordan, L J -- Lau, A F -- Kanemitsu, M Y -- Boynton, A L -- CA 2942/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 29;248(4963):1660-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2163545" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Cells, Cultured ; Chlorides/pharmacology ; DNA Replication/*drug effects ; Dimethyl Sulfoxide/pharmacology ; Enzyme Activation ; Genistein ; Inositol Phosphates/metabolism ; Isoflavones/pharmacology ; Kinetics ; Lithium/pharmacology ; Lithium Chloride ; Mice ; Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositols/metabolism ; Phosphorylation ; Platelet-Derived Growth Factor/*pharmacology ; Protein Kinase C/metabolism ; Protein-Tyrosine Kinases/metabolism ; Type C Phospholipases/*metabolism
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  • 29
    Publication Date: 1990-06-08
    Description: Cytolytic T lymphocyte (CTL) responses were evaluated in humans immunized with recombinant human immunodeficiency virus type 1 (HIV) envelope glycoprotein gp160. Some vaccinees had gp160-specific CTLs that were shown by cloning to be CD4+. Although induced by exogenous antigen, most gp160-specific CTL clones also recognized gp160 synthesized endogenously in target cells. These clones lysed autologous CD4+ T lymphoblasts infected with HIV. Of particular interest were certain vaccine-induced clones that lysed HIV-infected cells, recognized gp160 from diverse HIV isolates, and did not participate in "innocent bystander" killing of noninfected CD4+ T cells that had bound gp120.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Orentas, R J -- Hildreth, J E -- Obah, E -- Polydefkis, M -- Smith, G E -- Clements, M L -- Siliciano, R F -- 5T32CA09243/CA/NCI NIH HHS/ -- AI28108/AI/NIAID NIH HHS/ -- N01AI62515/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1990 Jun 8;248(4960):1234-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2190315" target="_blank"〉PubMed〈/a〉
    Keywords: Cells, Cultured ; Clone Cells ; Cytotoxicity, Immunologic ; Gene Products, env/*immunology ; HIV/*immunology ; HIV Envelope Protein gp160 ; HIV Seropositivity ; Humans ; Immunization ; Macromolecular Substances ; Protein Precursors/*immunology ; Recombinant Proteins/immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Vaccines/*immunology
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  • 30
    Publication Date: 1990-03-23
    Description: Cell cycle-regulated gene expression is essential for normal cell growth and development and loss of stringent growth control is associated with the acquisition of the transformed phenotype. The selective synthesis of histone proteins during the S phase of the cell cycle is required to render cells competent for the ordered packaging of replicating DNA into chromatin. Regulation of H4 histone gene transcription requires the proliferation-specific promoter binding factor HiNF-D. In normal diploid cells, HiNF-D binding activity is regulated during the cell cycle; nuclear protein extracts prepared from normal cells in S phase contain distinct and measurable HiNF-D binding activity, while this activity is barely detectable in G1 phase cells. In contrast, in tumor-derived or transformed cell lines, HiNF-D binding activity is constitutively elevated throughout the cell cycle and declines only with the onset of differentiation. The change from cell cycle-mediated to constitutive interaction of HiNF-D with the promoter of a cell growth-controlled gene is consistent with, and may be functionally related to, the loss of stringent cell growth regulation associated with neoplastic transformation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holthuis, J -- Owen, T A -- van Wijnen, A J -- Wright, K L -- Ramsey-Ewing, A -- Kennedy, M B -- Carter, R -- Cosenza, S C -- Soprano, K J -- Lian, J B -- New York, N.Y. -- Science. 1990 Mar 23;247(4949 Pt 1):1454-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2321007" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Cycle/*genetics ; Cell Line, Transformed ; Cells, Cultured ; DNA/genetics ; DNA-Binding Proteins/*metabolism ; Gene Expression Regulation, Neoplastic ; Histones/*genetics ; Humans ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; *Promoter Regions, Genetic ; RNA, Messenger/analysis ; Rats ; Sequence Homology, Nucleic Acid ; Transcription, Genetic ; Tumor Cells, Cultured
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  • 31
    Publication Date: 1990-03-23
    Description: The development and maintenance of the nervous system depends on proteins known as neurotrophic factors. Although the prototypical neurotrophic factor, nerve growth factor (NGF), has been intensively studied for decades, the discovery and characterization of additional such factors has been impeded by their low abundance. Sequence homologies between NGF and the recently cloned brain-derived neurotrophic factor (BDNF) were used to design a strategy that has now resulted in the cloning of a gene encoding a novel neurotrophic factor, termed neurotrophin-3 (NT-3). The distribution of NT-3 messenger RNA and its biological activity on a variety of neuronal populations clearly distinguish NT-3 from NGF and BDNF, and provide compelling evidence that NT-3 is an authentic neurotrophic factor that has its own characteristic role in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maisonpierre, P C -- Belluscio, L -- Squinto, S -- Ip, N Y -- Furth, M E -- Lindsay, R M -- Yancopoulos, G D -- New York, N.Y. -- Science. 1990 Mar 23;247(4949 Pt 1):1446-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2321006" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Brain-Derived Neurotrophic Factor ; Cells, Cultured ; Cloning, Molecular ; DNA/genetics ; Mice ; Molecular Sequence Data ; Nerve Growth Factors/biosynthesis/*genetics/physiology ; Nerve Tissue Proteins/biosynthesis/*genetics/physiology ; Neurons/physiology ; Polymerase Chain Reaction ; Rats ; Restriction Mapping ; Sequence Homology, Nucleic Acid
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  • 32
    Publication Date: 1990-08-17
    Description: The mechanisms underlying structural changes that accompany learning and memory have been difficult to investigate in the intact nervous system. In order to make these changes more accessible for experimental analysis, dissociated cell culture and low-light-level video microscopy were used to examine Aplysia sensory neurons in the presence or absence of their target cells. Repeated applications of serotonin, a facilitating transmitter important in behavioral dishabituation and sensitization, produced growth of the sensory neurons that paralleled the long-term enhancement of synaptic strength. This growth required the presence of the postsynaptic motor neuron. Thus, both the structural changes and the synaptic facilitation of Aplysia sensorimotor synapses accompanying long-term behavioral sensitization can be produced in vitro by applying a single facilitating transmitter repeatedly. These structural changes depend on an interaction of the presynaptic neuron with an appropriate postsynaptic target.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glanzman, D L -- Kandel, E R -- Schacher, S -- GM 323099/GM/NIGMS NIH HHS/ -- NS 19595/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):799-802.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2389145" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aplysia/physiology/*ultrastructure ; Axons/ultrastructure ; Cells, Cultured ; Fluoresceins ; Fluorescent Dyes ; Memory/physiology ; Microscopy, Fluorescence ; Neurons, Afferent/drug effects/physiology/*ultrastructure ; Serotonin/pharmacology ; Synapses/physiology/*ultrastructure
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  • 33
    Publication Date: 1990-08-03
    Description: Human immunodeficiency virus (HIV) frequently causes neurological dysfunction and is abundantly expressed in the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients with HIV encephalitis or myelopathy. The virus is found mostly in cells of the monocyte-macrophage lineage within the CNS, but the possibility of infection of other glial cells has been raised. Therefore, the effects of different HIV-1 and HIV-2 strains were studied in primary cultures of adult human brain containing microglial cells, the resident CNS macrophages, and astrocytes. These cultures could be productively infected with macrophage-adapted HIV-1 isolates but not with T lymphocyte-adapted HIV-1 isolates or two HIV-2 isolates. As determined with a triple-label procedure, primary astrocytes did not express HIV gag antigens and remained normal throughout the 3-week course of infection. In contrast, virus replicated in neighboring microglial cells, often leading to their cell fusion and death. The death of microglial cells, which normally serve immune functions in the CNS, may be a key factor in the pathogenesis of AIDS encephalitis or myelopathy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watkins, B A -- Dorn, H H -- Kelly, W B -- Armstrong, R C -- Potts, B J -- Michaels, F -- Kufta, C V -- Dubois-Dalcq, M -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):549-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2200125" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Brain/*microbiology ; Cells, Cultured ; Fluorescent Antibody Technique ; HIV-1/pathogenicity/*physiology ; HIV-2/pathogenicity/physiology ; Humans ; Kinetics ; Neuroglia/*microbiology ; Species Specificity ; Virus Replication
