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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 463-466 
    ISSN: 1432-1041
    Keywords: sulphadamine ; isozianid interaction ; acetylator phenotyping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of concomitant administration of isoniazid (INH) on the acetylation of sulphadimidine has been studied in 6 healthy volunteers, previously identified as having the fast acetylator phenotype. INH was administered in a slow release form (500 mg tablet) 1 hour before the sulphadimidine. Acetylation of sulphadimidine was measured in plasma 6 h after its intake and in urine collected between 5 and 6 hours. INH significantly decreased the acetylated fraction of sulphadimidine in plasma from 69.0 to 54.0 and in urine from 85.9 to 81.2%. This was reflected in a significantly higher plasma concentration of unconjugated sulphadimidine and reduced urinary excretion of acetylated sulphadimidine. It is concluded that concomitant administration of INH inhibits acetylation of sulphadimidine. Fast acetylators at the border line of discrimination, may be misclassified if phenotyped with sulphadimidine during concomitant administration of INH.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: isoniazid ; slow acetylators ; toxic metabolites ; slow-release preparation ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To test the hypothesis that slow acetylators, who may have a greater risk of developing isoniazid hepatitis than rapid acetylators, are exposed to more acetylhydrazine and hydrazine, two toxic metabolites of isoniazid, the urinary excretion of hydrazino metabolites of isoniazid was measured following the ingestion of 300 mg isoniazid. Slow acetylators (n=7) excreted significantly more isoniazid (32.4 vs 9.2% dose), acetylhydrazine (3.1 vs 1.6% dose), and hydrazine (1.0 vs 0.4% dose) in 24 h than rapid acetylators (n=5), whereas the excretion of acetylisoniazid and diacetylhydrazine was significantly lower. As the acetylation (i.e. detoxification) of acetylhydrazine is inhibited in the presence of high concentrations of isoniazid, a study was also made of the effect of a slow-release preparation that results in lower plasma concentrations of isoniazid on the production of hydrazino metabolites. The ratio of acetylisoniazid to isoniazid in urine was significantly increased in slow acetylators from 0.84 to 1.02 following administration of the slow release preparation, indicating increased acetylation of isoniazid. However, the excretion of diacetylhydrazine relative to the excretion of acetylhydrazine and hydrazine did not change. It is concluded that exposure to toxic metabolites of isoniazid is increased in slow acetylators. Detoxification of the toxic metabolites was not enhanced by a slow-release preparation of isoniazid.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 513 (1987), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 469 (1986), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Human metaphase chromosomes, substituted with 5′-bromodeoxyuridine (BrdUrd) for one, two or three rounds of replication, were briefly pretreated with ultraviolet light (UV), in the presence of 33258 Hoechst, and subsequently digested with either exonuclease III or S1 nuclease. Pretreatment alone was not sufficient to induce sister chromatid differential staining (SCD), but allowed subsequent digestion with exonuclease III or S1. Such enzymes were found to induce SCD with ethidium bromide, as unifilarly BrdUrd-substituted chromatids (TB) were more resistant than bifilarly substituted chromatids (BB). Other experiments with DNase I or the AluI and HaeIII restriction endonucleases showed that only HaeIII was capable of inducing SCD by attacking BB more than TB chromatids preincubated with UV in the presence of Hoechst. SCD with exonuclease III/S1 nuclease seems to be due to (1) UV-induced DNA debromination occurring twice in BB as opposed to TB chromatids, and (2) alteration of chromatin protein structure occurring to a different extent in differently BrdUrd-substituted chromatids. Our findings with endonucleases, on the contrary, may depend on the capacity of enzymatic cleavage to cancel the different protein alterations induced differentially by UV in TB as opposed to BB chromatids.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Fixed human metaphase chromosomes, whose DNA had been substituted with 5′-bromodeoxyuridine (BrdUrd) for two rounds of replication (TB/BB) or for one round in BrdUrd followed by another round in thymidine (TT/BT), were treated with ultraviolet light (UV), in the presence or in the absence of 33258 Hoechst, to produce sister chromatid differentiation (SCD). Giemsa staining was compared with staining with monoclonal antibodies to double-stranded or single-stranded DNA. We confirmed that UV acts by debrominating BrdUrd-stubstituted DNA but showed that debromination alone cannot explain all our findings. We postulated that UV-induced protein-protein cross-linking, occurring to a different extent in differently BrdUrd-substituted chromatids, may also be invoked in explaining our data. Lastly, the different behaviour of unifilarly substituted TB as opposed to BT chromatids in UV-treated chromosomes, allowed us to hypothesize that such chromatids may differ depending on whether or not newly synthesized DNA is formed on a BrdUrd-containing strand.
