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Biomedical subjects

W G Robinson

Publications and source records attributed to W G Robinson.

13 recordsLinked to original sources
PubMed1996

Diabetic-like retinopathy ameliorated with the aldose reductase inhibitor WAY-121,509.

PURPOSE: To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), in preventing the retinopathy that develops in the galactose-fed rat model of diabetic ocular complications. METHODS: Sprague-Dawley rats were randomized into treatment and duration groups and fed diets with either 50% starch of 50% galactose with or without WAY-121,509 (25 mg/kg body weight per day). Progression of cataracts was monitored by slit-lamp biomicroscopy. After duration of 4, 8, 16, and 24 months, levels of plasma glucose and glycated hemoglobin, as well as erythrocyte and retinal galactose and galactitol, were measured in rats in each group. Retinal vasculatures of the 24-month rats were isolated by elastase digestion and analyzed by computer-assisted morphometry. RESULTS: Mature, diabetic-like cataracts developed within 5 weeks in all the galactose-fed, untreated rats, but only nonprogressive anterior cortical opacities were present in lenses of 85% of the ARI-treated galactosemic animals after 3 months. Plasma glucose remained the same in all groups. Erythrocyte and retinal galactose and glycated (galactosylated) hemoglobin were elevated with galactosemia and were unaffected by ARI treatment. Erythrocyte and retinal galactitol levels were decreased by 91% and 95%, respectively, with inhibitor treatment. At 24 months, capillary length, width, density, the number of microaneurysms, and the percent of capillary length involved in intraretinal microvascular abnormalities, expressed as hypercellular channels with diameters > 20 microns, were significantly increased by galactosemia and were attenuated in the galactose-fed, ARI-treated group. CONCLUSIONS: A dose of WAY-121,509 sufficient to reduce retinal polyol levels by 95% ameliorated the development of galactose-induced cataracts and diabetic-like retinopathy but was insufficient to prevent early lens opacifications or all the diabetic-like retinal microangiopathies.

Aldehyde Reductase↗
PubMed1991

Degenerated intramural pericytes ('ghost cells') in the retinal capillaries of diabetic rats.

One of the earliest histopathological signs of diabetic retinopathy is a selective loss of intramural pericytes from retinal capillaries. In the present study, the retinal vessels of rats with streptozotocin-induced diabetes (STZ Wistar) and rats with genetically-induced insulin dependent diabetes mellitus (BB Wistar) and non-insulin dependent diabetes mellitus (SHR/N-corpulent) were examined after 6 to 8 months duration for diabetes-related retinal microangiopathies. The SHR/N-corpulent (cp) rats were fed a 54% sucrose diet, whereas the STZ Wistar and BB Wistar rats were fed laboratory chow for 32 to 36 weeks. In all the diabetic rats, the retinal capillaries in enzyme-digested flat mounts exhibited an increase in periodic-acid-Schiff (PAS) staining and loss of pericytes compared to their respective euglycemic controls. Pericyte "ghosts", like those defined in human diabetes as intramural pockets lacking normal cell contents, were documented by high resolution micrographs in all the diabetic rats. Endothelial cell proliferation, capillary dilation, and varicose loop formation were noted in some of the diabetic rats. Hence, similar capillary lesions were found in very different groups of diabetic rats. The findings suggest that a chronic high tissue concentration of glucose is the underlying factor which triggers pathogenesis in the pericyte. Hyperglycemia-induced activation of endogenous aldose reductase of the polyol pathway is probably the initial insult, but other factors such as advanced glycosylation products may affect the final outcome.

Animals↗
PubMed1987

Toxicity of enzymically-oxidized low-density lipoprotein.

Intravenous injection of cholesterol oxidase into hyperlipidemic rabbits in which aortic atheromatous lesions have been induced by dietary means is lethal within hours, whereas injection of the same enzyme into normal rabbits has no visible adverse effect. The lethal effect of the enzyme is explicable by the finding that injection of cholesterol-oxidase treated low-density lipoprotein kills normal rabbits, in contrast to untreated low-density lipoprotein which does not. Enzymically oxidized low-density lipoprotein was also found to be cytotoxic for two human cell lines and for cultured bovine aortic endothelial cells. We suggest that in vivo enzymic conversion of low-density lipoprotein cholesterol to low-density lipoprotein cholestenone may possibly play a role in the initiation of atheromatous lesions in humans.

3-Hydroxysteroid Dehydrogenases↗
PubMed1981

Factor-dependent dissociation of wheat germ ribosomes.

Ribosome dissociation factor has been found in wheat germ acetone powder extracts. Further purification of the crude extract by pH an ammonium sulfate fractionations, DEAE-cellulose and CM-Sephadex column chromatography has resulted in the separation of two active fractions. The possibility that ribosome dissociation activity exhibited by either fraction is due to protease or nuclease is considered unlikely, based on results of experiments involving ribosome dissociation kinetics, subunit structural integrity, and treatment with a serine protease inhibitor. Wheat germ ribosome dissociation factor is not species-specific. Dissociation factor from both fractions will promote the dissociation of Escherichia coli 70-S as well as Artemia salina 80-S ribosomes. Although both dissociation factor activities show the same dependence on K+ and Mg2+ for optimal activity, the two activities exhibit significant differences in their sensitivity to sulfhydryl reagents and heat, and in their dependence on incubation temperature for activity. Certain properties of both factors suggest that neither factor is initiation factor eIF-3; however, the possibility that one or both factors are subunits of initiation factor eIF-3 remains to be determined.

Animals↗
PubMedDate not supplied

Chromosomal insertions and deletions in Streptococcus mutans.

Many isolates of Streptococcus mutans lack the ability to ferment melibiose and other sugars. We previously reported that this was commonly due to a chromosomal deletion and, in the present study, sequence information from the S. mutans genome project was used to design PCR primers to explore the nature and extent of the deletion. In all melibiose-negative strains examined, there was an incomplete insertion element, ISSmu3, in place of the 18-kb stretch of chromosome encoding the msm and GAL operons. Strains that were also unable to utilise beta-glucosides were found to have a separate 4 kb deletion in the BGL regulon that is proposed to be due to homologous recombination between two short stretches of identical sequence. The evidence is consistent with all the melibiose-negative strains examined being derived from a common ancestor.

Chromosome Deletion↗