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-06-15
    Description: T lymphocytes respond to foreign antigens both by producing protein effector molecules known as lymphokines and by multiplying. Complete activation requires two signaling events, one through the antigen-specific receptor and one through the receptor for a costimulatory molecule. In the absence of the latter signal, the T cell makes only a partial response and, more importantly, enters an unresponsive state known as clonal anergy in which the T cell is incapable of producing its own growth hormone, interleukin-2, on restimulation. Our current understanding at the molecular level of this modulatory process and its relevance to T cell tolerance are reviewed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwartz, R H -- New York, N.Y. -- Science. 1990 Jun 15;248(4961):1349-56.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2113314" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/immunology ; Antigens, CD4/immunology ; Antigens, CD8 ; Antigens, Differentiation, T-Lymphocyte/immunology ; Cells, Cultured ; Clone Cells/*immunology ; Gene Expression Regulation ; Gene Rearrangement, T-Lymphocyte ; *Immune Tolerance ; Interleukin-2/biosynthesis/genetics ; Mice ; *Models, Biological ; Receptors, Antigen, T-Cell/genetics/immunology ; Second Messenger Systems ; Signal Transduction ; T-Lymphocytes/*immunology ; Thymus Gland/immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 35
    Publication Date: 1990-01-26
    Description: Airway eosinophilia, epithelial desquamation, and hyperresponsiveness are characteristics of the airway inflammation underlying bronchial asthma. The contribution of intercellular adhesion molecule-1 (ICAM-1) to eosinophil migration and airway responsiveness was studied. ICAM-1 partially mediated eosinophil adhesion to to endothelium in vitro and was upregulated on inflamed bronchial endothelium in vivo. ICAM-1 expression was also upregulated on inflamed airway epithelium in vitro and in vivo. In a primate model of asthma, a monoclonal antibody to ICAM-1 attenuated airway eosinophilia and hyperresponsiveness. Thus, antagonism of ICAM-1 may provide a therapeutic approach to reducing airway inflammation, hyperresponsiveness, and asthma symptoms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wegner, C D -- Gundel, R H -- Reilly, P -- Haynes, N -- Letts, L G -- Rothlein, R -- New York, N.Y. -- Science. 1990 Jan 26;247(4941):456-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1967851" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Antigens/immunology ; Asthma/immunology/pathology/*physiopathology ; Cell Adhesion ; Cell Adhesion Molecules/analysis/immunology/*physiology ; Cells, Cultured ; Endothelium/pathology ; Eosinophils/*pathology ; Epithelium/metabolism ; Humans ; Immunization, Passive ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; Interferon-gamma/pharmacology ; Interleukin-1/pharmacology ; Lung/metabolism/pathology ; Macaca fascicularis ; Recombinant Proteins ; Tumor Necrosis Factor-alpha/pharmacology
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  • 36
    Publication Date: 1993-01-01
    Description: A myelin-associated protein from the central nervous system, the neurite growth inhibitor NI-35, inhibits regeneration of lesioned neuronal fiber tracts in vivo and growth of neurites in vitro. Growth cones of cultured rat dorsal root ganglion neurons arrested their growth and collapsed when exposed to liposomes containing NI-35. Before morphological changes, the concentration of free intracellular calcium ([Ca2+]i) showed a rapid and large increase in growth cones exposed to liposomes containing NI-35. Neither an increase in [Ca2+]i nor collapse of growth cones was detected in the presence of antibodies to NI-35. Dantrolene, an inhibitor of calcium release from caffeine-sensitive intracellular calcium stores, protected growth cones from collapse evoked by NI-35. Depletion of these caffeine-sensitive intracellular calcium stores prevented the increase in [Ca2+]i evoked by NI-35. The NI-35-evoked cascade of intracellular messengers that mediates collapse of growth cones includes the crucial step of calcium release from intracellular stores.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bandtlow, C E -- Schmidt, M F -- Hassinger, T D -- Schwab, M E -- Kater, S B -- NS24683/NS/NINDS NIH HHS/ -- NS28323/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 1;259(5091):80-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brain Research Institute, University of Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8418499" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caffeine/pharmacology ; Calcium/*metabolism ; Cells, Cultured ; Drug Carriers ; Fura-2 ; Ganglia, Spinal/*physiology ; Growth Inhibitors/*pharmacology ; Kinetics ; Liposomes ; Nerve Fibers/drug effects/*physiology/ultrastructure ; Neurons/drug effects/*physiology/ultrastructure ; Rats
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  • 37
    Publication Date: 1993-10-15
    Description: In cystic fibrosis (CF), absence or dysfunction of a phosphorylation-regulated chloride channel [CF transmembrane conductance regulator (CFTR)] leads to the loss or reduction of chloride secretion into the airways. Active sodium absorption is also increased in CF, and both of these ion transport changes could alter fluid transport across the airways. Under baseline conditions, cultured human airway epithelia from normal individuals absorbed fluid, and this absorption was increased in epithelia from patients with CF. In normal and CF epithelial cultures fluid absorption was inhibited by amiloride. Adenosine 3',5'-monophosphate stimulated fluid secretion in normal epithelial cultures but not in cultures from individuals with CF. In contrast, fluid secretion induced by nucleotide triphosphates (uridine triphosphate or adenosine triphosphate) was unaltered in cultures of epithelia from patients with CF, suggesting an approach to the treatment of CF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, C -- Finkbeiner, W E -- Widdicombe, J H -- McCray, P B Jr -- Miller, S S -- HL 42368/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 15;262(5132):424-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211164" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; Adenosine Triphosphate/pharmacology ; Adolescent ; Adult ; Amiloride/pharmacology ; Body Fluids/*metabolism ; Cells, Cultured ; Cyclic AMP/pharmacology ; Cystic Fibrosis/*metabolism ; Epithelial Cells ; Epithelium/metabolism ; Female ; Humans ; Male ; Middle Aged ; Nasal Mucosa/cytology/*metabolism ; Sodium/metabolism ; Sodium Channels/metabolism ; Trachea/cytology/*metabolism ; Uridine Triphosphate/pharmacology
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  • 38
    Publication Date: 1993-05-21
    Description: A potent neurotrophic factor that enhances survival of midbrain dopaminergic neurons was purified and cloned. Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer that is a distantly related member of the transforming growth factor-beta superfamily. In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake. These effects were relatively specific; GDNF did not increase total neuron or astrocyte numbers nor did it increase transmitter uptake by gamma-aminobutyric-containing and serotonergic neurons. GDNF may have utility in the treatment of Parkinson's disease, which is marked by progressive degeneration of midbrain dopaminergic neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, L F -- Doherty, D H -- Lile, J D -- Bektesh, S -- Collins, F -- New York, N.Y. -- Science. 1993 May 21;260(5111):1130-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Synergen, Inc., Boulder, CO 80301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493557" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Astrocytes/cytology/drug effects ; Base Sequence ; Cell Differentiation/drug effects ; Cell Line ; Cell Survival/drug effects ; Cells, Cultured ; Cloning, Molecular ; Dopamine/*biosynthesis ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Mesencephalon/cytology/*drug effects/metabolism ; Molecular Sequence Data ; Molecular Weight ; *Nerve Growth Factors ; Nerve Tissue Proteins/chemistry/genetics/isolation & purification/*pharmacology ; Neuroglia/*metabolism ; Neurons/cytology/*drug effects/metabolism ; Parkinson Disease/drug therapy ; Rats
