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  • Books
  • Articles  (19)
  • Life and Medical Sciences  (12)
  • Mice  (7)
  • 2015-2019  (2)
  • 1995-1999  (4)
  • 1985-1989  (7)
  • 1980-1984  (6)
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  • Books
  • Articles  (19)
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  • 1
    Publication Date: 1999-01-29
    Description: 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〉
    Keywords: 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
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1997-05-02
    Description: 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〉
    Keywords: 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
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-06-27
    Description: Cardiac progenitor cells are multipotent and give rise to cardiac endothelium, smooth muscle, and cardiomyocytes. Here, we define and characterize the cardiomyoblast intermediate that is committed to the cardiomyocyte fate, and we characterize the niche signals that regulate commitment. Cardiomyoblasts express Hopx, which functions to coordinate local Bmp signals to inhibit the Wnt pathway, thus promoting cardiomyogenesis. Hopx integrates Bmp and Wnt signaling by physically interacting with activated Smads and repressing Wnt genes. The identification of the committed cardiomyoblast that retains proliferative potential will inform cardiac regenerative therapeutics. In addition, Bmp signals characterize adult stem cell niches in other tissues where Hopx-mediated inhibition of Wnt is likely to contribute to stem cell quiescence and to explain the role of Hopx as a tumor suppressor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jain, Rajan -- Li, Deqiang -- Gupta, Mudit -- Manderfield, Lauren J -- Ifkovits, Jamie L -- Wang, Qiaohong -- Liu, Feiyan -- Liu, Ying -- Poleshko, Andrey -- Padmanabhan, Arun -- Raum, Jeffrey C -- Li, Li -- Morrisey, Edward E -- Lu, Min Min -- Won, Kyoung-Jae -- Epstein, Jonathan A -- 5-T32-GM-007170/GM/NIGMS NIH HHS/ -- K08 HL119553/HL/NHLBI NIH HHS/ -- K08 HL119553-02/HL/NHLBI NIH HHS/ -- R01 HL071546/HL/NHLBI NIH HHS/ -- U01 HL100405/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):aaa6071. doi: 10.1126/science.aaa6071.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Genetics, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. epsteinj@upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113728" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bone Morphogenetic Proteins/genetics/*metabolism ; Cell Lineage/genetics ; Gene Expression ; *Gene Expression Regulation, Developmental ; Heart/*embryology ; Homeodomain Proteins/genetics/*metabolism ; Mice ; Mice, Mutant Strains ; Molecular Sequence Data ; Muscle, Smooth/cytology/metabolism ; Myoblasts, Cardiac/cytology/*metabolism ; Organogenesis/*genetics ; Stem Cell Niche/genetics/physiology ; Tumor Suppressor Proteins/genetics/*metabolism ; Wnt Signaling Pathway/*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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeNiro, M J -- Epstein, S -- New York, N.Y. -- Science. 1981 Dec 18;214(4527):1374-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7313700" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Deuterium/*metabolism ; *Diet ; Hydrogen/*metabolism ; Mice ; Water/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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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-03-28
    Description: Groups of three to four mice were gavaged with aqueous solutions of 2 milligrams of morpholine, after which they were exposed to nitrogen dioxide in inhalation chambers at concentrations of 0.2 to 50 parts per million for up to 4 hours. At sequential intervals during the exposure, mice were frozen and pulverized in liquid nitrogen, and the mice powder was extracted with ice-cold 35 percent aqueous methanol and dichloromethane; organic-phase concentrates were analyzed for N-nitrosomorpholine with a thermal energy analyzer interfaced to a gas chromatograph. The N-nitrosomorpholine yields, ranging up to about 2.3 micrograms per mouse, were time-dependent relative to the duration of exposure to nitrogen dioxide and dose-dependent relative to the concentrations of nitrogen dioxide; control levels (in mice that were gavaged with morpholine or distilled water and then exposed to air instead of nitrogen dioxide) were less than 5 nanograms per mouse. These preliminary studies demonstrate the in vivo nitrosating potential of nitrogen oxides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iqbal, Z M -- Dahl, K -- Epstein, S S -- New York, N.Y. -- Science. 1980 Mar 28;207(4438):1475-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7361099" target="_blank"〉PubMed〈/a〉
