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  • Articles  (104)
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  • 1995-1999
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  • Articles  (104)
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  • 1
    Publication Date: 1992-07-03
    Description: Osteoclasts, the cells that resorb bone, develop from hematopoietic precursors of the bone marrow under the control of factors produced in their microenvironment. The cytokine interleukin-6 can promote hematopoiesis and osteoclastogenesis. Interleukin-6 production by bone and marrow stromal cells is suppressed by 17 beta-estradiol in vitro. In mice, estrogen loss (ovariectomy) increased the number of colony-forming units for granulocytes and macrophages, enhanced osteoclast development in ex vivo cultures of marrow, and increased the number of osteoclasts in trabecular bone. These changes were prevented by 17 beta-estradiol or an antibody to interleukin-6. Thus, estrogen loss results in an interleukin-6-mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jilka, R L -- Hangoc, G -- Girasole, G -- Passeri, G -- Williams, D C -- Abrams, J S -- Boyce, B -- Broxmeyer, H -- Manolagas, S C -- AI21761/AI/NIAID NIH HHS/ -- AR41313/AR/NIAMS NIH HHS/ -- CA36464/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Jul 3;257(5066):88-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Veterans Affairs Medical Center, Indiana University School of Medicine, Indianapolis 46202.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1621100" target="_blank"〉PubMed〈/a〉
    Keywords: Analysis of Variance ; Animals ; Antibodies, Monoclonal ; Bone Marrow Cells ; Cells, Cultured ; Estradiol/*pharmacology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Immunoglobulin G ; Interleukin-6/immunology/*physiology ; Mice ; Osteoclasts/*cytology/drug effects ; *Ovariectomy ; Recombinant Proteins/pharmacology ; Spleen/cytology ; Stem Cells/cytology/drug effects
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-01-24
    Description: Synaptic plasticity can be triggered by calcium flux into neurons through synaptically activated N-methyl-D-aspartate (NMDA) receptor channels. The amplitude and time course of the resulting intracellular calcium transient depend on the number of open NMDA receptor channels and the kinetics of their activation. Short applications of L-glutamate to outside-out patches from hippocampal neurons in the presence and absence of MK-801 revealed that about 30 percent of L-glutamate-bound channels are open at the peak of the current. This high probability of opening suggests that very few channels are required to guarantee a large, localized postsynaptic calcium transient.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jahr, C E -- NS21419/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jan 24;255(5043):470-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute L474, Oregon Health Sciences University, Portland 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1346477" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Cells, Cultured ; Dizocilpine Maleate/pharmacology ; Glutamates/*physiology ; Glutamic Acid ; Hippocampus/physiology ; In Vitro Techniques ; *Ion Channel Gating ; Rats ; Receptors, N-Methyl-D-Aspartate/*physiology
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  • 3
    Publication Date: 1992-05-01
    Description: Induction of ferritin synthesis in cultured cells by heme or iron is accompanied by degradation of the ferritin repressor protein (FRP). Intermediates in the degradative pathway apparently include FRP covalently linked in larger aggregates. The effect of iron on FRP degradation is enhanced by porphyrin precursors but is decreased by inhibitors of porphyrin synthesis, which implies that heme is an active agent. These results suggest that translational induction in this system may be caused by enhanced repressor degradation. While unique among translational regulatory systems, this process is common to a variety of other biosynthetic control mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goessling, L S -- Daniels-McQueen, S -- Bhattacharyya-Pakrasi, M -- Lin, J J -- Thach, R E -- AI 20484/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1992 May 1;256(5057):670-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Washington University, St. Louis, MO 63130.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1316633" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Aminolevulinate Synthetase/genetics ; Aminolevulinic Acid/pharmacology ; Animals ; Cell Line ; Cell Line, Transformed ; Ferritins/biosynthesis/*genetics ; Fibroblasts/metabolism ; Iron/pharmacology ; Iron Regulatory Protein 1 ; Iron-Regulatory Proteins ; Mice ; Papillomaviridae ; Porphobilinogen/pharmacology ; *Protein Biosynthesis ; RNA, Messenger/*genetics ; RNA-Binding Proteins/*metabolism ; Rabbits
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  • 4
    Publication Date: 1992-09-04
    Description: Mitogen-activated protein (MAP) kinases are 42- and 44-kD serine-threonine protein kinases that are activated by tyrosine and threonine phosphorylation in cells stimulated with mitogens and growth factors. MAP kinase and the protein kinase that activates it (MAP kinase kinase) were constitutively activated in NIH 3T3 cells infected with viruses containing either of two oncogenic forms (p35EC12, p3722W) of the c-Raf-1 protein kinase. The v-Raf proteins purified from cells infected with EC12 or 22W viruses activated MAP kinase kinase from skeletal muscle in vitro. Furthermore, a bacterially expressed v-Raf fusion protein (glutathione S-transferase-p3722W) also activated MAP kinase kinase in vitro. These findings suggest that one function of c-Raf-1 in mitogenic signaling is to phosphorylate and activate MAP kinase kinase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dent, P -- Haser, W -- Haystead, T A -- Vincent, L A -- Roberts, T M -- Sturgill, T W -- CA50661/CA/NCI NIH HHS/ -- DK41077/DK/NIDDK NIH HHS/ -- HD24926/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1992 Sep 4;257(5075):1404-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, University of Virginia, Charlottesville 22908.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1326789" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Cell Line ; Cell Line, Transformed ; Enzyme Activation/drug effects ; Immunosorbent Techniques ; Mice ; Mitogen-Activated Protein Kinase Kinases ; Muscles/enzymology ; Oncogene Proteins v-raf ; Phosphorylation ; Protein Kinases/*metabolism ; Proto-Oncogene Proteins/pharmacology ; Proto-Oncogene Proteins c-raf ; Recombinant Fusion Proteins/pharmacology ; Retroviridae Proteins, Oncogenic/genetics/*pharmacology
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-22
    Description: The growth-inhibiting peptide hormone somatostatin stimulates phosphotyrosine phosphatase activity in the human pancreatic cell line MIA PaCa-2. This hormonal activation was mediated by a pertussis toxin-sensitive guanosine 5'-triphosphate-binding protein (G protein) in the membranes of these cells. Activation of this G protein by somatostatin stimulated the dephosphorylation of exogenous epidermal growth factor receptor prepared from A-431 cells in vitro. This pathway may mediate the antineoplastic action of somatostatin in these cells and in human tumors and could represent a general mechanism of G protein coupling that is utilized by normal cells in the hormonal control of cell growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pan, M G -- Florio, T -- Stork, P J -- New York, N.Y. -- Science. 1992 May 22;256(5060):1215-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1350382" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Carcinoma, Squamous Cell ; Cell Line ; Cell Membrane/metabolism ; Dose-Response Relationship, Drug ; Enzyme Activation ; GTP-Binding Proteins/*metabolism ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Guanosine Diphosphate/analogs & derivatives/pharmacology ; Humans ; Kinetics ; Pancreatic Neoplasms ; Peptides/metabolism ; Pertussis Toxin ; Phosphorylation ; Protein Kinases/metabolism ; Protein Tyrosine Phosphatases/*metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Somatostatin/*pharmacology ; Thionucleotides/pharmacology ; Virulence Factors, Bordetella/pharmacology
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-02-07
    Description: Highly sulfated proteoglycans are correlated with axon boundaries in the developing central nervous system which suggests that these molecules affect neural pattern formation. In the developing mammalian retina, gradual regression of chondroitin sulfate may help control the onset of ganglion cell differentiation and initial direction of their axons. Changes induced by the removal of chondroitin sulfate from intact retinas in culture confirm the function of chondroitin sulfate in retinal histogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brittis, P A -- Canning, D R -- Silver, J -- New York, N.Y. -- Science. 1992 Feb 7;255(5045):733-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1738848" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Cell Differentiation/drug effects ; Cells, Cultured ; Chondroitin Lyases/pharmacology ; Chondroitin Sulfate Proteoglycans/pharmacology ; Chondroitin Sulfates/analysis/*physiology ; Immunohistochemistry ; Rats ; Retina/chemistry/cytology/*embryology ; Retinal Ganglion Cells/chemistry/*cytology ; Tubulin/analysis
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  • 7
    Publication Date: 1992-12-07
    Description: An adeno-associated virus vector encoding an antisense RNA was used to transduce stable intracellular resistance to human immunodeficiency virus-1 (HIV-1) in human hemopoietic and non-hemopoietic cell lines. The antisense targets are present in all HIV-1 transcripts and include the TAR sequence, which is critical for transcription and virus replication, and the polyadenylation signal. Cell lines expressing antisense RNA showed up to 95 percent inhibition of gene expression directed by the HIV-1 long terminal repeat and greater than 99 percent reduction in infectious HIV-1 production, with no detectable cellular toxicity. Because of their efficient transcription and inability to recombine with HIV-1, adeno-associated virus vectors represent a promising form of anti-retroviral gene therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chatterjee, S -- Johnson, P R -- Wong, K K Jr -- New York, N.Y. -- Science. 1992 Nov 27;258(5087):1485-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Rockville, MD 20852.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1359646" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; CD4-Positive T-Lymphocytes/microbiology ; Cell Line ; Chloramphenicol O-Acetyltransferase/genetics ; Dependovirus/*genetics ; Drug Resistance, Microbial/genetics ; Gene Products, tat/genetics ; Genetic Vectors/*genetics ; HIV Long Terminal Repeat/genetics ; HIV-1/*genetics/physiology ; Humans ; Molecular Sequence Data ; Neomycin/pharmacology ; RNA, Antisense/*genetics ; RNA, Messenger/genetics ; RNA, Viral/genetics ; Transfection ; Virus Replication/genetics ; tat Gene Products, Human Immunodeficiency Virus
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  • 8
    Publication Date: 1992-12-11
    Description: Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine that is chemotactic for lymphocytes and neutrophils, is also angiogenic. Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells. Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha. An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity. These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koch, A E -- Polverini, P J -- Kunkel, S L -- Harlow, L A -- DiPietro, L A -- Elner, V M -- Elner, S G -- Strieter, R M -- AR30692/AR/NIAMS NIH HHS/ -- AR41492/AR/NIAMS NIH HHS/ -- HL39926/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1798-801.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1281554" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis, Rheumatoid/physiopathology ; Base Sequence ; Cell Division/drug effects ; Cells, Cultured ; Chemotaxis/*drug effects ; Cornea/*drug effects/physiology ; Dose-Response Relationship, Drug ; Endothelium, Vascular/drug effects/*physiology ; Fibroblast Growth Factor 2/pharmacology ; Humans ; Interleukin-8/genetics/*pharmacology ; Macrophages/*physiology ; Mice ; Molecular Sequence Data ; Monocytes/physiology ; *Neovascularization, Pathologic ; Oligonucleotides, Antisense/*pharmacology ; Rabbits ; Rats ; Recombinant Proteins/pharmacology ; Synovial Fluid/physiology ; Tumor Necrosis Factor-alpha/genetics ; Umbilical Veins
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-10-23
    Description: Hemodynamic shear stress affects endothelial cell structure and function, but little is known about the signal transduction mechanisms involved in these processes. The effect of laminar shear stress on cytosolic pH (pHi) was examined in rat aortic endothelial cells cultured in glass capillary tubes. Shear stress forces led to a rapid decrease in pHi (maximal effect 0.09 pH unit at 13.4 dynes per square centimeter). Removal of specific ions or addition of exchange inhibitors suggests that in vascular endothelial cells shear stress forces activate both an alkali extruder, sodium ion-independent chloride-bicarbonate ion exchange, and an acid extruder, sodium-hydrogen ion exchange; the net effect in physiologic buffer with the bicarbonate ion is a decrease in pHi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ziegelstein, R C -- Cheng, L -- Capogrossi, M C -- New York, N.Y. -- Science. 1992 Oct 23;258(5082):656-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1329207" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bicarbonates/metabolism ; Carrier Proteins/physiology ; Cells, Cultured ; Chloride-Bicarbonate Antiporters ; Cytosol/*physiology ; Endothelium, Vascular/*physiology ; Hydrogen-Ion Concentration ; Membrane Proteins/physiology ; Rats ; Signal Transduction/physiology ; Sodium-Hydrogen Antiporter ; Stress, Mechanical
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  • 10
    Publication Date: 1992-01-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, R G -- Kamen, B A -- Rothberg, K G -- Lacey, S W -- New York, N.Y. -- Science. 1992 Jan 24;255(5043):410-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1310359" target="_blank"〉PubMed〈/a〉
    Keywords: Carrier Proteins/physiology ; Cell Membrane/*physiology/ultrastructure ; Cells, Cultured ; *Endocytosis ; Folate Receptors, GPI-Anchored ; Folic Acid/metabolism ; Glycolipids/physiology ; Glycosylphosphatidylinositols ; In Vitro Techniques ; Membrane Glycoproteins/physiology ; Phosphatidylinositols/physiology ; Receptors, Cell Surface/physiology
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  • 11
    Publication Date: 1992-11-27
    Description: The peak concentration and rate of clearance of neurotransmitter from the synaptic cleft are important determinants of synaptic function, yet the neurotransmitter concentration time course is unknown at synapses in the brain. The time course of free glutamate in the cleft was estimated by kinetic analysis of the displacement of a rapidly dissociating competitive antagonist from N-methyl-D-aspartate (NMDA) receptors during synaptic transmission. Glutamate peaked at 1.1 millimolar and decayed with a time constant of 1.2 milliseconds at cultured hippocampal synapses. This time course implies that transmitter saturates postsynaptic NMDA receptors. However, glutamate dissociates much more rapidly from alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Thus, the time course of free glutamate predicts that dissociation contributes to the decay of the AMPA receptor-mediated postsynaptic current.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clements, J D -- Lester, R A -- Tong, G -- Jahr, C E -- Westbrook, G L -- MH46613/MH/NIMH NIH HHS/ -- NS21419/NS/NINDS NIH HHS/ -- NS26494/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Nov 27;258(5087):1498-501.〈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/1359647" target="_blank"〉PubMed〈/a〉
    Keywords: 2-Aminoadipic Acid/pharmacology ; Action Potentials/physiology ; Animals ; Cells, Cultured ; Glutamates/*metabolism ; Glutamic Acid ; Hippocampus/cytology/physiology ; Models, Neurological ; Neurons/physiology ; Neurotransmitter Agents/*metabolism ; Piperazines/pharmacology ; Rats ; Receptors, N-Methyl-D-Aspartate/drug effects/physiology ; Synapses/drug effects/*metabolism ; Time Factors
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  • 12
    Publication Date: 1992-04-03
    Description: Interleukin-1 beta (IL-1 beta) mediates a wide range of immune and inflammatory responses. The active cytokine is generated by proteolytic cleavage of an inactive precursor. A complementary DNA encoding a protease that carries out this cleavage has been cloned. Recombinant expression in COS-7 cells enabled the cells to process precursor IL-1 beta to the mature form. Sequence analysis indicated that the enzyme itself may undergo proteolytic processing. The gene encoding the protease was mapped to chromosomal band 11q23, a site frequently involved in rearrangement in human cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cerretti, D P -- Kozlosky, C J -- Mosley, B -- Nelson, N -- Van Ness, K -- Greenstreet, T A -- March, C J -- Kronheim, S R -- Druck, T -- Cannizzaro, L A -- New York, N.Y. -- Science. 1992 Apr 3;256(5053):97-100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunex Corporation, Seattle, WA 98101.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1373520" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Caspase 1 ; Cell Line ; Chromosome Banding ; *Chromosomes, Human, Pair 11 ; Cloning, Molecular ; Enzyme Precursors/biosynthesis/*genetics/isolation & purification ; Humans ; Metalloendopeptidases/biosynthesis/*genetics/isolation & purification ; Molecular Sequence Data ; Neutrophils/enzymology ; Oligodeoxyribonucleotides ; Poly A/genetics/isolation & purification ; Polymerase Chain Reaction/methods ; RNA/genetics/isolation & purification ; RNA, Messenger/genetics ; Recombinant Proteins/biosynthesis/isolation & purification ; Transfection
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  • 13
    Publication Date: 1992-05-04
    Description: The molecular basis of skeletal muscle lineage determination was investigated by analyzing DNA control elements that regulate the myogenic determination gene myoD. A distal enhancer was identified that positively regulates expression of the human myoD gene. The myoD enhancer and promoter were active in myogenic and several nonmyogenic cell lines. In transgenic mouse embryos, however, the myoD enhancer and promoter together directed expression of a lacZ transgene specifically to the skeletal muscle lineage. These data suggest that during development myoD is regulated by mechanisms that restrict accessibility of myoD control elements to positive trans-acting factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldhamer, D J -- Faerman, A -- Shani, M -- Emerson, C P Jr -- CA-06927/CA/NCI NIH HHS/ -- HD-07796/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 24;256(5056):538-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1315077" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Line ; Chloramphenicol O-Acetyltransferase/genetics ; Cloning, Molecular ; Enhancer Elements, Genetic ; *Gene Expression Regulation ; Humans ; Mice ; Mice, Transgenic ; Muscle Proteins/*genetics ; Muscles/embryology/metabolism ; MyoD Protein ; Promoter Regions, Genetic ; Transcription, Genetic ; Transfection ; Tumor Cells, Cultured ; beta-Galactosidase/genetics
