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Biomedical subjects

J M Williamson

Publications and source records attributed to J M Williamson.

66 records · Page 4Linked to original sources
PubMed1981

Stimulation of hepatic glutathione formation by administration of L-2-oxothiazolidine-4-carboxylate, a 5-oxo-L-prolinase substrate.

5-Oxo-L-prolinase, the enzyme that catalyzes the conversion of 5-oxo-L-proline to L-glutamate coupled to the cleavage of ATP to ADP and Pi, also acts on L-2-oxothiazolidine-4-carboxylate (an analog of 5-oxoproline in which the 4-methylene moiety is replaced by sulfur) and ATP to yield cysteine and ADP. The enzyme, which exhibits an affinity for the analog similar to that for the natural substrate, is inhibited by the analog in vitro and in vivo. L-2-oxothiazolidine-4-carboxylate thus serves as a potent inhibitor of the gamma-glutamyl cycle at the step of 5-oxoprolinase. Administration of L-2-oxothiazolidine-4-carboxylate to mice that had been depleted of hepatic glutathione led to restoration of normal hepatic glutathione levels. Since L-2-oxothiazolidine-4-carboxylate is an excellent substrate of the enzyme, it may serve as an intracellular delivery system for cysteine and thus has potential as a therapeutic agent for conditions in which there is depletion of hepatic glutathione.

Amidohydrolases↗
PubMed1980

Toxoplasmosis in farmed red deer (Cervus elaphus) in Scotland.

Farming of red deer began in Scotland in 1970 when an experimental nucleus was established on a hill farm in Kincardineshire. From 1972 to 1977 sera from these animals were tested by the haemagglutination test (HA) and the Sabin-Feldman dye test (DT) for the presence of antibodies to Toxoplasma gondii. Overall, dye test antibodies (greater than or equal to 1/16) were detected in 32.5 per cent of sera and HA antibodies in only 9.8 per cent. On average 14.1 per cent of the deer tested in 1972, 1973 and 1975 were DT positive while a sharp rise to 51.4 per cent was noted in the 1974 animals. These antibody titres were not sustained nor were they reflected by the HA. Marked animals bled serially throughout the survey confirmed the general low level of antibody in the herd and the spasmodic rise in 1974. Experimentally infected deer showed a rise and subsequent fall in DT antibody levels with persistently low HA titres. Since the correlation between HA and DT antibody titres was generally poor the HA would be of limited value in screening for Toxoplasma antibody in farmed red deer sera. The direct agglutination test was used to examine selected sera and the results indicated its potential screening value.

Animals↗
PubMed1979

Purification and properties of L-Aspartate-alpha-decarboxylase, an enzyme that catalyzes the formation of beta-alanine in Escherichia coli.

L-Aspartate-alpha-decarboxylase, an enzyme that catalyzes the production of beta-alanine, has been purified to apparent homogeneity from Escherichia coli. The properties of the enzyme are: (a) pH optimum of 6.8 to 7.5, (b) temperature optimum of 55 degrees C, (c) Km for L-aspartate of 0.16 mM, and (d) molecular weight of 58,000. The activity of the enzyme is inhibited by reagents (hydroxylamine, phenylhydrazine, and sodium borohydride) that react with carbonyl groups, but no pyridoxal phosphate is present. The compound containing the carbonyl group has been identified as covalently bound pyruvate. Approximately 1 mol of pyruvate was found/mol of enzyme. That the enzyme has a biosynthetic function rather than a catabolic role is indicated by the observations that a mutant (designated as E. coli 99-2) which requires either beta-alanine or pantothenic acid for growth contains only trace amounts of enzyme activity, whereas it is present in substantial amounts in the parent strain (E. coli W) and in a spontaneous revertant of the mutant.

Alanine↗
PubMed1970

Red cell survival in biliary cirrhosis.

Studies were carried out on eight patients with primary biliary cirrhosis. Four patients were found to have a haemolytic anaemia; one had Coombs red cell antibodies. Two patients had evidence of splenic sequestration of red cells using the radio-chromium technique. There was a significant correlation between the red cell survival and the bromsulphthalein retention test and the red cell survival and the serum level of bilirubin. It was concluded that the anaemia of cirrhosis of the liver, including primary biliary cirrhosis, may be due to a number of mechanisms and a unifying hypothesis based on the degree of liver dysfunction is suggested.

Aged↗
PubMedDate not supplied

Intraperitoneal phenytoin suppresses kindled responses: effects on motor and electrographic seizures.

Controversy has arisen about the effectiveness of phenytoin against kindled seizures. It has been suggested that the reports of ineffectiveness could be accounted for by phenytoin being given by an intraperitoneal (i.p.) route in those experiments so that adequate serum concentrations were not achieved. Another possibility for the different results was dissimilar stimulus protocols employed in the various studies. The present study examined these issues. Doses of i.p. phenytoin were studied for their actions against kindled responses elicited with short (1 s) and long (10 s) stimulus trains through hippocampal electrodes. Serial application of the stimuli determined time-action relationships. Dose-dependent effects were demonstrated for all time points examined. There was a consistently greater suppression of kindled motor seizures than limbic behavioral seizures or electrographic seizures. Phenytoin either totally blocked or did not affect the duration of afterdischarges. Actions of phenytoin against responses by short duration stimuli were greater than against long duration stimuli. Additional pharmacokinetic studies compared i.p. versus intravenous (i.v.) phenytoin. After i.p. phenytoin, serum levels peaked later than after i.v. delivery, but were maintained in the 'therapeutic' range longer. The present experiments provide additional support for the idea that kindled seizures are a useful model for complex partial seizures in humans. In addition, they show that major actions of phenytoin are to decrease seizure spread and to elevate afterdischarge thresholds and that the i.p. route is appropriate for assaying the effect of phenytoin against kindled seizures in rats.

Animals↗