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Biomedical subjects

M Yudkoff

Publications and source records attributed to M Yudkoff.

At least 109 records · Page 6Linked to original sources
PubMed1983

Effects of conceptual age and dietary intake on protein metabolism in premature infants.

Protein turnover was studied in eight premature infants of conceptual age 26-37 weeks. A stochastic model based upon [15N]urea or [15N]ammonia excretion following a single injection of [15N]glycine was used to estimate rates of whole body protein synthesis and catabolism. The urinary 3-methylhistidine/creatinine ratio was determined to differentiate skeletal muscle protein breakdown from total protein catabolism. The rates of whole body protein synthesis ranged from 5.2 to 13.2 g X kg-1 X day-1 and protein catabolism ranged from 4.1 to 12.4 g X kg-1 X day-1. Linear regression analyses of conceptual age versus (a) whole body nitrogen flux, (b) protein synthesis, and (c) protein catabolism showed significant inverse relationships. A similar relationship obtained between conceptual age and the urine 3-methylhistidine/creatinine ratio. Muscle protein breakdown did not vary with conceptual age, but the fraction of whole body protein breakdown derived from muscle protein breakdown increased significantly with advancing maturation. The ratio net tissue protein gain/total body protein synthesis increased significantly with increasing body weight. Net tissue protein gain appeared to be directly related to protein and caloric intake. The ratio of the rate of whole body protein synthesis and protein intake was greatest in the youngest infants and declined with maturation. A similar relationship was not found between the ratio of protein synthesis and caloric intake and the degree of maturity. More than 90% of nitrogen entering the metabolic pool was used for protein synthesis and more than 50% of calories administered were similarly utilized. We conclude that: (a) protein turnover in premature infants is far more rapid than in term infants, children, or adults and is inversely related to conceptual age; (b) muscle protein turnover constitutes a greater fraction of overall turnover with advancing maturity; (c) energy and protein intake affect net tissue protein gain significantly in rapidly growing infants; and (d) the efficiency of protein synthesis as a function of protein intake is higher in the most immature infants.

Body Weight↗
PubMed1982

Determination of [amide-15N]glutamine in plasma with gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric method is described for determination of isotopic enrichment in [amide-15N]glutamine. The method involves the isolation of glutamine with an anionic exchange resin and the enzymatic hydrolysis of glutamine with glutaminase. The ammonia derived from the amide group is converted enzymatically to glutamic acid and isotopic enrichment in the latter compound is determined following formation of the N-TFA-glutaminate derivative. The method gave a linear result for [amide-15N]glutamine in the 0.5--21.5 atom % excess range with a mean coefficient of variance of 7.8%. Determination of plasma glutamine by isotope dilution showed a mean recovery of 94%. The appearance of plasma [amide-15N]glutamine was measured in a healthy adult following the intravenous administration of 15NH4Cl (350 mumol). A peak enrichment of 12 atom % excess was observed by 3.5 min.

Ammonia↗
PubMed1981

Rapid gas chromatographic-mass spectrometric analysis of [15N]urea: application to human metabolic studies.

A rapid gas chromatographic-mass spectrometric method for [15N]urea analysis is described which is based on the formation of a TFA-urea derivative. The method is extremely sensitive, being capable of detecting less than 0.2 atom % excess [15N]urea in as little as 50 microliter of plasma and 10 microliter of urine with a coefficient of variation of 11%. The method was used to measure in vivo the disappearance of [15N]urea from plasma and the incorporation of [15N]ammonium acetate into [15N]urea. The values obtained for urea pool size and flux are 4.5 +/- 0.30 g nitrogen/total body weight and 16.2 +/- 1.34 g nitrogen per 24 h per 1.73 m2. Following the ingestion of [15N]ammonium acetate nearly 90% of the 15N label was incorporated into [15N]urea by 30 min.

Adult↗
PubMed1981

Effects of cysteamine therapy in nephropathic cystinosis.

We studied the effects of cysteamine in five children with nephropathic cystinosis who were treated for up to 30 months. Cysteamine caused a decline in leukocyte cystine levels to the range seen in clinically unaffected heterozygotes; both plasma and urinary cystine diminished by more than half. Therapy had no effect on progressively declining creatinine clearance in three patients, but improvement occurred in the other two. Phosphaturia, glycosuria, aminociduria, and organic aciduria did not improve in any of the patients. Both blood lactate and the lactate pyruvate ratio were diminished. Growth velocity, which was abnormal in four of the five children, did not improve. No major side effects were noted. Therapy with cysteamine caused a consistent, dose-related decline in levels of cystine in leukocytes and in extracellular fluid, caused no improvement so far in renal tubular function or growth velocity, and improved creatinine clearance in some patients.

Amino Acids↗
PubMed1981

Cysteamine inhibition of [15N]-glycine turnover in cystinosis and of glycine cleavage system in vitro.

In order to clarify the hyperglycinemic effect of cysteamine treatment in children with nephropathic cystinosis, we measured [15N]-glycine turnover in three affected patients. Administration of cysteamine lowered the glycine flux and the glycine metabolic clearance rate but did not alter the glycine pool size. Formation of [15N]-serine from [15N]-glycine was lower in untreated patients than in control subjects and was reduced still further by cysteamine. Studies in vitro with isolated rat liver mitochondria and acetone extracts of mitochondria indicated that even low cysteamine concentrations (0.1 mM) inhibited the glycine cleavage system in both the direction of glycine oxidation and glycine synthesis. Cysteamine was a more potent inhibitor of the glycine cleavage system than any other sulfhydryl containing compound. Although no ill effects of cysteamine treatment were immediately apparent, patients receiving cysteamine should be monitored carefully for the appearance of any neurologic symptoms which might be referable to inhibition of the glycine cleavage system.

