Modulation of tissue vitamin E levels by physical exercise.
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Biomedical subjects
Publications and source records attributed to D S Wilson.
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Reactive oxygen species are considered to play an important role in cutaneous pathology. Enzymic and non-enzymic antioxidants can prevent oxidative damage but may be overcome by strong pro-oxidative stimuli. The acute effect of a single exposure to near ultraviolet (UVA)/visible radiation (greater than 320 nm) on various skin antioxidants was examined in hairless mice immediately after irradiation. Impairment of cutaneous catalase and glutathione reductase activity was observed. Superoxide dismutase and glutathione peroxidase were not significantly influenced. Inhibition of catalase may render skin more susceptible to the damaging effects of hydrogen peroxide and its reaction products such as the hydroxyl radical. Partially diminished glutathione reductase activity is not accompanied by a change in reduced/oxidized glutathione level immediately after irradiation. There was a tendential (not statistically significant) decrease in cutaneous tocopherol, ubiquinol + ubiquinone 9 and ascorbic acid levels, either indicating direct photodestruction or consumption by reaction products of photooxidative stress. This partial impairment of the cutaneous antioxidant defense system by near ultraviolet/visible light, showing that the most susceptible component in skin is catalase, suggests possible pharmacological interventions.
Four continuous cell lines constructed by transfecting BALB/c mouse fibroblast cells with an expression system that has the mutant c-Ha-ras gene under control of a truncated version of the mouse metallothionein-1 (mt-1) promoter were characterized for zinc-induced phenotype switching. These cells were selected for transformation in the presence of zinc, a known inducer of the mt-1 promoter. When the transfected cells were grown in medium depleted of zinc, there was a dramatic reduction in their soft agar cloning efficiency. Adding zinc back to the medium restored the transformed phenotype in a dose-dependent manner. Analysis of the intracellular p21 levels of induced and uninduced cells showed that zinc was modulating the expression of the transfected ras gene. In vivo studies done with syngeneic mice showed that zinc-induced cells were tumorigenic and formed metastatic lesions in the lungs of the inoculated animals.
The bluegill sunfish (Lepomis macrochirus) is considered a generalist predator, adept at feeding in both the littoral and open-water habitats of North American freshwater lakes. We demonstrate adaptive intraspecific variation in morphology and foraging behaviors within single lakes. This variation appears to make individual fish specialized for feeding in either the littoral or open-water habitat. Discovery of a complex polymorphism in such a well-studied species suggests that adaptive variation may be more common than is currently perceived.
The pharmacokinetics of 3-O-demethylfortimicin A were evaluated in 16 healthy adult male volunteers after bolus intramuscular (i.m.) and 30-min intravenous (i.v.) infusion administration of doses ranging from 0.25 to 16 mg/kg. Mean calculated peak levels of the drug in plasma after the 0.25-, 0.5-, 1-, 2-, 4-, 8-, and 16-mg/kg i.m. doses were 1.1, 1.9, 3.5, 4.9, 11.0, 21.8, and 41.3 micrograms/ml, respectively, occurring about 60 min after dosing. The biphasic decline in levels of the drug in plasma after i.v. administration was not apparent after i.m. dosing, presumably because absorption of the drug from the injection site obscured the alpha elimination phase. Mean calculated peak levels for the 1-, 2-, 4-, 8-, and 16-mg/kg 30-min i.v. infusions were 5.9, 12.2, 20.1, 36.7, and 66.4 micrograms/ml, respectively. A statistically significant trend of increasing apparent volume of distribution with increasing dose size was noted for the i.m. dose group only. Plasma drug clearance was dose level and route independent, with an excellent linear relationship between the area under the plasma drug level curve and the dose. The mean 0- to 48-h urinary recoveries of 3-O-demethylfortimicin A after the i.m. injections and i.v. infusions were 90 and 102%, respectively. After the i.m. dosings, the half-life of the drug in plasma averaged 2.0 h, and after the i.v. dosings it averaged 2.7 h. The results of the study indicated that most of the drug was cleared by renal mechanisms.