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  • 14
    Publication Date: 1992-07-17
    Description: Nerve growth factor (NGF) is required for the maturation and survival of sympathetic neurons, but the mechanisms controlling expression of the NGF receptor in developing neuroblasts have not been defined. MAH cells, an immortalized sympathoadrenal progenitor cell line, did not respond to NGF and expressed neither low-affinity NGF receptor (p75) nor p140trk messenger RNAs. Depolarizing concentrations of potassium chloride, but none of a variety of growth factors, induced expression of p140trk but not p75 messenger RNA. A functional response to NGF was acquired by MAH cells under these conditions, suggesting that expression of p75 is not essential for this response. Depolarization also permitted a relatively high proportion of MAH cells to develop and survive as neurons in fibroblast growth factor and NGF. These data establish a relation between electrical activity and neurotrophic factor responsiveness in developing neurons, which may operate in the functioning of the mature nervous system as well.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Birren, S J -- Verdi, J M -- Anderson, D J -- NS23476/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 17;257(5068):395-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1321502" target="_blank"〉PubMed〈/a〉
    Keywords: Blotting, Northern ; Cell Line ; Cell Line, Transformed ; Cell Membrane/*physiology ; Dose-Response Relationship, Drug ; Membrane Potentials ; Nerve Growth Factors/*biosynthesis ; Neurons/*metabolism/*physiology ; Potassium Chloride/pharmacology ; Proto-Oncogene Proteins/*biosynthesis ; RNA, Messenger/*biosynthesis ; Receptor, trkA ; Receptors, Cell Surface/*biosynthesis ; Receptors, Nerve Growth Factor ; Signal Transduction ; Time Factors ; Tretinoin/pharmacology
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  • 15
    Publication Date: 1992-12-21
    Description: Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor). GAF is translocated to the nucleus and binds a DNA element, the gamma-activated site. Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha. The IFN-gamma-dependent activation of the 91-kilodalton DNA binding protein required cytoplasmic phosphorylation of the protein on tyrosine. The 113-kilodalton ISGF-3 protein that is phosphorylated in response to IFN-alpha was not phosphorylated nor translocated to the nucleus in response to IFN-gamma. Thus the two different ligands result in tyrosine phosphorylation of different combinations of latent cytoplasmic transcription factors that then act at different DNA binding sites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shuai, K -- Schindler, C -- Prezioso, V R -- Darnell, J E Jr -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1808-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1281555" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cell Line ; Cell Nucleus/metabolism ; DNA-Binding Proteins/isolation & purification/*metabolism ; Electrophoresis, Gel, Two-Dimensional ; Electrophoresis, Polyacrylamide Gel ; GTP-Binding Proteins/*genetics ; Gene Expression Regulation/drug effects ; Interferon-alpha/pharmacology ; Interferon-gamma/*pharmacology ; Models, Biological ; Molecular Sequence Data ; Molecular Weight ; Oligodeoxyribonucleotides ; Phosphorylation ; Phosphotyrosine ; Promoter Regions, Genetic ; STAT1 Transcription Factor ; Signal Transduction/drug effects ; *Trans-Activators ; *Transcription, Genetic/drug effects ; Tyrosine/analogs & derivatives/analysis
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  • 16
    Publication Date: 1992-07-03
    Description: A proteinaceous elicitor of the plant defense reaction known as the hypersensitive response was isolated from Erwinia amylovora, the bacterium that causes fire blight of pear, apple, and other rosaceous plants. The elicitor, named harpin, is an acidic, heat-stable, cell-envelope-associated protein with an apparent molecular weight of 44 kilodaltons. Harpin caused tobacco leaf lamina to collapse and caused an increase in the pH of bathing solutions of suspension-cultured tobacco cells. The gene encoding harpin (hrpN) was located in the 40-kilobase hrp gene cluster of E. amylovora, sequenced, and mutated with Tn5tac1. The hrpN mutants were not pathogenic to pear, did not elicit the hypersensitive response, and did not produce harpin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wei, Z M -- Laby, R J -- Zumoff, C H -- Bauer, D W -- He, S Y -- Collmer, A -- Beer, S V -- New York, N.Y. -- Science. 1992 Jul 3;257(5066):85-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology, Cornell University, Ithaca, NY 14853.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1621099" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Bacterial Outer Membrane Proteins ; Bacterial Proteins/*genetics/isolation & purification/metabolism ; Cells, Cultured ; Erwinia/genetics/pathogenicity/*physiology ; Escherichia coli/genetics ; *Genes, Bacterial ; Membrane Proteins/*genetics/isolation & purification/metabolism ; Molecular Sequence Data ; *Multigene Family ; Plants, Toxic ; Restriction Mapping ; Tobacco/microbiology
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  • 17
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-06-05
    Description: Regulation of interleukin-2 (IL-2) gene expression by the p50 and p65 subunits of the DNA binding protein NF-kappa B was studied in nontransformed CD4+ T lymphocyte clones. A homodimeric complex of the NF-kappa B p50 subunit was found in resting T cells. The amount of p50-p50 complex decreased after full antigenic stimulation, whereas the amount of the NF-kappa B p50-p65 heterodimer was increased. Increased expression of the IL-2 gene and activity of the IL-2 kappa B DNA binding site correlated with a decrease in the p50-p50 complex. Overexpression of p50 repressed IL-2 promoter expression. The switch from p50-p50 to p50-p65 complexes depended on a protein that caused sequestration of the p50-p50 complex in the nucleus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, S M -- Tran, A C -- Grilli, M -- Lenardo, M J -- New York, N.Y. -- Science. 1992 Jun 5;256(5062):1452-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, National Institute for 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/1604322" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/*immunology ; Base Sequence ; Binding Sites ; Cell Line ; Cell Nucleus/physiology ; Chloramphenicol O-Acetyltransferase/genetics/metabolism ; Clone Cells ; Columbidae ; DNA/genetics ; *Gene Expression Regulation ; Interleukin-2/*genetics ; Macromolecular Substances ; Mice ; Molecular Sequence Data ; NF-kappa B/*metabolism ; Oligonucleotide Probes ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Recombinant Fusion Proteins/metabolism ; T-Lymphocyte Subsets/*immunology ; Transfection ; Tumor Necrosis Factor-alpha/pharmacology
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  • 18
    Publication Date: 1992-07-17
    Description: N-type calcium channels are omega-conotoxin (omega-CgTx)-sensitive, voltage-dependent ion channels involved in the control of neurotransmitter release from neurons. Multiple subtypes of voltage-dependent calcium channel complexes exist, and it is the alpha 1 subunit of the complex that forms the pore through which calcium enters the cell. The primary structures of human neuronal calcium channel alpha 1B subunits were deduced by the characterization of overlapping complementary DNAs. Two forms (alpha 1B-1 and alpha 1B-2) were identified in human neuroblastoma (IMR32) cells and in the central nervous system, but not in skeletal muscle or aorta tissues. The alpha 1B-1 subunit directs the recombinant expression of N-type calcium channel activity when it is transiently co-expressed with human neuronal beta 2 and alpha 2b subunits in mammalian HEK293 cells. The recombinant channel was irreversibly blocked by omega-CgTx but was insensitive to dihydropyridines. The alpha 1B-1 alpha 2b beta 2-transfected cells displayed a single class of saturable, high-affinity (dissociation constant = 55 pM) omega-CgTx binding sites. Co-expression of the beta 2 subunit was necessary for N-type channel activity, whereas the alpha 2b subunit appeared to modulate the expression of the channel. The heterogeneity of alpha 1B subunits, along with the heterogeneity of alpha 2 and beta subunits, is consistent with multiple, biophysically distinct N-type calcium channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, M E -- Brust, P F -- Feldman, D H -- Patthi, S -- Simerson, S -- Maroufi, A -- McCue, A F -- Velicelebi, G -- Ellis, S B -- Harpold, M M -- New York, N.Y. -- Science. 1992 Jul 17;257(5068):389-95.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉SIBIA, Inc., La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1321501" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calcium/metabolism ; Calcium Channels/*drug effects/*genetics/*metabolism ; Cell Line ; Female ; Humans ; Male ; Membrane Potentials ; Molecular Sequence Data ; Neuroblastoma/metabolism ; Peptides, Cyclic/*pharmacology ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Transfection ; omega-Conotoxin GVIA
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  • 19
    Publication Date: 1992-01-10
    Description: The interaction between the low molecular weight G protein ras p21 and a guanosine triphosphatase activating protein (GAP) uncouples a heterotrimeric G protein (Gk) from muscarinic receptors. Through the use of isolated atrial cell membranes and genetically engineered GAP deletion mutants, the src homology regions (SH2-SH3) at the amino terminus of GAP have been identified as the domains responsible for this effect. Deletion of the domain required to stimulate the guanosine triphosphatase activity of ras p21 relieves the requirement for ras p21 in this system. A model is presented that suggests that ras p21 induces a conformational change in GAP, which allows the SH2-SH3 regions of GAP to function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martin, G A -- Yatani, A -- Clark, R -- Conroy, L -- Polakis, P -- Brown, A M -- McCormick, F -- CA51992-01/CA/NCI NIH HHS/ -- HL36930/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1992 Jan 10;255(5041):192-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Cetus Corporation, Emeryville, CA 94608.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1553544" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Baculoviridae ; Cell Membrane/metabolism ; Cells, Cultured ; Cloning, Molecular ; GTP-Binding Proteins/*physiology ; GTPase-Activating Proteins ; Genetic Engineering ; Genetic Vectors ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Guanosine Triphosphate/pharmacology ; Guinea Pigs ; Heart/*physiology ; Heart Atria ; Models, Biological ; Polymerase Chain Reaction ; Potassium Channels/drug effects/*physiology ; Proteins/genetics/*physiology ; Proto-Oncogene Proteins p21(ras)/*metabolism ; Receptors, Muscarinic/drug effects/*physiology ; ras GTPase-Activating Proteins
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  • 20
    Publication Date: 1992-05-08
    Description: Mutant forms of the gene encoding the tumor suppressor p53 are found in numerous human malignancies, but the physiologic function of p53 and the effects of mutations on this function are unknown. The p53 protein binds DNA in a sequence-specific manner and thus may regulate gene transcription. Cotransfection experiments showed that wild-type p53 activated the expression of genes adjacent to a p53 DNA binding site. The level of activation correlated with DNA binding in vitro. Oncogenic forms of p53 lost this activity. Moreover, all mutants inhibited the activity of coexpressed wild-type p53, providing a basis for the selection of such mutants during tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kern, S E -- Pietenpol, J A -- Thiagalingam, S -- Seymour, A -- Kinzler, K W -- Vogelstein, B -- CA06973/CA/NCI NIH HHS/ -- CA09243/CA/NCI NIH HHS/ -- CA35494/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 May 8;256(5058):827-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1589764" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line ; Chloramphenicol O-Acetyltransferase/genetics/metabolism ; DNA-Binding Proteins/*genetics/*metabolism ; Exons ; *Gene Expression Regulation, Neoplastic ; *Genes, p53 ; Genetic Vectors ; Humans ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction/methods ; Recombinant Fusion Proteins/metabolism ; Repetitive Sequences, Nucleic Acid ; Saccharomyces cerevisiae/genetics/growth & development ; *Transcription, Genetic ; Transfection ; Tumor Suppressor Protein p53/*genetics/*metabolism ; beta-Galactosidase/genetics/metabolism
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  • 21
    Publication Date: 1992-05-29
    Description: The T cell receptor (TCR) zeta chain was attached to the TCR alpha and beta extracellular domains to induce efficient expression of alpha beta heterodimers that can recognize complexes of antigen with major histocompatibility complex (MHC) molecules. Chimeric constructs expressed in RBL-2H3 cells were efficiently transported to the cell surface uniquely as disulfide-linked heterodimers. Transfectants were activated by specific antigen-MHC complexes, which demonstrated that the expressed alpha beta was functional and that CD3 was not required for antigen-MHC binding. Constructs with thrombin cleavage sites were efficiently cleaved to soluble disulfide-linked heterodimers. Thus, attachment of TCR zeta domains and protease cleavage sites to TCR alpha and beta induces expression of demonstrably functional heterodimers that can be solubilized.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engel, I -- Ottenhoff, T H -- Klausner, R D -- New York, N.Y. -- Science. 1992 May 29;256(5061):1318-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism 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/1598575" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/immunology ; Disulfides ; Flow Cytometry ; Histocompatibility Antigens/metabolism ; Kinetics ; Macromolecular Substances ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction ; Receptors, Antigen, T-Cell/genetics/isolation & purification/*metabolism ; Solubility ; Transfection
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  • 22
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-09-18
    Description: Most calcium-activated potassium channels couple changes in intracellular calcium to membrane excitability by conducting a current with a probability that depends directly on submembrane calcium concentration. In rat adrenal chromaffin cells, however, a large conductance, voltage- and calcium-activated potassium channel (BK) undergoes rapid inactivation, suggesting that this channel has a physiological role different than that of other BK channels. The inactivation of the BK channel, like that of the voltage-gated Shaker B potassium channel, is removed by trypsin digestion and channels are blocked by the Shaker B amino-terminal inactivating domain. Thus, this BK channel shares functional and possibly structural homologies with other inactivating voltage-gated potassium channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Solaro, C R -- Lingle, C J -- New York, N.Y. -- Science. 1992 Sep 18;257(5077):1694-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anesthesiology, 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/1529355" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenal Glands/physiology ; Animals ; Calcium/*pharmacology ; Cattle ; Cell Line ; Cell Membrane/physiology ; Chromaffin System/physiology ; Electric Conductivity ; Ion Channel Gating/drug effects/physiology ; Male ; Membrane Potentials/physiology ; Potassium Channels/*physiology ; Rats ; Rats, Inbred Strains ; Trypsin/*pharmacology
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  • 23
    Publication Date: 1992-06-12
    Description: Glutamate-operated ion channels (GluR channels) of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate subtype are found in both neurons and glial cells of the central nervous system. These channels are assembled from the GluR-A, -B, -C, and -D subunits; channels containing a GluR-B subunit show an outwardly rectifying current-voltage relation and low calcium permeability, whereas channels lacking the GluR-B subunit are characterized by a doubly rectifying current-voltage relation and high calcium permeability. Most cell types in the central nervous system coexpress several subunits, including GluR-B. However, Bergmann glia in rat cerebellum do not express GluR-B subunit genes. In a subset of cultured cerebellar glial cells, likely derived from Bergmann glial cells. GluR channels exhibit doubly rectifying current-voltage relations and high calcium permeability, whereas GluR channels of cerebellar neurons have low calcium permeability. Thus, differential expression of the GluR-B subunit gene in neurons and glia is one mechanism by which functional properties of native GluR channels are regulated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burnashev, N -- Khodorova, A -- Jonas, P -- Helm, P J -- Wisden, W -- Monyer, H -- Seeburg, P H -- Sakmann, B -- New York, N.Y. -- Science. 1992 Jun 12;256(5063):1566-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1317970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Cell Membrane Permeability ; Cells, Cultured ; Cerebellum/*physiology ; Gene Expression ; Glutamates/physiology ; In Vitro Techniques ; Ion Channel Gating ; Neuroglia/*physiology ; Nucleic Acid Hybridization ; RNA, Messenger/genetics ; Rats ; Receptors, Kainic Acid ; Receptors, Neurotransmitter/*physiology
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  • 24
    Publication Date: 1992-09-04
    Description: The N-methyl-D-aspartate (NMDA) receptor forms a cation-selective channel with a high calcium permeability and sensitivity to channel block by extracellular magnesium. These properties, which are believed to be important for the induction of long-term changes in synaptic strength, are imparted by asparagine residues in a putative channel-forming segment of the protein, transmembrane 2 (TM2). In the NR1 subunit, replacement of this asparagine by a glutamine residue decreases calcium permeability of the channel and slightly reduces magnesium block. The same substitution in NR2 subunits strongly reduces magnesium block and increases the magnesium permeability but barely affects calcium permeability. These asparagines are in a position homologous to the site in the TM2 region (Q/R site) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that is occupied by either glutamine (Q) or arginine (R) and that controls divalent cation permeability of the AMPA receptor channel. Hence AMPA and NMDA receptor channels contain common structural motifs in their TM2 segments that are responsible for some of their ion selectivity and conductance properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burnashev, N -- Schoepfer, R -- Monyer, H -- Ruppersberg, J P -- Gunther, W -- Seeburg, P H -- Sakmann, B -- New York, N.Y. -- Science. 1992 Sep 4;257(5075):1415-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abteilung Zellphysiologie, Max-Planck-Institut fur Medizinische Forschung, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1382314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Asparagine/*chemistry ; Binding Sites ; Calcium/*metabolism/pharmacology ; Cell Line ; Electric Conductivity ; Glutamates/pharmacology ; Glutamic Acid ; Ion Channels/chemistry/*physiology ; Magnesium/metabolism/*pharmacology ; Mice ; Molecular Sequence Data ; Mutagenesis ; Oocytes/metabolism ; Permeability ; Rats ; Receptors, N-Methyl-D-Aspartate/chemistry/genetics/*physiology ; Structure-Activity Relationship ; Transfection ; Xenopus
