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A Gutman

Publications and source records attributed to A Gutman.

At least 73 records · Page 4Linked to original sources
PubMed1987

Identification of a third region of cell-specific alternative splicing in human fibronectin mRNA.

We describe here a third region of variability in human fibronectin (FN) due to alternative RNA splicing. Two other positions of alternative splicing have been reported previously (ED and IIICS). The third region involves a 273-nucleotide exon encoding exactly one 91-amino acid repeat of type III homology, located between the DNA- and the cell-binding domains of FN, which is either included in or excluded from FN mRNA. The two mRNA variants arising by an exon-skipping mechanism are present in cells known to synthesize the cellular form of FN. However, liver cells, which are the source of plasma FN, produce only messengers without the extra type III sequence. Therefore, the region described here resembles, both structurally and functionally, the previously described ED (for extra domain) region, located toward the C terminus of the molecule, between the cell- and heparin- (hep 2) binding domains. We conclude that both the extra type III repeat (named EDII) and ED represent sequences restricted to cellular FN. Combination of all the possible patterns of splicing in the three regions described to date may generate up to 20 distinct FN polypeptides from a single gene.

Amino Acid Sequence↗
PubMed1987

Muscle carnitine deficiency presenting as familial fatal cardiomyopathy.

Three siblings presented with fatal cardiomyopathy confirmed by electron microscopy, and normal serum but low muscle carnitine concentrations. A fourth had similar signs but remained asymptomatic. He was treated with carnitine orally which increased the concentration in muscle, though it remained below normal. Electron microscopic features were unchanged.

Cardiomyopathies↗
PubMed1986

Human fibronectin is synthesized as a pre-propolypeptide.

Fibronectins (FNs) are extracellular glycoproteins consisting of dimers or multimers of similar but not identical subunits. The subunit differences result from variations in internal primary sequence due to alternative splicing in at least 2 regions of the pre-mRNA. The complete amino acid sequence of mature human cellular FN has been reported recently from cDNA cloning and sequencing. The same approach has now enabled us to deduce, for the first time, that FN has a 26 amino acid signal peptide and that it undergoes proteolytic processing at its N-terminus to eliminate a 5 amino acid pro-sequence (Ser-Lys-Ser-Lys-Arg). The signal sequence matches the consensus format, while this pro-sequence is a distinctive, very hydrophilic and basic peptide.

Amino Acid Sequence↗
PubMed1986

Plasma calcium and phosphate levels in an adult noninsulin-dependent diabetic population.

Duplicate or triplicate measurements of fasting plasma glucose, calcium (Ca), phosphate (Pi), and glycosylated hemoglobins were performed on a group of non-insulin dependent diabetic patients and controls at 3-6 month intervals. In the diabetic group (48 males and 44 females), 18 were on diet only, 21 on diet and oral hypoglycemic treatment, and 51 on diet and insulin. These were a total of 217 measurements for each parameter. Results were compared to 416 measurements obtained from sex and age-matched controls. Plasma Ca levels were higher in the diabetic group (2.48 +/- 0.004 vs 2.38 +/- 0.006 mmol/liter) P less than 0.001; plasma Pi levels were similar to those of controls. The difference in plasma Ca was not influenced by age, sex, or mode of treatment. No correlation was found in the three treatment groups between plasma Ca and duration of diabetes nor with patients' weights. The results are consistent with the view that an alteration in calcium homeostasis accompanies the diabetic state.

Adult↗
PubMed1986

Characterization of stages in development of obesity-diabetes syndrome in sand rat (Psammomys obesus).

