Search PubMed⌕ Search

Biomedical subjects

A Gutman

Publications and source records attributed to A Gutman.

At least 55 records · Page 3Linked to original sources
PubMed1991

Fructose-1,6-diphosphatase deficiency in Israel.

The clinical and biochemical data on nine patients belonging to six families with fructose-1,6-diphosphatase deficiency are reported. Two of the six families were Jewish, three were Moslem Arabs and one was of Druze origin. All patients had had neonatal hypoglycemia, lactic acidosis and an abnormal fructose or glycerol loading test. At a later age, instances of hypoglycemia occurred in patients both with and without preceding illness. Hypoglycemic attacks were associated with severe hyperuricemia and metabolic acidosis. Therapeutic measures included a restriction in fructose intake and avoidance of prolonged fasting, particularly during febrile episodes.

Consanguinity↗
PubMed1990

Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein lipase and hepatic lipase: implications for the mechanisms of lipase action.

To explore how enzyme affinities and enzyme activities regulate hydrolysis of water-insoluble substrates, we compared hydrolysis of phospholipid-stabilized emulsions of medium-chain (MCT) versus long-chain triacylglycerols (LCT). Because substrate solubility at the emulsion surface might modulate rates of hydrolysis, the ability of egg yolk phosphatidylcholine to solubilize MCT was examined by NMR spectroscopy. Chemical shift measurements showed that 11 mol % of [13C]carbonyl enriched trioctanoin was incorporated into phospholipid vesicles as a surface component. Similar methods with [13C]triolein showed a maximum solubility in phospholipid bilayers of 3 mol % (Hamilton & Small, 1981). Line widths of trioctanoin surface peaks were half that of LCT, and relaxation times, T1, were also shorter for trioctanoin, showing greater mobility for MCT in phospholipid. In assessing the effects of these differences in solubility on lipolysis, we found that both purified bovine milk lipoprotein lipase and human hepatic lipase hydrolyzed MCT at rates at least 2-fold higher than for LCT. With increasing concentrations of MCT, saturation was not reached, indicating low affinities of lipase for MCT emulsions, but with LCT emulsion incubated with lipoprotein lipase, saturation was reached at relatively low concentration, demonstrating higher affinity of lipase for LCT emulsions. Differences in affinity were also demonstrated in mixed incubations where increasing amounts of LCT emulsion resulted in decreased hydrolysis of MCT emulsions. Increasing MCT emulsion amounts had little or no effect on LCT emulsion hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites.

PEA3 is a transcription factor which binds to the polyoma virus enhancer and whose activity is regulated by the expression of a number of oncogenes. We show here that PEA3 also binds specifically to the collagenase and fos cellular promoters. On the collagenase promoter, PEA3 acts synergistically with AP-1 to achieve maximum levels of transcription activation by 12-O-tetradecanoylphorbol-13-acetate (TPA), and non-nuclear oncoproteins, thereby defining a TPA- and oncogene-responsive unit (TORU). From a comparative study of the collagenase TORU and the analogous polyoma virus TORU, we conclude that both the binding affinity of the PEA3 motif and the spacing between PEA3 and AP-1 modulate transcription activation induced by oncogene expression.

Base Sequence↗
PubMed1990

Experimental model of acute appendicitis in the rabbit with determination of leucine amino peptidase (LAP) and acid phosphatase (acid-P) activities in portal blood samples.

The activities of leucine amino peptidase (LAP) and acid phosphatase (Acid-P), conceivable markers of acute appendicitis, were determined in the portal blood of rabbits with acute appendicitis. An experimental model of acute appendicitis was established using No.-O silk ties to block the base of the appendix. The clinical and histopathological picture of acute appendicitis was seen after 12 hr in all the rabbits in the model group (9/9) and in none of the control group. Catheterization of the superior mesenteric vein was performed in rabbits with acute appendicitis, and portal blood samples were taken at 0, 6, and 12 hr for assay of LAP and Acid-P activities. No statistically significant difference between the experimental group and the control group, in the activities of LAP and Acid-P, was found at any time interval. The experimental model of acute appendicitis in the rabbit which is described here is simple and carries a high rate of success. This is probably the first report of using continuous catheterization and repeated sampling of portal blood, for the measurement of enzyme activities, in an experimental model of acute appendicitis. It was concluded that serum LAP and Acid-P activities cannot be used as markers for acute appendicitis.

Acid Phosphatase↗
PubMed1990

Carnitine palmitoyltransferase deficiency: a common cause of recurrent myoglobinuria.

