Lalit M. Ambani

Rapid prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism: a sensitive assay using cultured cells.

SummaryA sensitive, reliable, and easily performed procedure is described for the prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism using cultured amniotic cells and skin fibroblasts. With this assay, control fibroblast lines incorporated a mean of 6.89 nanoatoms 14C/mg protein from [1-14C]propionate into trichloroacetic acid (TCA)-precipitable cell material in 10h. Twenty-five mutant fibroblast lines from patients with propionicacidemia or one of the methylmalonicacidemias fixed 0.04 to 0.93 nanoatoms 14C/mg. Considerable variation was observed, both among and within discrete mutant classes, with respect to the residual amount of propionate pathway activity, possibly reflecting further molecular heterogeneity in these disorders.We applied this procedure to cultured amniotic cells from controls and 4 midtrimester pregnancies at risk for methylmalonicacidemia and diagnosed one fetus with a methylmalonyl CoA apomutase defect and 3 fetuses which were unaffected.

Start Hesitation — A Side Effect of Long-Term Levodopa Therapy

THE side effects of levodopa therapy in patients with Parkinsons disease are numerous and prevalent. Reports of short-term clinical trials emphasize the frequency of gastrointestinal and cardiovas...

Modification of the tremorigenic activity of physostigmine

Abstract Drugs which reduce central catecholamine activity increased the tremorigenic action physostigmine (0·25 mg/kg) in the rat. The potentiation of physostigmine tremor induced by these neuroleptic drugs was quantitated measuring the ratio of post- to prephysostigmine motor activity; this ratio may be useful index of catecholamine/cholinergic balance. Of the compounds tested, chlorpromazine HC1 (15 mg/kg) and reserpine (10 mg/kg) had the greatest potentiating effect on the tremor-producing action of physostigmine. LDOPA (500 mg/kg) reduced the tremor induced by physostigmine in rats pre-treated with reserpine, but not in rats pre-treated with chlorpromazine.

Quantification of melanin in hepatic and cardiac lipofuscin

Melanin pigment in liver and heart tissue, obtained at autopsy from patients, was isolated and quantified. The quantity of melanin extracted was directly proportional to lipofuscin granule counts. Infrared and electron spin resonance spectrographs of the isolated pigments from liver and heart showed absorption characteristics identical to those of known melanins. The pigment was absent in fetal and neonatal life, increased in brown atrophy of the heart and liver, and diminished in livers with fatty metamorphosis.

L-dihydroxyphenylalanine: effect on levels of amino acids in rat brain.

LARGE doses of r-dihydroxyphenylalanine (L-DOPA) are used in the treatment of Parkinsons disease (COTZIAS, VAN WOERT and SCHIFFER, 1967; YAHR et al., 1969). Since L-DOPA is a neutral aromatic amino acid, it is conceivable that long-term therapy with these large doses could alter the metabolism of other amino acids. L-DOPA might be expected to compete with other aromatic amino acids for common pathways of decarboxylation (ROBERTS, ROTHSTEIN and BAXTER, 1958), transamination (AXELROD and BLACK, 1968), and intestinal (SAUNDERS and ISSELBACHER, 1966), renal tubular (BEYER et al., 1947) and blood to brain (LAJTHA and Tom, 1963) transport. In this communication we describe the effects of the administration of L-DOPA to the rat on the levels of other amino acids in the brain.

Variable expression of Marfan syndrome in monozygotic twins

A pair of monozygotic twins with the Marfan syndrome with variable expression is presented. One of the twins, in addition to more severe musculoskeletal and ocular manifestations, had coarctation of the aorta as the cardiovascular manifestation of this syndrome. Analysis of red cell antigens, serum proteins and dermatoglyphic examination suggests a high probability of monozygosity. Accordingly, the variation in expression of this autosomal dominant disorder between the twins is most likely due to the modifying influences of environmental factors. Also noteworthy is the fact that the resected coarctation tissue domonstrated the histopathologic changes characteristic of cystic medial necrosis, and thus served as an additional piece of evidence supporting the diagnosis of the Marfan syndrome. This was of particular importance in view of the absence of any family history of this syndrome and the absence of ectopia lentis or the more typical cardiovascular manifestations in either twin.

l-Dihydroxyphenylalanine: Effect on Levels of Free Amino Acids in Rat Liver

Summary The concentrations of liver free amino acids in l-Dopa-treated and control rats were assayed by a Jeol amino acid analyzer. Subcutaneous injections of 500 mg/kg l-Dopa daily for 8 days increased the concentrations of isoleucine, methionine, threonine and tyrosine. 1000 mg/kg l-Dopa produced an even greater increase in the concentration of tyrosine and threonine in the liver as well as inducing a significant increase in hepatic-aspartic acid and serine. Only glutamic acid decreased after chronic l-Dopa treatment (1000 mg/kg). These effects of l-Dopa on hepatic-free amino acid levels are discussed with reference to some of the known metabolic actions of this drug.