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  • 25
    Publication Date: 1992-02-07
    Description: The 39- to 43-amino acid amyloid beta protein (beta AP), which is deposited as amyloid in Alzheimer's disease, is encoded as an internal peptide that begins 99 residues from the carboxyl terminus of a 695- to 770-amino acid glycoprotein referred to as the amyloid beta protein precursor (beta APP). To clarify the processing that produces amyloid, carboxyl-terminal derivatives of the beta APP were analyzed. This analysis showed that the beta APP is normally processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives. The two largest derivatives in human brain have the entire beta AP at or near their amino terminus and are likely to be intermediates in the pathway leading to amyloid deposition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Estus, S -- Golde, T E -- Kunishita, T -- Blades, D -- Lowery, D -- Eisen, M -- Usiak, M -- Qu, X M -- Tabira, T -- Greenberg, B D -- AG06656/AG/NIA NIH HHS/ -- AG08012/AG/NIA NIH HHS/ -- AG08992/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 1992 Feb 7;255(5045):726-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1738846" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/*biosynthesis ; Amyloid beta-Protein Precursor/chemistry/genetics/*metabolism ; Cell Line ; Cell Membrane/chemistry ; Cerebral Cortex/chemistry ; Glycosylation ; Humans ; Immunoblotting ; Immunosorbent Techniques ; Molecular Weight ; Peptide Fragments/chemistry/isolation & purification/*metabolism ; Transfection
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  • 26
    Publication Date: 1992-02-14
    Description: T cell signaling via the CD4 surface antigen is mediated by the associated tyrosyl protein kinase p56lck. The 42-kilodalton mitogen-activated protein (MAP) kinase (p42mapk) was tyrosyl-phosphorylated and activated after treatment of the murine T lymphoma cell line 171CD4+, which expresses CD4, with antibody to CD3. Treatment of the CD4-deficient cell line 171 with the same antibody did not result in phosphorylation or activation of p42mapk. Purified p56lck both tyrosyl-phosphorylated and stimulated the seryl-threonyl phosphotransferase activity of purified p44mpk, a MAP kinase isoform from sea star oocytes. A synthetic peptide modeled after the putative regulatory phosphorylation site in murine p42mapk (Tyr185) was phosphorylated by p56lck with a similar Vmax, but a fivefold lower Michaelis constant (Km) than a peptide containing the Tyr394 autophosphorylation site from p56lck. MAP kinases may participate in protein kinase cascades that link Src family protein-tyrosyl kinases to seryl-threonyl kinases such as those encoded by rsk and raf, which are putative substrates of MAP kinases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ettehadieh, E -- Sanghera, J S -- Pelech, S L -- Hess-Bienz, D -- Watts, J -- Shastri, N -- Aebersold, R -- R126604/PHS HHS/ -- New York, N.Y. -- Science. 1992 Feb 14;255(5046):853-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomedical Research Centre, University of British Columbia, Vancouver, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1311128" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD3 ; Antigens, Differentiation, T-Lymphocyte/physiology ; Calcium-Calmodulin-Dependent Protein Kinases ; Cell Line ; Glycogen Synthase Kinase 3 ; In Vitro Techniques ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Lymphoma, T-Cell ; Mice ; Molecular Sequence Data ; Oncogene Proteins, Viral/*physiology ; Phosphorylation ; Protein Kinases/*physiology ; Protein-Tyrosine Kinases/*physiology ; Receptors, Antigen, T-Cell/physiology ; Signal Transduction/*physiology ; T-Lymphocytes/physiology
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  • 27
    Publication Date: 1992-12-28
    Description: Opiate drugs have potent analgesic and addictive properties. These drugs interact with receptors that also mediate the response to endogenous opioid peptide ligands. However, the receptors for opioids have eluded definitive molecular characterization. By transient expression in COS cells and screening with an iodinated analog of the opioid peptide enkephalin, a complementary DNA clone encoding a functional delta opioid receptor has been identified. The sequence shows homology to G protein-coupled receptors, in particular the receptors for somatostatin, angiotensin, and interleukin-8.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Evans, C J -- Keith, D E Jr -- Morrison, H -- Magendzo, K -- Edwards, R H -- DA05010/DA/NIDA NIH HHS/ -- P50 DA005010/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 18;258(5090):1952-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, University of California, School of Medicine, Los Angeles 90024-1759.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1335167" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding, Competitive ; Blotting, Northern ; Blotting, Southern ; Cell Line ; Cyclic AMP/metabolism ; Diprenorphine/metabolism ; Enkephalin, D-Penicillamine (2,5)- ; Enkephalins/pharmacology ; Etorphine/pharmacology ; Gene Expression ; Humans ; Kinetics ; Models, Structural ; Molecular Sequence Data ; Naloxone/pharmacology ; Narcotics/pharmacology ; Protein Structure, Secondary ; Receptors, Opioid, delta/chemistry/*genetics/*metabolism ; Sequence Homology, Amino Acid ; Transfection ; Tumor Cells, Cultured
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  • 28
    Publication Date: 1992-01-03
    Description: The p107 protein and the retinoblastoma protein (RB) both bind specifically to two viral oncoproteins, the SV40 T antigen (T) and adenoviral protein E1A (E1A). Like RB, p107 contains a segment (the pocket) that, alone, can bind specifically to T, E1A, and multiple cellular proteins. Cyclin A bound to the p107 pocket, but not the RB pocket. Although both pockets contain two, related collinear subsegments (A and B), the unique sequence in the p107 pocket that occupies the space between A and B is required for the interaction with cyclin A.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ewen, M E -- Faha, B -- Harlow, E -- Livingston, D M -- New York, N.Y. -- Science. 1992 Jan 3;255(5040):85-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1532457" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus Early Proteins ; Amino Acid Sequence ; Antigens, Polyomavirus Transforming/*metabolism ; Base Sequence ; Binding Sites ; Cell Line ; Cloning, Molecular ; Cyclins/*metabolism ; Escherichia coli/genetics ; Eye Neoplasms ; Glutathione Transferase/genetics/metabolism ; Humans ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; *Nuclear Proteins ; Oligodeoxyribonucleotides ; Oncogene Proteins, Viral/genetics/*metabolism ; Protein Conformation ; Proteins/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Retinoblastoma ; Retinoblastoma Protein/genetics/*metabolism ; Retinoblastoma-Like Protein p107 ; Structure-Activity Relationship
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  • 29
    Publication Date: 1992-04-10
    Description: Nitric oxide (NO) conveys a variety of messages between cells, including signals for vasorelaxation, neurotransmission, and cytotoxicity. In some endothelial cells and neurons, a constitutive NO synthase is activated transiently by agonists that elevate intracellular calcium concentrations and promote the binding of calmodulin. In contrast, in macrophages, NO synthase activity appears slowly after exposure of the cells to cytokines and bacterial products, is sustained, and functions independently of calcium and calmodulin. A monospecific antibody was used to clone complementary DNA that encoded two isoforms of NO synthase from immunologically activated mouse macrophages. Liquid chromatography-mass spectrometry was used to confirm most of the amino acid sequence. Macrophage NO synthase differs extensively from cerebellar NO synthase. The macrophage enzyme is immunologically induced at the transcriptional level and closely resembles the enzyme in cytokine-treated tumor cells and inflammatory neutrophils.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xie, Q W -- Cho, H J -- Calaycay, J -- Mumford, R A -- Swiderek, K M -- Lee, T D -- Ding, A -- Troso, T -- Nathan, C -- AI30165/AI/NIAID NIH HHS/ -- CA43610/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 10;256(5054):225-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beatrice and Samuel A. Seaver Laboratory, Department of 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/1373522" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Oxidoreductases/biosynthesis/*genetics ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cells, Cultured ; Cloning, Molecular ; Codon ; Enzyme Induction ; Interferon-gamma/pharmacology ; Isoenzymes/biosynthesis/*genetics ; Kinetics ; Lipopolysaccharides ; Macrophages/drug effects/*enzymology ; Mammary Neoplasms, Experimental ; Mice ; Molecular Sequence Data ; Molecular Weight ; Neutrophils/drug effects/enzymology ; Nitric Oxide Synthase ; Oligodeoxyribonucleotides ; Poly A/genetics ; RNA/genetics ; RNA, Messenger ; Rats ; Sequence Homology, Nucleic Acid ; Transcription, Genetic
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-22
    Description: Activation of B lymphocytes by engagement of their immunoglobulin M antigen receptors results in phosphorylation of a number of proteins on tyrosine residues. One such protein is p95vav, the product of the vav proto-oncogene. Tyrosine phosphorylation of p95vav occurred within seconds of immunoglobulin M cross-linking and was independent of other events induced during stimulation of B cells, such as protein kinase C activation, guanosine triphosphate-binding protein signaling, and calcium mobilization. Moreover, engagement of antigen receptors induced the rapid (approximately 5 seconds) and transient (approximately 60 seconds) association of p95vav with a 70-kilodalton tyrosine-phosphorylated protein, Vap-1, an interaction mediated by the Src homology 2 domain of p95vav. These results suggest that the vav proto-oncogene participates in the signaling processes that mediate the antigen-induced activation of B lymphocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bustelo, X R -- Barbacid, M -- New York, N.Y. -- Science. 1992 May 22;256(5060):1196-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1375396" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/analysis ; Animals ; B-Lymphocytes/immunology/*physiology ; *Cell Cycle Proteins ; Cell Line ; Kinetics ; *Lymphocyte Activation ; Mice ; Phosphorylation ; Phosphotyrosine ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins c-vav ; *Proto-Oncogenes ; Tyrosine/analogs & derivatives/analysis
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  • 31
    Publication Date: 1992-01-03
    Description: The products of the adenovirus early region 1A (E1A) gene are potent oncoproteins when tested in standard transformation and immortalization assays. Many of the changes induced by E1A may be due to its interaction with cellular proteins. Four of these cellular proteins are the retinoblastoma protein (pRB), p107, cyclin A, and p33cdk2. The pRB and p107 proteins are structurally related and have several characteristics in common, including that they both bind to the SV40 large T oncoprotein as well as to E1A. Cyclin A and p33cdk2 are thought to function in the control of the cell cycle. They bind to one another, forming a kinase that closely resembles the cell cycle-regulating complexes containing p34cdc2. Cyclin A is now shown to bind to p107 in the absence of E1A. The association of p107 with cyclin A suggests a direct link between cell cycle control and the function of p107.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faha, B -- Ewen, M E -- Tsai, L H -- Livingston, D M -- Harlow, E -- CA 13106/CA/NCI NIH HHS/ -- CA 55339/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Jan 3;255(5040):87-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Charlestown 02129.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1532458" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus Early Proteins ; Amino Acid Sequence ; Antibodies, Monoclonal ; CDC2 Protein Kinase/metabolism ; Cell Line ; Cyclins/immunology/isolation & purification/*metabolism ; Electrophoresis, Polyacrylamide Gel ; Glutathione Transferase/genetics/isolation & purification ; Humans ; Methionine/metabolism ; Molecular Sequence Data ; *Nuclear Proteins ; Oncogene Proteins, Viral/*metabolism ; Proteins/genetics/*metabolism ; Recombinant Fusion Proteins/isolation & purification ; Retinoblastoma Protein/metabolism ; Retinoblastoma-Like Protein p107
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butz, S -- Stappert, J -- Weissig, H -- Kemler, R -- New York, N.Y. -- Science. 1992 Aug 21;257(5073):1142-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1509266" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cadherins/*chemistry/metabolism ; Cattle ; Cell Line ; Cytoskeletal Proteins/*chemistry/metabolism ; Desmoplakins ; Dogs ; Humans ; Mice ; Molecular Sequence Data ; Sequence Homology, Nucleic Acid ; *Trans-Activators ; Xenopus ; Xenopus Proteins ; beta Catenin ; gamma Catenin
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  • 33
    Publication Date: 1992-08-07
    Description: Immune responses in lymphocytes require cellular accumulation of large amounts of calcium (Ca2+) from extracellular sources. In the T cell tumor line Jurkat, receptors for the Ca(2+)-releasing messenger inositol 1,4,5-trisphosphate (IP3) were localized to the plasma membrane (PM). Capping of the T cell receptor-CD3 complex, which is associated with signal transduction, was accompanied by capping of IP3 receptors. The IP3 receptor on T cells appears to be responsible for the entry of Ca2+ that initiates proliferative responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khan, A A -- Steiner, J P -- Klein, M G -- Schneider, M F -- Snyder, S H -- DA-00074/DA/NIDA NIH HHS/ -- MH-18501/MH/NIMH NIH HHS/ -- P01-HL27867/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Aug 7;257(5071):815-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University School of Medicine, Department of Neuroscience, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323146" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, CD/metabolism ; Antigens, CD3 ; Antigens, Differentiation, T-Lymphocyte/analysis/*metabolism ; Burkitt Lymphoma ; Calcium/*metabolism ; *Calcium Channels ; Cell Line ; Cell Membrane/*metabolism ; Cells, Cultured ; Concanavalin A/pharmacology ; Fluorescent Antibody Technique ; Humans ; Inositol 1,4,5-Trisphosphate/*metabolism ; Inositol 1,4,5-Trisphosphate Receptors ; Kinetics ; Receptors, Antigen, T-Cell/analysis/*metabolism ; Receptors, Cell Surface/analysis/*metabolism ; *Receptors, Cytoplasmic and Nuclear ; Second Messenger Systems ; T-Lymphocytes/*immunology
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  • 34
    Publication Date: 1992-05-01
    Description: A form of learning in the marine mollusk Aplysia, long-term sensitization of the gill- and siphon-withdrawal reflex, results in the formation of new synaptic connections between the presynaptic siphon sensory neurons and their target cells. These structural changes can be mimicked, when the cells are maintained in culture, by application of serotonin, an endogenous facilitating neurotransmitter in Aplysia. A group of cell surface proteins, designated Aplysia cell adhesion molecules (apCAM's) was down-regulated in the sensory neurons in response to serotonin. The deduced amino acid sequence obtained from complementary DNA clones indicated that the apCAM's are a family of proteins that seem to arise from a single gene. The apCAM's are members of the immunoglobulin class of cell adhesion molecules and resemble two neural cell adhesion molecules, NCAM and fasciclin II. In addition to regulating newly synthesized apCAM, serotonin also altered the amount of preexisting apCAM on the cell surface of the presynaptic sensory neurons. By contrast, the apCAM on the surface of the postsynaptic motor neuron was not modulated by serotonin. This rapid, transmitter-mediated down-regulation of a cell adhesion molecule in the sensory neurons may be one of the early molecular changes in long-term synaptic facilitation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayford, M -- Barzilai, A -- Keller, F -- Schacher, S -- Kandel, E R -- New York, N.Y. -- Science. 1992 May 1;256(5057):638-44.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1585176" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Aplysia/*metabolism ; Blotting, Northern ; Cell Adhesion Molecules, Neuronal/chemistry/genetics/*metabolism ; Cells, Cultured ; Cloning, Molecular ; DNA/chemistry/genetics ; Fluorescent Antibody Technique ; Molecular Sequence Data ; Motor Neurons/drug effects/metabolism ; Neuronal Plasticity/*physiology ; Neurons, Afferent/drug effects/metabolism ; Protein Sorting Signals/chemistry ; Serotonin/pharmacology ; Synapses/*physiology
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  • 35
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-11-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amato, I -- New York, N.Y. -- Science. 1992 Nov 13;258(5085):1084.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1439816" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion ; Cell Division ; *Cell Physiological Phenomena ; Cells, Cultured ; Electronics
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  • 36
    Publication Date: 1992-09-25
    Description: A silicon-based device, dubbed a microphysiometer, can be used to detect and monitor the response of cells to a variety of chemical substances, especially ligands for specific plasma membrane receptors. The microphysiometer measures the rate of proton excretion from 10(4) to 10(6) cells. This article gives an overview of experiments currently being carried out with this instrument with emphasis on receptors with seven transmembrane helices and tyrosine kinase receptors. As a scientific instrument, the microphysiometer can be thought of as serving two distinct functions. In terms of detecting specific molecules, selected biological cells in this instrument serve as detectors and amplifiers. The microphysiometer can also investigate cell function and biochemistry. A major application of this instrument may prove to be screening for new receptor ligands. In this respect, the microphysiometer appears to offer significant advantages over other techniques.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McConnell, H M -- Owicki, J C -- Parce, J W -- Miller, D L -- Baxter, G T -- Wada, H G -- Pitchford, S -- New York, N.Y. -- Science. 1992 Sep 25;257(5078):1906-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Stanford University, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1329199" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biotechnology ; *Cell Physiological Phenomena ; Cells, Cultured ; Culture Media ; HIV Infections/physiopathology ; Humans ; *Hydrogen-Ion Concentration ; In Vitro Techniques ; Potentiometry/*instrumentation ; Receptors, Cell Surface/physiology ; Silicon
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  • 37
    Publication Date: 1992-01-24
