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  • Chemistry  (39)
  • Mice  (7)
  • 2010-2014  (4)
  • 1995-1999  (9)
  • 1990-1994  (18)
  • 1985-1989  (15)
  • 1
    Publikationsdatum: 1999-01-29
    Beschreibung: A carbapenem antibiotic, L-786,392, was designed so that the side chain that provides high-affinity binding to the penicillin-binding proteins responsible for bacterial resistance was also the structural basis for ameliorating immunopathology. Expulsion of the side chain upon opening of the beta-lactam ring retained antibacterial activity while safely expelling the immunodominant epitope. L-786,392 was well tolerated in animal safety studies and had significant in vitro and in vivo activities against methicillin- and vancomycin-resistant Staphylococci and vancomycin-resistant Enterococci.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosen, H -- Hajdu, R -- Silver, L -- Kropp, H -- Dorso, K -- Kohler, J -- Sundelof, J G -- Huber, J -- Hammond, G G -- Jackson, J J -- Gill, C J -- Thompson, R -- Pelak, B A -- Epstein-Toney, J H -- Lankas, G -- Wilkening, R R -- Wildonger, K J -- Blizzard, T A -- DiNinno, F P -- Ratcliffe, R W -- Heck, J V -- Kozarich, J W -- Hammond, M L -- New York, N.Y. -- Science. 1999 Jan 29;283(5402):703-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Merck Research Laboratories, Rahway, NJ 07065, USA. hugh_rosen@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9924033" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antibodies/blood ; *Bacterial Proteins ; Carbapenems/chemistry/*immunology/metabolism/*pharmacology/toxicity ; Carrier Proteins/metabolism ; Dipeptidases/metabolism ; *Drug Design ; Drug Resistance, Microbial ; Drug Resistance, Multiple ; Enterococcus/drug effects ; Erythrocytes/immunology ; Haptens ; *Hexosyltransferases ; Humans ; Immunodominant Epitopes ; Immunoglobulin G/blood ; Lactams/chemical synthesis/chemistry/metabolism/*pharmacology ; Lymphocyte Activation ; Macaca mulatta ; Mice ; Mice, Inbred DBA ; Microbial Sensitivity Tests ; Muramoylpentapeptide Carboxypeptidase/metabolism ; Penicillin-Binding Proteins ; *Peptidyl Transferases ; Staphylococcal Infections/drug therapy ; Staphylococcus/drug effects ; Thiazoles/chemical synthesis/chemistry/metabolism/*pharmacology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2011-11-15
    Beschreibung: Intestinal epithelial stem cell identity and location have been the subject of substantial research. Cells in the +4 niche are slow-cycling and label-retaining, whereas a different stem cell niche located at the crypt base is occupied by crypt base columnar (CBC) cells. CBCs are distinct from +4 cells, and the relationship between them is unknown, though both give rise to all intestinal epithelial lineages. We demonstrate that Hopx, an atypical homeobox protein, is a specific marker of +4 cells. Hopx-expressing cells give rise to CBCs and all mature intestinal epithelial lineages. Conversely, CBCs can give rise to +4 Hopx-positive cells. These findings demonstrate a bidirectional lineage relationship between active and quiescent stem cells in their niches.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705713/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705713/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeda, Norifumi -- Jain, Rajan -- LeBoeuf, Matthew R -- Wang, Qiaohong -- Lu, Min Min -- Epstein, Jonathan A -- R01 HL071546/HL/NHLBI NIH HHS/ -- U01 HL100405/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2011 Dec 9;334(6061):1420-4. doi: 10.1126/science.1213214. Epub 2011 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22075725" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Cycle ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cells, Cultured ; Epithelial Cells/*cytology ; Homeodomain Proteins/analysis/genetics ; Intestinal Mucosa/*cytology/drug effects ; Intestine, Small/*cytology/drug effects ; Mice ; Models, Biological ; Multipotent Stem Cells/*cytology/physiology ; Paneth Cells/cytology ; *Stem Cell Niche ; Tamoxifen/pharmacology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2013-08-10
