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Biomedical subjects

M S Patel

Publications and source records attributed to M S Patel.

At least 145 records · Page 8Linked to original sources
PubMed1986

Deficiency of the pyruvate dehydrogenase component in pyruvate dehydrogenase complex-deficient human fibroblasts. Immunological identification.

A previously reported deficiency of "total" pyruvate dehydrogenase complex activity is further characterized. Dihydrolipoyl transacetylase (E2) and lipoamide dehydrogenase (E3) activities in the patient's fibroblasts were normal. Pyruvate dehydrogenase activity (E1) was 33% of that in fibroblasts from an age-matched control. The amounts of each of the components of pyruvate dehydrogenase complex were analyzed using an immunoblot technique and specific antibodies. Levels of components E2 and E3 were the same in fibroblasts from the patient and control, confirming the activity measurements. However, the levels of E1 alpha and E1 beta were reduced markedly in fibroblasts from the patient. Thus, impairment in the pyruvate dehydrogenase complex activity was due to a reduction in the amount of the E1 component of the complex.

Acetyltransferases↗
PubMed1985

Modulation by dexamethasone of the pyruvate dehydrogenase-complex activity in 3T3-L1 adipocytes.

Chronic exposure of 3T3-L1 pre-adipocytes to dexamethasone plus 3-isobutyl-1-methylxanthine (IBMX) with or without insulin caused a significant increase in the specific activity of 'total' pyruvate dehydrogenase complex (PDC) and in the percentage of the 'active' form of the complex compared with cells exposed to a chronic insulin treatment or an acute treatment (2 days) with dexamethasone plus IBMX. In acute-drug-switch-over experiments, dexamethasone also caused an increase in the percentage of 'active' PDC in 3T3-L1 adipocytes. The results show that, in 3T3-L1 adipocytes, dexamethasone, even in the absence of insulin, increases the proportion of PDC in its 'active' form. The mechanism of the dexamethasone effect remains to be investigated.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Changes in the activity of 'active' pyruvate dehydrogenase complex in the newborn of normal and diabetic rats.

At birth, hepatic 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar. The 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p less than 0.05). The greatest increase in both 'active' and 'dichloroacetate-activated' pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats. Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of 'active' pyruvate dehydrogenase complex activity within 1 h (p less than 0.01). Similar treatment caused no significant increases in the newborn of severely diabetic rats. The transient increases in 'active' pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.

Animals↗
PubMed1985

Regulation of succinyl-CoA:3-oxoacid CoA-transferase in developing rat brain: responsiveness associated with prenatal but not postnatal hyperketonemia.

Activities of ketone body-metabolizing enzymes in rat brain rise 3- to 5-fold during the suckling period, then fall more than 50% after weaning. Our purpose was to determine the mechanism of the developmental changes in activity of 3-oxoacid CoA-transferase in rat brain and to study its regulation by dietary modification. Purified rat brain 3-oxoacid CoA-transferase was used to generate specific antibody. Immunotitrations of the enzyme from brains of 4-, 24-, and 90-day-old rats indicated that changes in 3-oxoacid CoA-transferase activity during development are due to changes in content of the enzyme protein. Pulse-labeling studies showed that changes in enzyme specific activity reflected changes in its relative rate of synthesis, which increased 2.5-fold between the nineteenth day of gestation and the third postnatal day, remained at this high level until the twelfth postnatal day, and declined thereafter, returning by Day 38 to the level observed in utero. The enzyme is apparently degraded very slowly during early postnatal life. Fetal hyperketonemia induced by feeding pregnant rats a high-fat diet was associated with an increase in the relative rate of synthesis of 3-oxoacid CoA-transferase in brains of 19-day-old fetuses and newborn rats and with an increase in the specific activity of the enzyme at birth. To examine the role of postnatal hyperketonemia in the development of the enzyme in brains of suckling rats, neonates received intragastric cannulas and were fed, for up to 13 days, a modified milk formula low in fat. Postnatal hyperketonemia was abolished but cerebral 3-oxoacid CoA-transferase specific activity on Days 10 and 17 was not significantly affected. Thus, the physiological hyperketonemia caused by the high fat content of rat milk is not required for the normal development of 3-oxoacid CoA-transferase in rat brain.