Six patients with carnitine palmitoyltransferase (CPT) deficiency were diagnosed. Five were males aged 12-48 years and one was a 7-year-old girl. Severe myoglobinuria with renal shut-down led to the diagnosis in four, the main cause of myoglobinuria being prolonged exertion. Other precipitating factors included febrile illnesses, fasting and sleep deprivation. Between attacks, EMG, serum creatine kinase (CK) activity and the response of serum lactate to ischemic exercise were normal in all patients. The diagnosis of CPT deficiency was based on assay of the enzyme by the isotope exchange assay in leukocyte, muscle or cultured skin fibroblast homogenates. CPT activity assayed by the forward assay under standard conditions was normal. CPT deficiency seems to be a common cause of exercise-induced myoglobinuria. Prompt diagnosis can lead to avoidance of risk factors and prevention of rhabdomyolysis and its consequences.

Adult↗
PubMed1990

Skeletal assessment in neuroblastoma--the pitfalls of iodine-123-MIBG scans.

This study was carried out to compare iodine-123 metaiodobenzylguanidine ([I123I]MIBG) and technetium-99m-methylene diphosphonate bone scans (99mTc-MDP) in the detection of skeletal involvement by neuroblastoma. Forty-four children with neuroblastoma underwent both [123I] MIBG and 99mTc-MDP scans within a 4-wk period; bone marrow examination also was performed; all these investigations were done both at diagnosis and at follow-up. At diagnosis, four children with Stage 4 disease had normal [123I]MIBG scans but abnormal 99mTc-MDP scans, while at follow-up there were four children with negative [123I]MIBG studies who later died from disseminated neuroblastoma. All eight scans are considered false-negative. In 24 children, the [123I]MIBG revealed more extensive disease with 161 positive sites while the 99mTc-MDP scan showed only 100 positive sites; 34 of these sites were common to both studies. This study shows that underassessment of skeletal involvement by neuroblastoma occurred using [123I]MIBG scans and that one cannot therefore substitute [123I]MIBG for 99mTc-MDP bone scans in the staging of neuroblastoma.

3-Iodobenzylguanidine↗
PubMed1989

PEA3 is a nuclear target for transcription activation by non-nuclear oncogenes.

We have found that the activity of the transcription factor PEA3 is regulated by the expression of non-nuclear oncogenes. This factor, although distinct from PEA1 (AP1), is activated by the same oncogenes (v-src, polyoma (Py) middle T, c-Ha-ras, v-mos, v-raf), by tetradecanoyl phorbol-acetate (TPA) and by serum components. We present evidence that PEA3 and PEA1 co-operate in the response of the polyoma virus (Py) alpha domain to oncogene expression. However, in contrast to PEA1, c-fos does not appear to be necessary for activation of PEA3, suggesting that PEA3 is a fos independent target for regulation of transcription by non-nuclear oncogenes.

Animals↗
PubMed1989

Estimation of glucose carbon recycling in children with glycogen storage disease: A 13C NMR study using [U-13C]glucose.

A stable isotope procedure to estimate hepatic glucose carbon recycling and thereby elucidate the mechanism by which glucose is produced in patients lacking glucose 6-phosphatase is described. A total of 10 studies was performed in children with glycogen storage disease type I (GSD-I) and type III (GSD-III) and control subjects. A primed dose-constant nasogastric infusion of D-[U-13C]glucose (greater than 99% 13C-enriched) or an infusion diluted with nonlabeled glucose solution was administered following different periods of fasting. Hepatic glucose carbon recycling was estimated from 13C NMR spectra. The recycling parameters were derived from plasma beta-glucose C-1 splitting pattern, doublet/singlet values of plasma glucose C-1 in comparison to doublet/singlet values of known mixtures of [U-13C]glucose and unlabeled glucose as a function of 13C enrichment of glucose C-1. The fractional glucose C-1 enrichment of plasma glucose samples was analyzed by 1H NMR spectroscopy and confirmed by gas chromatography/mass spectroscopy. The values obtained for GSD-I patients coincided with the standard [U-13C]glucose dilution curve. These results indicate that the plasma glucose of GSD-I subjects comprises only a mixture of 99% 13C-enriched D-[U-13C]glucose and unlabeled glucose but lacks any recycled glucose. Significantly different glucose carbon recycling values were obtained for two GSD-III patients in comparison to GSD-I patients. Our results eliminate a mechanism for glucose production in GSD-I children involving gluconeogenesis. However, glucose release by amylo-1,6-glucosidase activity would result in endogenous glucose production of non-13C-labeled and nonrecycled glucose carbon, as was found in this study. In GSD-III patients gluconeogenesis is suggested as the major route for endogenous glucose synthesis. The contribution of the triose-phosphate pathway in these patients has been determined. The significant difference of the glucose C-1 splitting pattern in plasma GSD-III and control subjects, in comparison to GSD-I plasma, can be used as a parameter for estimating glucose recycling. This approach can be developed as a noninvasive diagnostic test for inborn enzymatic defects involving gluconeogenesis.