    Beschreibung: Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine--composed of attenuated, aseptic, purified, cryopreserved PfSPZ--was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 x 10(5) PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seder, Robert A -- Chang, Lee-Jah -- Enama, Mary E -- Zephir, Kathryn L -- Sarwar, Uzma N -- Gordon, Ingelise J -- Holman, LaSonji A -- James, Eric R -- Billingsley, Peter F -- Gunasekera, Anusha -- Richman, Adam -- Chakravarty, Sumana -- Manoj, Anita -- Velmurugan, Soundarapandian -- Li, MingLin -- Ruben, Adam J -- Li, Tao -- Eappen, Abraham G -- Stafford, Richard E -- Plummer, Sarah H -- Hendel, Cynthia S -- Novik, Laura -- Costner, Pamela J M -- Mendoza, Floreliz H -- Saunders, Jamie G -- Nason, Martha C -- Richardson, Jason H -- Murphy, Jittawadee -- Davidson, Silas A -- Richie, Thomas L -- Sedegah, Martha -- Sutamihardja, Awalludin -- Fahle, Gary A -- Lyke, Kirsten E -- Laurens, Matthew B -- Roederer, Mario -- Tewari, Kavita -- Epstein, Judith E -- Sim, B Kim Lee -- Ledgerwood, Julie E -- Graham, Barney S -- Hoffman, Stephen L -- VRC 312 Study Team -- 3R44AI055229-06S1/AI/NIAID NIH HHS/ -- 4R44AI055229-08/AI/NIAID NIH HHS/ -- 5R44AI058499-05/AI/NIAID NIH HHS/ -- N01-AI-40096/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1359-65. doi: 10.1126/science.1241800. Epub 2013 Aug 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA. rseder@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23929949" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Administration, Intravenous ; Adult ; Animals ; Cytokines/immunology ; Female ; Humans ; Immunity, Cellular ; Malaria Vaccines/*administration & dosage/adverse effects/*immunology ; Malaria, Falciparum/*prevention & control ; Male ; Mice ; Plasmodium falciparum/*immunology ; Sporozoites/immunology ; T-Lymphocytes/immunology ; Vaccination/adverse effects/methods
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 1997-05-02
    Beschreibung: Mutations in the tumor suppressor gene PATCHED (PTC) are found in human patients with the basal cell nevus syndrome, a disease causing developmental defects and tumors, including basal cell carcinomas. Gene regulatory relationships defined in the fruit fly Drosophila suggest that overproduction of Sonic hedgehog (SHH), the ligand for PTC, will mimic loss of ptc function. It is shown here that transgenic mice overexpressing SHH in the skin develop many features of basal cell nevus syndrome, demonstrating that SHH is sufficient to induce basal cell carcinomas in mice. These data suggest that SHH may have a role in human tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oro, A E -- Higgins, K M -- Hu, Z -- Bonifas, J M -- Epstein, E H Jr -- Scott, M P -- AR39959/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1997 May 2;276(5313):817-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305-5427, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9115210" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Basal Cell Nevus Syndrome/*genetics/metabolism/pathology ; Carcinoma, Basal Cell/*genetics/metabolism/pathology ; Embryo, Mammalian ; *Gene Expression Regulation, Neoplastic ; Hedgehog Proteins ; Humans ; Intracellular Signaling Peptides and Proteins ; Keratinocytes/metabolism ; Male ; Membrane Proteins/genetics/metabolism ; Mice ; Mice, SCID ; Mice, Transgenic ; Mutation ; Neoplasm Transplantation ; Protein Biosynthesis ; Proteins/*genetics/metabolism ; Receptors, Cell Surface ; Skin/pathology ; Skin Neoplasms/*genetics/metabolism/pathology ; Skin Transplantation ; *Trans-Activators
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Publikationsdatum: 2012-05-25
    Beschreibung: An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zeigerer, Anja -- Gilleron, Jerome -- Bogorad, Roman L -- Marsico, Giovanni -- Nonaka, Hidenori -- Seifert, Sarah -- Epstein-Barash, Hila -- Kuchimanchi, Satya -- Peng, Chang Geng -- Ruda, Vera M -- Del Conte-Zerial, Perla -- Hengstler, Jan G -- Kalaidzidis, Yannis -- Koteliansky, Victor -- Zerial, Marino -- England -- Nature. 2012 May 23;485(7399):465-70. doi: 10.1038/nature11133.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22622570" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Polarity ; Cells, Cultured ; Endocytosis ; Endosomes/*metabolism ; Gene Knockdown Techniques ; Hepatocytes/cytology/metabolism ; Isoenzymes/biosynthesis/deficiency/genetics/metabolism ; Lipoproteins, LDL/metabolism ; Liver/cytology/enzymology/metabolism ; Lysosomes/*metabolism ; Mice ; Multivesicular Bodies/metabolism ; Organ Specificity ; Protein Biosynthesis ; RNA Interference ; RNA, Messenger/analysis/genetics ; Time Factors ; Vesicular Transport Proteins/metabolism ; rab5 GTP-Binding Proteins/biosynthesis/deficiency/genetics/*metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Publikationsdatum: 2011-09-10