Animals↗
PubMed1985

Effect of glucose and insulin administration on hepatic adenylate energy charge and the cytosolic redox state in the neonates of normal and insulin-treated diabetic rats.

At birth and during the first 3 postnatal hours, the concentrations of hepatic ATP and the adenylate energy charge were significantly higher in neonates of insulin-treated diabetic rats compared to age-matched neonates of normal rats. However, a significant reduction in these parameters was observed after 3 postnatal hours in neonates of insulin-treated diabetic rats compared to normal rats. Administration of glucose to newborns of insulin-treated diabetic rats at birth did not prevent the lowering of hepatic ATP concentrations and the adenylate energy charge in 6-hour-old neonates. In contrast, the administration of glucose or insulin to the newborns of normal rats at birth caused a reduction in the concentration of hepatic ATP and the adenylate energy charge only at 1 h after birth. The postnatal increase in the hepatic cytosolic redox state (NAD+/NADH) in the neonates of insulin-treated diabetic rats was similar to that observed in the neonates of normal rats during the first 3 postnatal hours; however, a significant reduction in this parameter was observed only in the neonates of insulin-treated diabetic rats after the third postnatal hour. Administration of glucose to the neonates of insulin-treated diabetic rats did not prevent the decline in the cytosolic redox state in these neonates at the sixth postnatal hour.

Adenine Nucleotides↗
PubMed1984

Turnover of succinyl-CoA:3-oxoacid CoA-transferase in glioma and neuroblastoma cells. Specific influence of acetoacetate in neuroblastoma cells.

The specific activity of succinyl-CoA:3-oxo-acid CoA-transferase (3-oxoacid CoA-transferase, EC 2.8.3.5) increases significantly during growth in culture in both mouse neuroblastoma N2a and rat glioma C6 cells. To investigate the mechanism(s) responsible for this, antibody specific for rat brain 3-oxoacid CoA-transferase was raised in rabbits. Immunotitrations of 3-oxoacid CoA-transferase from neuroblastoma and glioma cells on days 3 and 7 of growth after subculture showed that the ratio of 3-oxoacid CoA-transferase activity to immunoprecipitable enzyme protein remained constant, indicating that differences in specific activity of the enzyme at these times in both cell types reflect differences in concentration of enzyme protein. In glioma cells, the relative rate of 3-oxoacid CoA-transferase synthesis was about 0.04-0.05% throughout 9 days in culture. In contrast, the relative rate of synthesis of 3-oxo-acid CoA-transferase in neuroblastoma cells was about 0.07-0.08% on days 3, 5 and 7 after subculture, but fell to 0.052% on day 9. The degradation rates of total cellular protein (t1/2 = 28 h) and 3-oxoacid CoA-transferase (t1/2 = 46-50 h) were similar in both cell lines. The rise in specific activity of the enzyme in both cell lines from days 3 to 7 without a significant increase in the relative rate of synthesis reflects a slow approach to steady-state conditions for the enzyme secondary to its slow degradation. Differences in 3-oxoacid CoA-transferase specific activity between the two cell lines are apparently due to a difference of about 60% in relative rates of enzyme synthesis. The presence of 0.5 mM-acetoacetate in the medium significantly increased the specific activity of 3-oxoacid CoA-transferase in neuroblastoma cells during the early exponential growth phase. This treatment increased the relative rate of synthesis of 3-oxoacid CoA-transferase by 23% (P less than 0.025) in these cells on day 3, suggesting that substrate-mediated induction of enzyme synthesis is a mechanism of regulation of 3-oxoacid CoA-transferase.

3-Hydroxybutyric Acid↗
PubMed1984

Evidence for the intrusion of polyoxyethylene into the hydrocarbon core of non-ionic surfactant micelles.

