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Biomedical subjects

C Mohan

Publications and source records attributed to C Mohan.

At least 73 records · Page 4Linked to original sources

The value and limitation of iloprost infusion in decreasing skeletal muscle necrosis.

Iloprost has been shown to minimize skeletal muscle necrosis when administered before the onset of ischemia in animal experiments, possibly by preventing neutrophil activation. Since patients with acute limb ischemia are seen after the process has begun, we investigated whether iloprost can be protective when given only during reperfusion. After anesthesia, 18 adult mongrel dogs underwent a standard isolated gracilis muscle preparation. In six control animals (group I) the gracilis muscle was subjected to 6 hours of ischemia followed by 48 hours of reperfusion. Group II animals (n = 6) received intravenous infusion of iloprost at a dose of 0.45 microgram/kg/hr beginning 1 hour before the onset of muscle ischemia and throughout the experiment (6 hours of ischemia and 1 hour of reperfusion). In addition to the continuous infusion, they received 0.45 microgram/kg intravenous boluses of iloprost 10 minutes before the induction of ischemia and 10 minutes before reperfusion. Group III animals (n = 6) had a similar ischemic interval, but were given a bolus of iloprost of 0.45 microgram/kg at end ischemia followed by continuous infusion of 0.45 microgram/kg/hr for 48 hours during reperfusion. Muscle biopsies were obtained at baseline and after 1 hour of reperfusion in all groups. Additional biopsies were obtained at 48 hours of reperfusion in groups I and III. Myeloperoxidase activity, a marker of neutrophil activation, was measured in all muscle biopsies. At the end of reperfusion, the gracilis muscle was harvested in all animals and weighed. Muscle necrosis was estimated by serial transection, nitroblue tetrazolium histochemical staining followed by computerized planimetry.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

HLA in Singapore Chinese with rheumatoid arthritis.

The HLA-A, B, C, DR and DQ antigens were determined in 50 Singapore Chinese patients with rheumatoid arthritis (RA). There was a significant increase in the prevalence of HLA-Bw46, DRw53 and DQ3 in patients with RA. The linkage disequilibrium between Bw46 and DRw53 explains this association. This major histocompatibility complex association differs from the HLA-DR4 link in Caucasian populations and suggests that RA is an immunogenetically heterogeneous disease.

Adult↗

Amphibolic role of the Krebs cycle in the insulin-stimulated protein synthesis.

It has been a generally held view that insulin does not significantly affect the incorporation of amino acids into liver protein. This interpretation was based on data obtained from studies using the branched chain amino acids, which are poorly metabolized by the hepatic tissue. The effect of insulin on 14CO2 formation and protein incorporation of several 1-14C-labeled or U-14C-labeled amino acids was studied in isolated rat hepatocytes and diaphragm pieces. It was shown that insulin enhanced 14CO2 formation and protein incorporation primarily of those carbons of amino acids which are metabolized through the mitochondrial Krebs cycle. Using aminooxyacetic acid (0.5 mM), a potent inhibitor of the transamination reaction, it was shown that there exists an "insulin-sensitive" pool of glutamate which is preferentially utilized for protein synthesis in the presence of insulin. The insulin effect on protein incorporation of 14C-labeled glutamate generated in the Krebs cycle was abolished in the presence of aminooxyacetic acid. We interpret these results to signify that mitochondrial transamination of alpha-ketoglutarate to glutamate is essential for insulin stimulation of 14C incorporation into hepatocyte protein.

Alanine↗

Differential effects of insulin, epinephrine, and glucagon on rat hepatocyte mitochondrial activity.

Oxidation of [2,3-14C]succinate carbons in the mitochondrial Krebs cycle was used as a probe to investigate the effects of insulin, epinephrine, glucagon, and 2,4-dinitrophenol (2,4-DNP) on isolated rat hepatocytes. Epinephrine, glucagon, and 2,4-DNP had a far greater stimulatory effect on 14CO2 formation from [2,3-14C]succinate than insulin. Unlike insulin, epinephrine and glucagon had no significant effect on the anabolic utilization of succinate carbons for protein synthesis. Our results suggest that although epinephrine, glucagon, and 2,4-DNP enhance the movement of tracer carbons through the Krebs cycle, only insulin is capable of enhancing amphibolite utilization for protein synthesis.

2,4-Dinitrophenol↗

Ammonia inhibits insulin stimulation of the Krebs cycle: further insight into mechanism of hepatic coma.