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1993 Feb 5;259(5096):762-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430328" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/physiology ; Caenorhabditis elegans/embryology/genetics ; Cell Death/*physiology ; Cells, Cultured ; Embryo, Nonmammalian/physiology ; Nerve Growth Factors/physiology ; Nervous System/cytology/*embryology ; Neurons/cytology/*physiology ; Protein-Tyrosine Kinases/genetics ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogenes
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-02
    Description: Histamine is a neuromodulator in the brain, and the hippocampus is one of the regions of the brain that is innervated by histaminergic neurons. When applied to cultured hippocampal neurons, histamine selectively increased by up to tenfold the amplitude of the component of synaptic transmission that was mediated by N-methyl-D-aspartate (NMDA) receptors. Spontaneous miniature synaptic currents and the current elicited by applied NMDA also were enhanced, indicating that the histamine effect was expressed primarily postsynaptically. These results suggest that histamine may modulate processes involving NMDA receptors, such as the induction of long-term potentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bekkers, J M -- New York, N.Y. -- Science. 1993 Jul 2;261(5117):104-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, John Curtin School of Medical Research, Australian National Univresity, Canberra, ACT.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8391168" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Cells, Cultured ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Hippocampus/cytology/drug effects/*physiology ; Histamine/*pharmacology ; Ion Channel Gating/drug effects ; N-Methylaspartate/*metabolism/pharmacology ; Rats ; Receptors, Histamine/physiology ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/*physiology ; Synaptic Transmission/*drug effects ; Virulence Factors, Bordetella/pharmacology
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-02
    Description: The diversity of the T cell receptor repertoire is generated by rearrangement of gene elements in immature thymocytes. To identify a thymic signal that induces this rearrangement, a variety of agents were tested for their ability to induce rearrangement of the T cell receptor beta gene in suspensions of thymocytes from mouse embryos at day 14 of gestation. Of 16 agents tested, only interleukin-7 (IL-7) induced V(D)J gene rearrangement and sustained expression of the RAG-1 and RAG-2 genes, which are known to control rearrangement. These data implicate IL-7, a cytokine that is abundantly expressed in embryonic thymus, in driving gene rearrangement during early T cell development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muegge, K -- Vila, M P -- Durum, S K -- New York, N.Y. -- Science. 1993 Jul 2;261(5117):93-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biological Carcinogenesis and Development Program, Program Resources Inc./Dyncorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7686307" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Cell Survival/drug effects ; Cells, Cultured ; *DNA-Binding Proteins ; Gene Expression ; *Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Genes, RAG-1 ; Hematopoietic Cell Growth Factors/pharmacology ; Interleukin-7/*pharmacology ; Ionomycin/pharmacology ; Mice ; Molecular Sequence Data ; Organ Culture Techniques ; Proteins/genetics ; Stem Cell Factor ; T-Lymphocytes/cytology/*immunology ; Tetradecanoylphorbol Acetate/pharmacology ; Thymus Gland/embryology/immunology ; Tumor Cells, Cultured
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-06-04
    Description: Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaku, D A -- Giffard, R G -- Choi, D W -- NS 01425/NS/NINDS NIH HHS/ -- NS 26907/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 4;260(5113):1516-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8389056" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Death/drug effects ; Cell Hypoxia/physiology ; Cells, Cultured ; Cerebral Cortex/cytology ; *Excitatory Amino Acid Antagonists ; Extracellular Space/*metabolism ; Glucose/deficiency ; *Hydrogen-Ion Concentration ; L-Lactate Dehydrogenase/metabolism ; Mice ; Nerve Degeneration/drug effects ; Neurons/*drug effects/enzymology ; Receptors, AMPA ; Receptors, Kainic Acid ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
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  • 43
    Publication Date: 1993-09-10
    Description: Interferons (IFNs) induce antiviral activity in many cell types. The ability of IFN-gamma to inhibit replication of ectromelia, vaccinia, and herpes simplex-1 viruses in mouse macrophages correlated with the cells' production of nitric oxide (NO). Viral replication was restored in IFN-gamma-treated macrophages exposed to inhibitors of NO synthase. Conversely, epithelial cells with no detectable NO synthesis restricted viral replication when transfected with a complementary DNA encoding inducible NO synthase or treated with organic compounds that generate NO. In mice, an inhibitor of NO synthase converted resolving ectromelia virus infection into fulminant mousepox. Thus, induction of NO synthase can be necessary and sufficient for a substantial antiviral effect of IFN-gamma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karupiah, G -- Xie, Q W -- Buller, R M -- Nathan, C -- Duarte, C -- MacMicking, J D -- CA43610/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 10;261(5127):1445-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7690156" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Oxidoreductases/*biosynthesis/metabolism ; Animals ; Arginine/analogs & derivatives/pharmacology ; Cell Line ; Cells, Cultured ; Ectromelia virus/drug effects/*physiology ; Ectromelia, Infectious/microbiology ; Enzyme Induction ; Female ; Humans ; Interferon-gamma/*pharmacology ; Macrophages/*microbiology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism/pharmacology ; Nitric Oxide Synthase ; Simplexvirus/drug effects/physiology ; Transfection ; Vaccinia virus/drug effects/physiology ; *Virus Replication/drug effects ; omega-N-Methylarginine
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  • 44
    Publication Date: 1993-04-02
    Description: Murine neural precursor cells and cell lines derived from them are stimulated by members of the heparin-binding fibroblast growth factor (FGF) family. The activity of FGF is regulated by heparan sulfate proteoglycans (HSPGs), and this interaction is an essential prerequisite for the binding of growth factor to the signal transducing receptors. Messenger RNA for FGF-2 was detectable in the neuroepithelium at embryonic day 9, and the HSPGs produced by these cells at this time preferentially bound FGF-2. However, at embryonic day 11, when messenger RNA for FGF-1 was first detectable, there was a switch in the binding specificity of the HSPG to FGF-1. Thus, a single species of HSPG undergoes a rapid, tightly controlled change in growth factor-binding specificity concomitant with the temporal expression of the FGFs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nurcombe, V -- Ford, M D -- Wildschut, J A -- Bartlett, P F -- New York, N.Y. -- Science. 1993 Apr 2;260(5104):103-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7682010" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Division ; Cells, Cultured ; Culture Media, Conditioned ; Epithelium/chemistry/embryology ; Fibroblast Growth Factor 1/genetics/*pharmacology ; Fibroblast Growth Factor 2/genetics/*pharmacology ; Gene Expression ; Gestational Age ; Heparan Sulfate Proteoglycans ; Heparitin Sulfate/*pharmacology ; Mice ; Molecular Weight ; Nervous System/chemistry/*embryology/metabolism ; Neurons/cytology ; Polysaccharide-Lyases/metabolism ; Proteoglycans/*pharmacology ; RNA, Messenger/analysis ; Signal Transduction/physiology ; Stem Cells/cytology
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  • 45
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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〉Curtis, T -- New York, N.Y. -- Science. 1993 Jan 1;259(5091):14.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8418488" target="_blank"〉PubMed〈/a〉
    Keywords: *AIDS Vaccines ; Acquired Immunodeficiency Syndrome/immunology/*transmission ; Animals ; Cells, Cultured ; *Hiv-1 ; Haplorhini ; Humans ; Kidney ; Male
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  • 46
    Publication Date: 1993-02-05