The intrinsic viscosities, [eta], of non-ionic surfactants of structure, CH3[CH2]m-1[OCH2OCH2]1.25mOH, were measured in water at 298 K. [eta] increased linearly with hydrocarbon chain length from m = 3 to m = 15, and between m = 17 and m = 31. There was a discontinuity between m = 15 and m = 17, which was attributed to intrusion of some polyoxyethylene into part of the hydrocarbon core for surfactants in which m greater than 15. This effect gave a micellar hydration which was lower than expected for the higher members of the series. Other factors relevant to the intrusion of polyoxyethylene into hydrocarbon are discussed.

Colloids↗
PubMed1984

A nuclear magnetic resonance (nmr) investigation of the micellar structure of a long-chain non-ionic surfactant.

Peak integrals, peak widths at half-height (delta nu 1/2), spin-lattice relaxation times (T1), and chemical shifts (delta) of the alkyl and oxyethylene protons of CH3(CH2)21[OCH2CH2]27OH (C22E27) were measured in D2O at various temperatures. The peak integrals, delta nu 1/2, and delta values of the alkyl protons showed a large dependence on temperature below 313K, while the values for the oxyethylene protons were unaffected by temperature. These observations were explained by considering an intrusion of some oxyethylene groups into the hydrocarbon core of the micelle.

Chemical Phenomena↗
PubMed1984

Central hypoventilation syndrome in pyruvate dehydrogenase complex deficiency.

The presentation and treatment of a central hypoventilation syndrome in a boy with pyruvate dehydrogenase complex (PDHC) deficiency are reported. Dephosphorylated PDHC was assayed in disrupted fibroblasts after pretreatment with dichloroacetate, a pyruvate dehydrogenase kinase inhibitor. Maximal specific activity of activated patient PDHC was 10% to 30% of control values. Patient PDHC activity was not increased by alterations in concentrations of pyruvate or cofactors (thiamine pyrophosphate [TPP], coenzyme A [CoA], oxidized form of nicotinamide adenine dinucleotide [NAD+]). Clinically, normalization of plasma lactate by a high-lipid diet did not prevent slowly progressive neurologic decline. The patient manifested intermittent ataxia, episodic profound weakness, moderate psychomotor retardation, ophthalmoplegia, and retinal pigment epithelial changes. A true central hypoventilation syndrome was documented on the basis of rigorous radiologic, electrophysiologic, and pulmonary function criteria. Theophylline, progesterone, and ritalin neither altered ventilatory response to CO2 nor permitted weaning from the ventilator. In contrast, peripheral chemoreceptor stimulants (intravenous doxapram; oral almitrine) effected an acute doubling of minute ventilation with appropriate decreases in PaCO2. However, a positive response to long-term therapy with almitrine could not be unequivocally shown. It was concluded that measurement of disrupted fibroblast PDHC following dichloroacetate activation constitutes an accurate assay for PDHC deficiency. PDHC deficiency must be considered in the differential diagnosis of the central hypoventilation syndrome; this appears to be the first report of such an association. Finally, a therapeutic trial of a peripheral chemoreceptor agonist is warranted in the management of central hypoventilation syndrome.

Almitrine↗
PubMed1983

Induction of the branched-chain 2-oxo acid dehydrogenase complex in 3T3-L1 adipocytes during differentiation.

The activities of 2-oxo acid dehydrogenase complexes were measured during hormone-mediated differentiation of 3T3-L1 preadipocytes into adipocytes. Specific activity of leucine-activated branched-chain 2-oxo acid dehydrogenase complex increased approx. 10-fold in 3T3-L1 adipocytes compared with 3T3-L1 preadipocytes. In contrast, specific activity of the 2-oxoglutarate dehydrogenase complex increased by only 3-fold in 3T3-L1 adipocytes. The three catalytic component enzymes of the branched-chain 2-oxo acid dehydrogenase complex and the pyruvate dehydrogenase complex showed concomitant increases in their specific activities. A close similarity in kinetics of induction of the branched-chain 2-oxo acid dehydrogenase complex and the pyruvate dehydrogenase complex in 3T3-L1 adipocytes suggests that a common mechanism may be involved in hormone-dependent increases in the activities of the catalytic components of these two complexes in 3T3-L1 adipocytes during differentiation.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1983

Induction of pyruvate dehydrogenase in 3T3-L1 cells during differentiation.