Oxidation of [2,3-14C]succinate in the intramitochondrial Krebs cycle was used as a probe to investigate the effect of ammonia on protein incorporation and Krebs cycle oxidation of succinate carbons in isolated rat hepatocytes. At low concentrations of ammonium chloride (0.1 to 0.5 mM) a slight increase in 14CO2 formation from [2,3-14C]succinate was observed, however, the stimulatory effect of insulin was significantly reduced. Insulin failed to cause any stimulation of succinate carbons incorporation into hepatocyte protein in the presence of ammonium chloride. Addition of ammonium chloride also depressed the movement of tracer carbons into the gluconeogenesis pathway. The activity of the amphibolic amino acid pool was significantly enhanced by ammonia. The data presented in this paper lend strong support to the Krebs-cycle depletion theory of hepatic coma. They also suggest that reduced mitochondrial Krebs cycle activity caused by increased amphibolic depletion of substrates results in loss of insulin sensitivity in ammonia toxicity.

Ammonium Chloride↗

Extracellular phosphate requirement for insulin action on isolated rat hepatocytes.

Isolated rat hepatocytes were prepared in KHB buffer, pH 7.4; were centrifuged and washed twice in KHB buffer containing various amounts of phosphate and calcium; and were incubated at 30 degrees in the presence of tracer [2,3-14C]succinate and a 0.5 mM concentration of each of the 20 natural amino acids. Hepatocytes washed and incubated in KHB buffer containing less than 0.1 mM phosphate failed to show any insulin stimulation of [2,3-14C]succinate oxidation or protein incorporation of tracer carbons. The absence or presence of extracellular phosphate did not alter the specific activity of 32P-adenine nucleotides; they remained the same in the presence or absence of insulin. The maximal insulin stimulatory effect on succinate oxidation and tracer incorporation into protein was observed in the presence of 1.18 mM phosphate and 1.9 mM calcium ion. The lack of external phosphate did not prevent the stimulation of succinate oxidation by either glucagon on epinephrine, whereas removal of calcium from the medium abolished their hormonal effects. The lack of medium calcium also prevented the insulin stimulation of succinate oxidation and protein synthesis. Our data indicate that a diminished insulin responsiveness in hypophosphatemic patients may be due to the insensitivity of mitochondria to insulin in the hypophosphatemic state.

Animals↗

A comparison of CO2 laser-assisted venous anastomoses and conventional suture techniques: patency, aneurysm formation, and histologic differences.

The expected patency and the potential complications of CO2 laser-welded end-to-end venous anastomoses have not been well established despite increasing clinical interest in the subject. To further study this relatively new technique we used the internal jugular veins (1.0 to 1.4 mm diameter) of 15 New Zealand White rabbits weighing 2.5 to 3.5 kg. On one randomly selected side, a laser-welded end-to-end anastomosis was performed in all animals by placing three equidistant stay sutures followed by welding the vein edges with a CO2 laser (spot size of 0.27 mm, power of 100 mW, and power density of 175 W/cm2). On the contralateral side, the vein was anastomosed with interrupted 10-0 nylon sutures in 10 animals, and in the remaining five animals a continuous 10-0 nylon suture technique was used. All anastomoses were surgically assessed at 30 days after operation. A significantly lower 30-day patency rate (p less than 0.05, Fisher's Exact Test) was found in anastomoses constructed by use of the continuous technique (20%) compared with either interrupted (90%) or the laser-assisted technique (87%). No significant difference was observed in 30-day patency between laser-assisted and conventional interrupted anastomoses. Anastomoses performed with the continuous and the laser-assisted technique required 12.5 +/- 1.3 and 12.9 +/- 3.0 minutes, respectively, whereas those constructed with interrupted technique required 19.1 +/- 4.5 minutes (p less than 0.05, Student-Neuman-Keuls' Test). No evidence of false or true aneurysm was noted in any of the animals. Histologic evaluation of laser-assisted anastomoses demonstrated early full-thickness coagulation necrosis of the wall with reendothelialization by 7 days and complete healing by 30 days after the procedure. Conventional anastomoses showed reendothelialization and minimal necrosis near the sutures at 7 days, but healing was complete by 30 days after the procedure. The patency rate of vein anastomoses performed with the CO2 laser is excellent and superior to the one obtained with continuous sutures, and except for less operating time, the former technique does not appear to offer any significant advantage over the conventional interrupted suture technique for small vein anastomosis in this animal model up to 1 month of follow-up.

Anastomosis, Surgical↗

Extraskeletal osteogenic sarcoma--a case report.

A rare case of extraskeletal osteogenic sarcoma of the right groin in a 50 year old Chinese lady is being presented. A wide excision of the tumour was done. The differential diagnosis are discussed. This is an extremely rare tumour and is just as malignant and aggressive, if not more so than its counterpart in the bone.

Diagnosis, Differential↗

Lack of insulin stimulation on Percoll-prepared or high-speed-centrifuged rat liver hepatocytes.

