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Biomedical subjects

V Barash

Publications and source records attributed to V Barash.

At least 37 records · Page 2Linked to original sources
PubMed1994

Modulation of fetal and placental metabolic pathways in response to maternal thyroid and glucocorticoid hormone excess.

Triiodothyronine (T3) treatment of pregnant rats for 6 days, 10 micrograms/100 g, resulted in a pronounced induction of enzymes related to gluconeogenesis and lipogenesis and of mitochondrial FAD-glycerophosphate dehydrogenase in the maternal liver, as previously observed in male rats. There was virtually no change in the activity of these enzymes in the placenta. However, there was a distinct induction of these enzymes in the fetal liver, even if increments in fetal serum and liver T3 were much smaller than on the maternal side. This indicates that changes in hepatic enzyme activities are a more sensitive index of fetal hyperthyroidism than T3 levels. The increased lipogenic capacity was expressed by greater incorporation of a tritium tracer into fatty acids. Administration of triamcinolone, 2 mg/100 g, for the last 5 days of gestation resulted in marked induction of maternal hepatic enzymes of lipogenesis, gluconeogenesis and of aspartate aminotransferase (ASAT), known to occur in male rats, as well as in a metabolic pattern of insulin resistance. The response of placental enzymes was limited to a small elevation in ASAT and phosphoenolpyruvate carboxykinase (PEPCK) activity. In the fetal liver there was no stimulation of lipogenic enzymes, but a marked induction of PEPCK and ASAT. The changes in the lipogenic capacity were confirmed by tritium incorporation into serum and liver fatty acids. These results demonstrate the marked sensitivity of specific fetal enzyme systems to the maternal iatrogenic hyperthyroidism or hypercorticism. The limited alterations in placental enzyme activities are in accord with the concept that placental metabolic stability fulfils a protective function toward the fetus.

Animals↗
PubMed1992

Familial hypotonia of childhood caused by isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency.

Hypotonia was the initial symptom in four siblings from a nonconsanguineous Tunisian-Jewish family. Plasma carnitine was severely deficient, and urinary organic acid analysis revealed increased excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. 3-Methylcrotonyl-coenzyme A carboxylase activity was reduced in skin fibroblasts; pyruvate carboxylase and serum biotinidase activities were normal. We conclude that 3-methylcrotonyl-coenzyme A carboxylase deficiency should be added to the list of metabolic causes of familial hypotonia of childhood.

Carbon-Carbon Ligases↗
PubMed1991

A radiometric assay for aspartoacylase activity in human fibroblasts: application for the diagnosis of Canavan's disease.

A new sensitive method for measuring aspartoacylase activity in human skin fibroblasts using [3H]N-acetyl-L-aspartic acid (NAA) is described. Optimal assay conditions and kinetic parameters for enzyme activity were determined. The enzyme was found to have maximal activity at pH 8.5, and the Michaelis constant for the substrate N-acetylaspartate was 1.8-2.0 mmol/l. Aspartoacylase activity in control cultured human fibroblasts was 9.2 +/- 1.8 nmol/h per mg protein, compared with 1.1 +/- 0.2 in seven Canavan patients and 3.5 +/- 0.9 in four patients' parents. This method for determining aspartoacylase activity is advantageous to the previously described spectrophotometric method since it is rapid, more sensitive and has less nonspecific interference. It is possible that application of this technique to cultured ammniotic and chorionic villi cells may be used for prenatal diagnosis of Canavan's disease.

Acetates↗
PubMed1991

Kinetic and immunologic evidence for the absence of glucose-6-phosphatase in early human chorionic villi and term placenta.

The existence of the enzyme glucose-6-phosphatase (G6Pase) in early and term human placenta was investigated by comparing the characteristics of placental microsomal glucose 6-phosphate (G6P) hydrolytic activity and liver G6Pase. Placental microsomes exhibited similar apparent Km values for G6P and beta-glycerophosphate in intact and deoxycholate-treated microsomes, heat stability at acidic pH, low latency of mannose 6-phosphate hydrolysis, very low activity of pyrophosphate: glucose phosphotransferase, and undetectable [U-14C]G6P transport into the placental microsomes, all of which indicated that specific G6Pase activity does not exist in placenta. Immunological evidence of the absence of both 36.5 kDa and T2 proteins, which represent the G6Pase catalytic protein and the phosphate/pyrophosphate transporter protein, respectively, confirmed that early and term human placenta are devoid of the multicomponent G6Pase enzyme.