The activity of the pyruvate dehydrogenase complex and the content and turnover of the pyruvate dehydrogenase component were measured during the differentiation of 3T3-L1 preadipocytes into 3T3-L1 adipocytes. The specific activity of "total" pyruvate dehydrogenase complex increased approximately 7-fold in 3T3-L1 adipocytes differentiated with a treatment of insulin plus dexamethasone plus 1-methyl-3-isobutyl xanthine. The ratio of "active" pyruvate dehydrogenase complex to total pyruvate dehydrogenase complex remained unaltered in both 3T3-L1 preadipocytes and adipocytes. A specific goat antibody to bovine kidney pyruvate dehydrogenase quantitatively precipitated both alpha and beta subunits of pyruvate dehydrogenase from solubilized 3T3-L1 adipocytes. Using immunoprecipitation and gel electrophoresis techniques, we demonstrated an approximate 6-fold increase in pyruvate dehydrogenase content in 3T3-L1 adipocytes as compared to 3T3-L1 preadipocytes. Pulse labeling experiments revealed an approximately 5-fold increase in the rates of synthesis of both alpha and beta subunits of pyruvate dehydrogenase in 3T3-L1 adipocytes after 6 days of the hormonal treatment compared to those observed in 3T3-L1 preadipocytes. In contrast, the half-lives of alpha and beta subunits of pyruvate dehydrogenase were not significantly altered in 3T3-L1 preadipocytes (41 h) and adipocytes (49 h). The 6-8-fold increment in the specific activity of the pyruvate dehydrogenase complex in 3T3-L1 adipocytes therefore results from increased rates of synthesis of alpha and beta subunits of pyruvate dehydrogenase.

Adipose Tissue↗
PubMed1983

Insulin receptors in developing rat liver: acquisition of down regulation in the immediate postnatal period.

Alterations in the high and low affinity insulin receptor concentrations in developing rat liver were investigated. The number of high affinity receptors in partially purified plasma membranes from fetal rats increased from Days 19 through 22 of gestation, with no further increase in binding during the postnatal period. Fetuses of diabetic rats had approximately three times as many high affinity insulin receptors as age-matched fetuses of normal rats; however, by 1 day after birth the receptor number decreased to the normal level. Neither the number of low affinity receptors nor the affinity of insulin binding to high or low affinity receptors changed during development or between offspring of normal and diabetic rats. These changes in the number of high affinity hepatic insulin receptors from prenatal animals did not correlate with the concentration of plasma insulin. When suckling pups were rendered diabetic the changes in the number of high affinity insulin receptors correlated with alterations in plasma insulin concentrations. The number of high affinity sites/microgram DNA in hepatocytes from Day 18 fetal rats was not altered when cells were cultured for 48 h in medium containing 0, 250, or 5000 microU/ml of added insulin. When cultured hepatocytes derived from 1-day-old and adult rats were maintained in medium with added insulin concentrations of 250 or 5000 microU/ml the number of high affinity receptors/microgram DNA decreased as compared to the number of high affinity receptors in hepatocytes cultured in medium with no added insulin. This decrease in receptor number was accompanied by an increase in the affinity of insulin binding to its high affinity receptors. The data show that (i) only the high affinity insulin receptor number increases in rat liver during the prenatal period, (ii) fetuses of diabetic rats show a greater increase in high affinity receptors than do fetuses of normal animals, and (iii) the phenomenon of down regulation for high affinity insulin receptors is not observed in fetal rat liver, but is acquired in the immediate postnatal period.

Animals↗
PubMed1983

Prevention and cure? Or: is an ounce of prevention worth a pound of cure?

A common problem of everyday life is that of deciding how much to spend to avoid something unpleasant happening, and then, if the worst comes to the worst, of deciding how much to spend to remedy the situation. This paper provides a framework for the analysis of such problems, focussing specifically on the appropriate allocation of expenditure on (preventative and curative) health care. A two-state (health and sickness) infinite horizon model is adopted, with movement between the states a first-order Markov process with probabilities which depend upon preventative and curative expenditure. The model is solved, and some counter-intuitive comparative static propositions obtained.

Attitude to Health↗