    Description: beta-Adrenergic receptor kinase (beta ARK) and beta-arrestin function in the homologous or agonist-activated desensitization of G protein-coupled receptors. The isoforms beta ARK-2 and beta-arrestin-2 are highly enriched in and localized to the dendritic knobs and cilia of the olfactory receptor neurons where the initial events of olfactory signal transduction occur. Odorants induce a rapid and transient elevation of adenosine 3',5'-monophosphate (cAMP), which activates a nonspecific cation channel and produces membrane depolarization. Preincubation of rat olfactory cilia with antibodies raised against beta ARK-2 and beta-arrestin-2 increased the odorant-induced elevation of cAMP and attenuated desensitization. These results suggest that beta ARK-2 and beta-arrestin-2 mediate agonist-dependent desensitization in olfaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dawson, T M -- Arriza, J L -- Jaworsky, D E -- Borisy, F F -- Attramadal, H -- Lefkowitz, R J -- Ronnett, G V -- NS 01578-01/NS/NINDS NIH HHS/ -- NS-02131/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 5;259(5096):825-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins Medical Institutions, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8381559" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/*metabolism ; *Arrestins ; Cells, Cultured ; Cyclic AMP/metabolism ; *Cyclic AMP-Dependent Protein Kinases ; Cytosol/metabolism ; Dendrites/physiology ; Eye Proteins/*metabolism ; G-Protein-Coupled Receptor Kinase 2 ; GTP-Binding Proteins/*metabolism ; Isoenzymes/metabolism ; Male ; Mechanoreceptors/*physiology ; Neurons/*physiology ; *Odors ; Olfactory Bulb/*physiology ; Protein Kinases/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta/*physiology ; Signal Transduction ; *Smell ; Testis/physiology ; Turbinates/*physiology ; beta-Adrenergic Receptor Kinases
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  • 47
    Publication Date: 1993-06-11
    Description: Elevated blood concentrations of lipoprotein(a) [Lp(a)] and its constituent, apolipoprotein(a) [apo(a)], constitute a major risk factor for atherosclerosis, but their physiological activities remain obscure. Lp(a) and purified apo(a) stimulated the growth of human smooth muscle cells in culture. This effect resulted from inhibition of plasminogen activation, and consequently the activation by plasmin of latent transforming growth factor-beta, which is an inhibitor of smooth muscle cell growth. Because smooth muscle proliferation is one of the hallmarks of atherosclerotic lesions, these results point to a plausible mechanism for the atherogenic activity of Lp(a).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grainger, D J -- Kirschenlohr, H L -- Metcalfe, J C -- Weissberg, P L -- Wade, D P -- Lawn, R M -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1993 Jun 11;260(5114):1655-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Cambridge, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8503012" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apolipoproteins/physiology ; Apoprotein(a) ; Cell Division/drug effects/physiology ; Cells, Cultured ; Fibrinolysin/physiology ; Humans ; Lipoprotein(a)/*physiology ; Muscle, Smooth, Vascular/*cytology/metabolism ; Plasminogen Activators/metabolism ; Rats ; Tamoxifen/pharmacology ; Transforming Growth Factor beta/physiology
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-11-12
    Description: Intense stimuli, such as trains of depolarizing pulses or the caffeine-induced release of calcium from intracellular stores, readily depress the secretory response in neuroendocrine cells. Secretory responses are restored by rest periods of minutes in duration. This recovery was accelerated when the concentration of cytosolic calcium was moderately increased and probably resulted from calcium-dependent replenishment of a pool of release-ready granules. Continuously increased concentrations of calcium led the over-filling of such a pool. Subsequently, secretory responses to stronger calcium stimuli were augmented. Hormone-induced calcium transients with a plateau phase of increased concentration of calcium may enhance the secretory response in this way.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Ruden, L -- Neher, E -- New York, N.Y. -- Science. 1993 Nov 12;262(5136):1061-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Membrane Biophysics, Max-Planck-Institut fur biophysikalische Chemie, Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235626" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenal Medulla/cytology/drug effects/metabolism/*secretion ; Animals ; Bradykinin/pharmacology ; Caffeine/pharmacology ; Calcium/*metabolism ; Catecholamines/metabolism/*secretion ; Cattle ; Cells, Cultured ; Chromaffin Granules/drug effects/*secretion ; Electric Conductivity ; Histamine ; Membrane Potentials ; Models, Biological ; Nystatin/pharmacology
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-10
    Description: Xlsirts are a family of interspersed repeat RNAs from Xenopus laevis that contain from 3 to 13 repeat units (each 79 to 81 nucleotides long) flanked by unique sequences. They are homologous to the mammalian Xist gene that is involved in X chromosome inactivation. Xlsirt RNA appears first in the mitochondrial cloud (Balbiani body) in stage 2 oocytes and is then translocated as island-like structures to the vegetal cortex at early stage 3 coincident with the localization of the germ plasm. Exogenous Xlsirt RNA injected into oocytes translocates to the location of the endogenous RNA at that particular stage. The Xlsirt RNA repeat sequences are required for translocation and can cause the translocation of heterologous unique RNAs to the vegetal cortex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kloc, M -- Spohr, G -- Etkin, L D -- New York, N.Y. -- Science. 1993 Dec 10;262(5140):1712-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Texas, M.D. Anderson Cancer Center, Houston 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7505061" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cells, Cultured ; Cloning, Molecular ; DNA, Complementary ; Female ; In Situ Hybridization ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oocytes/*metabolism ; Oogenesis ; RNA/chemistry/*metabolism ; *Repetitive Sequences, Nucleic Acid ; Xenopus laevis
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  • 50
    Publication Date: 1993-06-18
    Description: CD8+ T cells are a major defense against viral infections and intracellular parasites. Their production of interferon-gamma (IFN-gamma) and their cytolytic activity are key elements in the immune response to these pathogens. Mature mouse CD8+ T cells that were activated in the presence of interleukin-4 (IL-4) developed into a CD8-CD4- population that was not cytolytic and did not produce IFN-gamma. However, these CD8- cells produced large amounts of IL-4, IL-5, and IL-10 and helped activate resting B cells. Thus, CD8 effector functions are potentially diverse and could be exploited by infectious agents that switch off host protective cytolytic responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erard, F -- Wild, M T -- Garcia-Sanz, J A -- Le Gros, G -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1802-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Allergy/Immunology, Ciba-Geigy Ltd., Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8511588" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/analysis ; Antigens, CD8/*analysis ; B-Lymphocytes/*immunology ; Cell Line ; Cells, Cultured ; Cytotoxicity, Immunologic ; Immunophenotyping ; Interleukin-10/biosynthesis ; Interleukin-2/pharmacology ; Interleukin-4/biosynthesis/pharmacology ; Interleukin-5/biosynthesis ; Interleukins/*biosynthesis ; Ionomycin/pharmacology ; *Lymphocyte Activation ; Membrane Glycoproteins/genetics ; Mice ; Perforin ; Pore Forming Cytotoxic Proteins ; T-Lymphocyte Subsets/*immunology ; T-Lymphocytes, Cytotoxic/immunology ; Tetradecanoylphorbol Acetate/pharmacology
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  • 51
    Publication Date: 1993-01-29
    Description: A proportion of developing oligodendrocytes undergo natural cell death by apoptosis, and mature oligodendrocytes die, either by apoptosis or necrosis, in response to injurious signals such as cytotoxic cytokines and complement. Ciliary neurotrophic factor (CNTF), a trophic factor found in astrocytes in the central nervous system (CNS), promoted the survival and maturation of cultured oligodendrocytes. This trophic factor also protected oligodendrocytes from death induced by tumor necrosis factors (apoptosis) but not against complement (necrosis). These results suggest that CNTF functions in the survival of oligodendrocytes during development and may lead to therapeutic approaches for degenerative diseases of the CNS that involve oligodendrocyte destruction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Louis, J C -- Magal, E -- Takayama, S -- Varon, S -- NS16349/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 29;259(5095):689-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, San Diego, La Jolla 92093.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430320" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/physiology ; Cell Death/*drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Central Nervous System/physiology ; Ciliary Neurotrophic Factor ; Dose-Response Relationship, Drug ; Humans ; Kinetics ; Lymphotoxin-alpha/*pharmacology ; Nerve Growth Factors/*pharmacology ; Nerve Tissue Proteins/*pharmacology ; Oligodendroglia/cytology/drug effects/*physiology ; Recombinant Proteins/pharmacology ; Time Factors ; Tumor Necrosis Factor-alpha/*pharmacology