    Description: Drug resistance in human cancer is associated with overexpression of the multidrug resistance (MDR1) gene, which confers cross-resistance to hydrophobic natural product cytotoxic drugs. Expression of the MDR1 gene can occur de novo in human cancers in the absence of drug treatment. The promoter of the human MDR1 gene was shown to be a target for the c-Ha-Ras-1 oncogene and the p53 tumor suppressor gene products, both of which are associated with tumor progression. The stimulatory effect of c-Ha-Ras-1 was not specific for the MDR1 promoter alone, whereas a mutant p53 specifically stimulated the MDR1 promoter and wild-type p53 exerted specific repression. These results imply that the MDR1 gene could be activated during tumor progression associated with mutations in Ras and p53.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chin, K V -- Ueda, K -- Pastan, I -- Gottesman, M M -- New York, N.Y. -- Science. 1992 Jan 24;255(5043):459-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1346476" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Cell Line ; Drug Resistance ; *Gene Expression Regulation ; Genes, Tumor Suppressor ; Genes, ras ; In Vitro Techniques ; Membrane Glycoproteins/*genetics ; Mice ; P-Glycoprotein ; *Promoter Regions, Genetic ; Proto-Oncogene Proteins p21(ras)/*physiology ; Transcription, Genetic ; Tumor Suppressor Protein p53/*physiology
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  • 38
    Publication Date: 1992-07-10
    Description: In human immunodeficiency virus (HIV) infection, functional defects and deletion of antigen-reactive T cells are more frequent than can be explained by direct viral infection. On culturing, both CD4+ and CD8+ T cells from asymptomatic HIV-infected individuals died as a result of programmed cell death (apoptosis). Apoptosis was enhanced by activation with CD3 antibodies. Programmed cell death, associated with impaired T cell reactivity, may thus be responsible for the deletion of reactive T cells that contributes to HIV-induced immunodeficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyaard, L -- Otto, S A -- Jonker, R R -- Mijnster, M J -- Keet, R P -- Miedema, F -- New York, N.Y. -- Science. 1992 Jul 10;257(5067):217-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1352911" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*pathology ; Antigens, CD/physiology ; Antigens, CD8/immunology ; CD4-Positive T-Lymphocytes/pathology ; Cell Death/physiology ; Cell Division/immunology ; Cells, Cultured ; HIV Envelope Protein gp120/physiology ; *Hiv-1 ; Humans ; Male ; Microscopy, Electron ; T-Lymphocytes/*pathology ; Zinc/pharmacology
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-22
    Description: Multifunctional calcium-calmodulin-dependent protein kinase (CaM kinase) transduces transient elevations in intracellular calcium into changes in the phosphorylation state and activity of target proteins. By fluorescence emission anisotropy, the affinity of CaM kinase for dansylated calmodulin was measured and found to increase 1000 times after autophosphorylation of the threonine at position 286 of the protein. Autophosphorylation markedly slowed the release of bound calcium-calmodulin; the release time increased from less than a second to several hundred seconds. In essence, calmodulin is trapped by autophosphorylation. The shift in affinity does not occur in a site-directed mutant in which threonine at position 286 has been replaced by a non-phosphorylatable amino acid. These experiments demonstrate the existence of a new state in which calmodulin is bound to CaM kinase even though the concentration of calcium is basal. Calmodulin trapping provides for molecular potentiation of calcium transients and may enable detection of their frequency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, T -- Hanson, P I -- Stryer, L -- Schulman, H -- GM 40600/GM/NIGMS NIH HHS/ -- GM24032/GM/NIGMS NIH HHS/ -- MH45324/MH/NIMH NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 May 22;256(5060):1199-202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1317063" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding, Competitive ; Calcium/pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases ; Calmodulin/*metabolism ; Cell Line ; Egtazic Acid/pharmacology ; Kinetics ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Phosphorylation ; Protein Binding ; Protein Kinases/genetics/*metabolism ; Recombinant Proteins/metabolism ; Spectrometry, Fluorescence ; Threonine ; Time Factors ; Transfection
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  • 40
    Publication Date: 1992-08-14
    Description: The study of the human pathogen papillomaviruses (HPVs) has been hampered by the inability to propagate the virus in tissue culture. The addition of 12-O-tetradecanoyl phorbol-13-acetate to the media of organotypic (raft) cultures increased expression of physiological markers of keratinocyte differentiation and concomitantly induced production of virions. Capsid production was detected in differentiated suprabasal cells. Virions approximately 54 nanometers in size were observed by electron microscopy in raft tissue cross sections in the suprabasal layers. Virions purified through isopycnic gradients were found to contain type 31b DNA and exhibited an icosahedral shape similar to that of papillomaviruses found in clinical samples.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyers, C -- Frattini, M G -- Hudson, J B -- Laimins, L A -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):971-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, IL 60637.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323879" target="_blank"〉PubMed〈/a〉
    Keywords: Capsid/biosynthesis ; *Cell Differentiation ; Cell Line ; Epithelial Cells ; Epithelium/drug effects/microbiology ; Female ; Humans ; Microscopy, Electron ; Papillomaviridae/drug effects/*physiology/ultrastructure ; Tetradecanoylphorbol Acetate/pharmacology ; Uterine Cervical Neoplasms ; Virion/drug effects/physiology/ultrastructure ; *Virus Replication/drug effects
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  • 41
    Publication Date: 1992-03-27
    Description: Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reynolds, B A -- Weiss, S -- New York, N.Y. -- Science. 1992 Mar 27;255(5052):1707-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Calgary Faculty of Medicine, Alberta, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1553558" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/*cytology ; Cell Division/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Corpus Striatum/*cytology ; Culture Media, Serum-Free ; Epidermal Growth Factor/pharmacology ; Fluorescent Antibody Technique ; Glial Fibrillary Acidic Protein/metabolism ; In Vitro Techniques ; Intermediate Filament Proteins/metabolism ; Intermediate Filaments/metabolism ; Mice ; *Nerve Tissue Proteins ; Nestin ; Neurons/*cytology ; Phosphopyruvate Hydratase/metabolism
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-08-07
    Description: Analysis of neuronal migration in mouse cerebellar slice preparations by a laser scanning confocal microscope revealed that postmitotic granule cells initiate their migration only after the expression of N-type calcium channels on their plasmalemmal surface. Furthermore, selective blockade of these channels by addition of omega-conotoxin to the incubation medium curtailed cell movement. In contrast, inhibitors of L- and T-type calcium channels, as well as those of sodium and potassium channels, had no effect on the rate of granule cell migration. These results suggest that N-type calcium channels, which have been predominantly associated with neurotransmitter release in adult brain, also play a transient but specific developmental role in directed migration of immature neurons before the establishment of their synaptic circuits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Komuro, H -- Rakic, P -- New York, N.Y. -- Science. 1992 Aug 7;257(5071):806-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323145" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/pharmacology ; Calcium Channels/drug effects/*physiology ; Cell Movement/drug effects ; Cells, Cultured ; Cerebellum/cytology/*physiology ; In Vitro Techniques ; Kinetics ; Mice ; Mollusk Venoms/pharmacology ; Neurons/cytology/drug effects/*physiology ; Peptides, Cyclic/pharmacology ; Time Factors ; *omega-Conotoxins
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  • 43
    Publication Date: 1992-08-21
    Description: The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes an adenosine 3',5'-monophosphate (cyclic AMP)-activated chloride channel. In cystic fibrosis (CF) patients, loss of CFTR function because of a genetic mutation results in defective cyclic AMP-mediated chloride secretion across epithelia. Because of their potential role as an animal model for CF, mice with targeted disruption of the murine CFTR gene [CFTR(-/-)] were tested for abnormalities in epithelial chloride transport. In both freshly excised tissue from the intestine and in cultured epithelia from the proximal airways, the cyclic AMP-activated chloride secretory response was absent in CFTR(-/-) mice as compared to littermate controls. Thus, disruption of the murine CFTR gene results in the chloride transport abnormalities predicted from studies of human CF epithelia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clarke, L L -- Grubb, B R -- Gabriel, S E -- Smithies, O -- Koller, B H -- Boucher, R C -- GM20069/GM/NIGMS NIH HHS/ -- HL 42384/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 21;257(5073):1125-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of North Carolina, Chapel Hill 27514.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1380724" target="_blank"〉PubMed〈/a〉
    Keywords: Amiloride/pharmacology ; Animals ; Biological Transport ; Cells, Cultured ; Chlorides/*metabolism ; Colforsin/pharmacology ; Cyclic AMP/pharmacology ; Cystic Fibrosis/genetics/*metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator ; *Disease Models, Animal ; Epithelium/metabolism ; Intestines/metabolism ; Membrane Proteins/genetics/*physiology ; Mice ; Mutation ; Nose/metabolism ; Trachea/metabolism
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  • 44
    Publication Date: 1992-09-18
    Description: Regulation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is unusual in that phosphorylated channels require cytosolic adenosine triphosphate (ATP) to open. The CFTR contains two regions predicted to be nucleotide-binding domains (NBDs); site-directed mutations in each NBD have now been shown to alter the relation between ATP concentration and channel activity, which indicates that ATP stimulates the channel by direct interaction with both NBDs. The two NBDs are not, however, functionally equivalent: adenosine diphosphate (ADP) competitively inhibited the channel by interacting with NBD2 but not by interacting with NBD1. Four cystic fibrosis-associated mutations in the NBDs reduced absolute chloride channel activity, and one mutation also decreased the potency with which ATP stimulates channel activity. Dysfunction of ATP-dependent stimulation through the NBDs may be the basis for defective CFTR chloride channel activity in some cystic fibrosis patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, M P -- Welsh, M J -- New York, N.Y. -- Science. 1992 Sep 18;257(5077):1701-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1382316" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/*pharmacology ; Adenosine Triphosphate/*pharmacology ; Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Binding, Competitive ; Cell Line ; Chloride Channels ; Cyclic AMP/pharmacology ; Cystic Fibrosis/*genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Nucleotides/*metabolism ; Protein Kinases/metabolism
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  • 45
    Publication Date: 1992-09-18
    Description: The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a key mediator of the antiviral and antiproliferative effects of interferons (IFNs). Studies examining the physiological function of the kinase suggest that it participates in cell growth and differentiation by regulating protein synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and in vivo result in phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in malignant transformation, suggesting that dsRNA-PK may function as a suppressor of cell proliferation and tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koromilas, A E -- Roy, S -- Barber, G N -- Katze, M G -- Sonenberg, N -- AI22646/AI/NIAID NIH HHS/ -- RR00166/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1992 Sep 18;257(5077):1685-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1382315" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Division ; Cell Line ; *Cell Transformation, Neoplastic ; Cloning, Molecular ; DNA/genetics ; Enzyme Induction ; Gene Expression ; Humans ; Immunoblotting ; Interferons/*pharmacology ; Mice ; Molecular Sequence Data ; *Mutation ; Phosphorylation ; Protein Kinases/chemistry/*genetics/physiology ; Transfection ; eIF-2 Kinase
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-06-12
    Description: Modulation of synaptic efficacy may depend on the temporal correlation between pre- and postsynaptic activities. At isolated neuromuscular synapses in culture, repetitive postsynaptic application of acetylcholine pulses alone or in the presence of asynchronous presynaptic activity resulted in immediate and persistent synaptic depression, whereas synchronous pre- and postsynaptic coactivation had no effect. This synaptic depression was a result of a reduction of evoked transmitter release, but induction of the depression requires a rise in postsynaptic cytosolic calcium concentration. Thus, Hebbian modulation operates at isolated peripheral synapses in vitro, and transsynaptic retrograde interaction appears to be an underlying mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dan, Y -- Poo, M M -- NS 22764/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jun 12;256(5063):1570-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, NY 10027.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1317971" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; In Vitro Techniques ; Neural Inhibition ; Neuromuscular Junction/*physiology ; *Synaptic Transmission ; Xenopus laevis
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-01-24
    Description: The sporogonic cycle of the avian malaria parasite Plasmodium gallinaceum was completed in vitro. Ookinetes (motile zygotes) were seeded onto a murine basement membrane-like gel (Matrigel) in coculture with Drosophila melanogaster cells (Schneider's L2). Transformation into oocysts as well as subsequent growth and differentiation were observed in parasites attached to Matrigel and depended on the presence of L2 cells. Sporozoites were first observed on day 10 in culture. Specific circumsporozoite protein antigenicity was identified in mature oocysts and in sporozoites. It is now possible to follow the entire life cycle of Plasmodium in vitro.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warburg, A -- Miller, L H -- New York, N.Y. -- Science. 1992 Jan 24;255(5043):448-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Malaria Section, 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/1734521" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Protozoan/metabolism ; Cells, Cultured ; Drosophila melanogaster/cytology ; Extracellular Matrix ; In Vitro Techniques ; Microscopy, Electron ; Plasmodium/*growth & development/ultrastructure ; *Protozoan Proteins
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-08
    Description: Expression of the bcr-abl oncogene in multipotent progenitor cells (MPPCs) is implicated as a key event in the development of chronic myelogenous leukemia. Bone marrow enriched for MPPCs was infected with a retrovirus that carried bcr-abl. The mixed-lineage colonies that resulted were responsive to growth factors and could differentiate. These cells later became growth factor-independent but, when injected into severe combined immunodeficient mice, were not leukemogenic. Thus, the presence of bcr-abl alone does not cause growth factor independence, although it initiates a stepwise process. This system may prove useful in the study of other oncogenes that cause leukemia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gishizky, M L -- Witte, O N -- New York, N.Y. -- Science. 1992 May 8;256(5058):836-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1375394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow/drug effects ; Bone Marrow Cells ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cells, Cultured ; Clone Cells ; Drug Resistance, Microbial/genetics ; Fluorouracil/pharmacology ; Fusion Proteins, bcr-abl/*genetics ; Hematopoietic Cell Growth Factors/pharmacology ; Hematopoietic Stem Cells/*cytology/drug effects/physiology ; Humans ; Interleukin-3/pharmacology ; Macrophages/cytology/drug effects ; Mast Cells/cytology/drug effects ; Mice ; Rats ; Retroviridae/genetics ; Stem Cell Factor ; Transfection
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  • 49
    Publication Date: 1992-10-02
    Description: The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shoji, M -- Golde, T E -- Ghiso, J -- Cheung, T T -- Estus, S -- Shaffer, L M -- Cai, X D -- McKay, D M -- Tintner, R -- Frangione, B -- AG05891/AG/NIA NIH HHS/ -- AG06656/AG/NIA NIH HHS/ -- AR02594/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Oct 2;258(5079):126-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Gunma University, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1439760" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*cerebrospinal fluid ; Amino Acid Sequence ; Amyloid beta-Peptides/*biosynthesis ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Base Sequence ; Cell Line ; Immunoblotting ; Leukemia, Myeloid/*metabolism ; Molecular Sequence Data ; Neuroblastoma/*metabolism ; Transfection
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-17
    Description: Alterations in intracellular calcium levels activate several signal transduction pathways resulting in distinct patterns of gene expression. Here, a pathway for calcium-mediated signals is demonstrated that involves C/EBP beta, a member of the bZip family of transcription factors. In pituitary cells C/EBP beta was phosphorylated in response to increased intracellular calcium concentrations as a consequence of the activation of a calcium-calmodulin-dependent protein kinase. Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wegner, M -- Cao, Z -- Rosenfeld, M G -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):370-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093-0648.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1314426" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; CCAAT-Enhancer-Binding Proteins ; Calcimycin/pharmacology ; Calcium/*pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases ; Cell Line ; DNA/chemistry/genetics/metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Enzyme Activation/drug effects ; *Leucine Zippers ; Molecular Sequence Data ; Nuclear Proteins/chemistry/*metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Pituitary Gland/metabolism ; Protein Kinases/metabolism ; Signal Transduction/drug effects ; Transcription Factors/chemistry/*metabolism ; Transcription, Genetic/drug effects ; Transfection
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  • 51
    Publication Date: 1992-08-21
