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  • 1
    Publication Date: 1999-12-22
    Description: Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw). Increased tumor necrosis factor alpha production and induction of neuronal injury occurred when Abeta-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APPsw mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Abeta-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, J -- Town, T -- Paris, D -- Mori, T -- Suo, Z -- Crawford, F -- Mattson, M P -- Flavell, R A -- Mullan, M -- New York, N.Y. -- Science. 1999 Dec 17;286(5448):2352-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Roskamp Institute, University of South Florida, 3515 East Fletcher Avenue, Tampa, FL 33613, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10600748" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/metabolism ; Amyloid beta-Peptides/*metabolism/pharmacology ; Animals ; Antigens, CD40/biosynthesis/*metabolism ; CD40 Ligand ; Cell Death ; Cells, Cultured ; Interferon-gamma/pharmacology ; Interleukins/pharmacology ; Ligands ; Membrane Glycoproteins/*metabolism/pharmacology ; Mice ; Mice, Transgenic ; Microglia/cytology/immunology/*metabolism ; Neurons/cytology ; Peptide Fragments/pharmacology ; Phosphorylation ; Signal Transduction ; Tumor Necrosis Factor-alpha/biosynthesis/pharmacology ; tau Proteins/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1991-04-26
    Description: An orally effective, nonpeptide, vasopressin V1 receptor antagonist, OPC-21268, has been identified. This compound selectively antagonized binding to the V1 subtype of the vasopressin receptor in a competitive manner. In vivo, the compound acted as a specific antagonist of arginine vasopressin (AVP)-induced vasoconstriction. After oral administration in conscious rats, the compound also antagonized pressor responses to AVP. OPC-21268 can be used to study the physiological role of AVP and may be therapeutically useful in the treatment of hypertension and congestive heart failure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamamura, Y -- Ogawa, H -- Chihara, T -- Kondo, K -- Onogawa, T -- Nakamura, S -- Mori, T -- Tominaga, M -- Yabuuchi, Y -- New York, N.Y. -- Science. 1991 Apr 26;252(5005):572-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Second Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1850553" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Angiotensin II/pharmacology ; Animals ; Arginine Vasopressin/antagonists & inhibitors/metabolism/*pharmacology ; Binding, Competitive ; Blood Pressure/*drug effects ; Cell Membrane/metabolism ; Kidney/metabolism ; Kinetics ; Liver/metabolism ; Norepinephrine/pharmacology ; Piperidines/administration & dosage/*pharmacology ; Quinolones/administration & dosage/*pharmacology ; Rats ; Receptors, Angiotensin/*drug effects/metabolism ; Receptors, Vasopressin ; Time Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 1992-02-28
    Description: The primary defect arising from Zellweger syndrome appears to be linked to impaired assembly of peroxisomes. A human complementary DNA has been cloned that complements the disease's symptoms (including defective peroxisome assembly) in fibroblasts from a patient with Zellweger syndrome. The cause of the syndrome in this patient was a point mutation that resulted in the premature termination of peroxisome assembly factor-1. The homozygous patient apparently inherited the mutation from her parents, each of whom was heterozygous for that mutation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimozawa, N -- Tsukamoto, T -- Suzuki, Y -- Orii, T -- Shirayoshi, Y -- Mori, T -- Fujiki, Y -- New York, N.Y. -- Science. 1992 Feb 28;255(5048):1132-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Gifu University School of Medicine, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1546315" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cricetinae ; DNA Mutational Analysis ; Genes ; Genetic Complementation Test ; Humans ; Membrane Proteins/*genetics ; Microbodies/*ultrastructure ; Molecular Sequence Data ; Oligodeoxyribonucleotides/chemistry ; Pedigree ; Polymerase Chain Reaction ; Transfection ; Zellweger Syndrome/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-01-31
    Description: Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such 'talented' producers represent only a minute fraction of the entire, mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell- and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus 'Entotheonella' with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. 'Entotheonella' spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum 'Tectomicrobia'. The pronounced bioactivities and chemical uniqueness of 'Entotheonella' compounds provide significant opportunities for ecological studies and drug discovery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Micheal C -- Mori, Tetsushi -- Ruckert, Christian -- Uria, Agustinus R -- Helf, Maximilian J -- Takada, Kentaro -- Gernert, Christine -- Steffens, Ursula A E -- Heycke, Nina -- Schmitt, Susanne -- Rinke, Christian -- Helfrich, Eric J N -- Brachmann, Alexander O -- Gurgui, Cristian -- Wakimoto, Toshiyuki -- Kracht, Matthias -- Crusemann, Max -- Hentschel, Ute -- Abe, Ikuro -- Matsunaga, Shigeki -- Kalinowski, Jorn -- Takeyama, Haruko -- Piel, Jorn -- England -- Nature. 2014 Feb 6;506(7486):58-62. doi: 10.1038/nature12959. Epub 2014 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute of Microbiology, Eidgenossische Technische Hochschule Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland [2] Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany [3]. ; 1] Faculty of Science and Engineering, Waseda University Center for Advanced Biomedical Sciences, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan [2]. ; Institute for Genome Research and Systems Biology, Center for Biotechnology, Universitat Bielefeld, Universitatstrasse 25, 33594 Bielefeld, Germany. ; 1] Institute of Microbiology, Eidgenossische Technische Hochschule Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland [2] Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany. ; Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. ; Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Wurzburg, Julius-von-Sachs-Platz 3, 97082 Wurzburg, Germany. ; Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany. ; Department of Earth and Environmental Sciences, Palaeontology and Geobiology, Ludwig Maximilians University Munich, Richard-Wagner-Strasse 10, 80333 Munich, Germany. ; Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, California 94598, USA. ; Institute of Microbiology, Eidgenossische Technische Hochschule Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland. ; Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ; Faculty of Science and Engineering, Waseda University Center for Advanced Biomedical Sciences, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476823" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biosynthetic Pathways/genetics ; Deltaproteobacteria/*classification/genetics/*metabolism/physiology ; *Drug Discovery ; Environmental Microbiology ; Genes, Bacterial/genetics ; Genome, Bacterial/genetics ; Metagenomics ; Molecular Sequence Data ; Multigene Family/genetics ; Peptides/metabolism ; Polyketides/metabolism ; Porifera/metabolism/microbiology ; Single-Cell Analysis ; Symbiosis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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