Some nonaromatic analogues of amphetamine and alpha-methylbenzylamine were prepared and evaluated as competitive inhibitors of norepinephrine N-methyltransferase (NMT). All of the nonaromatic analogues were significantly more active than their aromatic counterparts [Ki for amphetamine = 740 microM; Ki for 1-cyclooctyl-2-aminopropane = 86 microM]. In order to determine if the aliphatic ring of these analogues bound to the same binding site as the phenyl ring of amphetamine and alpha-methylbenzylamine, the stereoselectivity of NMT toward the different compounds was determined. Stereochemical requirements for aromatic and nonaromatic inhibitors were similar (in all cases the S isomer was more potent at inhibiting NMT). The stereochemical preference expressed for phenylethanolamine substrates and corresponding nonaromatic analogues was also found to be the same; however, as the lipophilicity of the nonaromatic ethanolamine analogues was increased, a loss in both stereoselectivity and substrate activity occurred. The results presented here are consistent with an aromatic ring binding site that is part of, or bordered by, a large hydrophobic area. The larger, more hydrophobic nonaromatic phenylethanolamine derivatives are drawn into the hydrophobic area, which reduces side-chain hydroxy interactions necessary for substrate activity.
A simple model of coevolution in a subdivided population is considered. It is shown that, when there are frequency- and density-dependent interactions in each site, the sampling variation in numbers in each local site can lead to selection both through the dispersal process and through indirect effects. The model predicts that coevolved relationships between species can result from various interactions other than direct forms of competition and predation.
The clinical features of eight cases of carcinoma of the bronchus presenting as pain in the neck and arm, arising from a population of 320 000 in eight years, are described. The difficulties in establishing a diagnosis are discussed, and the implications for therapy and management are described. It would appear that carcinoma of the bronchus, whether local, as a Pancoast syndrome, or metastatic, is more common than is realized.
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According to traditional models, natural selection is largely insensitive to an organism's effect on its community. Effects on the community at large cannot feed back differentially to the organisms that cause them, and, hence, cannot lead to the differential fitness of the organisms. However, if a spatial variation exists in community composition, organisms do differentially feel their own effects on the community, and this leads to a form of evolution on the community level. Without violating the principle of individual selection, the concept of an organism that exists for the "function" its performs in its community may be valid in some cases.
In organisms possessing a dispersal phase the processes of mating, competition, feeding, and predation are often carried out within "trait-groups," defined as populations enclosed in areas smaller than the boundaries of the deme. A simple model shows that this can lead to the selection of "altruistic" traits that favor the fitness of the group over that of the individual. The extent of group selection that occurs depends mainly on the variation in the composition of genotypes between trait-groups. The traditional concepts of group and individual selection are seen as two extremes of a continuum, with systems in nature operating over the interval in between.
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Using direct visualization techniques, we recently confirmed earlier histologic studies that leukocytes accumulate primarily in the coronary capillaries of ischemic hearts during early reperfusion. The purpose of this study was to determine if pentoxifylline (PTX) would reduce leukocyte trapping in postischemic hearts. Isolated rat hearts were subjected to 30 min of 37 degrees C, no-flow ischemia. Hearts were initially reperfused with diluted whole blood containing fluorescent leukocytes. At 5, (R5), 20, and 35 min of reperfusion, the deposition of leukocytes in the coronary capillaries and venules was observed directly using intravital fluorescence microscopy. Three groups were studied: a non-ischemic control group (group I) and postischemic groups reperfused with diluted whole blood treated with vehicle group II or PTX (5 mM; group III). Postischemic reperfusion with unactivated blood caused a significant trapping of leukocytes in coronary capillaries throughout reperfusion (R5, group I = 2.0 +/- 0.3 vs. group II = 5.7 +/- 0.6 leukocytes/capillary field, p < 0.05). The addition of PTX reduced capillary leukocyte trapping below control values throughout reperfusion (R5, group III = 1.6 +/- 0.2 leukocytes/capillary field, p < 0.05). At R5, there was no statistically significant difference in leukocyte accumulation in venules for all groups (group I = 1.5 +/- 0.6, group II = 3.2 +/- 0.4, group III = 3.3 +/- 0.4 leukocytes/100 microns venule). During the reperfusion period, leukocyte persistence in the capillaries of postischemic hearts (36%) was greater than in the venules (13%). These data indicate that early in reperfusion after myocardial ischemia, leukocyte trapping occurs primarily in the coronary capillaries. PTX reduced early leukocyte trapping in the capillaries. The results also demonstrate that during reperfusion, the mechanisms affecting capillary retention are more persistent than those in the venule. These findings suggest that attempts to attenuate the damaging potential of early leukostasis in capillaries consider the biophysical properties of the leukocyte.