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S S Reddy

Publications and source records attributed to S S Reddy.

33 records · Page 2Linked to original sources

Altered expression and function of the insulin receptor in a family with lipoatrophic diabetes.

To determine the role of genetic defects in the insulin receptor in the insulin resistance of lipoatrophic diabetes mellitus, we studied insulin binding, insulin receptor autophosphorylation, and insulin receptor mRNA levels and performed Southern blot analysis of genomic DNA in four siblings, all of whom have some degree of insulin resistance and three of whom have lipoatrophy. The insulin receptor concentration in Epstein-Barr virus-transformed lymphocytes was about 30% of normal in all three lipoatrophic siblings (LA1, LA2, and LA3) and was 55% of normal in the nonlipoatrophic sibling (LAS). Insulin receptor mRNA concentrations in the lymphocytes paralleled insulin binding and ranged from 15-67% of the mean normal level. Insulin binding to fibroblasts was also reduced about 50% in the lipoatrophic siblings. In addition, insulin binding to fibroblasts of LAS and LA2 exhibited a rightward shift of the competition curve, suggesting reduced receptor affinity [ED50, 35 and 50 ng/mL (5845 and 8350 pmol/L); normal, 1-3 ng/mL (167-501 pmol/L)]. Receptor autophosphorylation determined using Triton X-100 extracts of the fibroblasts was decreased in LA1 and LA3, but normal in LA2 and LAS. Using restriction enzyme digests of genomic DNA and probes spanning the entire cDNA of the insulin receptor, no gross alterations in receptor gene structure were detected in any members of this family. In 2 of the lipoatrophic siblings (LA1 and LA3) and in the sibling with insulin resistance but no lipoatrophy (LAS), a unique variant BamHI site was detected using a probe to the alpha-subunit region. This site was not found in 200 normal or diabetic insulin receptor alleles. By use of probes 5' and 3' to the alpha-subunit probe and by genomic cloning analysis, this variant BamHI site was localized to an intron in the insulin receptor gene downstream of exon 3 which encodes amino acids 191-296 of the alpha-subunit of the receptor. These data indicate the complex nature of familial lipoatrophic diabetes mellitus, with alterations in insulin receptor expression and/or function in both clinically affected and non-affected siblings. Both the reduced insulin binding and reduced levels of insulin receptor mRNA in the lipoatrophic siblings suggest that an insulin receptor gene defect contributes to this syndrome. Several members of this family also carry a unique variant insulin receptor gene, which, however, could not be linked to a specific alteration in receptor expression or the presence of lipoatrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Restriction Enzymes↗

Microscopic peliosis of pancreatic islets in a woman with MEN-1 syndrome.

We report herein a case of histologically identified peliosis of pancreatic islets in the surgically removed portion of the pancreas of a 30-year-old woman with multiple endocrine neoplasm, type 1 (MEN-1) syndrome. In addition to microscopic peliosis, the pancreas contained multiple endocrine tumors producing insulin, glucagon, somatostatin, and growth hormone-releasing factor and showed evidence of widespread nesidioblastosis. It is uncertain whether peliosis of pancreatic islets and MEN-1 syndrome were coincidental or whether the two diseases were causally related. Since hormonal factors can result in hepatic peliosis, it is tempting to speculate that the endocrine imbalance secondary to MEN-1 syndrome might have played a role in the genesis of peliosis in this case. Although no direct proof of vascular damage was encountered, it is conceivable that escape of red blood cells from the circulation and their accumulation in tissue spaces was due to abnormal islet blood flow and increased capillary permeability.

Adult↗

Tumor-associated peripheral eosinophilia: two unusual cases.

Peripheral eosinophilia is a rare but recognized accompaniment of malignant disease. Two unusual cases, one with a histiocytic lymphoma and the other with cervical carcinoma, are described. In the first patient, pulmonary infiltrates developed at the height of the eosinophilia and in the second, the peripheral eosinophilia heralded the onset of disseminated disease. Tumor-associated peripheral eosinophilia is reviewed, and it is concluded that peripheral eosinophilia associated with a malignant setting is a marker of extensive disease and is thus associated with a poor prognosis.

Adult↗

Effect of yoga on exercise tolerance in normal healthy volunteers.

Twelve normal healthy volunteers (6 males and 6 females) undergoing yoga training for 90 days were studied for the effect of yoga on exercise tolerance. Their ages ranged from 18 to 28 years. The volunteers were taught only Pranayama for the first 20 days and later on yogic asanas were added. Sub-maximal exercise tolerance test was done on a motorized treadmill by using Balke's modified protocol, initially, after 20 days (Phase-I) and after 90 days of yoga training (Phase-II). Pyruvate and lactate in venous blood and blood gases in capillary blood were estimated immediately before and after the exercise. Minute ventilation and oxygen consumption were estimated before and during the test. Post exercise blood lactate was elevated significantly during initial and Phase-I, but not in Phase-II. There was significant reduction of minute ventilation and oxygen consumption only in males in Phase-I and II at the time when the volunteers reached their 80% of the predicted heart rate. Female volunteers were able to go to higher loads of exercise in Phase-I and II.

Adult↗

Reducing the incidence of coronary heart disease by managing hypertension: implications of syndrome X.

Syndrome X is a constellation of abnormalities; it appears to be strongly linked to insulin resistance and the risk of atherosclerosis. It consists of hypertension, glucose intolerance, obesity, dyslipidemia and, observed more recently, coagulation abnormalities. It is possible that treating blood pressure levels alone while ignoring or worsening other strongly associated risk factors has resulted in minimal effects on the incidence of coronary heart disease (CHD). Syndrome X has raised the awareness of these associated risk factors and has further led to the consideration of hypertension as a metabolic disease. The epidemiologic evidence in support of the link between insulin resistance and hypertension is reviewed, and the public health implications of these data are outlined.

Coronary Disease↗