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Biomedical subjects

R Ouellet

Publications and source records attributed to R Ouellet.

At least 37 records · Page 2Linked to original sources
PubMed1986

Kinetic abnormalities of carbamyl phosphate synthetase-I in a case of congenital hyperammonaemia.

A sensitive direct colourimetric method has been employed to measure kinetic parameters and pH dependence of carbamyl phosphate synthetase-I, in a liver sample from a 2 1/2-month-old girl, who died from complications of a late-developing congenital hyperammonaemia. The residual activity of carbamyl phosphate synthetase-I was 25%, whereas other urea cycle enzymes were within normal range. Apparent Km for ammonium ion (0.73 mmol/L) was significantly increased (normal range 0.24-0.51). Km for bicarbonate ion was normal, while Km for NAG showed a slight variation from normal. The pH dependence curve of the patient's enzyme was flat, as compared to two controls showing pH optima at 7.8. Radial immunodiffusion (Mancini) of the abnormal enzyme against human enzyme antiserum gave a cross-reacting material of 10-20%. The methodological approach presented can be used to characterize abnormal enzymes in cases of partial deficiency with only 100-200 mg of liver tissue.

Amino Acid Metabolism, Inborn Errors↗
PubMed1986

Significance of transported glycine in the conjugation of sodium benzoate in spf mutant mice with ornithine transcarbamylase deficiency.

3H-glycine and 14C-serine were injected intraperitoneally, during treatment of spf mutant mice with 2% sodium benzoate in drinking water. Urinary hippurate was separated by thin layer chromatography and counted for 3H and 14C labels representing transported and newly synthesized glycine, respectively. The specific activity of 3H-hippurate increased significantly in mutant and normal groups, while the increase of 14C was seen only in mutants. The ratio of specific activity 3H:14C showed significant increases in normal (0.99 to 1.93; p less than 0.01) and mutant (1.53 to 3.05; p less than 0.05) groups, which shows that glycine transported from body pools played a significantly greater role in the conjugation of benzoate, compared to glycine synthesized de novo from serine. In spf mice, benzoate treatment also resulted in a decrease in orotate excretion, indicating amelioration of the hyperammonemic state. It is postulated that the elimination of glycine transported from body pools may be the primary mechanism for the reduction of ammoniagenicity in benzoate therapy, and that the de novo synthesis of glycine may have a secondary effect.

Animals↗
PubMed1986

[Variability of enzyme activity and urinary orotic acid in ornithine transcarbamylase deficient spf/+ heterozygotic mice].

Urinary orotate excretion is used as a clinical parameter to distinguish female carriers of X-linked ornithine transcarbamylase deficiency. The value of this test has been considered doubtful due to a lack of knowledge about the true variability of hepatic enzyme activity and its effect on orotate synthesis. We have used a purebred population of spf/+ heterozygous females (n = 90), with an X-linked structural mutation of ornithine transcarbamylase, to study this variability in comparison with normal +/+ females (n = 19) and hemizygous spf/Y males (n = 20). Our results show that spf/+ heterozygotes have a mean hepatic enzyme activity equal to 64% of the normal group, as compared to 44-56% reported previously. They have a very wide variability (range 28-107 mumol/h/mg protein) which overlap the normal distribution curves of +/+ and spf/Y groups. Similar overlapping is shown in the distribution of urinary orotate excretion. The correlation studies indicate that the urinary orotate level as an index of hepatic enzyme deficiency is of value only in heterozygotes having an activity less than 50% of normal. This parameter cannot, therefore, be used to screen for all heterozygotes. However, it would still be valuable in distinguishing female-children at risk of developing hyperammonemic symptoms.

Animals↗
PubMed1985

Expression of ornithine transcarbamylase deficiency in the small intestine and colon of sparse-fur mutant mice.

Sparse-fur mutant mice have an X-linked deficiency of liver ornithine transcarbamylase (OTC), similar to congenital hyperammonemia type II seen in children. The purpose of the present study was to see whether the expression of enzyme deficiency in the small intestine and colon was similar to that in the liver. Our results show that the level of residual OTC activity in duodenal, jejunal, and ileal mucosa is not significantly different from that of the liver, both in mutant heterozygous female and hemizygous male mice. A highly significant (p less than 0.001) positive correlation was seen between the enzyme activity from all segments of the normal and mutant intestine and that of the liver. pH dependence of mucosal OTC was similar to liver enzyme, when compared within normal or hemizygous mutant mice. Apparent Km (ornithine) of the enzyme from normal or mutant small intestine did not show any significant differences when compared with OTC from normal or mutant livers, respectively. Apparent Km (carbamyl phosphate) from both organs of normal mice was also similar. However, Km (carbamyl phosphate) of mutant intestine and liver gave variable results on statistical comparisons. The specific activity in the proximal and distal colon of mutant mice was significantly lower (p less than 0.001) than normal mice, and showed a similar expression of enzyme deficiency as seen in the small intestine. The similarity of OTC deficiency in the intestine and liver of sparse-fur mice would provide a basis for investigating the use of mucosal biopsies in the confirmation and characterization of human disease.

