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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-10-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Linsk, R -- Gottesman, M -- Pernis, B -- New York, N.Y. -- Science. 1989 Oct 13;246(4927):261.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2799388" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation ; Genes, MHC Class I/physiology ; Immune Tolerance/*genetics ; Organ Specificity/*genetics ; Thymus Gland/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    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
    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: 2006-12-23
    Description: Synonymous single-nucleotide polymorphisms (SNPs) do not produce altered coding sequences, and therefore they are not expected to change the function of the protein in which they occur. We report that a synonymous SNP in the Multidrug Resistance 1 (MDR1) gene, part of a haplotype previously linked to altered function of the MDR1 gene product P-glycoprotein (P-gp), nonetheless results in P-gp with altered drug and inhibitor interactions. Similar mRNA and protein levels, but altered conformations, were found for wild-type and polymorphic P-gp. We hypothesize that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kimchi-Sarfaty, Chava -- Oh, Jung Mi -- Kim, In-Wha -- Sauna, Zuben E -- Calcagno, Anna Maria -- Ambudkar, Suresh V -- Gottesman, Michael M -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2007 Jan 26;315(5811):525-8. Epub 2006 Dec 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. kimchi@cber.fda.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17185560" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Membrane/metabolism ; Cercopithecus aethiops ; Codon ; Cyclosporine/pharmacology ; *Genes, MDR ; Haplotypes ; HeLa Cells ; Humans ; Mutagenesis, Site-Directed ; P-Glycoprotein/antagonists & inhibitors/*chemistry/genetics/*metabolism ; *Polymorphism, Single Nucleotide ; Protein Biosynthesis ; Protein Conformation ; *Protein Folding ; Protein Structure, Tertiary ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rhodamine 123/metabolism/pharmacology ; Sirolimus/pharmacology ; Substrate Specificity ; Transfection ; Verapamil/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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  • 4
    Publication Date: 2016-03-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Francis S -- Anderson, James M -- Austin, Christopher P -- Battey, James F -- Birnbaum, Linda S -- Briggs, Josephine P -- Clayton, Janine A -- Cuthbert, Bruce -- Eisinger, Robert W -- Fauci, Anthony S -- Gallin, John I -- Gibbons, Gary H -- Glass, Roger I -- Gottesman, Michael M -- Gray, Patricia A -- Green, Eric D -- Greider, Franziska B -- Hodes, Richard -- Hudson, Kathy L -- Humphreys, Betsy -- Katz, Stephen I -- Koob, George F -- Koroshetz, Walter J -- Lauer, Michael S -- Lorsch, Jon R -- Lowy, Douglas R -- McGowan, John J -- Murray, David M -- Nakamura, Richard -- Norris, Andrea -- Perez-Stable, Eliseo J -- Pettigrew, Roderic I -- Riley, William T -- Rodgers, Griffin P -- Sieving, Paul A -- Somerman, Martha J -- Spong, Catherine Y -- Tabak, Lawrence A -- Volkow, Nora D -- Wilder, Elizabeth L -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1405. doi: 10.1126/science.351.6280.1405-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Office of the Director, NIH, Bethesda, MD 20892, USA. collinsf@mail.nih.gov. ; Division of Program Coordination, Planning, and Strategic Initiatives, NIH, Bethesda, MD 20892, USA. ; National Center for Advancing Translational Science, NIH, Rockville, MD 20850, USA. ; National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. ; National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. ; National Center for Complementary and Integrative Health, NIH, Bethesda, MD 20892, USA. ; Office of Research on Women's Health, NIH, Bethesda, MD 20892, USA. ; National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. ; Office of AIDS Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. ; Clinical Center, NIH, Bethesda, MD 20892, USA. ; National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA. ; Fogarty International Center, NIH, Bethesda, MD 20892, USA. ; Office of Intramural Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Nursing Research, NIH, Bethesda, MD 20892, USA. ; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. ; Office of Research Infrastructure Programs, NIH, Bethesda, MD 20892, USA. ; National Institute on Aging, NIH, Bethesda, MD 20892, USA. ; Office of the Director, NIH, Bethesda, MD 20892, USA. ; National Library of Medicine, NIH, Bethesda, MD 20892, USA. ; National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. ; National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA. ; NINDS, NIH, Bethesda, MD 