Sand rats (Psammomys obesus) maintained on a diet providing a free choice between laboratory chow and salt bush (Atriplex halimus) were classified into four groups differing in extent of the diabetic syndrome: A, normoglycemic-normoinsulinemic; B, normoglycemic-hyperinsulinemic; C, hyperglycemic-hyperinsulinemic; or D, hyperglycemic with reduced insulin levels. The metabolic pattern of these groups was characterized by measuring the uptake of fatty acid-labeled, very-low-density lipoprotein-borne triglycerides (VLDL-TG) and [3H]-2-deoxyglucose (2-DOG) into muscle and adipose tissues; incorporation of [14C]alanine into glycogen in vivo; gluconeogenesis from lactate, pyruvate, and alanine in hepatocytes; the effect of insulin on glycogen synthesis from glucose; the oxidation of albumin-bound [1-14C]palmitate and [14C]glucose in strips of soleus muscle; activities of muscle and adipose tissue lipoprotein lipase; and activities of rate-limiting enzymes of glycolysis, gluconeogenesis, and fatty acid synthesis in liver. In group A, uptake of VLDL-TG and activity of lipoprotein lipase were higher in adipose tissue and lower in muscle than in albino rats. In the liver, gluconeogenesis and the activity of phosphoenolpyruvate carboxykinase, as well as lipid synthesis and the activity of NADP-malate dehydrogenase, were higher than in albino rats, whereas activity of pyruvate kinase was lower. In group B, uptake of VLDL-TG by adipose tissue and muscle and lipoprotein lipase activity were similar or higher than in group A. Uptake of 2-DOG by muscle and adipose tissue and activity of liver phosphoenolpyruvate carboxykinase were lower than in group A. In groups C and D, uptake of VLDL-TG and lipoprotein lipase activity in muscle were further increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1985

Fetal diabetes in rats and its effect on placental glycogen.

The role of fetal insulin in placental glycogen accumulation, which occurs despite insulin deficiency in maternal diabetes, was studied in rats. Streptozotocin was injected into fetuses of non-diabetic and streptozotocin-diabetic mothers on days 19.5 and 20.5 of gestation, causing fetal hypoinsulinaemia and pancreatic insulin depletion. Placental glycogen content of either 1.6 mg/g in non-diabetic rats or 6.5 mg/g in diabetic rats was not affected by fetal streptozotocin treatment. Glycogen distribution was also measured in the placenta to assess the effect of fetal hypoinsulinaemia on glycogen content in its fetal segment. The glycogen concentration ratio between the fetal and maternal segments in diabetic rats was approximately 0.3 and increased to approximately 0.5 in diabetic rats, without being affected by fetal hypoinsulinaemia. There was no significant effect of fetal hypoinsulinaemia on the activities of placental glycogen synthase or glycogen phosphorylase, both in non-diabetic and diabetic rats. Fetal hypoinsulinaemia was associated, however, with a marked decrease in fetal liver glycogen together with a decrease in fetal liver weight, which was more pronounced than the decrease in fetal body weight. Administration of insulin to the streptozotocin-treated fetuses restored the impaired glycogen synthesis (measured by incorporation of U-[14C]-glucose and 3H2O in the fetal liver) without affecting glycogen synthesis in the placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Proteolytic enzymes in human fetal membranes and amniotic fluid. A comparison of normal and premature ruptured membranes.

The amniotic and chorionic membranes obtained at term and term amniotic fluid contain a soluble protease activity which cleaves [14C]-labeled globin at acid pH. In contrast, a salt extract of the pellet fraction obtained from the fetal membranes displays only negligible protease activities at the pH range of 4-8. Specific activities of the proteases in the soluble and salt-extractable fractions of fetal membranes which were intact before onset of labor were not significantly different from the respective activities in cases of premature rupture of fetal membranes (PROM). However, the protease activity of the amniotic fluid was found to increase with advancing gestational age and to reach maximal activity at term. A heat-sensitive and nondializable protease inhibitory activity was found in term amniotic fluid. This inhibitory activity acted on the cytosolic protease of amniotic membranes from control and PROM cases, but not on the soluble protease of chorionic membranes, and had a similar potency in fluids from PROM cases or fluids collected at term. These results do not support a role for fetal membrane proteases, amniotic fluid proteases, or amniotic fluid protease inhibitory activities in the etiology of PROM. However, the observed changes in amniotic fluid protease activity with fetal age suggest a physiological role for the enzyme in normal fetal development.

Amniotic Fluid↗
PubMed1985

Incorporation of [14C]glucose into alpha-1,4 bonds of glycogen by leukocytes and fibroblasts of patients with type III glycogen storage disease.