Animals↗
PubMed1991

Autosomal recessive lethal infantile cytochrome C oxidase deficiency.

Three bedouin children with mitochondrial myopathy due to cytochrome c oxidase deficiency presented with progressive muscle weakness, failure to thrive, proximal renal tubular acidosis, and lactic acidemia leading to death. Two died by age 5 months and one by age 16 months. Cytochrome c oxidase was markedly reduced in skeletal muscle extracts of all three. Three other children of the same family with most probably the same metabolic aberration are also described. We suggest an autosomal recessive inheritance for this lethal mitochondrial myopathy.

Acidosis, Renal Tubular↗
PubMed1991

Hereditary branching enzyme dysfunction in adult polyglucosan body disease: a possible metabolic cause in two patients.

We describe 2 unrelated patients with adult polyglucosan body disease (APBD) diagnosed by sural nerve biopsy. Both patients were offspring of consanguineous marriages. They presented clinically with late onset pyramidal tetraparesis, micturition difficulties, peripheral neuropathy, and mild cognitive impairment. Magnetic resonance imaging of the brain revealed extensive white matter abnormalities in both. In search of a possible metabolic defect, we evaluated glycogen metabolism in these patients and their clinically unaffected children. Branching enzyme activity in the patients' polymorphonuclear leukocytes was about 15% of control values, whereas their children displayed values of 50 to 60%, suggesting a possible autosomal recessive mode of transmission. This is the first report of an inherited metabolic defect in patients with adult polyglucosan body disease. We suggest that branching enzyme dysfunction may be implicated in the pathogenesis of some patients with adult polyglucosan body disease.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1991

Apparent absence of glycogen branching enzyme activity in phosphofructokinase deficiency.

A 30-year-old woman with clinical features and biochemical findings of muscle phosphofructokinase deficiency was found to have a very low level of alpha-1,4-glucan:alpha-1,4-glucan-6-transglucosylase (branching enzyme, EC 2.4.1.18) activity in muscle. In contrast, branching enzyme activity in the leukocytes was in the range of control values. After sedimentation of the glycogen from muscle homogenates by centrifugation at 105,000 g, branching enzyme activity in muscle of the patient was similar to that of control subjects. This patient illustrates the possibility of falsely diagnosing branching enzyme deficiency when muscle glycogen content is elevated. It is likely that such an artefact may also cause a false positive diagnosis of branching enzyme deficiency in other metabolic diseases associated with glycogen accumulation.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1990

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: biochemical studies and family investigation of four generations.

3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) lyase activity was determined by the recently described spectrophotometric method of Wanders et al. (1988a) in polymorphonuclear leukocytes and lymphocytes obtained from 33 members of a highly consanguineous Arab-Bedouin family belonging to four generations. Seven subjects were obligatory heterozygotes (parents and grandparents of three propositi); in seven additional subjects enzyme activity in both cell types was in the heterozygote range. No asymptomatic homozygotes were found. The results support the proposed autosomal recessive mode of inheritance of this disorder.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Lethal hypoglycemia and hypothermia induced by administration of low doses of tumor necrosis factor to adrenalectomized rats.