20892, USA. ; Office of Extramural Research, NIH, Bethesda, MD 20892, USA. ; National Institute of General Medical Sciences, NIH, Bethesda, MD 20892, USA. ; National Cancer Institute, NIH, Bethesda, MD 20892, USA. ; Office of Management, NIH, Bethesda, MD 20892, USA. ; Office of Disease Prevention, NIH, Bethesda, MD 20892, USA. ; Center for Scientific Review, NIH, Bethesda, MD 20892, USA. ; Center for Information Technology, NIH, Bethesda, MD 20892, USA. ; National Institute on Minority Health and Health Disparities, NIH, Bethesda, MD 20892, USA. ; National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD 20892, USA. ; Office of Behavioral and Social Sciences Research, NIH, Bethesda, MD 20892, USA. ; National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. ; National Eye Institute, NIH, Bethesda, MD 20892, USA. ; National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA. ; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. ; National Institute on Drug Abuse, NIH, Bethesda, MD 20892, USA. ; Office of Strategic Coordination, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013720" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*economics ; Humans ; National Institutes of Health (U.S.)/*economics
    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
    Publication Date: 1986-05-02
    Description: The development of simultaneous resistance to multiple structurally unrelated drugs is a major impediment to cancer chemotherapy. Multidrug resistance in human KB carcinoma cells selected in colchicine, vinblastine, or Adriamycin is associated with amplification of specific DNA sequences (the multidrug resistance locus, mdr1). During colchicine selection resistance is initially accompanied by elevated expression of a 4.5-kilobase mdr1 messenger RNA (mRNA) without amplification of the corresponding genomic sequences. During selection for increased levels of resistance, expression of this mRNA is increased simultaneously with amplification of mdr1 DNA. Increased expression and amplification of mdr1 sequences were also found in multidrug-resistant sublines of human leukemia and ovarian carcinoma cells. These results suggest that increased expression of mdr1 mRNA is a common mechanism for multidrug resistance in human cells. Activation of the mdr1 gene by mutations or epigenetic changes may precede its amplification during the development of resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, D W -- Fojo, A -- Chin, J E -- Roninson, I B -- Richert, N -- Pastan, I -- Gottesman, M M -- New York, N.Y. -- Science. 1986 May 2;232(4750):643-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3457471" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Colchicine/pharmacology ; Cricetinae ; Cricetulus ; DNA, Neoplasm/genetics ; Doxorubicin/pharmacology ; *Drug Resistance ; Female ; *Gene Amplification ; Humans ; Leukemia, Lymphoid/drug therapy ; Neoplasms/*drug therapy/genetics ; Nucleic Acid Hybridization ; Ovarian Neoplasms/drug therapy ; RNA, Messenger/genetics ; Vinblastine/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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  • 6
    Publication Date: 1987-05-29
    Description: Preneoplastic and neoplastic liver nodules and hepatocytes isolated from regenerating rat liver have been shown to be resistant to a broad range of carcinogenic agents. This phenomenon was studied by measuring the expression of the multidrug-resistant (mdr) gene in normal liver cells and in preneoplastic and neoplastic nodules and regenerating liver. Levels of messenger RNA for the mdr gene, which encodes P-glycoprotein, were elevated in both preneoplastic and neoplastic lesions. Expression of the mdr gene also reached high levels in regenerating rat liver 24 to 72 hours after partial hepatectomy. These results show that the expression of the mdr gene can be regulated in liver and is likely to be responsible for part of the multidrug-resistance phenotype of carcinogen-initiated hepatocytes and regenerating liver cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thorgeirsson, S S -- Huber, B E -- Sorrell, S -- Fojo, A -- Pastan, I -- Gottesman, M M -- New York, N.Y. -- Science. 1987 May 29;236(4805):1120-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3576227" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinogens/*pharmacology ; Drug Resistance/*genetics ; *Genes ; Humans ; Liver/drug effects ; Liver Neoplasms, Experimental/chemically induced ; Liver Regeneration/*drug effects ; Male ; Precancerous Conditions/chemically induced ; RNA, Messenger/genetics ; 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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