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Biomedical subjects

B Revsin

Publications and source records attributed to B Revsin.

17 recordsLinked to original sources

Cystic fibrosis manifesting with acrodermatitis enteropathica-like eruption. Association with essential fatty acid and zinc deficiencies.

A refractory dermatitis resembling acrodermatitis enteropathica was the manifesting sign in a 5-month-old male infant with cystic fibrosis, preceding pulmonary and gastrointestinal tract symptoms by two months. The eruption was clearly nutritionally responsive. Biochemical evidence was shown for deficiencies of zinc, essential fatty acids, and protein. Altered prostaglandin metabolism was also demonstrated.

Acrodermatitis↗

Fate of prostaglandin E2 in suckling rats after intragastric administration.

[3H]Prostaglandin E2 was administered intragastrically to suckling rats at 10 micrograms and 0.1 microgram doses. At the higher dose, 91% of the radioactive label was recoverable at zero time, decreasing to 29% at 5 h. At the lower dose, 40% of the dose was recoverable at zero time, decreasing to 8% at 5 h. With time, the radioactivity in the stomach showed a steady decrease whereas it increased in the tissues. At the 10 microgram dose of [3H]prostaglandin E2 the amount of radioactivity showed a steady increase in the small intestine lumen and small intestine wall. In liver and kidney the maximum amount of radioactive label was found at 1 h. After 1 h the radioactivity began to decline in the liver, while the kidney remained at the same level for the entire 5-h period. At the 0.1 microgram dose of [3H]prostaglandin E2 the radioactivity in the small intestine lumen reached a maximum 3 h after gavage and thereafter declined. The amount of label in the small intestine wall increased for the entire 5 h. In liver and kidney the radioactivity peaked at 1 h, remained at the same level until the 3rd h, then exhibited a decline. Quantitation of the unmetabolized prostaglandin E2 reaching the various organs studied was possible 30 and 60 min after administration of the 10 micrograms dose of prostaglandin E2. At 30 min 42.9% of radioactive label present in the liver could be shown to be authentic prostaglandin E2. This corresponded to 0.64% of the original dose. At 60 min only 22.8% of the radioactive label found in the liver could be shown to be authentic prostaglandin E2, which corresponded to 0.46% of the administered dose. Similar results were found in the small intestine lumen, the small intestine wall and in the kidney. At 3 and 5h, none of the radioactivity found in these organs could be identified as authentic prostaglandin E2.

Animals↗

A new variant of methylmalonic acidemia-defective coenzyme-apoenzyme binding in cultured fibroblasts.

Cultured fibroblasts from a patient with methylmalonic acidemia, clinically responsive to vitamin B-12, were studied in vitro. Kinetic analysis revealed abnormal binding of the coenzyme, 5'-deoxyadenosylcobalamin, for its methylmalonyl-CoA carbonylmutase apoenzyme, i.e., KM of 3.8 X 10(-5) M versus control KM of 1.5 X 10(-8) M. These data are interpreted as indicating a structural defect of the apoenzyme at the coenzyme binding site, and represent another variant of this genetic disorder.

Amino Acid Metabolism, Inborn Errors↗

Effect of valine on propionate metabolism in control and hyperglycinemic fibroblasts and in rat liver.

Measurement of methylmalonyl-CoA mutase and propionyl-CoA carboxylase activities in lysates from fibroblasts derived from control, nonketotic hyperglycinemia, propionic acidemia, and both vitamin B12-responsive and -nonresponsive variants of methylmalonic acidemia showed only one abnormality: a 59% decrease in carboxylase activity in the nonketotic hyperglycinemic lysates (P less than 0.01). When fibroblasts from all cell types were grown on valine-supplemented (24 mM) media, mutase activity was generally inhibited. As for carboxylase activity, control lines were inhibited 35% as compared to controls without valine and propionic acidemia activity was undetectable. On the other hand, carboxylase activity in both methylmalonic acidemia variants was increased 40% and nonketotic hyperglycinemia carboxylase activity was increased 80% (P less than 0.01) when grown on valine-supplemented media. Isoleucine could not substitute for valine in producing increased carboxylase activity in these mutants. Glycine cleavage activity in fresh rat liver homogenates (11.1 micronmol/gm protein/90 min) did not vary significantly when 24 mM valine was added to the reaction (9.9 micronmol/mg protein/90 min). Therefore, the hyperglycinemia observed in both ketotic and nonketotic forms is probably not caused by a direct effect of valine on the glycine cleavage reaction. These data suggest that the presence of increased amounts of propionic acid in serum or urine does not necessarily rule out the possibility of nonketotic hyperglycinemia due to the decreased activity of the carboxylase enzyme.

Carboxy-Lyases↗

Detection of errors in methylmalonyl-CoA metabolism by using amniotic fluid.

We report a method for rapid prenatal detection of methylmalonic acidemia, consisting of measuring methylmalonly-CoA mutase (EC 5.4.99.2) activity in non-cultured amniotic cells and measuring the concentration of methylmalonate in the amniotic fluid. Immediate stabilization of the mutase activity in the non-cultured amniotic cell by its coenzyme adenosycobalamin, and use of methylmalonyl-CoA with high specific activity gives mutase activity comparable to that of cultured amniotic cells or normal fibroblasts. Consequently, findings of low mutase activity and a hight concentration of methylmalonate in the amniotic fluid allows accurate diagnosis of the vitamin B12-nonresponsive form of methylmalonic acidemia. These results can be obtained in two days. For the vitamin B12-responsive form, the correct diagnosis depends upon finding amniotic fluid methylmalonate, because cells from these patients will display normal methylmalony-CoA mutase activity after adenosylcobalamin is added. Problems in interpreting data on bloody samples and the limitations of the method are discussed.

Amniotic Fluid↗

Low-dose intravenous insulin infusion in patients with diabetic ketoacidosis: biochemical effects in children.

Twenty-five episodes of diabetic ketoacidosis in 20 children were treated with continuous low-dose intravenous insulin infusion. Stable serum immunoreactive insulin concentrations were produced, along with prompt falls in glucose, beta-hydroxybutyrate, and glucagon levels, and a steadily increasing bicarbonate level. Neither hypokalemia nor hypophosphatemia developed. Elevated serum alanine concentrations were found during ketoacidosis in contrast to the lowered concentrations found in adults, and were correlated inversely with plasma glucagon concentrations. The treatment regimen described is safe, easy to use, efficacious, and resulted in prompt correction of the observed biochemical alterations in children with diabetic ketoacidosis.

Adolescent↗

A simple, rapid method for prenatal detection of defects in propionate metabolism.

Incorporation of radiolabel from propionate-1(-14)C into protein (TCA insoluble material) in fibroblasts or amniotic fluid cells, provides a rapid, simple means of detecting fetuses with inborn errors of propionate metabolism using small numbers of cells. Controls were easily differentiated from mutant lines over differing media pH conditions. This method was successfully used to diagnose correctly a normal fetus at risk for methylmalonic acidemia. This method can be used as an adjunct in diagnosis, but cannot replace direct enzyme analysis.

Amniotic Fluid↗

Propionate metabolism in fetal livers of 15 to 19 weeks' gestation.

Extracts of hepatic tissue obtained from saline-induced abortuses were analyzed for methylmalonyl CoA carbonylmutase (MM) and propionyl CoA carboxylase (PC) activity. MM activity was similar to control values, which suggests that abortion material may be used to confirm the prenatal diagnosis of methylmalonic acidemia. Confirmation of a presumptive propionic acidemia diagnosis is more tenuous due to the instability of PC and the possibility that saline may induce PC activity.

Abortion, Induced↗