    Keywords: Amines/metabolism ; Animals ; Ascorbic Acid/pharmacology ; Biotransformation ; Dose-Response Relationship, Drug ; Mice ; Morpholines/*metabolism ; Nitrogen Dioxide/antagonists & inhibitors/*metabolism ; Nitrosamines/*metabolism ; 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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  • 6
    Publication Date: 2015-01-07
    Description: Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ling, Losee L -- Schneider, Tanja -- Peoples, Aaron J -- Spoering, Amy L -- Engels, Ina -- Conlon, Brian P -- Mueller, Anna -- Schaberle, Till F -- Hughes, Dallas E -- Epstein, Slava -- Jones, Michael -- Lazarides, Linos -- Steadman, Victoria A -- Cohen, Douglas R -- Felix, Cintia R -- Fetterman, K Ashley -- Millett, William P -- Nitti, Anthony G -- Zullo, Ashley M -- Chen, Chao -- Lewis, Kim -- AI085612/AI/NIAID NIH HHS/ -- T-RO1AI085585/AI/NIAID NIH HHS/ -- England -- Nature. 2015 Jan 22;517(7535):455-9. doi: 10.1038/nature14098. Epub 2015 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NovoBiotic Pharmaceuticals, Cambridge, Massachusetts 02138, USA. ; 1] Institute of Medical Microbiology, Immunology and Parasitology-Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany [2] German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany. ; Antimicrobial Discovery Center, Northeastern University, Department of Biology, Boston, Massachusetts 02115, USA. ; 1] German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany [2] Institute for Pharmaceutical Biology, University of Bonn, Bonn 53115, Germany. ; Department of Biology, Northeastern University, Boston, Massachusetts 02115, USA. ; Selcia, Ongar, Essex CM5 0GS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25561178" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/biosynthesis/chemistry/isolation & ; purification/*pharmacology ; Betaproteobacteria/chemistry/genetics ; Biological Products/chemistry/isolation & purification/pharmacology ; Cell Wall/chemistry/drug effects/metabolism ; Depsipeptides/biosynthesis/chemistry/isolation & purification/*pharmacology ; Disease Models, Animal ; *Drug Resistance, Microbial/genetics ; Female ; Mice ; Microbial Sensitivity Tests ; Microbial Viability/*drug effects ; Molecular Sequence Data ; Multigene Family/genetics ; Mycobacterium tuberculosis/cytology/*drug effects/genetics ; Peptidoglycan/biosynthesis ; Staphylococcal Infections/drug therapy/microbiology ; Staphylococcus aureus/chemistry/cytology/*drug effects/genetics ; Teichoic Acids/biosynthesis ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 1986-10-17
    Description: 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〉
    Keywords: Amino Acid Sequence ; Animals ; Computer Simulation ; Humans ; *Interleukin-2/genetics/physiology ; Mice ; Models, Molecular ; Structure-Activity Relationship
    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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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 1 (1980), S. 73-97 
    ISSN: 0886-1544
    Keywords: nematodes ; muscle structure ; mutants ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A search for new mutants with altered body-wall muscle cell structure has been undertaken in the nematode C elegans. One-hundred seventeen mutants were isolated after mutagenesis with ethyl methanesulfonate or ultraviolet light, enrichment by a motility-requiring test, and screening by polarized light microscopy; 102 of these mutants were in ten previously established genes, whereas 15 mutants permitted the identification of seven new complementation groups in C elegans. Two of the new genes map on linkage group I (unc-94 and unc-95) and four genes are sex linked (unc-96, unc-97, unc-98, and unc-99). One complementation group (unc-100) could not be mapped because of the special characteristics of its cohort mutants. Representative mutants of the mapped genes were examined by polarized light and electron microscopy. All of the mutants exhibit disruptions of the normal A and I band organization of thick and thin filaments. Several of the mutants produce collections of thin filament-like structures. In one of these cases, HE177 demonstrated collections of somewhat wider, intermediate-sized filaments as well, and the HE195 mutant produces paracrystalline aggregates of thin filaments amidst looser arrangements of similar structures. The mutants in newly identified genes, as well as the new mutants in previously established genetic loci, have promise as tools in the study of myofibrillar assembly and function. Among the 22 complementation groups associated with body-wall structure in C elegans, it is likely that some genes code for regulatory and morphogenetic functions in addition to the well-studied structural, contractile, and calcium-associated proteins in muscle.