An increased sensitivity of adrenalectomized (Adex) rats to intravenous (IV) injection of recombinant human tumor necrosis factor (rHuTNF) was manifested by a marked increase in the rate of mortality. The rats that died exhibited severe hypoglycemia and hypothermia. Administration of 2.5 or 10 micrograms/100 g body weight (3% or 12%) of the lethal dose in sham-operated rats (90 micrograms/100 g body weight) rHuTNF caused a mortality rate of 50% or 100%, respectively, within 4 hours of its injection. Pre-administration of dexamethasone or intermittent glucose infusion protected the animals from the lethal effect of rHuTNF. Indomethacin did not change the mortality rate in rHuTNF-treated Adex rats, but prevented it in sham-operated rats. The rats that died exhibited a marked decrease in body temperature, but only Adex rats developed hypoglycemia after low doses of TNF. Pretreatment with dexamethasone prevented the hypothermia in both Adex and sham-operated rats, while indomethacin was effective only in sham-operated rats and did not prevent the hypothermia or the hypoglycemia in Adex rats. In the surviving rHuTNF-treated Adex rats, a rapid increase in body temperature occurred, blood glucose decreased to 30 mg/dL, serum insulin concentration decreased to 6 microU/mL, liver glycogen content was reduced by 98%, and a significant reduction in liver phosphoeonolpyruvate carboxykinase (PEPCK) and liver microsomal glucose-6-phosphatase activities was observed. Repeated administration of glucose IV to rHuTNF-treated Adex rats caused an increase in blood glucose and insulin concentrations, and some repletion in liver glycogen content. Injection of rHuTNF, 2.5 to 10 micrograms/100 g body weight, to sham-operated rats caused a significant but slower increase in body temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1990

Microsomal hexose-6-phosphate and 6-phosphogluconate dehydrogenases in extrahepatic tissues: human placenta and pig kidney cortex.

An oxidative pathway of glucose-6-phosphate was found in the microsomal fraction of two extra-hepatic tissues: human placenta and pig kidney cortex. Oxidation activity in microsomes, measured by the formation of 14CO2 from [1-14C] glucose-6-phosphate, was observed only after Triton X-100 treatment and in the presence of methylene blue and NADP. Hexose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were present in a latent form and required treatment with detergent for full activation. Our results suggest that these enzymes are located in the luminal space of placental and kidney microsomes, and that, as in the liver, they generate NADPH on the inner side of the endoplasmic reticulum when G6P and NADP are available.

Animals↗
PubMed1990

Phosphofructokinase deficiency (Tarui disease) associated with hepatic glucuronyltransferase deficiency (Gilbert's syndrome): a case and family study.

Tarui disease is a rare, genetically determined glycogen storage myopathy caused by the total lack of phosphofructokinase (PFK) enzymatic activity in the muscles and partially deficient enzymatic activity in the erythrocytes. We describe a patient with this disorder, who presented with exercise intolerance, painful cramps, elevation of muscle enzyme levels in the serum, compensated hemolysis with paradoxically elevated hemoglobin levels and gout with overproduction of uric acid. This patient had a partial hepatic uridine diphosphoglucuronate-glucuronyltransferase deficiency (Gilbert's syndrome). The coexistence of these two enzymatic deficiencies resulted in a complex clinical picture, especially during and after muscular effort. Screening of the patient's family revealed asymptomatic PFK deficiency in the erythrocytes of both parents and sister.

Adult↗
PubMed1989

Glycogen storage disease, Fanconi nephropathy, abnormal galactose metabolism and mitochondrial myopathy.

We present a 4-year-old male suffering from profound muscular weakness, enzymatically undefined glycogen storage disease. Fanconi nephropathy and impaired galactose utilization. Distorted mitochondria, intramitochondrial fat droplets and partial deficiencies of pyruvate dehydrogenase complex, succinate: cytochrome c oxidoreductase, and cytochrome c oxidase have been found in muscle tissue. The causal relationship between mitochondrial myopathy, glycogen storage disease, Fanconi nephropathy and impaired utilization of galactose is discussed.

Child, Preschool↗
PubMed1989

Propionic acidemia--biochemical studies.

The first documented case of propionic acidemia in Israel is described. Diagnosis was based on three independent methods: analysis of urinary organic acids by gas chromatography/mass spectrometry, assay of propionyl CoA carboxylase activity and oxidation of 1-14C-propionate by cultured skin fibroblasts. The use of more than one method for confirmation of the diagnosis is considered to be of importance in providing an additional margin of safety in cases where genetic counseling and prenatal diagnosis in future pregnancies are indicated.

Ammonia↗