Biomedical subjects
Publications and source records attributed to C McGowan.
In fission yeast p34cdc2/cyclin is activated at the G2/M boundary by dephosphorylation of Tyr15 of the p34cdc2 subunit. Two protein phosphatases carry out this dephosphorylation event. The major activity is encoded by cdc25, which is a distantly related member of the protein tyrosine phosphatase family. A minor activity is provided by a newly identified fission yeast protein tyrosine phosphatase.
In this paper, we have described the critical experiments leading to the discovery and analysis of the cdc25 M-phase inducer. We have shown that timing of mitosis is sensitive to the level of cdc25+ expression and that the cellular concentration of p80cdc25 increases as cells approach mitosis. From these observations we conclude that, in S. pombe, rate of accumulation of p80cdc25 plays an important role in determining the timing of mitosis. We postulate that under a given set of conditions, a critical level of p80cdc25 activity is required to undergo mitosis. The actual level that is required can vary depending on ploidy, growth rate, nutritional status of the cell, and perhaps other parameters. These signals may be monitored through the weel pathway leading to tyrosyl phosphorylation of p34cdc2. We have shown that p80cdc25 encodes a phosphate that acts by directly dephosphorylating the Tyr-15 residue of p34cdc2. Our studies strongly indicate that this aspect of the mitotic control network is generally conserved among eukaryotes. It is conceivable, however, that the mode of regulation of cdc25 activity may vary from species to species. Clearly, in S. cerevisiae the cdc25+ homolog, MIH1, in contrast to cdc25+, is not rate-limiting for M-phase onset. It will be important to determine whether the level of cdc25+ homologs in other organisms also oscillates during the cell cycle, or whether their activity is controlled by localization or posttranslational mechanisms, such as phosphorylation. Furthermore, our finding of more than one cdc25+ homolog in a single species suggests an additional level of complexity to the control of M-phase onset by cdc25 in higher eukaryotes that will require further investigation.
The effects of vitamin B6 status and lead (Pb) toxicity on aspects of glutathione (GSH) metabolism in rats were examined in a 2 x 2 factorial experiment. The administration of 2000 ppm Pb as Pb acetate.3H2O significantly (P less than 0.05) increased hepatic GSH levels in rats receiving B6-adequate (+B6) but decreased GSH in rats fed B6-deficient (-B6) diets. The addition of Pb to the +B6 diet also increased hepatic glutathione reductase (GSSG-R) activity. Plasma pyridoxal phosphate (PLP), cystathionine and valine levels were decreased by the -B6 diets independent of the presence of Pb. Plasma arginine, alanine, serine and proline levels were increased by Pb in both -B6 and +B6 groups. Glycine levels were increased in -B6 rats only in the absence of Pb while taurine was decreased by Pb only in +B6 rats. There were significant -B6 x Pb interactions for hepatic GSH, cysteine and GSSG-R as well as plasma valine, glycine and proline. These results suggest an influence of B6 status on Pb-induced changes in hepatic GSH, possibly through its role as a co-factor for enzymes involved in amino acid metabolism.
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1. Growing chicks (Gallus domesticus) were fed a selenium-deficient diet supplemented with 0 or 2000 ppm lead (Pb) and 0 or 0.1 ppm selenium (Se). 2. Selenium addition stimulated growth at 0 but not at 2000 ppm Pb, while Pb depressed growth at both levels of Se. 3. Selenium addition stimulated Se-dependent glutathione peroxidase (GSH-Px) activity in liver, but Pb was without effect on GSH-Px activity. 4. Lead addition increased non-protein sulfhydryl (NPSH) concentrations in liver, kidney and thigh muscle. NPSH levels were not altered by Se. 5. The reported antagonism between Pb and Se does not appear to be mediated through effects on GSH-Px or NPSH metabolism.
The most complete account of the hind leg muscles of the kiwi was published a century ago by Sir Richard Owen, in his seventy-fifth year. This extensively-cited work has several omissions and errors, and while certain of these were corrected by subsequent authors, sufficient uncertainty remains to warrant a reinvestigation. In the present study a detailed description of the hind leg musculature is given, based upon dissections of two frozen specimens. An indication of the possible function of each muscle is given by assessing its size, action, and fiber-arrangement, together with tentative data on the relative abundance of twitch and tonus fibers. The correlation between surface features of bones and muscle attachments is investigated with a view to interpreting palaeontological material. Although the limb and pelvic bones are marked by numerous features which suggest muscle attachments, relatively few can be positively identified with specific muscles. Only 23% of the muscle origins and insertions can be identified, and, with three possible exceptions, no indication of relative size is given by the scars. The possibility of being able to reconstruct the musculature of the kiwi from its skeletal anatomy, much less that of its extinct relatives, is remote.
The relationship between pulmonary arterial pressure (Ppa) and blood (Q) was determined during normoxia and hypoxia in ventilated pig lungs perfused in situ with the animal's own blood. Hypoxia shifted the Ppa-Q relationship to the right and decreased its slope, indicating pulmonary vasoconstriction. Carbon monoxide (11.5% in the inspired gas) and metyrapone ditartrate (10 mg/min into the perfusate) caused vasodilation when oxygenation was normal and reduced the vasoconstriction caused by hypoxia. Since the only pharmacological property CO and metyrapone are thought to have in common at the concentrations employed is the ability to bind to the heme iron of cytochrome P-450, these results are consistent with the hypothesis that desaturation of this cytochrome leads to pulmonary vasoconstriction. Prostaglandin F2alpha, infused into the pulmonary artery at 0.01 mg/min, when oxygenation was normal, had effects on the Ppa-Q relationship similar to those of hypoxia. The F2alpha response was also reduced by CO and metyrapone, suggesting either that P-450 was involved in the F2alpha response or that CO and metyrapone were toxic to pulmonary vascular smooth muscle. Proadifen hydrochloride (1 mg/min), which is thought to bind to the protein moiety of P-450 also reduced the hypoxic response, but was a vasoconstrictor during normoxia and did not affect the F2alpha response.
Two experiments were conducted in which varying levels of lead (up to 2000 ppm as lead acetate trihydrate) and selenium (up to 40 ppm as Na2SeO3) were fed, either alone or in combination, to chicks from day-old through 18 or 20 d. Lead additions depressed growth in a dose-dependent manner without affecting mortality. Selenium addition at 20 ppm was severely growth inhibitory, but mortality was not affected. The growth inhibition of 20 ppm Se was partially alleviated by feeding it in combination with 2000 ppm Pb; however, mortality was increased significantly by the combination. In contrast 40 ppm Se resulted in almost complete cessation of growth and 85% mortality, whereas the combination with 2000 ppm Pb partially overcame the growth inhibition and eliminated the excess mortality. When Pb or Se were fed alone, hepatic levels of the fed element were elevated. There were further significant elevations of hepatic levels of both elements when fed in combination at identical dietary concentrations as the single element additions. The results suggest that Pb and Se are antagonistic. The nature of the interaction of these elements is such that although 2000 ppm Pb partially overcomes the growth inhibition by 20 or 40 pm Se, the reverse (relief of Pb inhibition by Se) is not observed.