Carbon Isotopes↗
PubMed1989

Glucose recycling and production in glycogenosis type I and III: stable isotope technique study.

Glucose carbon recycling, endogenous glucose production, and glucose turnover rates were measured, by stable isotope methodology, in five patients with glycogen storage disease type I (GSD-I), two patients with glycogen storage disease type III (GSD-III), and three control children. A primed-constant infusion of D-[U-13C]glucose was administered nasogastrically to fasted subjects. The isotopic enrichments and 13C isotopomer distribution of plasma glucose were measured by chemical ionization gas chromatography mass spectroscopy. In response to increasing rates of glucose infusion, endogenous glucose production decreased, whereas the rate of glucose appearance or total glucose flux increased. Recycling of infused D-[U-13C]-glucose, calculated from changes in the isotopomer distribution of plasma [13C]glucose, was not detectable in GSD-I but reached 50% in GSD-III. In GSD-I the gluconeogenic pool was found to be highly labeled and recycled, whereas plasma glucose was diluted but not recycled. It is suggested that in GSD-I dilution of plasma glucose is due to release of glucose from branch points in glycogen. We propose that studies of the extent of glucose recycling and of isotopic enrichment of gluconeogenic precursors can be used as a noninvasive test for diagnosis of GSD-I and other defects in glucose production.

Blood Glucose↗
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↗
PubMed1988

Glucose recycling and production in children with glycogen storage disease type I, studied by gas chromatography/mass spectrometry and (U-13C)glucose.

Glucose recycling and production were determined in plasma of three children with glycogen storage disease type I (GSD-I) in comparison to normal children. A primed-constant infusion of (U-13C)glucose was introduced nasogastrically at different rates. Endogenous glucose production rates were found to be correlated with rates of glucose infusion. A range of glucose production of 3.5-1.8 mg kg-1 min-1 was found when glucose infusion rates increased from 0.13 to 6 mg kg-1 min-1. The isotopomer distribution of the infused (U-13C)glucose and the plasma glucose in GSD-I children, measured by chemical ionization gas chromatography/mass spectrometry, were identical, indicating absence of glucose recycling. However, a significant change in the isotopomer distribution of plasma glucose was observed in normal subjects. It is suggested that the origin of endogenous glucose production in GSD-I children, during (U-13C)glucose infusion, is from non-labelled sources. The absence of glucose recycling is indicative of a deficiency of glucose 6-phosphatase activity in the liver of GSD-I patients.

Alanine↗
PubMed1988

Familial carnitine deficiency: further evidence for autosomal recessive transmission with variable expression.

Carnitine deficiency occurring in families has been rarely reported and the genetic transmission has not yet been clearly elucidated. Five members of one family showing marked heterogeneity of carnitine deficiency states are presented. In three patients, there was no correlation between measurable carnitine levels in serum and muscle and the clinical findings. The parents, who are remote relatives from an isolated village in Kurdistan (Iraq), had low muscle carnitine levels; however, they were asymptomatic. One son, with systemic carnitine deficiency causing muscle weakness and recurrent episodes of severe hepatic encephalopathy, died at 3 years of age. His brother had mild proximal muscle weakness associated with low muscle carnitine levels. He was successfully treated with L-carnitine and prednisone. A daughter is asymptomatic, but with low serum and muscle levels of carnitine. The marked heterogeneity of carnitine deficiency states within one family, where both parents had low muscle carnitine levels, suggests an autosomal recessive inheritance with variable expression.

Carnitine↗
PubMed1988

Pyruvate carboxylase activity in chorionic villi: possibility of application to prenatal diagnosis.

Pyruvate carboxylase (PC) activity was assayed in 27 chorionic villi samples (CVS) obtained at 9-12 weeks of gestation. The kinetic properties of the CVS enzyme were similar to those of liver PC; more than 75% of PC activity was recovered in the mitochondrial fraction of CVS. Apparent Km for pyruvate, ATP, acetyl CoA and HCO3- in the presence of saturation concentrations of the other reactants, were 0.3, 0.44, 0.015 and 6.0 mmol/l, respectively. The optimum pH was 7.5-8.0. The activity of PC in CVS was 3.2 +/- 0.3 nmol/min/mg protein, which is severalfold higher than that of amniotic fluid fibroblasts.

Cell Fractionation↗