In two patients assay of alpha-1,6-amyloglucosidase activity by incorporation of [14C]glucose into glycogen revealed normal activity in leukocytes, erythrocytes, and fibroblasts, whereas no activity was detected in liver and muscle. No activity in any tissue was found when enzyme activity was assayed by following the release of glucose from a phosphorylase limit dextrin. Labeling of glycogen by incubation with crude tissue homogenates according to the protocol used for the [14C]glucose method and subsequent degradation of the outer portion of the polysaccharide molecule with beta-amylase showed that with tissues from normal controls more than 90% of the label of the glycogen was retained in the limit dextrin. When fibroblasts or leukocytes of the patients served as enzyme source up to 80% of the label was released after incubation with beta-amylase or phosphorylase a. Addition of Tris to the assay inhibited enzyme activity in fibroblast homogenates of the patients and of controls to the same extent and had no effect on the distribution of the label between supernatant and limit dextrin after beta-amylolysis of the labeled glycogen. A pH curve performed with fibroblast preparations from the patients and a normal control did not reveal differences in the effect of changes in pH on [14C]glucose incorporation. We propose that incorporation of [14C]glucose into glycogen by the enzyme present in the patients' cells was into alpha-1,4 linkages in glycogen.

Cells, Cultured↗
PubMed1985

Effect of furosemide on urinary excretion of 4-hydroxy-3-methoxymandelic acid (VMA).

Excretion of VMA was measured in 10 healthy volunteers before and after intake of 40 mg furosemide and in 3 patients with congestive heart failure who were intermittently treated with 80 mg furosemide. In healthy volunteers furosemide caused an increase in VMA excretion from 5.0 +/- 0.5 to 7.8 +/- 0.9 mg/24 h and from 2.0 +/- 0.2 to 2.9 +/- 0.3 mg/g creatinine (mean +/- SE). Excretion of catecholamines was slightly increased in some subjects, but did not reach the upper limit of normal in any case. Furosemide induced an acute increase in urinary VMA that could have derived from inhibition of renal tubular reabsorption. Administration of furosemide might result, on occasion, in a false positive test for pheochromocytoma.

Catecholamines↗
PubMed1984

Case report: spurious hypokalemia in myeloproliferative disorders.

Four patients with myeloproliferative disorders and hypokalemia due to an artifactual in vitro phenomenon are described. Hypokalemia was due to an increased potassium uptake by the abnormal white blood cells. Spurious hypokalemia may explain in part the electrolyte disturbances found in many leukemic patients.

Adult↗
PubMed1984

Effect of heparin on serum and tissue lipases in the developing rat.

The frequent inclusion of heparin in fluids used for total parenteral nutrition in infants, prompted an investigation of the ability of heparin to release lipoprotein lipase (LPL) and hepatic lipase (HL) from the endothelial surface into the circulation, and of the effect of heparin on tissue stores of lipase in the postnatal period. In rat pups, plasma postheparin lipolytic activity (PHLA) released by IP administration of heparin (0.5 unit/g body wt) was 15% of adult values at birth and increased rapidly to reach 60% on day 10. Repeated doses of heparin (in adult rats, given 0.1 unit/g IV) at 1 and 4 h after the initial dose did not affect the maximal response to heparin. In all age groups 80% of PHLA was inhibited by 0.5 M NaCl, suggesting a mostly nonhepatic origin for the released enzyme. Heart, lung, and liver lipase activities of rat pups were not significantly different from controls not given heparin. The pattern of change in tissue enzyme content was similar for heart and lung, but different from hepatic lipase. LPL activity in the former increased from 10 and 30% to 60 and 100% of adult values between birth and 10 days while in the latter enzyme activity exceeded adult levels at birth and decreased to 50% of adult values during the latter half of the suckling period (days 10-21). Our results demonstrate that heparin does not cause depletion of tissue lipases in the postnatal period. The parallel increases in LPL content of peripheral tissues and PHLA suggest that in all age groups heparin-induced release of LPL into the circulation is proportional to tissue lipolytic activity.

Age Factors↗
PubMed1984

Recurrent Reye-like syndrome: possible association with Krebs cycle abnormality.

During a 7-year period, a 15-year-old boy experienced recurrent attacks that clinically and pathologically resembled Reye's syndrome. The attacks were precipitated by prolonged exercise, fasting or infections. An extensive investigation failed to identify a toxic cause or specific metabolic disorder. Low 14CO2 production after in vitro incubation of the patient's liver with 14C-labeled palmitate, citrate and glutamine suggested a defect in the Krebs cycle or the oxidative phosphorylation pathway. This error may be responsible for the recurrent Reye-like syndrome attacks.

Adolescent↗
PubMed1983

Mechanism of placental glycogen deposition in diabetes in the rat.