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  • 7
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two previous single case reports from the literature showed the presence or absence of centromeric antigens at the site of the inactive centromeres in one (X;X) and in one (9;11) dicentric chromosome. We studied nine different dicentric chromosomes using anticentromeric antibodies and immunofluorescence techniques. In the four autosomal dicentrics the inactive centromere was consistently positive while the dicentrics composed of two X chromosomes were either positive or negative; one case of (X;Y) dicentric was negative. The results indicate that the X chromosome mode of replication may be involved in the suppression of immunofluorescence at the site of the inactive centromere and that one centromere of the dicentric chromosome may lose its function but conserve some of its antigenic properties. This indicates that not all these antigens play a rôle in the microtubules-centromere interaction.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Water, air & soil pollution 27 (1986), S. 403-410 
    ISSN: 1573-2932
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract The effects of atmospheric Pb pollution on moss nematofauna were studied in an industrial area in the Po river plain (Northern Italy). Moss samples, affected by Pb pollution, were taken monthly for a year from eight stations. About 15 000 specimens were extracted and identified. The nematode community proved to be sensitive to Pb pollution. The total biomass of nematodes, the number of species, and the Shannon diversity index significantly decrease for an increase of the Pb content in the moss, while the density of individuals does not seem to be affected by pollution. The nematode suborder Dorylaimina is by far the most sensitive to Pb.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 28 (1986), S. 1672-1689 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A structured mathematical model for cellular metabolism in Escherichia coli has been extended to encompass the mechanistic structure surrounding the kinetics and control of transcription and translation. The dependence of transcription on RNA polymerase and the mechanism of translation initiation have been explicitly included. This model correctly simulates cell growth, cell composition, and the timing of chromosome synthesis as a function of extracellular substrate concentration for glucose-limited balanced growth. Simulation results for the subpopulation of RNA polymerase engaged in transcription and for the distribution of this subpopulation among different promoter sites agree closely with experimental findings, as do calculated estimates of the active ribosomal fraction. In addition, the existence of an antitermination system for transcription of stable RNA operons is supported by model results. This model should provide a useful framework for investigating metabolic perturbations to E. coli, such as those resulting from insertion of extra-chromosomal vectors into the cells.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A mechanistically detailed single-cell model E. coli B/r-A was adapted to simulate the effects of vector presence on cell metabolism. Competition for RNA polymerase between chromosome and plasmid DNA is explicitly included. Distribution of active ribosomes among chromosome- and plasmid-derived messenger RNA, another key facet of host-plasmid interactions, is also treated in detail. Simulations of recombinant cell growth rate and cloned-gene productivity as a function of relative plasmid number per cell agree closely with experimental results. Model prediction of the variation of cell cycle parameters C and D with plasmid number are roughly consistent with available data. Models of this class can be used to simulate changes in productivity resulting from specific alterations in the expression vector. The effects of changing cloned-gene promoter and ribosome binding strengths and of augmenting cell transcription or translation capacity have been studied using the recombinant cell model. Results suggest that cloned-gene expression is limited by cellular transcription capacity. These and other parametric studies, conveniently implemented using the computer cell, provide important guidance for future experiments directed at better understanding of host-plasmid interactions and at optimizing recombinant system productivity.
    Additional Material: 2 Ill.
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