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  • 1
    ISSN: 1432-0983
    Keywords: Fission yeast ; Membrane ATPase ; Amino acid uptake ; Drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Cyh3 and cyh4, multiple drug resistant strains of Schizosaccharomyces pombe, show a much reduced uptake of trichodermin, chloramphenicol, cycloheximide, L-lysine, glycine, L-threonine, L-glutamine, L-arginine and L-glutamic acid when compared to wild type. The plasma membrane and mitochondrial ATPase activities of these mutants are also greatly reduced. Since the uptake of such compounds is likely to be driven by a proton electrochemical gradient set up by the membrane ATPase it is suggested that the primary effect of these mutations is at the level of the membrane ATPase. Another drug resistant strain, cyh1, which is resistant only to high levels of cycloheximide, shows increased uptake of trichodermin, L-lysine, glycine, L-threonine, L-glutamine when compared to wild type. The plasma membrane and mitochondrial ATPases of cyh1 are considerably greater than those of wild type. It has been shown previously that cyh1 possesses an altered 60S ribosonal subunit protein when compared to wild type and this makes it resistant to cycloheximide. There is no obvious explanation as to how this change could lead to the alterations in drug and amino acid uptake and in ATPase activities observed.
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  • 2
    ISSN: 1432-0983
    Keywords: Fission yeast ; Drug resistance ; Lipid and sterol composition ; Membranes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The whole cell lipid and sterol content of the drug resistant strains cyh1, cyh3 and cyh4 was compared with that of wild type by thin layer and gas liquid chromatography and by UV spectrophotometric analysis. The cyh3 and cyh4 strains had a decreased content of the unsaturated 18:1 fatty acid oleic acid, a decreased content of ergosterol and an increased content of 24,28 dehydroergosterol with respect to wild type. The cyh1 strain, however, only showed a decreased content of ergosterol and an increased content of 24,28 dehydro-ergosterol when compared to wild type.
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  • 3
    ISSN: 1573-904X
    Keywords: relaxin ; pharmacokinetics ; metabolism ; protein ; mass spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Two forms of chemically synthesized human relaxin (hRlx and hRlx-2) were administered as 88 µg/kg intravenous bolus doses to pregnant and nonpregnant rhesus monkeys. No significant differences in pharmacokinetics were observed between pregnant and nonpregnant animals for either form of relaxin; however, clearance of hRlx (3.1–3.4 ml/min/kg) was significantly slower than clearance of hRlx-2 (6.2–6.5 ml/min/kg) in both pregnant and nonpregnant animals. Although the terminal half-lives for hRlx and hRlx-2 were similar (148–157 min), the initial and steady-state volumes of distribution were somewhat larger for hRlx-2 (71–85 and 398–418 ml/kg, respectively) than for hRlx (61–65 and 294–319 ml/kg, respectively). The metabolism of hRlx-2 was also investigated in pregnant and non-pregnant rhesus monkeys after iv bolus (0.44 mg/kg) or 60-min infusion (1.1 mg/kg) administration. Fast atom bombardment mass spectral analysis of the relaxin immunoreactivity isolated from the plasma indicated that hRlx-2 was partially degraded by removal of amino acids from the C terminus of the B chain. The percentage of intact material declined over a 60-min time course. At 60 min post-dose, intact hRlx-2 was ∼46–64% of the detected material. Degraded forms representing loss of one and four amino acids (hRlx) from the C terminus of the B chain were ∼11–13 and ∼19–34% of the detectable material, respectively.
    Type of Medium: Electronic Resource
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