    Description: Anergy is a mechanism of T lymphocyte tolerance induced by antigen receptor stimulation in the absence of co-stimulation. Anergic T cells were shown to have a defect in antigen-induced transcription of the interleukin-2 gene. Analysis of the promoter indicated that the transcription factor AP-1 and its corresponding cis element were specifically down-regulated. Exposure of anergic T cells to interleukin-2 restored both antigen responsiveness and activity of the AP-1 element.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, S M -- Beverly, B -- Tran, A C -- Brorson, K -- Schwartz, R H -- Lenardo, M J -- New York, N.Y. -- Science. 1992 Aug 21;257(5073):1134-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of 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/1509265" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens/*immunology ; Base Sequence ; Binding Sites ; Blotting, Northern ; Cell Line ; Concanavalin A/pharmacology ; *Gene Expression Regulation ; *Immune Tolerance ; Interleukin-2/*genetics/pharmacology ; Mice ; Molecular Sequence Data ; Mutation ; Promoter Regions, Genetic/genetics ; Proto-Oncogene Proteins c-jun/*physiology ; RNA, Messenger/metabolism ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/*immunology ; Transcription, Genetic ; Transfection
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  • 52
    Publication Date: 1992-05-22
    Description: The Ah (dioxin) receptor binds a number of widely disseminated environmental pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons, and mediates their carcinogenic effects. The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). The Ah receptor nuclear translocator protein (Arnt) is required for Ah receptor function. Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. Furthermore, Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. Arnt contains a basic helix-loop-helix motif, which may be responsible for interacting with both the XRE and the ligand-binding subunit.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reyes, H -- Reisz-Porszasz, S -- Hankinson, O -- CA 28868/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 May 22;256(5060):1193-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of California, Los Angeles 90024.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1317062" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies ; Aryl Hydrocarbon Receptor Nuclear Translocator ; Base Sequence ; Cell Line ; Cells, Cultured ; Cytochrome P-450 Enzyme System/genetics ; DNA/genetics/metabolism ; DNA-Binding Proteins/genetics/isolation & purification/*metabolism ; Humans ; Hydrocarbons/metabolism ; Mice ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Proteins/genetics/isolation & purification/*metabolism ; Receptors, Aryl Hydrocarbon ; Receptors, Drug/genetics/isolation & purification/*metabolism ; Recombinant Proteins/isolation & purification/metabolism ; Tetrachlorodibenzodioxin/metabolism ; *Transcription Factors ; Transcription, Genetic ; Transfection
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  • 53
    Publication Date: 1992-09-25
    Description: Observation of filamentous actin (F-actin) in living cells is currently limited to the resolution of the light microscope. Higher resolution procedures require sample fixation and preclude dynamic studies. The atomic force microscope (AFM) can image and manipulate samples at very high, sometimes atomic resolution by scanning a fine tip over the surface of interest and detecting physical interactions between the tip and sample. This study demonstrates that F-actin can be readily resolved in living cells with the AFM and that the dynamic properties of F-actin are easily observed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henderson, E -- Haydon, P G -- Sakaguchi, D S -- New York, N.Y. -- Science. 1992 Sep 25;257(5078):1944-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology and Genetics, Iowa State University, Ames 50011.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1411511" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*ultrastructure ; Actins/*physiology ; Animals ; *Cell Movement ; Cells, Cultured ; In Vitro Techniques ; Membrane Fluidity ; Microscopy/*methods ; Neuroglia/*ultrastructure ; Xenopus laevis
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  • 54
    Publication Date: 1992-03-06
    Description: Peptides extracted from HLA-A2.1 class I major histocompatibility complex (MHC) molecules expressed on the antigen processing mutant CEMx721.174.T2 were characterized by electrospray ionization-tandem mass spectrometry. Only seven dominant peptides were found, in contrast to over 200 associated with HLA-A2.1 on normal cells. These peptides were derived from the signal peptide domains of normal cellular proteins, were usually larger than nine residues, and were also associated with HLA-A2.1 in normal cells. These results suggest that proteolysis of signal peptide domains in the endoplasmic reticulum is a second mechanism for processing and presentation of peptides for association with class I molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henderson, R A -- Michel, H -- Sakaguchi, K -- Shabanowitz, J -- Appella, E -- Hunt, D F -- Engelhard, V H -- AI20963/AI/NIAID NIH HHS/ -- GM37537/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Mar 6;255(5049):1264-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1546329" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigen-Presenting Cells/*immunology ; Antigens/chemistry/immunology/*metabolism ; Cell Line ; Chromatography, High Pressure Liquid ; HLA-A2 Antigen/chemistry/*metabolism ; Humans ; Mass Spectrometry ; Molecular Sequence Data ; Mutation ; Peptides/chemistry/immunology/*metabolism ; Protein Sorting Signals/chemistry ; T-Lymphocytes/immunology
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  • 55
    Publication Date: 1992-04-24
    Description: Protein tyrosine phosphorylation is a common mechanism of signaling in pathways that regulate T cell receptor-mediated cell activation, cell proliferation, and the cell cycle. Because human immunodeficiency virus (HIV) is though to affect normal cell signaling, tyrosine phosphorylation may be associated with HIV cytopathicity. In both HIV-infected cells and transfected cells that stably express HIV envelope glycoproteins undergoing HIVgp41-induced cell fusion, a 30-kilodalton protein was phosphorylated on tyrosine with kinetics similar to those of syncytium formation and cell death. When tyrosine phosphorylation was inhibited by the protein tyrosine kinase inhibitor herbimycin A, envelope-mediated syncytium formation was coordinately reduced. These studies show that specific intracellular signals, which apparently participate in cytopathicity, are generated by HIV and suggest strategies by which the fusion process might be interrupted.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, D I -- Tani, Y -- Tian, H -- Boone, E -- Samelson, L E -- Lane, H C -- New York, N.Y. -- Science. 1992 Apr 24;256(5056):542-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunoregulation, 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/1570514" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, CD4/physiology ; Benzoquinones ; Cell Line ; Cytopathogenic Effect, Viral/*physiology ; HIV Envelope Protein gp41/genetics/physiology ; HIV-1/*physiology ; Humans ; Lactams, Macrocyclic ; Phosphoproteins/*metabolism ; Phosphorylation ; Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism ; Quinones/pharmacology ; Receptors, Antigen, T-Cell/physiology ; Rifabutin/analogs & derivatives ; Signal Transduction/*physiology ; T-Lymphocytes/microbiology/*physiology ; Transfection ; Tyrosine/*metabolism ; Viral Envelope Proteins/genetics/physiology
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  • 56
    Publication Date: 1992-02-07
    Description: The approximately 120-kilodalton amyloid beta protein precursor (beta APP) is processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives that includes potentially amyloidogenic forms with the approximately 4-kilodalton amyloid beta protein (beta AP) at or near their amino terminus. In order to determine if these derivatives are processed in a secretory pathway or by the endosomal-lysosomal system, (i) deletion mutants that produce the normal set of carboxyl-terminal derivatives and shortened secreted derivatives were analyzed and (ii) the effect of inhibitors of endosomal-lysosomal processing was examined. In the secretory pathway, cleavage of the beta APP occurs at a single site within the beta AP to generate one secreted derivative and one nonamyloidogenic carboxyl-terminal fragment, whereas, in the endosomal-lysosomal system, a complex set of carboxyl-terminal derivatives is produced that includes the potentially amyloidogenic forms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Golde, T E -- Estus, S -- Younkin, L H -- Selkoe, D J -- Younkin, S G -- New York, N.Y. -- Science. 1992 Feb 7;255(5045):728-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuropathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1738847" target="_blank"〉PubMed〈/a〉
    Keywords: Ammonium Chloride/pharmacology ; Amyloid/*biosynthesis ; Amyloid beta-Protein Precursor/genetics/*metabolism ; Base Sequence ; Cell Line ; Endopeptidases/metabolism ; Humans ; Leupeptins/pharmacology ; Lysosomes/metabolism ; Molecular Sequence Data ; Mutagenesis ; Peptide Fragments/*metabolism/secretion ; Transfection
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  • 57
    Publication Date: 1992-12-11
    Description: Class II major histocompatibility complexes bind peptides in an endosome-like compartment. When the class II null cell line 721.174 was transfected with class II DR3 genes, DR molecules were produced in normal amounts. However, the DR molecules were abnormally conformed and unstable because deletion of an antigen-processing gene had impaired intracellular formation of most class II-peptide complexes. Yet, 70 percent of the DR molecules still bore peptides, 80 percent of which were 21- to 24-amino acid fragments of the class II-associated invariant chain. These peptides were rare on DR3 from control cells. Thus, a defect in the main antigen-processing pathway revealed a process in which DR molecules bind long peptides derived from proteins present in the same compartment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sette, A -- Ceman, S -- Kubo, R T -- Sakaguchi, K -- Appella, E -- Hunt, D F -- Davis, T A -- Michel, H -- Shabanowitz, J -- Rudersdorf, R -- AI15486/AI/NIAID NIH HHS/ -- AI18634/AI/NIAID NIH HHS/ -- GM37537/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1801-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, University of Wisconsin, Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1465617" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cell Line ; Gene Deletion ; *Genes, MHC Class II ; HLA-DR Antigens/*genetics/*metabolism ; HLA-DR3 Antigen/*genetics/metabolism ; Humans ; Kinetics ; Macromolecular Substances ; Molecular Sequence Data ; Peptides/*metabolism ; Transfection
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  • 58
    Publication Date: 1992-10-23
    Description: Dopamine-containing neurons of the mammalian midbrain are required for normal behavior and movements. In vivo they fire action potentials in bursts, but in vitro they discharge regularly spaced action potentials. Burst firing in vitro has now been shown to be robustly induced by the glutamate agonist N-methyl-D-aspartate (NMDA) although not by the non-NMDA agonists kainate or quisqualate. The hyperpolarization between bursts of action potentials results from electrogenic sodium ion extrusion by a ouabain-sensitive pump. This mechanism of burst generation in mammalian neurons may be important in the pathophysiology of schizophrenia and Parkinson's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, S W -- Seutin, V -- North, R A -- New York, N.Y. -- Science. 1992 Oct 23;258(5082):665-7.〈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/1329209" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/physiology ; Animals ; Cells, Cultured ; Dopamine/*physiology ; Kainic Acid/pharmacology ; N-Methylaspartate/*pharmacology ; Neurons/*drug effects/physiology ; Quisqualic Acid/pharmacology ; Rats ; Sodium/physiology ; Sodium-Potassium-Exchanging ATPase/*physiology ; Synaptic Transmission/*physiology
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-10-09
    Description: Two types of calcium (Ca2+) signaling-propagating intercellular Ca2+ waves of increasing intracellular Ca2+ concentration ([Ca2+]i) and nonpropagating oscillations in [Ca2+]i-co-exist in a variety of cell types. To investigate this difference in Ca2+ signaling, airway epithelial cells were loaded with heparin, an inositol 1,4,5-triphosphate (IP3) receptor antagonist, by pulsed, high-frequency electroporation. Heparin inhibited propagation of intercellular Ca2+ waves but not oscillations of [Ca2+]i. In heparin-free cells, Ca2+ waves propagated through cells displaying [Ca2+]i oscillations. Depletion of intracellular Ca2+ pools with the Ca2+-pump inhibitor thapsigargin also inhibited the propagation of Ca2+ waves. These studies demonstrate that the release of Ca2+ by IP3 is necessary for the propagation of intercellular Ca2+ waves and suggest that IP3 moves through gap junctions to communicate intercellular Ca2+ waves.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boitano, S -- Dirksen, E R -- Sanderson, M J -- New York, N.Y. -- Science. 1992 Oct 9;258(5080):292-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, UCLA School of Medicine, CA 90024.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1411526" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/*metabolism ; Cells, Cultured ; Chondroitin Sulfates/pharmacology ; Electric Stimulation ; Epithelium/drug effects/metabolism ; Fluorescent Dyes ; Heparin/pharmacology ; Inositol 1,4,5-Trisphosphate/pharmacology/*physiology ; Intercellular Junctions/physiology ; Respiratory System/drug effects/metabolism ; Signal Transduction/*physiology ; Terpenes/pharmacology ; Thapsigargin
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  • 60
    Publication Date: 1992-05-15
    Description: The basic helix-loop-helix (bHLH) protein MyoD is a transcription factor that is important for the induction of the myogenic phenotype. The DNA binding basic region (13 amino acids) is necessary for recognition of the consensus MyoD binding site, for transcriptional activation, and for conversion of fibroblasts to muscle. In contrast, the non-tissue-specific bHLH protein E12 can bind to the MyoD binding site but does not induce myogenesis. Here, it is shown that only two amino acids in the MyoD basic region and a single amino acid from the junction, which separates the basic region and helix 1, are sufficient for myogenic specificity when substituted into the corresponding region of E12. These findings suggest that the recognition of particular determinants in the basic region is required for conversion of fibroblasts to muscle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, R L -- Weintraub, H -- New York, N.Y. -- Science. 1992 May 15;256(5059):1027-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute Laboratory, 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/1317057" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Cell Differentiation ; Cell Line ; DNA/metabolism ; DNA Probes ; DNA-Binding Proteins/chemistry/metabolism/pharmacology ; Fibroblasts/cytology ; Fluorescent Antibody Technique ; Molecular Sequence Data ; Muscle Proteins/chemistry/genetics/*physiology ; Muscles/*cytology ; MyoD Protein ; Protein Conformation ; Structure-Activity Relationship ; Transcription Factors/chemistry/metabolism/pharmacology ; Transfection
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 61
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-29
    Description: During replication, hepatitis delta virus (HDV) switches from production of small to large delta antigen. Both antigen isoforms have an HDV genome binding domain and are packaged into hepatitis B virus (HBV)-derived envelopes but differ at their carboxy termini. The large antigen was shown to contain a terminal CXXX box and undergo prenylation. The large, but not the small, antigen formed secreted particles when expressed singly with HBV surface antigen. Mutation of Cys211 in the CXXX box of the large antigen abolished both prenylation and particle formation, suggesting that this site is important for virion morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glenn, J S -- Watson, J A -- Havel, C M -- White, J M -- New York, N.Y. -- Science. 1992 May 29;256(5061):1331-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of California, San Francisco 94143-0450.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1598578" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Sequence ; Animals ; Antigens, Viral/genetics/isolation & purification/*metabolism ; Cell Line ; Cysteine ; Hepatitis Delta Virus/genetics/metabolism/*physiology ; Hepatitis delta Antigens ; Mevalonic Acid/*metabolism ; Mice ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Proline/metabolism ; Protein Biosynthesis ; RNA, Messenger/metabolism ; Rabbits ; Reticulocytes/metabolism ; Serine ; Transfection ; Virus Replication
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-03
    Description: Lymphocytes must proliferate and differentiate in response to low concentrations of a vast array of antigens. The requirements of broad specificity and sensitivity conflict because the former is met by low-affinity antigen receptors, which precludes achieving the latter with high-affinity receptors. Coligation of the membrane protein CD19 with the antigen receptor of B lymphocytes decreased the threshold for antigen receptor-dependent stimulation by two orders of magnitude. B lymphocytes proliferated when approximately 100 antigen receptors per cell, 0.03 percent of the total, were coligated with CD19. The B cell resolves its dilemma by having an accessory protein that enables activation when few antigen receptors are occupied.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carter, R H -- Fearon, D T -- AI-22833/AI/NIAID NIH HHS/ -- AI-28191/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 3;256(5053):105-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, 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/1373518" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Antigens, CD/genetics/*immunology ; Antigens, CD19 ; Antigens, Differentiation, B-Lymphocyte/genetics/*immunology ; B-Lymphocytes/*immunology ; Cell Line ; Cells, Cultured ; DNA Replication ; Humans ; Kinetics ; L Cells (Cell Line) ; *Lymphocyte Activation ; Mice ; Receptors, Antigen, B-Cell/*immunology ; Recombinant Proteins/immunology ; Thymidine/metabolism
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  • 63
    Publication Date: 1992-09-18
    Description: Human cyclin E, originally identified on the basis of its ability to function as a G1 cyclin in budding yeast, associated with a cell cycle-regulated protein kinase in human cells. The cyclin E-associated kinase activity peaked during G1, before the appearance of cyclin A, and was diminished during exit from the cell cycle after differentiation or serum withdrawal. The major cyclin E-associated kinase in human cells was Cdk2 (cyclin-dependent kinase 2). The abundance of the cyclin E protein and the cyclin E-Cdk2 complex was maximal in G1 cells. These results provide further evidence that in all eukaryotes assembly of a cyclin-Cdk complex is an important step in the biochemical pathway that controls cell proliferation during G1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koff, A -- Giordano, A -- Desai, D -- Yamashita, K -- Harper, J W -- Elledge, S -- Nishimoto, T -- Morgan, D O -- Franza, B R -- Roberts, J M -- New York, N.Y. -- Science. 1992 Sep 18;257(5077):1689-94.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Sciences, 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/1388288" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism ; *CDC2-CDC28 Kinases ; Cell Line ; Cyclin-Dependent Kinase 2 ; *Cyclin-Dependent Kinases ; Cyclins/*metabolism ; Flow Cytometry ; G1 Phase/*physiology ; Humans ; Immunoblotting ; Immunosorbent Techniques ; Protein Kinases/*metabolism ; *Protein-Serine-Threonine Kinases ; Rats