    Additional Material: 15 Ill.
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  • 9
    ISSN: 0730-2312
    Keywords: hypersensitivity ; granulomas ; skin ; athymic nude mice ; biomedical analysis ; angiotensin-converting enzyme ; eosinophil chemotactic factor ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Activities of angiotensin-converting enzyme (ACE), other proteinases, and eosinophil chemotactic factor (ECF-G) are known to be elevated in hepatic hypersensitivity granulomas of thymus intact (nu/+) mice after Schistosoma mansoni infection. The enzyme activities also increase, but to a lesser degree in hepatic granulomas of athymic nude (nu/nu) mice, and ECF-G is not detectable. In this study isolated hepatic granulomas from nu/+ mice were grafted into the skin of uninfected nu/nu mice, and changes in those cellular functions were determined to examine whether the newly formed granulomas by recipient nu/nu cells acquire the functional activities as well as the histological appearance of nu/+ granulomas. ACE and ECF-G rapidly disappeared from grafted sites during the first 5 days, corresponding to loss of nu/+ cells from the graft. Reduction in activities of arylsulfatases, lysozyme, and acid phosphatase also occurred, but to a lesser extent. Recovery of ACE and ECF-G activities to the levels seen in nu/+ hepatic granulomas was observed by 14 days after grafting when nu/nu cells had accumulated in the grafts and formed new granulomas. Other enzymes increased to approximately half the levels seen in grafted donor granulomas. Circulating eosinophilia also increased. The findings indicate that nu/nu cells that accumulated in the skin grafts not only morphologically mimicked nu/+ type granulomas but also demonstrated nu/+ levels of cellular function. Analysis of skin granulomas developing in nu/+ mice after grafting of nu/+ hepatic granulomas showed the similar histology and enzymatic changes, whereas the skin sites inoculated with purified schistosome eggs alone caused neither significant histological changes nor elevation of ACE activity.
    Additional Material: 2 Ill.
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  • 10
    ISSN: 0730-2312
    Keywords: nuclear bodies ; promyelocytic leukemia protein ; herpes simplex virus ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The promyelocytic leukemia protien fused to the retinoic acid receptor in t(15;17) acute promyelocytic leukemia, the primary biliary cirrhosis autoantigen, Sp100, as well as the incompletely charterized protien NDP55, are co-localized in specific immunohistochemically defined nuclear domains (ND10), which are potential equyivalents of ultrastructurally defined nuclear bodies. We investigated whether the distribution of these proteins depends on environmental conditions and whether ND10 correlate with nuclear bodies. Certain nuclear bodies and ND10 react in a similar bodies, which herpes simplex virus infection or heat shock modify both. Redistribution of ND10-associated proteins to hundreds of small sites throughout the chromatin was inducible by stress in the form of heat shock and exposure to Cd++ ions. The change of distribution was rapid and independent of proteins synthesis, and thus not part of the classical heat shock response. The very rapid redistribution of these proteins after heat shock, together with the development of ND10 upon interferon actication, raises the possibility that ND10 represent storage sites of certain matrix proteins readily accessible throughout the chromatin in response to stress or other effectors that induce global nuclear changes. © 1995 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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