Animals↗
PubMed1984

Synthesis, receptor binding, and target-tissue uptake of carbon-11 labeled carbamate derivatives of estradiol and hexestrol.

The reaction of ethyl chloroformate with amino compounds has been evaluated as a simple route to carbon-11 labeling of steroid hormone-receptor-based imaging agents. Both a 17 beta-amino analogue of estradiol and an aminoethyl derivative of the nonsteroidal estrogen hexestrol with potential affinity for the estrogen receptor were studied. The unlabeled carbamate derivatives of the amino estrogens were prepared by standard methods, and the 11C-labeled analogues were synthesized from [11C]ethyl chloroformate, generated by purging ethanol with [11C]phosgene. Both carbamates showed weak in vitro binding affinity for the estrogen receptor, and only the 11C-labeled hexestrol exhibited a small but significant estrogen-responsive uterus uptake in immature rats.

Animals↗
PubMed1983

A new French-Canadian family affected by hyperargininaemia.

A new French-Canadian family from the province of Quebec is reported, in which a male child was diagnosed as hyperargininaemic after showing positive tests for cystinuria on neonatal screening. The child has no residual activity of erythrocyte arginase, and a plasma arginine level of 633 mumol/l. Both parents have 32-38% of arginase activity. A newborn sister has normal enzyme levels. The propositus did not show abnormal plasma ammonia elevation even after a protein tolerance test (1.5 g protein/kg body weight) but excretes high levels of urinary orotate (845 mg/g creatinine). At 3 1/2 years of age the hyperargininaemic child had started showing abnormal gait, ataxia and slowing of intellectual development. It is suggested that all newborn children showing cystinuria-lysinuria pattern of amino acid excretion be tested for arginase deficiency.

Adult↗
PubMed1982

Activity of orotate metabolizing enzyme complex and various urea-cycle enzymes in mutant mice with ornithine transcarbamylase deficiency.

The overall activity of the enzyme complex consisting of orotate phosphoribosyl transferase and orotidine monophosphate decarboxylase, and of various enzymes of the urea cycle, has ben studied in sparse-fur (spf) mutant mice with ornithine transcarbamylase deficiency. The enzyme complex has a lower overall activity, which could be caused by disturbed pyrimidine metabolism due to hyperammonemia. Other enzymes of the urea cycle do not show any significant change.

Animals↗
PubMed1981

Ammonia metabolism in a family affected by hyperargininemia.

A French-Canadian family, with a 14-year old mentally retarded girl, was investigated for hyperargininemia. The girl showed a fasting plasma ammonia N concentration of 100 micrograms/dl (normal : 50.5 +/- 13 micrograms/dl), and a two-hour post protein load level of 183 micrograms/dl (normal : 51.6 +/- 17.6 micrograms/dl). Plasma urea N was lower than normal in the post-load sample. Arginine concentrations were 11 times normal in the plasma, 47 times normal in the urine and 4 times normal in erythrocytes. Measurement of erythrocyte arginase showed only 1% activity in the propositus, and 52-54% in the parents and a sibling as compared to controls. In heterozygous members of the family, the Km (arginine) was similar to controls. Column chromatography of serum amino acids in the propositus showed arginine to be 17.6 S.D. higher than the normal mean. A characteristic cystine-lysinuria pattern of urinary amino acids was also seen. Measurement of other urinary nitrogenous metabolites showed low urinary urea and excessive orotic aciduria. On "normal" food intake, the patient excreted 122 mg of orotic acid/24 h, as against 3.7 mg by the sibling and 3.9 mg by the mother. It is postulated that the level of ornithine in hepatocyte mitochondria is critical to the disposal of carbamyl phosphate. The lack of normal regeneration of ornithine by liver arginase, and an excessive urinary excretion may be responsible for its low mitochondrial concentration. This would cause diversion of unmetabolised carbamyl phosphate towards orotic acid synthesis or ammonia production.

Adolescent↗
PubMed1978

Improving trend in hypertension control in a black inner city community.

Throughout the 1960's repeated findings indicated a poor state of management for hypertension in widely diverse communities across the United States. In the early years of the 1970's similarly derived findings showed a substantial improvement in hypertension management. These trends are confirmed in two random samples of a black urban population studied in 1971 and in 1973 indicating more than a twofold improvement in blood pressure control over that period. This improvement was noticeable in all subgroups of the population at risk although young black males continue to have a less favorable status of detection and control of hypertension.

Adult↗