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  • 1
    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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  • 2
    Publication Date: 1986-08-15
    Description: Transplantation of normal, immature, fetal hematopoietic cells into a preimmune fetal recipient with a congenital hemoglobinopathy may allow partial reconstitution of normal hemoglobin production without the complications associated with postnatal bone marrow transplantation (immunosuppression and the occurrence of graft versus host disease). In order to test this hypothesis the naturally occurring polymorphism at the beta-hemoglobin locus of the sheep was used as a marker for engraftment and hematopoietic chimerism. Intraperitoneal injection of allogeneic fetal stem cells into normal fetal lambs resulted in hematopoietic chimerism in three of four surviving recipients. This chimerism has been sustained for 6 months after birth and 9 months after engraftment, without evidence of graft versus host disease, and without the use of immunosuppressive therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flake, A W -- Harrison, M R -- Adzick, N S -- Zanjani, E D -- AM-24027/AM/NIADDK NIH HHS/ -- AM-29890/AM/NIADDK NIH HHS/ -- AM-30914/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1986 Aug 15;233(4765):776-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2874611" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chimera ; Female ; Fetus ; Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation ; Hemoglobin A/*analysis ; Hemoglobins/*analysis ; Pregnancy ; Sheep ; Transplantation, Homologous
    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: 1986-12-12
    Description: The hypogonadal (hpg) mouse lacks a complete gonadotropin-releasing hormone (GnRH) gene and consequently cannot reproduce. Introduction of an intact GnRH gene into the genome of these mutant mice resulted in complete reversal of the hypogonadal phenotype. Transgenic hpg/hpg homozygotes of both sexes were capable of mating and producing offspring. Pituitary and serum concentrations of luteinizing hormone, follicle-stimulating hormone, and prolactin were restored to those of normal animals. Immunocytochemistry and in situ hybridization showed that GnRH expression was restored in the appropriate hypothalamic neurons of the transgenic hpg animals, an indication of neural-specific expression of the introduced gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mason, A J -- Pitts, S L -- Nikolics, K -- Szonyi, E -- Wilcox, J N -- Seeburg, P H -- Stewart, T A -- New York, N.Y. -- Science. 1986 Dec 12;234(4782):1372-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3097822" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Follicle Stimulating Hormone/blood ; Gene Expression Regulation ; *Genetic Engineering ; Gonadotropin-Releasing Hormone/genetics ; Histocytochemistry ; Hypogonadism/*genetics ; Hypothalamus/analysis/cytology ; Infertility/genetics/*therapy ; Luteinizing Hormone/blood ; Male ; Mice ; Mutation ; Neurons/analysis ; Phenotype ; Prolactin/blood ; Tissue Distribution
    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: 1986-11-21
    Description: Issues regarding the use of epidemiology in drug abuse research are discussed and systems for monitoring national trends and identifying risk factors are described. Data indicate a general decline in marijuana use among youth, a cohort aging effect among heroin and marijuana users, and increased prevalence and health consequences associated with cocaine use.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kozel, N J -- Adams, E H -- New York, N.Y. -- Science. 1986 Nov 21;234(4779):970-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3490691" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/complications ; Adolescent ; Adult ; Child ; Cocaine ; Epidemiologic Methods ; Female ; Heroin ; Humans ; Male ; Marijuana Abuse/epidemiology ; Population Surveillance ; Risk ; Substance-Related Disorders/*epidemiology
    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: 1986-01-24
    Description: A semisterile male translocation heterozygote [t(2; 14) 1Gso] that exhibited neurological symptoms and an inability to swim (diver) was found among the offspring of male mice treated with triethylenemelamine. All breeding and cytogenetic data showed a complete concordance between translocation heterozygosity and the neurological disorders. Homozygosity for the translocation seemed to be lethal at an early embryonic stage. Despite the distinctive neurologic symptoms, no anatomic or histological defects in either the ear or in the central nervous system were observed. Thus, a balanced chromosomal translocation can produce disease with an inheritance pattern that mimics a single dominant gene defect.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rutledge, J C -- Cain, K T -- Cacheiro, N L -- Cornett, C V -- Wright, C G -- Generoso, W M -- New York, N.Y. -- Science. 1986 Jan 24;231(4736):395-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3941902" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosome Mapping ; Female ; Heterozygote ; Humans ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Neurologic Mutants/*genetics ; Muscular Dystrophies/genetics ; *Translocation, Genetic ; Triethylenemelamine/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: 1986-09-26
    Description: Although the kidney is a major source of prorenin, the precursor of renin, there are extrarenal sources for plasma prorenin that have not been identified. The selective increase in plasma prorenin at the time of ovulation suggested that one of these sources might be the ovary. Prorenin was therefore measured in fluid aspirated from 18 ovarian follicles and in plasma collected from three women who were undergoing in vitro fertilization. The follicular fluid contained high concentrations of prorenin that were approximately 12 times higher than plasma prorenin. The prorenin from follicular fluid was immunochemically identical to kidney and plasma prorenin. Thus, the ovary is a likely source for the ovulatory peak of plasma prorenin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glorioso, N -- Atlas, S A -- Laragh, J H -- Jewelewicz, R -- Sealey, J E -- HL-18323-SCR/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1986 Sep 26;233(4771):1422-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3529392" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensinogen/blood/secretion ; Antigen-Antibody Complex ; Enzyme Precursors/blood/*secretion ; Female ; Fertilization in Vitro ; Humans ; Immune Sera ; Ovarian Follicle/*enzymology ; Renin/blood/*secretion
    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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  • 7
    Publication Date: 1986-01-24
    Description: Retinal photoreceptor cell dystrophies have been widely observed in humans and in animals, but pathogenetic mechanisms are known in only a few such disorders, and successful therapeutic intervention has been reported in fewer still. Spontaneously hypertensive albino rats develop a retinal photoreceptor cell dystrophy with onset late in the first year or early in the second year of life. Between 60 and 70 percent of the animals are affected. A substantial reduction in the prevalence and severity of the dystrophy occurred in such animals whose diet contained 30 percent (by weight) D-galactose. Neither an inhibitor of the enzyme aldose reductase, present in the diet, nor diabetes mellitus, induced by streptozotocin, had any statistically significant influence on the dystrophy. Ambient light and systolic blood pressure levels also did not seem to influence the course of the disorder. The mechanism by which galactose exerts its effect is unknown, but a mutant enzyme with an elevated Michaelis constant (Km) for galactose is plausible.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frank, R N -- Keirn, R J -- Keirn, G V -- Mancini, M A -- Khoury, J K -- EY-02566/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1986 Jan 24;231(4736):376-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3941900" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Animals ; Blood Pressure ; Diabetes Mellitus, Experimental/complications ; Female ; Galactose/*therapeutic use ; Humans ; Imidazoles/therapeutic use ; *Imidazolidines ; Rats ; *Rats, Inbred SHR ; *Rats, Inbred Strains ; Retina/pathology ; Retinal Degeneration/complications/*drug therapy/pathology
    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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