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  • 64
    Publication Date: 1992-08-14
    Description: The immunosuppressant rapamycin inhibited proliferation of the H4IIEC hepatoma cell line. Rapamycin, but not its structural analog FK506, also inhibited the basal and insulin-stimulated activity of the p70 ribosomal protein S6 kinase. By contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated protein (MAP) kinase activity were unaffected by drug. Rapamycin treatment of COS cells transfected with recombinant p70 S6 kinase completely inhibited the appearance of the hyperphosphorylated form of p70 S6 kinase concomitant with the inhibition of enzyme activity toward 40S subunits. Thus, rapamycin inhibits a signal transduction element that is necessary for the activation of p70 S6 kinase and mitogenesis but unnecessary for activation of p85 Rsk S6 kinase or MAP kinase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Price, D J -- Grove, J R -- Calvo, V -- Avruch, J -- Bierer, B E -- P01 CA39542/CA/NCI NIH HHS/ -- R01 DK17776/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):973-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diabetes Unit, Massachusetts General Hospital, Boston.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1380182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium-Calmodulin-Dependent Protein Kinases ; Cell Line ; Chromatography, Ion Exchange ; Cyclosporine/pharmacology ; Immunosuppressive Agents/*pharmacology ; Insulin/pharmacology ; Kinetics ; Liver Neoplasms, Experimental ; Polyenes/*pharmacology ; *Protein Kinase Inhibitors ; Protein Kinases/genetics/isolation & purification/*metabolism ; Recombinant Proteins/antagonists & inhibitors/isolation & purification ; Ribosomal Protein S6 Kinases ; Ribosomes/enzymology ; Sirolimus ; Tacrolimus/pharmacology ; Tetradecanoylphorbol Acetate/pharmacology ; Transfection
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  • 65
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayflick, L -- New York, N.Y. -- Science. 1992 Aug 21;257(5073):1027.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1472243" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Fetus ; Humans ; Research/*legislation & jurisprudence
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  • 66
    Publication Date: 1992-07-17
    Description: The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finkel, M S -- Oddis, C V -- Jacob, T D -- Watkins, S C -- Hattler, B G -- Simmons, R L -- GM-37753/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 17;257(5068):387-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Pittsburgh School of Medicine, PA 15213.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1631560" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arginine/analogs & derivatives/pharmacology ; Cells, Cultured ; Cricetinae ; Cytokines/*pharmacology ; Dose-Response Relationship, Drug ; Drug Interactions ; Endocardium/cytology ; Epithelium/physiology ; Interleukin-2/pharmacology ; Interleukin-6/pharmacology ; Microscopy, Electron ; Myocardial Contraction/*drug effects ; Nitric Oxide/*pharmacology ; Tumor Necrosis Factor-alpha/pharmacology ; omega-N-Methylarginine
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  • 67
    Publication Date: 1992-08-14
    Description: The alpha 2A-adrenergic receptor (adrenoceptor) was stably expressed in AtT20 mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase, inhibited voltage-dependent calcium currents, and increased inwardly rectifying potassium currents. An aspartic acid residue (Asp79) highly conserved among guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to asparagine; in cells transfected with the mutant alpha 2-receptor, agonists inhibited adenylyl cyclase and calcium currents but did not increase potassium currents. Because distinct G proteins appear to couple adrenoceptors to potassium and calcium currents, the present findings suggest that the mutant alpha 2-adrenoceptor cannot achieve the conformation necessary to activate G proteins that mediate potassium channel activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Surprenant, A -- Horstman, D A -- Akbarali, H -- Limbird, L E -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):977-80.〈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/1354394" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic alpha-Agonists/pharmacology ; Animals ; Asparagine ; Aspartic Acid ; Brimonidine Tartrate ; Calcium Channels/drug effects/metabolism/*physiology ; Cell Line ; Clonidine/pharmacology ; GTP-Binding Proteins/metabolism ; Membrane Potentials/drug effects ; *Mutagenesis, Site-Directed ; Potassium Channels/drug effects/metabolism/*physiology ; Quinoxalines/pharmacology ; Receptors, Adrenergic, alpha/drug effects/metabolism/*physiology ; Receptors, Neurotransmitter/drug effects/*physiology ; Receptors, Somatostatin ; Recombinant Proteins/drug effects/metabolism ; Somatostatin/metabolism/pharmacology ; Transfection
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  • 68
    Publication Date: 1992-07-10
    Description: The adoptive transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. The application of this approach to human disease would require the isolation and in vitro expansion of human antigen-specific T cells and evidence that such T cells persist and function in vivo after transfer. Cytomegalovirus-specific CD8+ cytotoxic T cell (CTL) clones could be isolated from bone marrow donors, propagated in vitro, and adoptively transferred to immunodeficient bone marrow transplant recipients. No toxicity developed and the clones provided persistent reconstitution of CD8+ cytomegalovirus-specific CTL responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Riddell, S R -- Watanabe, K S -- Goodrich, J M -- Li, C R -- Agha, M E -- Greenberg, P D -- CA18029/CA/NCI NIH HHS/ -- P01 CA018029/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 10;257(5067):238-41.〈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/1352912" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, CD3 ; Antigens, CD8/immunology ; Antigens, Differentiation, T-Lymphocyte/immunology ; Bone Marrow Transplantation/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cytomegalovirus Infections/*prevention & control ; Humans ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Vaccination/*methods
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  • 69
    Publication Date: 1992-08-07
    Description: The zeta subunit of the T cell antigen receptor (TCR) exists primarily as a disulfide-linked homodimer. This receptor subunit is important in TCR-mediated signal transduction and is a substrate for a TCR-activated protein tyrosine kinase. The zeta chain was found to undergo ubiquitination in response to receptor engagement. This posttranslational modification occurred in normal T cells and tumor lines. Both nonphosphorylated and phosphorylated zeta molecules were modified, and at least one other TCR subunit, CD3 delta, was also ubiquitinated after activation of the receptor. These findings suggest an expanded role for ubiquitination in transmembrane receptor function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cenciarelli, C -- Hou, D -- Hsu, K C -- Rellahan, B L -- Wiest, D L -- Smith, H T -- Fried, V A -- Weissman, A M -- New York, N.Y. -- Science. 1992 Aug 7;257(5071):795-7.〈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/1323144" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD3 ; Antigens, Differentiation, T-Lymphocyte/immunology/metabolism ; Cells, Cultured ; Hybridomas/immunology ; Lymphocyte Activation/*physiology ; Macromolecular Substances ; Mice ; Mice, Inbred C57BL ; Molecular Weight ; *Protein Processing, Post-Translational ; Receptors, Antigen, T-Cell/immunology/isolation & purification/*metabolism ; Spleen/immunology ; T-Lymphocytes/*immunology ; Ubiquitins/isolation & purification/*metabolism
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  • 70
    Publication Date: 1992-12-11
    Description: Mice transgenic for the human T cell leukemia virus (HTLV-I) Tax gene develop fibroblastic tumors that express NF-kappa B-inducible early genes. In vitro inhibition of NF-kappa B expression by antisense oligodeoxynucleotides (ODNs) inhibited growth of these culture-adapted Tax-transformed fibroblasts as well as an HTLV-I-transformed human lymphocyte line. In contrast, antisense inhibition of Tax itself had no apparent effect on cell growth. Mice treated with antisense to NF-kappa B ODNs showed rapid regression of transplanted fibrosarcomas. This suggests that NF-kappa B expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I-associated disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kitajima, I -- Shinohara, T -- Bilakovics, J -- Brown, D A -- Xu, X -- Nerenberg, M -- CA50234/CA/NCI NIH HHS/ -- MH47680/MH/NIMH NIH HHS/ -- NS01330/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1792-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1299224" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Base Sequence ; Cell Division/drug effects ; Cell Line ; Cell Transformation, Neoplastic ; Fibrosarcoma/*drug therapy/pathology ; *Genes, pX ; Human T-lymphotropic virus 1/*genetics ; Humans ; Kinetics ; Lymphocytes ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; NF-kappa B/*antagonists & inhibitors/genetics ; Oligodeoxyribonucleotides ; Oligonucleotides, Antisense/*pharmacology/*therapeutic use
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  • 71
    Publication Date: 1992-01-17
    Description: An immunodominant determinant for cytotoxic T lymphocytes (CTLs) exists in the hypervariable portion of human immunodeficiency virus-1 (HIV-1) gp160. Three mouse CTL lines (specific for isolates MN, RF, and IIIB) were examined for recognition of homologous determinants from distinct isolates. Only MN-elicited CTLs showed extensive interisolate cross-reactivity. Residue 325 played a critical role in specificity, with MN-elicited CTLs responding to peptides with an aromatic or cyclic residue and IIIB-induced cells recognizing peptides with an aliphatic residue at this position. CTL populations with broad specificities were generated by restimulation of IIIB-gp160 primed cells with MN-type peptides that have an aliphatic substitution at 325. This represents an approach to synthetic vaccines that can generate broadly cross-reactive CTLs capable of effector function against a wide range of HIV isolates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, H -- Nakagawa, Y -- Pendleton, C D -- Houghten, R A -- Yokomuro, K -- Germain, R N -- Berzofsky, J A -- New York, N.Y. -- Science. 1992 Jan 17;255(5042):333-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1372448" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/immunology ; Amino Acid Sequence ; Animals ; Cell Line ; Cross Reactions ; Epitopes/immunology ; Gene Products, env/genetics/*immunology ; HIV Antigens/immunology ; HIV Envelope Protein gp160 ; HIV-1/*immunology ; In Vitro Techniques ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Protein Precursors/genetics/*immunology ; Sequence Homology, Nucleic Acid ; T-Lymphocytes, Cytotoxic/*immunology ; Vaccination
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  • 72
    Publication Date: 1992-03-27
    Description: Id is a helix-loop-helix (HLH) protein that represses activity of several basic helix-loop-helix (bHLH) proteins involved in cell type--specific transcription and cell lineage commitment. The myeloid precursor cell line 32DC13(G) expressed Id messenger RNA, which was transiently decreased when cells were induced to terminally differentiate with granulocyte--colony-stimulating factor. Concomitant with the decrease of Id messenger RNA was the appearance in nuclear extracts of DNA binding proteins that recognized a canonical E-box motif, a DNA binding site for some bHLH proteins. Constitutive expression of an Id complementary DNA in 32DC13(G) cells blocked their ability to differentiate and to induce E-box-binding activity. These results suggest that Id and, hence, bHLH proteins function in the process of myeloid differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kreider, B L -- Benezra, R -- Rovera, G -- Kadesch, T -- CA 10815/CA/NCI NIH HHS/ -- CA 21124/CA/NCI NIH HHS/ -- CA 25875/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Mar 27;255(5052):1700-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1372755" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation/*drug effects ; Cells, Cultured ; DNA-Binding Proteins/*physiology ; Gene Expression ; Granulocyte Colony-Stimulating Factor/pharmacology ; Hematopoiesis/*drug effects ; In Vitro Techniques ; Inhibitor of Differentiation Protein 1 ; Interleukin-3/pharmacology ; Macromolecular Substances ; RNA, Messenger/genetics ; *Repressor Proteins ; *Transcription Factors
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  • 73
    Publication Date: 1992-05-22
    Description: The N-methyl D-aspartate (NMDA) receptor subtype of glutamate-gated ion channels possesses high calcium permeability and unique voltage-dependent sensitivity to magnesium and is modulated by glycine. Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% identical in sequence. These are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor subunits, including the NMDA receptor subunit NMDAR1 (NR1). Upon expression in cultured cells, the new subunits yielded prominent, typical glutamate- and NMDA-activated currents only when they were in heteromeric configurations with NR1. NR1-NR2A and NR1-NR2C channels differed in gating behavior and magnesium sensitivity. Such heteromeric NMDA receptor subtypes may exist in neurons, since NR1 messenger RNA is synthesized throughout the mature rat brain, while NR2 messenger RNA show a differential distribution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monyer, H -- Sprengel, R -- Schoepfer, R -- Herb, A -- Higuchi, M -- Lomeli, H -- Burnashev, N -- Sakmann, B -- Seeburg, P H -- New York, N.Y. -- Science. 1992 May 22;256(5060):1217-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Biology, University of Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1350383" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Brain/*physiology ; Cell Line ; Cloning, Molecular ; DNA/genetics ; Glutamates/pharmacology ; Glutamic Acid ; Glycine/pharmacology ; Macromolecular Substances ; Magnesium/pharmacology ; Membrane Potentials/drug effects ; Molecular Sequence Data ; Multigene Family ; N-Methylaspartate/pharmacology ; Oligonucleotide Probes ; Organ Specificity ; Peptides ; RNA, Messenger/genetics/metabolism ; Rats ; Receptors, N-Methyl-D-Aspartate/*genetics/*metabolism ; Recombinant Proteins/drug effects/metabolism ; Sequence Homology, Nucleic Acid ; Transfection
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  • 74
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-24
    Description: The mammalian splicing factor SC35 is required for the first step in the splicing reaction and for spliceosome assembly. The cloning and characterization of a complementary DNA encoding this protein revealed that it is a member of a family of splicing factors that includes mammalian SF2/ASF. This family of proteins is characterized by the presence of a ribonucleoprotein (RNP)-type RNA binding motif and a carboxyl-terminal serine-arginine-rich (SR) domain. A search of the DNA sequence database revealed that the thymus-specific exon (ET) of the c-myb proto-oncogene is encoded on the antisense strand of the SC35 gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fu, X D -- Maniatis, T -- GM42231/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 24;256(5056):535-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1373910" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Baculoviridae/genetics ; Base Sequence ; Binding Sites ; Blotting, Northern ; Cell Line ; Cloning, Molecular ; Codon ; DNA/chemistry/*isolation & purification ; Exons ; Humans ; Molecular Sequence Data ; *Nuclear Proteins ; Proteins/chemistry/*genetics ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-myb ; RNA/metabolism ; *RNA Splicing ; *Ribonucleoproteins ; Sequence Homology, Nucleic Acid ; Transfection
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 75
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoffman, M -- New York, N.Y. -- Science. 1992 Mar 20;255(5051):1510-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1549780" target="_blank"〉PubMed〈/a〉
    Keywords: Cells, Cultured ; Nitrogen/metabolism ; Saccharomyces cerevisiae/*physiology
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  • 76
    Publication Date: 1992-12-11
    Description: The telomeres of Xq and Yq have been observed to associate during meiosis, and in rare cases a short synaptonemal complex is present. Molecular cloning of loci from Xqter and Yqter has revealed that their sequence homology extends over 400 kilobases, which suggests the possibility of genetic exchange. This hypothesis was tested by the development of two highly informative microsatellite markers from yeast artificial chromosome clones that carried Xqter sequences and the following of their inheritance in a set of reference pedigrees from the Centre d'Etude du Polymorphisme Humain in Paris, France. From a total of 195 informative male meioses, four recombination events between these loci were observed. In three cases, paternal X alleles were inherited by male offspring, and in one case a female offspring inherited her father's Y allele. These data support the existence of genetic exchange at Xq-Yq, which defines a second pseudoautosomal region between the sex chromosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freije, D -- Helms, C -- Watson, M S -- Donis-Keller, H -- HG00100/HG/NHGRI NIH HHS/ -- HG00201/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1784-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, 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/1465614" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Cell Line ; Chromosome Banding ; Chromosome Mapping ; Chromosomes, Fungal ; Cloning, Molecular ; DNA/*genetics ; Factor VIII/genetics ; Female ; Gene Conversion ; Genetic Linkage ; Haplotypes ; Humans ; Hybrid Cells ; Male ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Pedigree ; Polymerase Chain Reaction/methods ; Recombination, Genetic ; Rodentia ; Saccharomyces cerevisiae/genetics ; Sequence Homology, Nucleic Acid ; Telomere/*physiology/ultrastructure ; *X Chromosome ; *Y Chromosome
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  • 77
    Publication Date: 1992-08-14