Rat liver hepatocytes isolated from a 30-31% percoll density gradient at 10,000g are refractory toward insulin stimulation of 14CO2 formation and 14C-incorporation into protein from [2,3-14C]succinate. Basal hepatocyte oxidation of succinate was not impaired by the presence of 5% percoll in the incubation medium nor was it impaired when percoll-free hepatocytes were used that had been isolated after centrifugation at 9000g; however, in both instances the stimulatory effect of insulin was lost. Hepatocyte damage may have occurred in these processes. This is in contrast to previous work which shows that insulin (10 mU/ml) will stimulate [2,3-14C]succinate oxidation and [2,3-14C]succinate carbon incorporation into protein in non-percoll-treated hepatocytes (isolated by centrifugation at 10g) by about 29%. We conclude that the latter procedure although more time consuming is the more gentle method of choice and leaves the hepatocyte in a form more closely related to an in vivo state than does treatment with a percoll density gradient at 10,000g.

Animals↗

Cholecysto-duodeno-colic fistula--a case report.

A rare case of cholecysto-duodenal-colic fistula presenting with non-faeculent vomiting, diarrhoea and loss of weight and appetite is reported. This fistula was demonstrated both by barium and endoscopic studies. She was treated with a simple closure of the fistulous tract and a cholecystectomy with good results. The surgical management of this condition is simple and rewarding.

Aged↗

The polysome as a terminal for the creatine phosphate energy shuttle.

The role of the creatine phosphate shuttle in the energetics of muscle protein synthesis in isolated polysomes, from rat hindlimb muscle, was studied. Triton X-100-treated polysomes, following their centrifugation through a 1 M sucrose gradient, contained 38 mU/mg RNA of bound creatine kinase. In the presence of pH 5 enzyme (obtained from rat liver), 0.5 mM ATP, and 1 microM GTP, amino acid (leucine) incorporation by polysomes in the presence of 8 mM creatine phosphate was twice that in the presence of an exogenous ATP regenerating system of 10 mM phospho(enol)pyruvate and 10 U/ml pyruvate kinase. Since added creatine kinase had no effect on incorporation supported by creatine phosphate it is clear that endogenous creatine kinase allows sufficient regeneration of ATP. These data also suggest that nucleoside diphosphokinase must have been associated with the polysome for phosphate was transferred to GTP from [33P]creatine phosphate, and the specific activities of ATP and GTP increased at equal rates, reaching the specific activity of creatine phosphate at 8 min. We conclude that skeletal muscle polysomes have bound creatine kinase activity and they act as terminals for the creatine phosphate energy shuttle. Creatine phosphate regenerates GTP, probably through an intermediate reaction catalyzed by nucleoside diphosphokinase. This provided an added support for the hypothesis of compartmentation of enzymes and substrates and that the transport form of energy between the mitochondria and energy utilizing sites in muscle is creatine phosphate rather than ATP, which extends the general role of the creatine phosphate energy shuttle.

Adenosine Triphosphate↗

Evaluation of specific immunoglobulin E by enzyme-linked immunosorbent assay in hydatid disease.

The diagnostic significance of elevated hydatid-specific immunoglobulin E (IgE) as measured by enzyme-linked immunosorbent assay (ELISA) was evaluated against hydatid-specific IgG ELISA and Casoni's intradermal test in surgically proven cases of hydatidosis. A specific IgE ELISA did not correlate with IgG ELISA or Casoni's intradermal test, although its recorded sensitivity was 87%. The specific IgE ELISA was at the same time false-positive in 57.14% of the cases because of its cross-reactions with cases of ascariasis and taeniasis, unlike Casoni's intradermal test and specific IgG ELISA. It is suggested that, in a helminth-infested population, the determination of specific IgE levels is not better than Casoni's intradermal or specific IgG ELISA tests.

Antibodies, Helminth↗

Effect of insulin on the metabolic distribution of carbons 1, 2, and 3 of pyruvate.

It has long been known that the carbons of pyruvate are converted to CO2 at different points in the metabolic process. This report deals with the observation that insulin affects the oxidation of carbons 2 and 3 primarily and has little effect on the oxidation of the carboxyl carbon. Oxidation of different carbons of pyruvate and their incorporation into various metabolic components was studied in isolated rat hepatocytes. Insulin stimulated the 14CO2 production from [2-14C]- and [3-14C]pyruvate and from [U-14C]alanine. However, it had little or no effect on the activity of the pyruvate dehydrogenase complex as measured by the evolution of 14CO2 from [1-14C]pyruvate or [1-14C] alanine. Insulin also stimulated the incorporation of carbons 2 and 3 of pyruvate into protein but had no effect on the incorporation of carbon 1. Incorporation of [1-14C]- and [U-14C]alanine into protein was differentially enhanced by insulin in a manner similar to that of the pyruvate carbons. The fact that insulin stimulates the incorporation of [1-14C]alanine into protein but not [1-14C]pyruvate suggests the possibility of a compartmentation of pyruvate metabolism in the isolated hepatocytes. These studies show that the stimulation of [2-14C]- and [3-14C]pyruvate incorporation into protein involves the stimulatory effect of insulin on the activity of the Krebs cycle which is evident from the fact that insulin did not stimulate the pyruvate carbons to enter protein via alanine but the incorporation via glutamate was increased by about 40%.

Alanine↗