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  • 52
    Publication Date: 1993-01-15
    Description: Rab geranylgeranyl transferase (GG transferase) is a two-component enzyme that attaches 20-carbon isoprenoid groups to cysteine residues in Rab proteins, a family of guanosine triphosphate-binding proteins that regulate vesicular traffic. The mutant gene in human choroideremia, an X-linked form of retinal degeneration, encodes a protein that resembles component A of rat Rab GG transferase. Lymphoblasts from choroideremia subjects showed a marked deficiency in the activity of component A, but not component B, of Rab GG transferase. The deficiency was more pronounced when the substrate was Rab3A, a synaptic vesicle protein, than it was when the substrate was Rab1A, a protein of the endoplasmic reticulum. The data imply the existence of multiple component A proteins, one of which is missing in choroideremia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seabra, M C -- Brown, M S -- Goldstein, J L -- HL 20948/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 15;259(5093):377-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8380507" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Alkyl and Aryl Transferases ; Cell Line, Transformed ; Cells, Cultured ; Choroid/chemistry ; Choroideremia/*genetics ; Female ; GTP-Binding Proteins/analysis/*metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Lymphocyte Activation ; Male ; Middle Aged ; Mutation ; Nerve Tissue Proteins/analysis/*metabolism ; Photoreceptor Cells/chemistry ; Pigment Epithelium of Eye/chemistry ; Protein Prenylation ; Retina/chemistry ; Substrate Specificity ; Transferases/*deficiency/genetics ; rab1 GTP-Binding Proteins ; rab3 GTP-Binding Proteins
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  • 53
    Publication Date: 1993-01-29
    Description: Nonsense mutations create a premature signal for the termination of translation of messenger RNA. Such mutations have been observed to cause a severe reduction in the amount of mutant allele transcript or to generate a peptide truncated at the carboxyl end. Analysis of fibrillin transcript from a patient with Marfan syndrome revealed the skipping of a constitutive exon containing a nonsense mutation. Similar results were observed for two nonsense mutations in the gene encoding ornithine delta-aminotransferase from patients with gyrate atrophy. All genomic DNA sequences flanking these exons that are known to influence RNA splicing were unaltered, which suggests that nonsense mutations can alter splice site selection in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dietz, H C -- Valle, D -- Francomano, C A -- Kendzior, R J Jr -- Pyeritz, R E -- Cutting, G R -- AR-41135/AR/NIAMS NIH HHS/ -- HG-00373/HG/NHGRI NIH HHS/ -- RR-00722/RR/NCRR NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1993 Jan 29;259(5095):680-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430317" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cells, Cultured ; DNA/*genetics/isolation & purification ; *Exons ; Female ; Fibroblasts/physiology ; Humans ; Male ; Marfan Syndrome/*genetics ; Microfilament Proteins/*genetics ; Molecular Sequence Data ; *Mutation ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction/methods ; Reference Values
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  • 54
    Publication Date: 1993-10-22
    Description: Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunner, H G -- Nelen, M -- Breakefield, X O -- Ropers, H H -- van Oost, B A -- NS 21921/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 22;262(5133):578-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University Hospital Nijmegen, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211186" target="_blank"〉PubMed〈/a〉
    Keywords: *Aggression ; Cell Line ; Cells, Cultured ; Female ; *Genes ; Humans ; Intellectual Disability/enzymology/*genetics ; Male ; Monoamine Oxidase/deficiency/*genetics ; Pedigree ; Phenotype ; *Point Mutation ; Skin/enzymology ; Syndrome ; X Chromosome
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  • 55
    Publication Date: 1993-01-22
    Description: The function of neuropeptide Y, one of the most abundant peptide transmitters of the mammalian brain, remains unclear because of a lack of specific receptor antagonists. An antisense oligodeoxynucleotide corresponding to the NH2-terminus of the rat Y1 receptor was constructed and added to cultures of rat cortical neurons. This treatment resulted in a reduced density of Y1 (but not Y2) receptors and diminished the decrease in adenosine 3',5'-monophosphate (cAMP) usually seen after Y1 receptor activation. Repeated injection of the same oligodeoxynucleotide into the lateral cerebral ventricle of rats was followed by a similar reduction of cortical Y1 (but not Y2) receptors. Such antisense-treated animals displayed behavioral signs of anxiety. Thus, specific inhibition of neurotransmitter receptor expression can be accomplished in the living brain and demonstrates that altered central neuropeptide Y transmission produces an anxiety-like state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wahlestedt, C -- Pich, E M -- Koob, G F -- Yee, F -- Heilig, M -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):528-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8380941" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Anxiety ; Base Sequence ; Cells, Cultured ; Cerebral Cortex/*physiology ; Cyclic AMP/metabolism ; Down-Regulation ; Embryo, Mammalian ; Learning ; Male ; Molecular Sequence Data ; Neurons/drug effects/*physiology ; Neuropeptide Y/*physiology ; Oligodeoxyribonucleotides ; Oligonucleotides, Antisense/*pharmacology ; Polymerase Chain Reaction ; Rats ; Rats, Wistar ; Receptors, Neuropeptide Y/*drug effects/*genetics/metabolism
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  • 56
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-02
    Description: Regenerating optic nerves from fish produce a factor that is cytotoxic to oligodendrocytes. The cytotoxic factor is recognized by antibodies to interleukin-2 (IL-2) and has the apparent molecular size of a dimer of IL-2. An enzyme, identified as a nerve transglutaminase, was purified from regenerating optic nerves of fish and was found to catalyze dimerization of human IL-2. The dimerized IL-2, unlike monomeric IL-2, is cytotoxic to oligodendrocytes from rat brain in culture. The results suggest that posttranslational modification of a cytokine can alter its activity. Under conditions in which oligodendrocytes inhibit neuronal regeneration, dimerization of IL-2 might provide a mechanism to permit nerve growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eitan, S -- Schwartz, M -- New York, N.Y. -- Science. 1993 Jul 2;261(5117):106-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8100369" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Newborn ; Brain/cytology ; Cell Survival/drug effects ; Cells, Cultured ; Fishes ; Interleukin-2/*metabolism/pharmacology ; Molecular Sequence Data ; *Nerve Regeneration ; Oligodendroglia/cytology/*drug effects ; Optic Nerve/enzymology/*physiology ; Transglutaminases/isolation & purification/*metabolism
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  • 57
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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〉Marx, J -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):457-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8424167" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/etiology/genetics/*metabolism ; Amyloid beta-Peptides/biosynthesis/genetics/*metabolism ; Brain/*metabolism ; Cells, Cultured ; Humans ; Lysosomes/metabolism
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  • 58
    Publication Date: 1993-02-19
    Description: Ligand-gated ion channels gated by glutamate constitute the major excitatory neurotransmitter system in the mammalian brain. The functional modulation of GluR6, a kainate-activated glutamate receptor, by adenosine 3',5'-monophosphate-dependent protein kinase A (PKA) was examined with receptors expressed in human embryonic kidney cells. Kainate-evoked currents underwent a rapid desensitization that was blocked by lectins. Kainate currents were potentiated by intracellular perfusion of PKA, and this potentiation was blocked by co-application of an inhibitory peptide. Site-directed mutagenesis was used to identify the site or sites of phosphorylation on GluR6. Although mutagenesis of two serine residues, Ser684 and Ser666, was required for complete abolition of the PKA-induced potentiation, Ser684 may be the preferred site of phosphorylation in native GluR6 receptor complexes. These results indicate that glutamate receptor function can be directly modulated by protein phosphorylation and suggest that a dynamic regulation of excitatory receptors could be associated with some forms of learning and memory in the mammalian brain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, L Y -- Taverna, F A -- Huang, X P -- MacDonald, J F -- Hampson, D R -- New York, N.Y. -- Science. 1993 Feb 19;259(5098):1173-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8382377" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Brain/*physiology ; Cells, Cultured ; Concanavalin A/pharmacology ; Evoked Potentials/drug effects ; Humans ; Kainic Acid/*pharmacology ; Kidney ; Kinetics ; Membrane Potentials/drug effects ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligodeoxyribonucleotides ; Protein Kinases/*metabolism ; Receptors, Glutamate/drug effects/genetics/*physiology ; Receptors, Kainic Acid ; Serine ; Wheat Germ Agglutinins/pharmacology