    Description: The peptide binding cleft of the class I human histocompatibility antigen, HLA-A2, contains conserved amino acid residues clustered in the two ends of the cleft in pockets A and F as well as polymorphic residues. The function of two conserved tyrosines in the A pocket was investigated by mutating them to phenylalanines and of a conserved tyrosine and threonine in the F pocket by mutating them to phenylalanine and valine, respectively. Presentation of influenza virus peptides and of intact virus to cytolytic T lymphocytes (CTLs) was then examined. The magnitude of the reduction seen by the mutation of the two tyrosines in the A pocket suggests that hydrogen bonds involving them have a critical function in the binding of the NH2-terminal NH3+ of the peptide nonamer and possibly of all bound peptide nonamers. In contrast, the mutations in the F pocket had no effect on CTL recognition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Latron, F -- Pazmany, L -- Morrison, J -- Moots, R -- Saper, M A -- McMichael, A -- Strominger, J L -- AI 20182/AI/NIAID NIH HHS/ -- CA 47554/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):964-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1380181" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Binding Sites ; Cell Line ; Cloning, Molecular ; Epitopes/immunology/metabolism ; HLA-A2 Antigen/chemistry/genetics/*metabolism ; Influenza A virus ; Kinetics ; Models, Molecular ; Mutagenesis, Site-Directed ; Oligopeptides/immunology/*metabolism ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; T-Lymphocytes, Cytotoxic/*immunology ; Transfection ; Viral Proteins/metabolism
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  • 78
    Publication Date: 1992-07-31
    Description: gamma-Aminobutyric acidA (GABAA) receptors are ligand-gated ion channels that mediate inhibitory synaptic transmission in the central nervous system. The role of protein phosphorylation in the modulation of GABAA receptor function was examined with cells transiently transfected with GABAA receptor subunits. GABAA receptors consisting of the alpha 1 and beta 1 or the alpha 1, beta 1, and gamma 2 subunits were directly phosphorylated on the beta 1 subunit by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA). The phosphorylation decreased the amplitude of the GABA response of both receptor types and the extent of rapid desensitization of the GABAA receptor that consisted of the alpha 1 and beta 1 subunits. Site-specific mutagenesis of the serine residue phosphorylated by PKA completely eliminated the PKA phosphorylation and modulation of the GABAA receptor. In primary embryonic rat neuronal cell cultures, a similar regulation of GABAA receptors by PKA was observed. These results demonstrate that the GABAA receptor is directly modulated by protein phosphorylation and suggest that neurotransmitters or neuropeptides that regulate intracellular cAMP levels may modulate the responses of neurons to GABA and consequently have profound effects on synaptic excitability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moss, S J -- Smart, T G -- Blackstone, C D -- Huganir, R L -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1992 Jul 31;257(5070):661-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Howard Hughes Medical Institute, 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/1323140" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; Colforsin/pharmacology ; Cyclic AMP/*pharmacology ; Electric Conductivity ; Immunosorbent Techniques ; Kinetics ; Mice ; Mutagenesis, Site-Directed ; Neurons/drug effects/physiology ; Peptide Mapping ; Phosphorylation ; Protein Kinases/*metabolism ; Rats ; Receptors, GABA-A/genetics/*physiology ; Recombinant Proteins/physiology ; Transfection ; Zinc/pharmacology ; gamma-Aminobutyric Acid/pharmacology
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  • 79
    Publication Date: 1992-06-19
    Description: A hybrid receptor was constructed that contained the extracellular binding domain of the human growth hormone (hGH) receptor linked to the transmembrane and intracellular domains of the murine granulocyte colony-stimulating factor receptor. Addition of hGH to a myeloid leukemia cell line (FDC-P1) that expressed the hybrid receptor caused proliferation of these cells. The mechanism for signal transduction of the hybrid receptor required dimerization because monoclonal antibodies to the hGH receptor were agonists whereas their monovalent fragments were not. Receptor dimerization occurs sequentially--a receptor binds to site 1 on hGH, and then a second receptor molecule binds to site 2 on hGH. On the basis of this sequential mechanism, which may occur in many other cytokine receptors, inactive hGH analogs were designed that were potent antagonists to hGH-induced cell proliferation. Such antagonists could be useful for treating clinical conditions of hGH excess, such as acromegaly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fuh, G -- Cunningham, B C -- Fukunaga, R -- Nagata, S -- Goeddel, D V -- Wells, J A -- New York, N.Y. -- Science. 1992 Jun 19;256(5064):1677-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1535167" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal ; Cell Division/drug effects ; Cell Line ; DNA Replication/drug effects ; Dose-Response Relationship, Drug ; Growth Hormone/analysis/physiology ; Humans ; Models, Molecular ; Receptors, Granulocyte Colony-Stimulating Factor/physiology ; Receptors, Somatotropin/*physiology ; Signal Transduction/physiology ; Transfection
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  • 80
    Publication Date: 1992-10-09
    Description: Approximately half of the neurons produced during embryogenesis normally die before adulthood. Although target-derived neurotrophic factors are known to be major determinants of programmed cell death--apoptosis--the molecular mechanisms by which trophic factors interfere with cell death regulation are largely unknown. Overexpression of the bcl-2 proto-oncogene in cultured sympathetic neurons has now been shown to prevent apoptosis normally induced by deprivation of nerve growth factor. This finding, together with the previous demonstration of bcl-2 expression in the nervous system, suggests that the Bcl-2 protein may be a major mediator of the effects of neurotrophic factors on neuronal survival.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia, I -- Martinou, I -- Tsujimoto, Y -- Martinou, J C -- CA-50551/CA/NCI NIH HHS/ -- CA-51864/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Oct 9;258(5080):302-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Centre Medical Universitaire, Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1411528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/*genetics ; Cell Death/*genetics ; Cells, Cultured ; Ganglia, Sympathetic/cytology ; Gene Expression ; Humans ; Nerve Growth Factors/physiology ; Neurons/*physiology ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins c-bcl-2 ; Rats ; Sympathetic Nervous System/*cytology ; Transfection
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  • 81
    Publication Date: 1992-07-24
    Description: Genetic and sequence information are reported for an angiotensin II-reactive antibody (Ab1, MAb 110) and an anti--anti-idiotypic antibody (Ab3, MAb 131) that have identical antigen binding properties and that are related by an anti-idiotypic antibody (Ab2-beta) that satisfies accepted biochemical criteria for an internal image-bearing antibody. The sequences of the variable regions of the Ab3 and of the Ab1 are nearly identical, even though the Ab1 is an antibody to a peptide and the Ab3 is an antibody to a globular protein. Significantly, amino acid residues that make critical contacts with antigen in the crystal structure of the Ab3-antigen complex are highly conserved in Ab1, suggesting that the epitopes of the Ab2-beta recognized by the Ab3 do indeed resemble the bound structure of the antigen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia, K C -- Desiderio, S V -- Ronco, P M -- Verroust, P J -- Amzel, L M -- 6M 44692/PHS HHS/ -- New York, N.Y. -- Science. 1992 Jul 24;257(5069):528-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry, Johns Hopkins University Medical School, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1636087" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Angiotensin II/chemistry/*immunology ; Animals ; Antibodies, Anti-Idiotypic/chemistry/genetics/*immunology ; Antibodies, Monoclonal/chemistry/genetics/*immunology ; Antigen-Antibody Complex ; Base Sequence ; Cell Line ; Hybridomas/immunology ; Immunoglobulin Heavy Chains/genetics/immunology ; Immunoglobulin Light Chains/genetics/immunology ; Immunoglobulin Variable Region/chemistry/genetics/immunology ; Mice ; Mice, Inbred BALB C/immunology ; Models, Molecular ; Molecular Sequence Data ; Plasmacytoma ; Protein Conformation
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  • 82
    Publication Date: 1992-05-29
    Description: Immunophilins, a family of proteins that exhibit rotamase (peptidyl-prolyl cis-trans isomerase) activity in vitro, are expressed in many organisms and most tissues. Although some immunophilins can mediate the immunosuppressive actions of FK506, rapamycin, and cyclosporin A, the physiological role of the unligated proteins is not known. A 59-kilodalton member of the FK506- and rapamycin-binding class was found to associate in the absence of these drugs with two heat shock proteins (hsp90 and hsp70) and the glucocorticoid receptor (GR). Together, these proteins make up the inactive GR, thus biochemically linking two families of proteins proposed to be involved in protein folding and assembly as well as two potent immunosuppressive modalities.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tai, P K -- Albers, M W -- Chang, H -- Faber, L E -- Schreiber, S L -- DK41881/DK/NIDDK NIH HHS/ -- GM-38627/GM/NIGMS NIH HHS/ -- HD28034/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1992 May 29;256(5061):1315-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Obstetrics and Gynecology, Medical College of Ohio, Toledo 43699.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1376003" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Isomerases/isolation & purification/*metabolism ; Amino Acid Sequence ; Animals ; Antibodies, Monoclonal ; Carrier Proteins/isolation & purification/*metabolism ; Cell Line ; Heat-Shock Proteins/isolation & purification/*metabolism ; Humans ; Kinetics ; Macromolecular Substances ; Molecular Sequence Data ; Molecular Weight ; Peptidylprolyl Isomerase ; Polyenes/metabolism ; Rats ; Receptors, Glucocorticoid/isolation & purification/*metabolism ; Sequence Homology, Nucleic Acid ; Sirolimus ; Tacrolimus/metabolism ; Tacrolimus Binding Proteins
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  • 83
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-11-27
    Description: During differentiation in the thymus, immature T cells progress through an ordered sequence of developmental stages that are best characterized by variable expression of the co-receptor molecules CD4 and CD8. Crosslinking of T cell receptor (TCR) molecules on precursor thymocytes was found to block their differentiation into CD4+CD8+ cells by eliminating messenger RNA's encoding two families of developmentally important molecules: the co-receptor molecules CD4 and CD8 and the recombination activating genes 1 and 2. TCR-induced post-transcriptional regulation in early thymocytes was specific for selective messenger RNA's, required protein synthesis, and was itself developmentally regulated. These data identify a post-transcriptional mechanism that is influenced by TCR signals and that regulates early thymocyte development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahama, Y -- Singer, A -- New York, N.Y. -- Science. 1992 Nov 27;258(5087):1456-62.〈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/1439838" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/genetics ; Antigens, CD8/genetics ; Cell Differentiation/physiology ; Cells, Cultured ; Fetus/cytology ; Gene Rearrangement, T-Lymphocyte/genetics ; Genes, RAG-1/genetics ; Mice ; Protein Synthesis Inhibitors/pharmacology ; Protein-Tyrosine Kinases/genetics ; RNA Processing, Post-Transcriptional/physiology ; RNA, Messenger/metabolism ; Receptors, Antigen, T-Cell, alpha-beta/genetics/*physiology ; Signal Transduction/physiology ; T-Lymphocytes/*cytology/drug effects ; Tetradecanoylphorbol Acetate/pharmacology ; Thymus Gland/cytology/embryology
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  • 84
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-17
    Description: 3T3-L1 adipoblasts that express large amounts of c-Myc cannot terminally differentiate, raising the possibility that Myc inhibits the expression of genes that promote adipogenesis. The CCAAT/enhancer binding protein (C/EBP alpha) is induced during 3T3-L1 adipogenesis when cells commit to the differentiation pathway. Transfection of 3T3-L1 adipoblasts with the gene that encodes C/EBP alpha caused overt expression of the adipocyte morphology. Expression of Myc prohibited the normal induction of C/EBP alpha and prevented adipogenesis. Enforced expression of C/EBP alpha overcame the Myc-induced block to differentiation. These results provide a molecular basis for the regulation of adipogenesis and implicate Myc and C/EBP alpha as pivotal controlling elements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freytag, S O -- Geddes, T J -- CA51748/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):379-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Research Program, Henry Ford Hospital, Detroit, MI 48202.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1566086" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/*cytology/metabolism ; Animals ; Base Sequence ; CCAAT-Enhancer-Binding Proteins ; Cell Differentiation ; Cell Division ; Cell Line ; DNA-Binding Proteins/genetics/*physiology ; *Gene Expression Regulation ; Molecular Sequence Data ; Nuclear Proteins/genetics/*physiology ; Plasmids ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-myc/genetics/*physiology ; RNA, Messenger/analysis ; Rats ; Transfection
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  • 85
    Publication Date: 1992-05-01
    Description: The long-term facilitation of synaptic efficacy that is induced by serotonin in dissociated cell cultures of sensory and motor neurons of Aplysia is accompanied by the growth of new synaptic connections. This growth is associated with a down-regulation in the sensory neuron of Aplysia cell adhesion molecules (apCAMs). To examine the mechanisms of this down-regulation, thin-section electron microscopy was combined with immunolabeling by gold-conjugated monoclonal antibodies specific to apCAM. Within 1 hour, serotonin led to a 50% decrease in the density of gold-labeled complexes at the surface membrane of the sensory neuron. This down-regulation was achieved by a heterologous, protein synthesis-dependent activation of the endosomal pathway, which leads to internalization and apparent degradation of apCAM. The internalization is particularly prominent at sites where the processes of the sensory neurons contact one another and may act there to destabilize process-to-process contacts that normally inhibit growth. In turn, the endocytic activation may lead to a redistribution of membrane components to sites where new synapses form.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, C H -- Chen, M -- Keller, F -- Kandel, E R -- GM32099/GM/NIGMS NIH HHS/ -- MH37134/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1992 May 1;256(5057):645-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, NY.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1585177" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anisomycin/pharmacology ; Antibodies, Monoclonal ; Aplysia/*physiology ; Cell Adhesion Molecules/*metabolism ; Cell Membrane/metabolism/ultrastructure ; Cells, Cultured ; Coated Pits, Cell-Membrane/metabolism/ultrastructure ; Endocytosis/*drug effects ; Immunohistochemistry ; Microscopy, Electron ; Motor Neurons/physiology/ultrastructure ; Neurons, Afferent/physiology/ultrastructure ; Serotonin/*pharmacology ; Synapses/*physiology/ultrastructure ; Wheat Germ Agglutinins/metabolism
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  • 86
    Publication Date: 1992-06-05
    Description: The phagocyte respiratory burst oxidase is a flavin-adenine dinucleotide (FAD)-dependent dehydrogenase and an electron transferase that reduces molecular oxygen to superoxide anion, a precursor of microbicidal oxidants. Several proteins required for assembly of the oxidase have been characterized, but the identity of its flavin-binding component has been unclear. Oxidase activity was reconstituted in vitro with only the purified oxidase proteins p47phox, p67phox, Rac-related guanine nucleotide (GTP)-binding proteins, and membrane-bound cytochrome b558. The reconstituted oxidase required added FAD, and FAD binding was localized to cytochrome b558. Alignment of the amino acid sequence of the beta subunit of cytochrome b558 (gp91phox) with other flavoproteins revealed similarities to the nicotinamide adenine dinucleotide phosphate (reduced) (NADPH)-binding domains. Thus flavocytochrome b558 is the only obligate electron transporting component of the NADPH oxidase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rotrosen, D -- Yeung, C L -- Leto, T L -- Malech, H L -- Kwong, C H -- New York, N.Y. -- Science. 1992 Jun 5;256(5062):1459-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Host Defenses, 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/1318579" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cell Line ; Cell-Free System ; Cytochrome b Group/*blood/genetics/isolation & purification ; Ferredoxin-NADP Reductase/genetics/metabolism ; Humans ; Insects ; Molecular Sequence Data ; NADH, NADPH Oxidoreductases/*blood/genetics/isolation & purification ; NADP/metabolism ; NADPH Oxidase ; Neutrophils/*enzymology ; Phagocytes/*enzymology ; Plants/enzymology ; Recombinant Proteins/chemistry/metabolism ; Sequence Homology, Nucleic Acid ; Superoxides/blood ; Transfection
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  • 87
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-03-13
    Description: Gene amplification, one example of genetic instability, is of prognostic and clinical importance in neoplasia. In tumorigenic cells, gene amplification occurs at a very high frequency, whereas in normal diploid fibroblasts the event is undetectable by the clonogenic assay. To investigate genetic control of gene amplification, amplification frequency was measured in hybrids of tumorigenic cells and normal diploid cells. The ability to amplify an endogenous gene behaved as a recessive genetic trait, and control of gene amplification potential segregated independently of tumorigenicity and immortality.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tlsty, T D -- White, A -- Sanchez, J -- New York, N.Y. -- Science. 1992 Mar 13;255(5050):1425-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, Department of Pathology and Curriculum in Genetics, School of Medicine, University of North Carolina, Chapel Hill 27599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1542791" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartate Carbamoyltransferase/antagonists & inhibitors/genetics ; Aspartic Acid/analogs & derivatives/pharmacology ; Cell Line ; Cell Transformation, Neoplastic/*genetics ; Drug Resistance/genetics ; Gene Amplification/*genetics ; Gene Expression Regulation, Enzymologic ; Genes, Dominant ; Genes, Recessive ; Humans ; *Hybrid Cells/drug effects/enzymology ; Mutation ; Phenotype ; Phosphonoacetic Acid/analogs & derivatives/pharmacology ; Suppression, Genetic ; Tumor Cells, Cultured
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  • 88
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tofilon, P J -- Deen, D F -- Marton, L J -- New York, N.Y. -- Science. 1992 Nov 20;258(5086):1378.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1455236" target="_blank"〉PubMed〈/a〉
