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Biomedical subjects

R Griffiths

Publications and source records attributed to R Griffiths.

At least 181 records · Page 10Linked to original sources
PubMed1981

Characterization of a structural glycoprotein from bovine ligamentum nuchae exhibiting dual amine oxidase activity.

A structural glycoprotein has been extracted from bovine ligamentum nuchae by using 5 M guanidine hydrochloride containing a disulfide bond reducing agent and purified by preparative gel electrophoresis. The isolated material appeared to be monodisperse, with a molecular weight of approximately 34000, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by analytical ultracentrifugation. It contains 10% carbohydrate comprising mannose, N-acetylglucosamine, galactose, and sialic acid in a 6:5:3:3 molar ratio. The glycoprotein has been assayed for peptidyl-lysine oxidase activity by using [3H]lysine-aortic elastin, prepared from 15- to 17-day-old chick embryos, as a substrate. In the absence of free lysine, the specific activity of the preparation over a 2-h incubation was approximately 60 X 10(4) dpm/mg of purified protein. Addition of 10 mM lysine resulted in an approximately 50% decrease in the specific activity. Free lysine was shown to act as a substrate for the glycoprotein preparation as indicated by control experiments using [3H]lysine in place of the aortic substrate. These results demonstrate that the glycoprotein exhibits a dual amine oxidase activity. In the presence of 0.27 mM beta-aminopropionitrile fumarate, a concentration which completely inhibits peptidyl-lysine oxidase activity in other lysyl oxidases, the glycoprotein preparation was inhibited by approximately 14%. In the absence of 5 M guanidine hydrochloride and reducing agent, the glycoprotein undergoes aggregation which in the presences of copper ions results in the formation of cylindrical tactoids, the diameter of which (11 nm) corresponds closely to that of the fibrils which in the majority of connective tissue matrices constitute the microfibrillar component mainly associated with elastic fibers.

Amino Acid Oxidoreductases↗
PubMed1981

Cimetidine-a clinical and pharmacokinetic study.

1 The effect of six months therapy with cimetidine (800 mg or 1600 mg/day) and subsequent withdrawal was studied in 19 patients with duodenal ulceration. 2 The overall rates of healing were 63% and 79% of patients after 3 and after 6 months of treatment respectively. The longer course (6 months) or the higher dose (1600 mg) did not result in significantly increased rates of ulcer healing. 3 Abrupt withdrawal of cimetidine resulted in the recurrence of severe symptoms in 15 patients (79%). 4 Pharmacokinetic studies showed the mean elimination half-life of cimetidine to be 100 +/- 25 min, the total body cimetidine clearance 652 +/- 223 ml/min, the mean volume of distribution at steady state 65 +/- 181 and the overall bioavailability 78%. 5 Long term cimetidine treatment does not result in drug accumulation or changes in its pharmacokinetic profile. 6 Inter-individual differences in clinical and endoscopic response to cimetidine cannot be explained by pharmacokinetic differences.

Cimetidine↗
PubMed1977

The molecular defect in a case of (cystathionine beta-synthase)-deficient homocystinuria.

1. Cystathionine beta-synthase activity isolated from fibroblast cultures obtained from the skin of a normal and a homocystinuric individual were both cross-reactive with normal human liver cystathionine beta-synthase antibody. 2. Isoelectric focusing revealed a substantial difference in the isoelectric points of the normal and abnormal fibroblast enzymes. 3. Treatment of purified samples of normal and abnormal fibroblast enzymes with sodium dodecylsulphate followed by polyacrylamide gel electrophoresis indicated that both normal and abnormal enzymes were composed of two sub-units of molecular weights 53000 and 70000. 4. A combination of urea and sodium dodecylsulphate treatment revealed that the respective 53000 molecular weight sub-units were different. 5. It has been concluded that the molecular defect in the case of pyridoxine non-responsive homocystinuria examined in the present investigation arises as a result of an alteration in the structural gene which codes for the lower molecular weight sub-unit of cystathionine beta-synthase.

Cross Reactions↗
PubMed1976

Studies on the use of skin fibroblasts for the measurement of cystathionine synthase activity with respect to homocystinuria.

The levels of cystathionine synthase have been examined in cultured skin fibroblasts obtained from a patient suffering from pyridoxine-non-responsive homocystinuria and compared with the normal and heterozygous states. Levels of synthase activity were found to vary with time in culture and composition of culture media. The physical properties of normal and abnormal synthase activities were markedly different. It has been concluded that caution has to be exercised when using cell culture methods for the purpose of defining normal, heterozygous and homozygous states with reference to homocystinuria.

Adolescent↗
PubMed1976

Effect of induced elevated plasma levels of homocystine and methionine in rats on collagen and elastin structures.

Young growing rats were intraperitoneally injected with mixtures of homocystine and methionine for several weeks. The growth of the animals was inhibited. After 3 weeks 25% of the rats died and isolation of tail tendon collagen and aorta elastin showed that these proteins were deficient in chemical cross-links. Seventy-five % of the rats survived further injections for another 3 weeks and isolated collagen and elastin were found to be normal in cross-linking. The variability in susceptibility of these rats to homocystine-methionine treatment is discussed in relationship to human homocystinuria. It is speculated that the variability is due to variability in in vivo homocysteine levels.

Animals↗
PubMed1975

Experimental models for the modification of human drug self-administration: Methodological developments in the study of ethanol self-administration by alcoholics.

Experimental studies of human ethanol self-administration are reviewed, and a description is provided of the procedural evolution that has oc-urred in the experimental study of the determinants of human ethanol self-administration. Human experimental models of alcoholism have been established within residential laboratories which permit chronic availability of ethanol to volunteer alcoholic subjects. Experimentation within such environments has progressed from observational and descriptive studies of experimental intoxication to studies that manipulate experimental variables so as to modify (reduce) ethanol self-administration by alcoholic subjects. To observe systematic effects of manipulated variables it has been necessary to develop sensitive baselines of ethanol self-administration. When ethanol intake has been relatively unrestricted, wide spontaneous fluctuations have made difficult the evaulation of manipulated variables. When a variety of restrictions on ethanol availability have been imposed, sensitive self-administration baselines have been established which have permitted the direct experimental assessment of some of the determinants of ethanol self-administration. Six methodological principles are suggested for enhancing the information yield of future research on the determinants of ethanol self-administration. The same general methodology is suggested for research with other varieties of drug self-administration.

Administration, Oral↗