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-21
    Description: Mechanical stresses were applied directly to cell surface receptors with a magnetic twisting device. The extracellular matrix receptor, integrin beta 1, induced focal adhesion formation and supported a force-dependent stiffening response, whereas nonadhesion receptors did not. The cytoskeletal stiffness (ratio of stress to strain) increased in direct proportion to the applied stress and required intact microtubules and intermediate filaments as well as microfilaments. Tensegrity models that incorporate mechanically interdependent struts and strings that reorient globally in response to a localized stress mimicked this response. These results suggest that integrins act as mechanoreceptors and transmit mechanical signals to the cytoskeleton. Mechanotransduction, in turn, may be mediated simultaneously at multiple locations inside the cell through force-induced rearrangements within a tensionally integrated cytoskeleton.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, N -- Butler, J P -- Ingber, D E -- CA45548/CA/NCI NIH HHS/ -- HL-33009/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 May 21;260(5111):1124-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Respiratory Biology Program, Harvard School of Public Health, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7684161" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/physiology ; Amino Acid Sequence ; Antigens, CD29 ; Cell Membrane/*physiology ; Cells, Cultured ; Cytoskeleton/*physiology ; Endothelium, Vascular/*cytology ; Integrins/*physiology ; Intermediate Filaments/physiology ; Magnetics ; Microspheres ; Microtubules/physiology ; Molecular Sequence Data ; Oligopeptides/metabolism ; *Signal Transduction ; Stress, Mechanical
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Travis, J -- New York, N.Y. -- Science. 1993 Aug 27;261(5125):1114.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8356445" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/therapy ; Cells, Cultured ; Endoplasmic Reticulum/*metabolism ; Gene Products, env/metabolism ; Genetic Therapy/*methods ; HIV/*metabolism ; HIV Antibodies/*genetics/metabolism ; HIV Envelope Protein gp120/*immunology ; HIV Envelope Protein gp160 ; Humans ; *Protein Engineering ; Protein Precursors/metabolism
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  • 61
    Publication Date: 1993-03-12
    Description: Betacellulin, a member of the epidermal growth factor family, has been identified in the conditioned medium of cell lines derived from mouse pancreatic beta cell tumors. Betacellulin is a 32-kilodalton glycoprotein that appears to be processed from a larger transmembrane precursor by proteolytic cleavage. The carboxyl-terminal domain of betacellulin has 50 percent sequence similarity with that of rat transforming growth factor alpha. Betacellulin is a potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shing, Y -- Christofori, G -- Hanahan, D -- Ono, Y -- Sasada, R -- Igarashi, K -- Folkman, J -- CA 70118/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Mar 12;259(5101):1604-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, Children's Hospital, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8456283" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Sequence ; Animals ; Base Sequence ; Betacellulin ; Cell Division/drug effects ; Cells, Cultured ; DNA Replication/drug effects ; Endothelium, Vascular/cytology/drug effects ; Epidermal Growth Factor/pharmacology ; Growth Substances/*genetics/isolation & purification/pharmacology ; Humans ; *Intercellular Signaling Peptides and Proteins ; Islets of Langerhans/physiopathology ; Kinetics ; Mice ; Molecular Sequence Data ; Muscle, Smooth, Vascular/cytology/drug effects ; Oligodeoxyribonucleotides ; Pancreatic Neoplasms/*physiopathology ; Pigment Epithelium of Eye/cytology/drug effects ; Polymerase Chain Reaction/methods ; Protein Precursors/genetics ; Rats ; Receptor, Epidermal Growth Factor/metabolism ; Recombinant Proteins/pharmacology ; Sequence Homology, Amino Acid ; Thymidine/metabolism ; Transforming Growth Factor alpha/genetics
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  • 62
    Publication Date: 1993-05-14
    Description: CD4+ helper T cells mediate resistance to tuberculosis, presumably by enhancing the antimicrobial activity of macrophages within which the Mycobacterium tuberculosis organism grows. A first step in resistance should be the presentation of mycobacterial antigens by macrophages to CD4+ T cells. However, when the antigenic stimulus is limited to organisms growing in human monocytes, the organisms become sequestered from immune CD4+ T cells. This block in presentation is selective for growing mycobacteria and not for other stimuli. Sequestration would allow replicating organisms to persist in infected individuals and may contribute to virulence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pancholi, P -- Mirza, A -- Bhardwaj, N -- Steinman, R M -- AI24775/AI/NIAID NIH HHS/ -- AR39552/AR/NIAMS NIH HHS/ -- MOI-RR00102/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1993 May 14;260(5110):984-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8098550" target="_blank"〉PubMed〈/a〉
    Keywords: Antigen-Presenting Cells/*immunology ; BCG Vaccine/immunology ; CD4-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Humans ; Macrophages/immunology/*microbiology ; Monocytes/immunology/*microbiology ; Mycobacterium bovis/growth & development/*immunology ; Tuberculin/immunology ; Tuberculosis/immunology
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  • 63
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-10-15
    Description: Glutamate receptors mediate excitatory neurotransmission in the brain and are important in the formation of memory and in some neurodegenerative disorders. A complementary DNA clone that encoded a 33-kilodalton protein (GR33) was obtained by screening a library with an antibody generated against glutamate binding proteins. The sequence of GR33 is identical to that of the recently reported presynaptic protein syntaxin. When GR33 was expressed in Xenopus oocytes, it formed glutamate-activated ion channels that are pharmacologically similar to those of N-methyl-D-aspartate receptors but with different electrophysiological properties. Mutation of the leucine 278 residue in the single putative transmembrane segment of GR33 affects the properties of the channel. Thus, in vivo GR33 may be a presynaptic glutamate receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smirnova, T -- Stinnakre, J -- Mallet, J -- New York, N.Y. -- Science. 1993 Oct 15;262(5132):430-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de genetique moleculaire de la neurotransmission et des processus neurodegeneratifs, Centre National de la Recherche Scientifique (CNRS), Gif sur Yvette, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8105537" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Surface/chemistry ; Brain/embryology ; Brain Chemistry ; Calcium/metabolism ; Cells, Cultured ; Cloning, Molecular ; Glutamates/pharmacology ; Glutamic Acid ; Humans ; Membrane Potentials ; Mutagenesis, Site-Directed ; N-Methylaspartate/pharmacology ; Nerve Tissue Proteins/chemistry ; Neurons/chemistry ; Oocytes ; Rats ; Rats, Wistar ; Receptors, Glutamate/chemistry/genetics/*metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Receptors, Presynaptic/chemistry/genetics/*metabolism ; Syntaxin 1 ; Xenopus
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-15