The metabolic basis for glycogen accumulation in the placenta of rats with diabetes induced by streptozotocin on day 12 of pregnancy was studied on days 15 and 20. On day 15 glycogen content of the placenta was 1.5-fold higher in the diabetic than in the control rats and this difference increased to greater than fivefold on day 20 of gestation whether calculated per g tissue or per total placenta. Accumulation of glycogen was associated with increased specific activities of both glycogen synthase and phosphorylase. The activities of these enzymes regulating synthase and phosphorylase activities and the activity of acid alpha-glucosidase were not significantly affected by diabetes. Glucose-6-phosphate concentration of the placenta was 67 and 23 nmol/g in diabetic and control rats, respectively. Incubation of placental homogenates with glucose increased the rate of inactivation of phosphorylase and activation of glycogen synthase. These results indicate that the enhanced glucogenesis in diabetes is not due to changes in the activities of these enzymes, as measured in vitro under standard conditions. The factors promoting glycogen accumulation in vivo are related to the abundance of glucose and glucose-6-phosphate as substrates for glycogen synthesis, which may also cause an increase in the activity ratio glycogen synthase a/phosphorylase a. In addition, the high intracellular glucose-6-phosphate concentration is likely to enable glycogen synthase b to contribute to glycogen synthesis.

Animals↗
PubMed1983

Correction by bromocriptine of hypothalamic dysfunction and post-prandial hypoglycaemic symptoms in a 31-year-old woman.

A 31-year old female presented with recurrent episodes of post-prandial hypoglycaemic symptoms. Basal serum levels of ACTH, cortisol, GH, insulin and glucagon were normal. An adrenaline test demonstrated a normal peripheral response. An exercise test failed to produce ACTH, cortisol or FFA responses. Insulin (0.1 u/kg)-induced-hypoglycaemia failed to elevate serum ACTH, cortisol or GH. Metyrapone and ACTH tests were normal, demonstrating adequate hypophyseal and adrenal function. These findings suggested that the patient suffered from hypothalamic dysfunction. Bromocriptine (Parlodel, 7.5 mg/d for 5 weeks) resulted in an improved general condition, accompanied by a decrease in sugar consumption. Following treatment, FFA, ACTH and cortisol responses to exercise test were normal, as were ACTH, cortisol and GH responses to insulin-induced hypoglycaemia. It is concluded that bromocriptine may be useful in the treatment of post-prandial hypoglycaemic symptoms associated with hypothalamic dysfunction.

Adult↗
PubMed1983

Lipogenesis in the sand rat (Psammomys obesus).

Synthesis of fatty acids was measured in the liver and in epididymal adipose tissue of sand rats and albino rats. In chow-fed sand rats the rate of hepatic lipogenesis, as measured by the incorporation of 3H2O into fatty acids, was four- to sevenfold higher than in albino rats and in sand rats on a low-calorie saltbush diet. The contribution of [14C]glucose to lipogenesis in sand rat liver was lower than in albino rats. In fed sand rats lipogenesis incorporating 3H2O was stimulated by casein but not by glucose. In adipose tissue, lipogenesis measured 1 h after administration of 3H2O was much lower in sand rats than in albino rats. In vitro incorporation of [14C]glucose or acetate into adipose tissue fatty acids was negligible. In adipose tissue, uptake of very-low-density lipoproteins (VLDL) and lipoprotein lipase activity were sevenfold higher than in albino rats. Activities of NADP-malate dehydrogenase, acetyl CoA carboxylase, and fatty acid synthetase were considerably higher in the liver of chow-fed sand rats than in albino rats. It was concluded that obesity in sand rats originates from hepatic lipogenesis without a significant contribution of local fatty acid synthesis in adipose tissue.

Acetates↗
PubMed1983

Glycogen metabolism of normal human myometrium and leiomyoma--possible hormonal control.

Glycogen concentration and the activities of enzymes of glycogen metabolism in myometrium of pre- and postmenopausal and pregnant women and in myomas were determined. Glycogen concentration in muscle from nonpregnant women was about 3 mg/g and rose to 13 mg/g in tissues obtained during cesarean sections. The activities of glycogen synthase phosphatase and phosphorylase were also markedly higher in myometrium of pregnant women. In 5 out of 8 myomas glycogen concentration and enzyme activities were similar to those found at the end of pregnancy. These observations suggest that glycogen metabolism of the myometrium is under the control of hormones and that the local hormonal environment of myomas may be different from that of the surrounding tissue.

Adult↗