Coenzyme A↗
PubMed1981

Niemann-Pick disease type B: prenatal diagnosis and enzymatic and chemical studies on fetal brain and liver.

Patients with Niemann-Pick disease type A have a severe neurovisceral disease caused by a deficiency of lysosomal sphingomyelinase activity in all tissues examined. The patients with the type B form have signs and symptoms related to storage of sphingomyelin in the spleen, liver, and lungs, while neurologically they remain normal. They also have a severe deficiency of lysosomal sphingomyelinase activity in all tissues previously examined. Here the brain and liver of a fetus with Niemann-Pick disease type B are examined for enzymatic anc chemical changes. Despite careful analysis, no measurable lysosomal sphingomyelinase could be measured in either organ. Lipid changes were comparable to those observed in fetuses aborted with Niemann-Pick disease type A. The affected child in this family is now age 3 and remains neurologically normal but continues to show organ enlargement and lung infiltration of lipids. It appears that the lack of neurological involvement in type B patients cannot be due to an obvious presence of significant lysosomal sphingomyelinase activity in brain.

Adult↗
PubMed1980

Absent phenylalanine hydroxylase activity without phenylketonuria.

A male infant is described who never manifested phenylketonuria even though phenylalanine hydroxylase activity was undetectable in liver tissue. Plasma phenylalanine were elevated in the range typical of PKU patients when the baby was at breast and declined with institution of a low phenylalanine diet. Physical and psychomotor development were normal with the baby on the latter treatment. The results indicate that the absence of phenylketonuria does not rule out phenylalanine hydroxylase activity.

Breast Feeding↗
PubMed1980

The pancytopenia of isovaleric acidemia.

Severe pancytopenia developed in two infants with isovaleric acidemia. Previous reports indicate these hematologic abnormalities are a leading cause of death in affected infants. Our findings suggest that the pancytopenia may be due to arrested maturation of hematopoietic precursors. Prompt transfusion of appropriate blood components prevented complications due to the hematologic abnormalities.

Amino Acid Metabolism, Inborn Errors↗
PubMed1979

Late-onset nonketotic hyperglycinemia and spinocerebellar degeneration.

Investigation of a 15-year old boy with progressive optic atrophy and spinocerebellar degeneration revealed elevated plasma, cerebrospinal fluid, and urine glycine concentrations. During an oral glycine loading test, the patient's plasma glycine concentration rose to a higher level than control values, although the initial rate of rise was slower; there was no concomitant rise in the plasma serine concentration. An oral serine loading test resulted in a prompt rise of both glycine and serine serum concentrations. The renal glycine clearance was elevated, and the renal tubular glycine reabsorption was diminished. These findings of decreased intestinal uptake and increased renal tubular glycine clearance suggest that a generalized derangement of glycine entry into cells may account for the phenotypic manifestations of the disorder.

Adolescent↗
PubMed1979

On the clinical significance of the plasma alpha-amino-n-butyric acid:leucine ratio.

The ratio of plasma alpha-aminobutyric acid to plasma leucine that has been proposed as a specific biochemical marker of alcoholic liver injury, was measured in normal children an children with a variety of metablic disorders. The ratio was found to be lower in children that in adults. It was elevated in children with Reye's syndrome, tyrosinemia, homocystinuria, nonketotic hyperglycinemia, and ornithine transcarbamylase deficiency. The results indicate that an elevated ratio is not specific for adults with alcoholic liver injury and that the ratio may be high even without the presence of clinically apparent hepatic disease. An altered ratio may reflect the presence of an inherent metabolic defect.

Adult↗
PubMed1978

Glycine therapy in isovaleric acidemia.

The therapeutic efficacy of oral glycine was tested in a 3-year-old girl with isovaleric acidemia. An oral leucine load (25 mg/kg) caused a rise of the blood levels of isovaleric, lactic, and pyruvic acids as well as an increase of urinary excretion of the ketone bodies. These changes did not occur when oral glycine (250 mg/kg) was given with the leucine. Glycine supplementation favored the formation of isovalerylglycine, a nontoxic conjugate of isovaleric acid which is excreted rapidly. Excretion of isovalerylglycine rose threefold when leucine and glycine were administered simultaneously. Chronic glycine therapy was tolerated well and may have prevented one episode of ketoacidosis.

Acidosis↗
PubMed1978

The ontogeny of sugar transport in kidney.

Concentrative uptake of alpha-methyl-d-glucoside (AMG) by isolated renal tubule fragments from the newborn Sprague-Dawley rat has been demonstrated and the validity of this phenomenon confirmed by an in vivo demonstration of AMG uptake by the newborn kidney cortex. A kinetic analysis of the entry phenomenon in the newborn tubule reveals the presence of two distinct membrame transport systems for AMG, only one of which is present in the adult tubule. All transport of sugar in both newborn and adult tubules was phlorizin-sensitive, but was only partially ingibited in Na+-free buffer. Glucose was shown to inhibit uptake competitively on the shared, high capacity system. Uptake on the high affinity system in the newborn represents 15-20% of the total at physiologic sugar concentrations. It is concluded that active sugar transport is a characteristic of the newborn rat kidney and that the isolated tubule preparation is a more accurate reflection of this phenomenon than is the renal cortical slice.

Age Factors↗