    Description: Carbon monoxide, an activator of guanylyl cyclase, is formed by the action of the enzyme heme oxygenase. By in situ hybridization in brain slices, discrete neuronal localization of messenger RNA for the constitutive form of heme oxygenase throughout the brain has been demonstrated. This localization is essentially the same as that for soluble guanylyl cyclase messenger RNA. In primary cultures of olfactory neurons, zinc protoporphyrin-9, a potent selective inhibitor of heme oxygenase, depletes endogenous guanosine 3',5'-monophosphate (cGMP). Thus, carbon monoxide, like nitric oxide, may be a physiologic regulator of cGMP. These findings, together with the neuronal localizations of heme oxygenase, suggest that carbon monoxide may function as a neurotransmitter.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Verma, A -- Hirsch, D J -- Glatt, C E -- Ronnett, G V -- Snyder, S H -- DA00266/DA/NIDA NIH HHS/ -- MH18501/MH/NIMH NIH HHS/ -- NS02131/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1993 Jan 15;259(5093):381-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Walter Reed Army Medical Center, Washington, DC 20307.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7678352" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Aminolevulinate Synthetase/analysis/genetics ; Amino Acid Oxidoreductases/analysis/genetics ; Animals ; Animals, Newborn ; Base Sequence ; Brain/*enzymology ; Carbon Monoxide/*metabolism ; Cells, Cultured ; Cyclic GMP/*metabolism ; Guanylate Cyclase/analysis/genetics ; Heme Oxygenase (Decyclizing)/*analysis/genetics ; In Situ Hybridization ; Molecular Sequence Data ; NADPH-Ferrihemoprotein Reductase/analysis/genetics ; Neurons/*enzymology ; Neurotransmitter Agents/*metabolism ; Nitric Oxide Synthase ; Oligodeoxyribonucleotides/chemistry ; RNA, Messenger/analysis ; Rats
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  • 65
    Publication Date: 1993-06-11
    Description: A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, R G -- Cheng, K -- Schoen, W R -- Pong, S S -- Hickey, G -- Jacks, T -- Butler, B -- Chan, W W -- Chaung, L Y -- Judith, F -- New York, N.Y. -- Science. 1993 Jun 11;260(5114):1640-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Animal Science Research, Merck Research Laboratories, Rahway, NJ 07065.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8503009" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Benzazepines/*pharmacology ; Cells, Cultured ; Dogs ; Growth Hormone/*drug effects/secretion ; Male ; Membrane Potentials/drug effects ; Molecular Sequence Data ; Oligopeptides/chemistry/pharmacology ; Pituitary Gland, Anterior/drug effects/secretion ; Rats ; Second Messenger Systems/drug effects ; Stereoisomerism ; Structure-Activity Relationship ; Tetrazoles/*pharmacology
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  • 66
    Publication Date: 1993-04-16
    Description: Toxoplasma gondii is a protozoan pathogen that produces severe disease in humans and animals. This obligate intracellular parasite provides an excellent model for the study of how such pathogens are able to invade, survive, and replicate intracellularly. DNA encoding chloramphenicol acetyltransferase was introduced into T. gondii and transiently expressed with the use of three vectors based on different Toxoplasma genes. The ability to introduce genes and have them efficiently and faithfully expressed is an essential tool for understanding the structure-function relation of genes and their products.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soldati, D -- Boothroyd, J C -- New York, N.Y. -- Science. 1993 Apr 16;260(5106):349-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8469986" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Chloramphenicol O-Acetyltransferase/genetics ; *Gene Expression ; *Genes, Protozoan ; Genetic Vectors ; Humans ; Toxoplasma/*genetics ; *Transfection
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  • 67
    Publication Date: 1993-10-08
    Description: Interferons, which induce several intracellular antiviral proteins, also induce an extracellular soluble protein that inhibits vesicular stomatitis virus (VSV) infection. This 28-kilodalton soluble protein was purified to homogeneity and identified by protein sequencing as the ligand-binding domain of the human 160-kilodalton low density lipoprotein receptor (LDLR). The existence of an antiviral soluble LDLR was confirmed by immunoaffinity chromatography with monoclonal antibody to LDLR. This soluble receptor mediates most of the interferon-triggered antiviral activity against VSV, apparently by interfering with virus assembly or budding, and not by inhibiting virus attachment to cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, D G -- Tal, N -- Novick, D -- Barak, S -- Rubinstein, M -- New York, N.Y. -- Science. 1993 Oct 8;262(5131):250-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211145" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antiviral Agents/*biosynthesis/chemistry/isolation & purification ; Cell Line ; Cells, Cultured ; Chromatography, Affinity ; Culture Media, Serum-Free ; Cytopathogenic Effect, Viral ; HeLa Cells ; Humans ; Interferon-beta/pharmacology ; Interferon-gamma/*pharmacology ; Molecular Sequence Data ; Molecular Weight ; Receptors, LDL/*biosynthesis/chemistry/isolation & purification ; Solubility ; Vesicular stomatitis Indiana virus/growth & development
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  • 68
    Publication Date: 1993-12-10
    Description: Peripheral blood mononuclear cells (PBMCs) from many asymptomatic individuals infected with human immunodeficiency virus-type 1 (HIV) are unresponsive as measured by in vitro T cell proliferation and interleukin-2 (IL-2) production to influenza virus and synthetic peptides of HIV envelope (Env). Strong influenza virus- and Env-stimulated IL-2 responses and T cell proliferation were restored when cultures were stimulated in the presence of IL-12. Interferon-gamma production by PBMCs from HIV seropositive (HIV+) patients was also restored with IL-12. Furthermore, in vitro antigen-specific production of IL-2 and proliferation of PBMCs from HIV- donors were suppressed by antibody to IL-12, but were not enhanced by addition of exogenous IL-12. Thus, IL-12 may be limiting in PBMCs from HIV+ but not HIV- individuals. These findings demonstrate that IL-12 can restore HIV-specific cell-mediated immunity in vitro in HIV-infected individuals and suggest a potential use of IL-12 in augmenting the diminished immunologic functions associated with HIV infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clerici, M -- Lucey, D R -- Berzofsky, J A -- Pinto, L A -- Wynn, T A -- Blatt, S P -- Dolan, M J -- Hendrix, C W -- Wolf, S F -- Shearer, G M -- New York, N.Y. -- Science. 1993 Dec 10;262(5140):1721-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7903123" target="_blank"〉PubMed〈/a〉
    Keywords: Cells, Cultured ; Gene Products, env/immunology ; HIV Infections/*immunology ; HIV-1/*immunology ; Humans ; Immunity, Cellular ; Influenza A virus/immunology ; Interferon-gamma/biosynthesis ; Interleukin-12 ; Interleukin-2/biosynthesis/pharmacology ; Interleukins/immunology/*pharmacology ; Killer Cells, Natural/immunology ; Leukocytes, Mononuclear/immunology ; Lymphocyte Activation ; Phytohemagglutinins/immunology ; Recombinant Proteins/pharmacology ; T-Lymphocytes, Helper-Inducer/*immunology
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  • 69
    Publication Date: 1993-09-10
    Description: Mycobacterium tuberculosis infects one-third of the world's human population. This widespread infection depends on the organism's ability to escape host defenses by gaining entry and surviving inside the macrophage. DNA sequences of M. tuberculosis have been cloned; these confer on a nonpathogenic Escherichia coli strain an ability to invade HeLa cells, augment macrophage phagocytosis, and survive for at least 24 hours inside the human macrophage. This capacity to gain entry into mammalian cells and survive inside the macrophage was localized to two distinct loci on the cloned M. tuberculosis DNA fragment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arruda, S -- Bomfim, G -- Knights, R -- Huima-Byron, T -- Riley, L W -- TW00018/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 10;261(5127):1454-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of International Medicine, Cornell University Medical College, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8367727" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/genetics ; Cells, Cultured ; *Cloning, Molecular ; DNA, Bacterial/genetics ; Escherichia coli/*genetics/physiology ; *Genes, Bacterial ; HeLa Cells ; Humans ; Macrophages/*microbiology ; Molecular Sequence Data ; Mycobacterium tuberculosis/*genetics/pathogenicity/physiology ; Virulence
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-11-19
    Description: A mutant mouse strain has been generated in which a rearranged immunoglobulin heavy (H) chain variable (V) region gene is placed into the heavy chain locus in its natural position, replacing the JH elements. In homozygous mutant mice, essentially all B cells in the spleen express the transgenic VH region in their antibodies. The proper location of the transgene relative to the constant region genes allows it to participate in isotype switching and undergo somatic hypermutation. Immunoglobulin transgenic mice generated in this fashion by gene targeting should prove useful for the exploration of immunoregulatory mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taki, S -- Meiering, M -- Rajewsky, K -- New York, N.Y. -- Science. 1993 Nov 19;262(5137):1268-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genetics, University of Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235657" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Base Sequence ; Cells, Cultured ; *Genes, Immunoglobulin ; Homozygote ; *Immunoglobulin Class Switching ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Variable Region/*genetics ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, Y H -- New York, N.Y. -- Science. 1993 Oct 15;262(5132):376-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular and Cell Biology, National University of Singapore, Republic of Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7692598" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cytokines/*metabolism/pharmacology ; Humans ; Interferons/metabolism/pharmacology ; Interleukins/metabolism/pharmacology ; Mice ; Models, Biological ; Phosphoprotein Phosphatases/*metabolism ; Phosphorylation ; Protein Kinases/*metabolism ; *Signal Transduction ; T-Lymphocytes/metabolism ; Tumor Necrosis Factor-alpha/metabolism/pharmacology