    Beschreibung: Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in 〉/=80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-gamma (IFN-gamma). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-gamma-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Epstein, J E -- Tewari, K -- Lyke, K E -- Sim, B K L -- Billingsley, P F -- Laurens, M B -- Gunasekera, A -- Chakravarty, S -- James, E R -- Sedegah, M -- Richman, A -- Velmurugan, S -- Reyes, S -- Li, M -- Tucker, K -- Ahumada, A -- Ruben, A J -- Li, T -- Stafford, R -- Eappen, A G -- Tamminga, C -- Bennett, J W -- Ockenhouse, C F -- Murphy, J R -- Komisar, J -- Thomas, N -- Loyevsky, M -- Birkett, A -- Plowe, C V -- Loucq, C -- Edelman, R -- Richie, T L -- Seder, R A -- Hoffman, S L -- 5R44AI055229-07/AI/NIAID NIH HHS/ -- 5R44AI058375-05/AI/NIAID NIH HHS/ -- 5R44AI058499-05/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Oct 28;334(6055):475-80. doi: 10.1126/science.1211548. Epub 2011 Sep 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21903775" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adolescent ; Adult ; Animals ; Antibodies, Protozoan/blood/immunology ; Antigens, Protozoan/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Humans ; Injections, Intravenous ; Injections, Subcutaneous ; Interferon-gamma/biosynthesis/immunology ; Liver/*immunology ; Macaca mulatta ; Malaria Vaccines/administration & dosage/adverse effects/*immunology ; Malaria, Falciparum/*prevention & control ; Mice ; Middle Aged ; Plasmodium falciparum/*immunology ; Rabbits ; Sporozoites/*immunology ; Vaccines, Attenuated/administration & dosage/adverse effects/immunology ; Young Adult
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 1986-10-17
    Beschreibung: The critical role of interleukin-2 (IL-2) in immune response heightens the need to know its structure in order to understand its activity. New computer-assisted predictive methods for the assignment of secondary structure together with a method to predict the tertiary structure of a protein from data on its primary sequence and secondary structure were applied to IL-2. This method generated four topological families of structures, of which the most plausible is a right-handed fourfold alpha-helical bundle. Members of this family were shown to be compatible with existing structural data on disulfide bridges and monoclonal antibody binding for IL-2. Experimental estimates of secondary structure from circular dichroism and site-directed mutagenesis data support the model. A region likely to be important in IL-2 binding to its receptor was identified as residues Leu36, Met38, Leu40, Phe42, Phe44, and Met46.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, F E -- Kosen, P A -- Kuntz, I D -- Epstein, L B -- Ciardelli, T L -- Smith, K A -- CA27903/CA/NCI NIH HHS/ -- GM34197/GM/NIGMS NIH HHS/ -- MOJ JD17001/PHS HHS/ -- etc. -- New York, N.Y. -- Science. 1986 Oct 17;234(4774):349-52.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3489989" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; Computer Simulation ; Humans ; *Interleukin-2/genetics/physiology ; Mice ; Models, Molecular ; Structure-Activity Relationship
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    New York : Wiley-Blackwell
    Biopolymers 29 (1990), S. 543-547 
    ISSN: 0006-3525
    Schlagwort(e): Chemistry ; Polymer and Materials Science
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: A fast Monte Carlo integration algorithm with varying time step is described for cooperative binding of ligands of arbitrary length to a one-dimensional lattice. This algorithm is particularly suitable for strongly cooperative or anticooperative systems, i.e., when the time scales for different kinetic events are very different. As an application, the kinetics of a bimodal two-ligand system are briefly discussed.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 34 (1987), S. 677-687 
    ISSN: 0021-8995
    Schlagwort(e): Chemistry ; Polymer and Materials Science
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie , Maschinenbau , Physik
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part A: Polymer Chemistry 33 (1995), S. 1227-1234 
    ISSN: 0887-624X
    Schlagwort(e): polyanilines ; derivatives ; chemical synthesis ; oxidation state ; Chemistry ; Polymer and Materials Science
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Syntheses of parent polyaniline and methyl, methoxy, and ethoxy ortho-substituted polyanilines were performed using the conventional chemical methodology and monitored using the new open-circuit-potential (Voc) profile technique. The intermediate pernigraniline oxidation state was identified and isolated at the Voc maximum (A) during the conventional chemical synthesis of poly(o-methoxyaniline) in the emeraldine oxidation state. The introduction of the substituent on the aniline ring leads to longer polymerization times and lower Voc values. Syntheses in the presence of two different monomers in solution were also investigated and showed preferential polymerization of the monomer with the lowest Voc potential. All polymers produced were characterized by elemental analysis, gel permeation chromatography, UV-VIS spectroscopy, and cyclic voltammetry. The influence of the substituent on the Voc profile and on the polymer characteristics are rationalized in terms of steric and electronic effects. © 1995 John Wiley & Sons, Inc.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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