    Keywords: Carmustine/toxicity ; Cell Death ; Cells, Cultured ; *DNA Damage ; In Vitro Techniques ; Polyamines/*metabolism ; Sister Chromatid Exchange/drug effects
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  • 89
    Publication Date: 1992-12-18
    Description: Retinoids have a broad spectrum of biological activities and are useful therapeutic agents. Their physiological activities are mediated by two types of receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). RARs, as well as several related receptors, require heterodimerization with RXRs for effective DNA binding and function. However, in the presence of 9-cis-retinoic acid, a ligand for both RARs and RXRs, RXRs can also form homodimers. A series of retinoids is reported that selectively activates RXR homodimers but does not affect RAR-RXR heterodimers and thus demonstrates that both retinoid response pathways can be independently activated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lehmann, J M -- Jong, L -- Fanjul, A -- Cameron, J F -- Lu, X P -- Haefner, P -- Dawson, M I -- Pfahl, M -- CA50676/CA/NCI NIH HHS/ -- P01 CA51993/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 18;258(5090):1944-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Center, La Jolla Cancer Research Foundation, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1335166" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Chloramphenicol O-Acetyltransferase/genetics/metabolism ; Kinetics ; Macromolecular Substances ; Molecular Structure ; Receptors, Cell Surface/drug effects/genetics/*metabolism ; *Receptors, Retinoic Acid ; Recombinant Fusion Proteins/metabolism ; Retinoid X Receptors ; Retinoids/chemistry/*metabolism/pharmacology ; Structure-Activity Relationship ; *Transcription Factors ; Transcription, Genetic ; Transfection ; Tretinoin/metabolism/pharmacology
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  • 90
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-10-23
    Description: Evidence is presented that suggests a role for transmembrane domain interactions in the assembly of class II major histocompatibility complex (MHC) molecules. Mutations in the transmembrane domains of the class II MHC alpha or beta chains resulted in proteins that did not generate complexes recognized by conformation-dependent antibodies and that were largely retained in the endoplasmic reticulum. Insertion of the alpha and beta transmembrane domains into other proteins allowed the chimeric proteins to assemble, suggesting a direct interaction of the alpha and beta transmembrane domains. The interactions were mediated by a structural motif involving several glycine residues on the same face of a putative alpha helix.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cosson, P -- Bonifacino, J S -- New York, N.Y. -- Science. 1992 Oct 23;258(5082):659-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism 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/1329208" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cloning, Molecular ; DNA Mutational Analysis ; Endoplasmic Reticulum/metabolism ; Glycine/metabolism ; Histocompatibility Antigens Class II/*biosynthesis/chemistry/genetics ; Mice ; Molecular Sequence Data ; *Protein Conformation ; Receptors, Interleukin-2/*biosynthesis/chemistry/genetics ; Recombinant Fusion Proteins/*biosynthesis/chemistry/genetics
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  • 91
    Publication Date: 1992-03-13
    Description: In vitro and in vivo model systems for the study of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) were used to evaluate compounds for their potential as therapeutic agents. A sulfated polysaccharide-peptidoglycan compound (SP-PG) produced by bacteria controlled the in vitro growth of acquired immunodeficiency syndrome (AIDS)-associated, KS-derived spindle-shaped cells (AIDS-KS cells) at noncytotoxic concentrations. Angiogenesis induced by AIDS-KS cells in the chicken chorioallantoic membrane assay was blocked by SP-PG, which also inhibited the vascular hyperpermeability response and the angiogenesis associated with the induction of KS-like lesions that develop after subcutaneous inoculation of AIDS-KS cells into nude mice. Suramin, pentosan polysulfate, and interferon alpha, which are currently in use for therapy of KS, were either less effective than SP-PG or much more cytotoxic, or both.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakamura, S -- Sakurada, S -- Salahuddin, S Z -- Osada, Y -- Tanaka, N G -- Sakamoto, N -- Sekiguchi, M -- Gallo, R C -- New York, N.Y. -- Science. 1992 Mar 13;255(5050):1437-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, University of Southern California, Los Angeles 90033.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1371891" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/complications ; Animals ; Arthrobacter ; Arylsulfatases ; Capillary Permeability/drug effects ; Cell Division/drug effects ; Cells, Cultured ; Endothelium, Vascular/cytology/drug effects ; Fibroblasts/drug effects ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic/*prevention & control ; *Peptidoglycan ; Polysaccharides/*pharmacology ; Sarcoma, Kaposi/etiology/*pathology ; Tumor Cells, Cultured
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  • 92
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-07-03
    Description: Activation of protein-tyrosine kinases (PTKs) is required for signal transduction during T cell activation, although the pathway used during thymic selection is unknown. An in vitro system was established in which T cell receptor transgenic thymocytes underwent clonal deletion in response to peptide antigen. The effects of two PTK-specific inhibitors, herbimycin A and genistein, on the clonal deletion of immature thymocytes and the activation of mature thymocytes were examined. Clonal deletion occurred while T cell activation was inhibited and when no p56lck activity was evident. Thus, p56lck is not required for the antigen-stimulated step of clonal deletion of immature thymocytes, and negative selection proceeds via a distinct pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakayama, K -- Loh, D Y -- New York, N.Y. -- Science. 1992 Jul 3;257(5066):94-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, 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/1621101" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzoquinones ; Cells, Cultured ; Chickens ; DNA Replication ; Genistein ; Isoflavones/pharmacology ; L Cells (Cell Line) ; Lactams, Macrocyclic ; *Lymphocyte Activation/drug effects ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Mice ; Mice, Transgenic ; Ovalbumin/immunology ; Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism ; Quinones/pharmacology ; Receptors, Antigen, T-Cell/*genetics/immunology ; Rifabutin/analogs & derivatives ; *Signal Transduction ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/drug effects/*immunology ; Transfection
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  • 93
    Publication Date: 1992-05-22
    Description: The proto-oncogene designated erbB2 or HER2 encodes a 185-kilodalton transmembrane tyrosine kinase (p185erbB2), whose overexpression has been correlated with a poor prognosis in several human malignancies. A 45-kilodalton protein heregulin-alpha (HRG-alpha) that specifically induced phosphorylation of p185erbB2 was purified from the conditioned medium of a human breast tumor cell line. Several complementary DNA clones encoding related HRGs were identified, all of which are similar to proteins in the epidermal growth factor family. Scatchard analysis of the binding of recombinant HRG to a breast tumor cell line expressing p185erbB2 showed a single high affinity binding site [dissociation constant (Kd) = 105 +/- 15 picomolar]. Heregulin transcripts were identified in several normal tissues and cancer cell lines. The HRGs may represent the natural ligands for p185erbB2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holmes, W E -- Sliwkowski, M X -- Akita, R W -- Henzel, W J -- Lee, J -- Park, J W -- Yansura, D -- Abadi, N -- Raab, H -- Lewis, G D -- New York, N.Y. -- Science. 1992 May 22;256(5060):1205-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1350381" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Breast Neoplasms/genetics ; Cell Line ; Chromatography, High Pressure Liquid ; Codon ; Culture Media ; DNA-Binding Proteins/genetics/isolation & purification/*metabolism ; Epidermal Growth Factor/genetics ; Female ; Glycoproteins/*metabolism ; Humans ; Kinetics ; Molecular Sequence Data ; Neuregulins ; Oligonucleotide Probes ; Phosphorylation ; Protein Conformation ; Protein-Tyrosine Kinases/*genetics ; Proto-Oncogene Proteins/*genetics ; *Proto-Oncogenes ; Receptor, ErbB-2 ; Sequence Homology, Nucleic Acid ; Transfection
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  • 94
    Publication Date: 1992-01-03
    Description: The multichain T cell antigen receptor functions by interacting with and activating one or more nonreceptor tyrosine kinases. The cytoplasmic tail of the zeta chain can activate T cells independently of the rest of the receptor complex. The function of the remaining invariant CD3 chains remains unknown. A 22-amino acid region of the cytoplasmic tail of CD3 epsilon was also able to independently activate T cells. Stimulation of T cells by means of the cytoplasmic tails of either zeta or CD3 epsilon resulted in quantitatively distinct patterns of tyrosine phosphorylation, suggesting activation of different biochemical pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Letourneur, F -- Klausner, R D -- New York, N.Y. -- Science. 1992 Jan 3;255(5040):79-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism 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/1532456" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD3 ; Antigens, Differentiation, T-Lymphocyte/genetics/*metabolism ; Cell Line ; Cell Membrane/immunology/metabolism ; Chimera ; Clone Cells ; Humans ; Interleukin-2/biosynthesis ; Kinetics ; *Lymphocyte Activation ; Macromolecular Substances ; Mice ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Phosphorylation ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases/genetics/*metabolism ; Receptors, Antigen, T-Cell/genetics/*metabolism ; Receptors, Interleukin-2/genetics/metabolism ; T-Lymphocytes/enzymology/*immunology ; Transfection
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  • 95
    Publication Date: 1992-07-03
    Description: Ryanodine receptors (RyRs) are intracellular channels that release calcium ions from the sarcoplasmic reticulum (SR) in response to either plasma membrane depolarization (in skeletal muscle) or increases in the concentration of intracellular free Ca2+ (in the heart). A gene (beta 4) encoding a ryanodine receptor (similar to, but distinct from, the muscle RyRs) was identified. The beta 4 gene was expressed in all tissues investigated, with the exception of heart. Treatment of mink lung epithelial cells (Mv1Lu) with transforming growth factor beta (TGF-beta) induced expression of the beta 4 gene together with the release of Ca2+ in response to ryanodine (but not in response to caffeine, the other drug active on muscle RyRs). This ryanodine receptor may be important in the regulation of intracellular Ca2+ homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giannini, G -- Clementi, E -- Ceci, R -- Marziali, G -- Sorrentino, V -- New York, N.Y. -- Science. 1992 Jul 3;257(5066):91-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1320290" target="_blank"〉PubMed〈/a〉
    Keywords: 2-Aminopurine/pharmacology ; Amino Acid Sequence ; Animals ; Calcium/*metabolism ; Calcium Channels/drug effects/physiology ; Cell Line ; Cell Membrane/metabolism ; Cloning, Molecular ; Cycloheximide/pharmacology ; Gene Expression/drug effects ; Mink ; Molecular Sequence Data ; Muscles/*physiology ; RNA, Messenger/genetics/metabolism ; Receptors, Cholinergic/drug effects/*genetics/*physiology ; Ryanodine Receptor Calcium Release Channel ; Sarcoplasmic Reticulum/metabolism ; Sequence Homology, Nucleic Acid ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription, Genetic/drug effects ; Transfection ; Transforming Growth Factor beta/*pharmacology
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  • 96
    Publication Date: 1992-05-22
    Description: The rational design and biological actions of a new class of DNA-cleaving molecules with potent and selective anticancer activity are reported. These relatively simple enediyne-type compounds were designed from basic chemical principles to mimic the actions of the rather complex naturally occurring enediyne anticancer antibiotics, particularly dynemicin A. Equipped with locking and triggering devices, these compounds damage DNA in vitro and in vivo on activation by chemical or biological means. Their damaging effects are manifested in potent anticancer activity with remarkable selectivities. Their mechanism of action involves intracellular unlocking and triggering of a Bergman reaction, leading to highly reactive benzenoid diradicals that cause severe DNA damage. The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicolaou, K C -- Dai, W M -- Tsay, S C -- Estevez, V A -- Wrasidlo, W -- New York, N.Y. -- Science. 1992 May 22;256(5060):1172-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1589797" target="_blank"〉PubMed〈/a〉
    Keywords: Antibiotics, Antineoplastic/*chemical synthesis/pharmacology ; Antineoplastic Agents/*pharmacology ; Cell Line ; Cell Survival/drug effects ; *DNA Damage ; Dose-Response Relationship, Drug ; Drug Design ; Female ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Structure-Activity Relationship ; Tumor Cells, Cultured
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  • 97
    Publication Date: 1992-10-09
    Description: Altered processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease. To investigate whether cellular APP processing is controlled by cell-surface neurotransmitter receptors, human embryonic kidney (293) cell lines were transfected with the genes for human brain muscarinic acetylcholine receptors. Stimulation of m1 and m3 receptor subtypes with carbachol increased the basal release of APP derivatives within minutes of treatment, indicating that preexisting APP is released in response to receptor activation. Receptor-activated APP release was blocked by staurosporine, suggesting that protein kinases mediate neurotransmitter receptor-controlled APP processing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nitsch, R M -- Slack, B E -- Wurtman, R J -- Growdon, J H -- New York, N.Y. -- Science. 1992 Oct 9;258(5080):304-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1411529" target="_blank"〉PubMed〈/a〉
    Keywords: Alkaloids/pharmacology ; Alzheimer Disease/*metabolism ; Amyloid beta-Protein Precursor/*secretion ; Atropine/pharmacology ; Blotting, Western ; Brain Chemistry ; Carbachol/pharmacology ; Cell Line ; Embryo, Mammalian ; Humans ; Kidney ; Kinetics ; Protein Kinase C/antagonists & inhibitors/metabolism ; Receptors, Muscarinic/drug effects/genetics/*physiology ; Staurosporine ; Transfection
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  • 98
    Publication Date: 1992-03-06
    Description: Antigens recognized by T cells are expressed as peptides bound to major histocompatibility complex (MHC) molecules. Microcapillary high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to fractionate and sequence subpicomolar amounts of peptides isolated from the MHC molecule HLA-A2.1. Of 200 different species quantitated, eight were sequenced and four were found in cellular proteins. All were nine residues long and shared a distinct structural motif. The sensitivity and speed of this approach should enhance the analysis of peptides from small quantities of virally infected and transformed cells as well as those associated with autoimmune disease states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hunt, D F -- Henderson, R A -- Shabanowitz, J -- Sakaguchi, K -- Michel, H -- Sevilir, N -- Cox, A L -- Appella, E -- Engelhard, V H -- AI20963/AI/NIAID NIH HHS/ -- GM37537/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Mar 6;255(5049):1261-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Virginia, Charlottesville 22903.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1546328" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens/chemistry/immunology/*metabolism ; Cell Line ; Chromatography, High Pressure Liquid ; HLA-A2 Antigen/*metabolism ; Humans ; Immunosorbent Techniques ; *Mass Spectrometry ; Molecular Sequence Data ; Peptides/chemistry/immunology/*metabolism ; T-Lymphocytes/immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-01-24
    Description: Secretion of gonadotropic hormones from pituitary gonadotropes in response to gonadotropin-releasing hormone (GnRH) is essential for regulation of reproductive potential. Gonadotropes from male rats exhibited an unusual form of cellular excitation that resulted from periodic membrane hyperpolarization. GnRH induced an oscillatory release of intracellular Ca2+ via a guanosine triphosphate (GTP) binding protein-coupled phosphoinositide pathway and hyperpolarized the gonadotrope periodically by opening apamin-sensitive Ca(2+)-activated K+ (SK) channels. Each hyperpolarization was terminated by firing of a few action potentials that may result from removal of inactivation from voltage-gated Na+ and Ca2+ channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tse, A -- Hille, B -- New York, N.Y. -- Science. 1992 Jan 24;255(5043):462-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1734523" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apamin/pharmacology ; Calcium/*metabolism ; Cells, Cultured ; GTP-Binding Proteins/physiology ; Gonadotropin-Releasing Hormone/*physiology ; In Vitro Techniques ; Inositol 1,4,5-Trisphosphate/physiology ; Membrane Potentials ; Periodicity ; Pituitary Gland, Anterior/cytology/*physiology ; Potassium Channels/physiology ; Rats
    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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  • 100
    Publication Date: 1992-07-24
    Description: Laboratory isolates of human immunodeficiency virus type-1 (HIV-1) such as HTLV-IIIB are generally T cell line-tropic and highly sensitive to neutralization by soluble CD4 (sCD4), a potential antiviral agent that is undergoing clinical trial. However, many primary HIV-1 isolates are macrophage-tropic and sCD4-resistant. Envelope V3 loop sequences derived from primary HIV-1 isolates were sufficient to confer on HTLV-IIIB not only the tissue tropism but also the degree of sCD4 neutralization resistance characteristic of their HIV-1 strains of origin. Single amino acid changes in the V3 loop enhanced sCD4 resistance by up to tenfold. These observations suggest that the tissue tropism and sCD4 neutralization sensitivity of HIV-1 isolates are regulated by similar mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hwang, S S -- Boyle, T J -- Lyerly, H K -- Cullen, B R -- AI28233/AI/NIAID NIH HHS/ -- AI28662/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 24;257(5069):535-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1636088" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD4/*immunology ; Cell Line ; Cells, Cultured ; Gene Products, gag/*immunology ; HIV Envelope Protein gp120/*immunology ; HIV-1/*immunology/isolation & purification ; Humans ; Kinetics ; Molecular Sequence Data ; Neutralization Tests ; Proviruses/immunology ; T-Lymphocyte Subsets/*immunology ; Transfection ; Virion/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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