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  • 72
    Publication Date: 1993-04-09
    Description: Cyclic adenosine monophosphate (cAMP)-dependent protein kinase, labeled with fluorescein and rhodamine on the catalytic and regulatory subunits, respectively, was injected into Aplysia sensory neurons either in culture or in intact cell clusters. Energy transfer between the subunits, a measure of cytosolic cAMP concentration ([cAMP]), and compartmentation of the dissociated subunits were monitored by confocal fluorescence microscopy. Bath application of serotonin produced a much greater elevation of [cAMP] in the processes than in the central bodies of the neurons. The resulting gradients must drive a sizable centripetal flux of cAMP because direct microinjection of cAMP showed that it diffused readily. Perinuclear increases in [cAMP] slowly caused the translocation of the freed catalytic subunit into the nucleus to an extent proportional to the percentage of its dissociation from the regulatory subunit.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bacskai, B J -- Hochner, B -- Mahaut-Smith, M -- Adams, S R -- Kaang, B K -- Kandel, E R -- Tsien, R Y -- New York, N.Y. -- Science. 1993 Apr 9;260(5105):222-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093-0647.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7682336" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Methyl-3-isobutylxanthine/pharmacology ; Animals ; Aplysia ; Cell Compartmentation ; Cell Nucleus/enzymology/metabolism ; Cells, Cultured ; Cyclic AMP/*metabolism ; Cytoplasm/enzymology/metabolism ; Diffusion ; Fluorescein ; Fluoresceins ; Microinjections ; Neurons, Afferent/drug effects/enzymology/*metabolism ; Protein Kinases/*metabolism ; Rhodamines ; Serotonin/pharmacology
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  • 73
    Publication Date: 1993-04-09
    Description: Calcium ions (Ca2+) act as an intracellular second messenger and can enter neurons through various ion channels. Influx of Ca2+ through distinct types of Ca2+ channels may differentially activate biochemical processes. N-Methyl-D-aspartate (NMDA) receptors and L-type Ca2+ channels, two major sites of Ca2+ entry into hippocampal neurons, were found to transmit signals to the nucleus and regulated gene transcription through two distinct Ca2+ signaling pathways. Activation of the multifunctional Ca(2+)-calmodulin-dependent protein kinase (CaM kinase) was evoked by stimulation of either NMDA receptors or L-type Ca2+ channels; however, activation of CaM kinase appeared to be critical only for propagating the L-type Ca2+ channel signal to the nucleus. Also, the NMDA receptor and L-type Ca2+ channel pathways activated transcription by means of different cis-acting regulatory elements in the c-fos promoter. These results indicate that Ca2+, depending on its mode of entry into neurons, can activate two distinct signaling pathways. Differential signal processing may provide a mechanism by which Ca2+ controls diverse cellular functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bading, H -- Ginty, D D -- Greenberg, M E -- 2F32 NS 08764/NS/NINDS NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Apr 9;260(5105):181-6.〈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/8097060" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium Channels/metabolism ; Calcium-Calmodulin-Dependent Protein Kinases ; Cells, Cultured ; DNA-Binding Proteins/genetics ; *Gene Expression Regulation ; Genes, fos ; Glutamates/pharmacology ; Glutamic Acid ; Hippocampus/*metabolism ; Neurons/*metabolism ; Nuclear Proteins/genetics ; Protein Kinases/metabolism ; Rats ; Receptors, N-Methyl-D-Aspartate/metabolism ; Regulatory Sequences, Nucleic Acid ; Second Messenger Systems ; Serum Response Factor ; *Signal Transduction ; Transcription Factors/genetics ; 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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  • 74
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-14
    Description: The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human health care. A new field, tissue engineering, applies the principles of biology and engineering to the development of functional substitutes for damaged tissue. This article discusses the foundations and challenges of this interdisciplinary field and its attempts to provide solutions to tissue creation and repair.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Langer, R -- Vacanti, J P -- New York, N.Y. -- Science. 1993 May 14;260(5110):920-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02319.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biomedical Engineering ; *Bioprosthesis ; Cells, Cultured ; Culture Techniques ; Ectoderm ; Endoderm ; Humans ; Mesoderm ; *Tissue Transplantation
    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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  • 75
    Publication Date: 1993-04-23
    Description: Development of the appropriate CD4+ T helper (TH) subset during an immune response is important for disease resolution. With the use of naive, ovalbumin-specific alpha beta T cell receptor transgenic T cell, it was found that heat-killed Listeria monocytogenes induced TH1 development in vitro through macrophage production of interleukin-12 (IL-12). Moreover, inhibition of macrophage production of IL-12 may explain the ability of IL-10 to suppress TH1 development. Murine immune responses to L. monocytogenes in vivo are of the appropriate TH1 phenotype. Therefore, this regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate TH phenotype.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hsieh, C S -- Macatonia, S E -- Tripp, C S -- Wolf, S F -- O'Garra, A -- Murphy, K M -- 1 PO1 A131238-01/PHS HHS/ -- 5 T32 GM07200-17/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Apr 23;260(5107):547-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8097338" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/cytology/*immunology ; Cell Differentiation ; Cells, Cultured ; Interferon-gamma/secretion ; Interleukin-10/pharmacology ; Interleukin-12 ; Interleukin-2/biosynthesis ; Interleukins/biosynthesis/*immunology/pharmacology ; Listeria monocytogenes/*immunology ; Macrophages/*immunology ; Mice ; Mice, Transgenic ; Phenotype ; Receptors, Antigen, T-Cell, alpha-beta/immunology
    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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  • 76
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-10-29
    Description: A change in the probability of neurotransmitter release (Pr) is an important mechanism underlying synaptic plasticity. Although Pr is often assumed to be the same for all terminals at a single synapse, this assumption is difficult to reconcile with the nonuniform size and structure of synaptic terminals in the central nervous system. Release probability was measured at excitatory synapses on cultured hippocampal neurons by analysis of the progressive block of N-methyl-D-aspartate receptor-mediated synaptic currents by the irreversible open channel blocker MK-801. Release probability was nonuniform (range of 0.09 to 0.54) for terminals arising from a single axon, the majority of which had a low Pr. However, terminals with high Pr are more likely to be affected by the activity-dependent modulation that occurs in long-term potentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosenmund, C -- Clements, J D -- Westbrook, G L -- MH46613/MH/NIMH NIH HHS/ -- NS26494/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 29;262(5134):754-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health Sciences University, Portland 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7901909" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Baclofen/pharmacology ; Cells, Cultured ; Dizocilpine Maleate/pharmacology ; Glutamates/*metabolism ; Glutamic Acid ; Hippocampus/metabolism/*physiology ; Neuronal Plasticity/physiology ; Neurotransmitter Agents/*metabolism ; Rats ; Receptors, N-Methyl-D-Aspartate/drug effects/physiology ; Synapses/metabolism ; Synaptic Transmission/drug effects/*physiology
    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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