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Biomedical subjects

M Viswanathan

Publications and source records attributed to M Viswanathan.

At least 127 records · Page 7Linked to original sources

Evidence for induction of cytochrome P-450I in patients with tropical chronic pancreatitis.

Theophylline kinetics, as an in vivo probe for the potentially toxic cytochrome P-450I pathway of drug metabolism, were studied in 11 healthy volunteers and 11 patients with calcific chronic pancreatitis at Madras, South India. Theophylline clearance was faster in the patients than controls [median 69 (range 39-114) vs 45 (33-56) ml h-1 kg-1, p = 0.003]. In keeping with this finding, detailed social histories identified a higher exposure level in the patients to xenobiotics that are inducers of cytochrome P-450I and/or yield reactive metabolites upon processing thereby (score 7, 4-11 vs 3, 2-9, p = 0.002). However, the concentration of D-glucaric acid in urine, as a marker of phase II conjugating pathways of drug metabolism, was similar in patients and controls. This pattern of drug metabolism could predispose to oxidant stress: hence micronutrient antioxidant supplements may have therapeutic (or even prophylactic) value in tropical chronic pancreatitis.

Adolescent↗

Myxococcus xanthus msDNA.Mx162 exists as a complex with proteins.

Myxococcus xanthus, a myxobacterium, contains a peculiar branched RNA-linked DNA called msDNA. Reverse transcriptase has been shown to be required for the production of msDNA. Existence of proteins that bind to one of the two msDNAs in M. xanthus, msDNA.Mx162, was examined by gel retardation assays. Total cell-free extract yielded two distinct retarded bands. Both bands were sensitive to treatment with proteinase K, indicating that there is a protein(s) that is able to bind to msDNA. Further, the formation of the bands was inhibited by the addition of nonradioactive msDNA but not by a large excess of poly(dA) in the presence of a 5000-fold excess of poly(dI.dC).poly(dI.dC). In vivo footprinting using dimethyl sulfate revealed that the deoxynucleotide stretch from 60 to 161 is protected. When a M. xanthus cell lysate was centrifuged in a 16-30% glycerol gradient, msDNA was found to sediment in two peaks: a major peak corresponding in size to 14 S, and a minor one at 5 S. These results indicate that msDNA.Mx162 exists as a complex with specific proteins in the cell.

Base Sequence↗

The genetic predisposition to fibrocalculous pancreatic diabetes.

Fibrocalculous pancreatic diabetes (previously known as tropical pancreatic diabetes) is a rare cause of diabetes confined to countries within the tropical belt. The aetiology of fibrocalculous pancreatic diabetes is thought to be environmental although the agent(s) is unknown. We have investigated a possible genetic basis of this disease by looking for restriction fragment length polymorphisms of genes implicated in the aetiology of diabetes mellitus. Seventy-six Dravidian patients with fibrocalculous pancreatic diabetes were studied, and the restriction fragment length polymorphisms obtained compared to racially matched control subjects (n = 94), patients with Type 2 (non-insulin-dependent) diabetes (n = 87) and Type 1 (insulin-dependent) diabetes (n = 58). No association of fibrocalculous pancreatic diabetes was found with restriction fragment length polymorphisms of the insulin receptor gene. Although no association of fibrocalculous pancreatic diabetes was found with polymorphism of the HLA DR alpha/DQ alpha/DX alpha genes, an association was found with the Taq 1 restriction fragment length polymorphisms of the DQ beta gene (DQ beta T2/T6 present in 39% of patients with fibrocalculous pancreatic diabetes compared to 19% in control subjects; p = 0.01; corrected p value = 0.04) which is similar to that found in Type 1 but not Type 2 diabetes. An association of fibrocalculous pancreatic diabetes was also found with the hypervariable region in the 5-prime flanking region of the insulin gene; 40% of patients possessed the class 3 allele compared to 9.5% of control subjects p = 0.0001; corrected p value = 0.0008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Testicular function in biotin-deficient adult rats.

We have studied testicular function in the biotin-deficient rat biochemically and morphologically. Serum testosterone and luteinizing hormone (LH) levels were decreased significantly in the deficient rats. Administration of biotin or gonadotropins to the deficient rats reversed this decrease in serum testosterone. There was no difference in the serum cholesterol level between the control and biotin-deficient rats. A significant degree of sloughing of seminiferous tubule germinal epithelium was noticed in the biotin-deficient rat testes. Biotin treatment of biotin-deficient rats reversed this condition whereas testosterone treatment was without any effect. The development and maintenance of morphological and functional integrity of the seminiferous tubules appears to require a biotin-mediated step in addition to testosterone.

Animals↗

Familial aggregation in tropical fibrocalculous pancreatic diabetes.

There is very little information on the genetic factors associated with fibrocalculous pancreatic diabetes (FCPD). Ninety-eight first-degree relatives of FCPD patients were subjected to detailed studies, which included glucose tolerance tests, x-ray films of the abdomen, ultrasonography, and studies of exocrine pancreatic function. The study shows that there is a familial aggregation of FCPD with evidence of vertical transmission of the disease from parent to offspring in some families. Routine screening of families of FCPD probands helped to pick up cases in the stage of impaired glucose tolerance. There is heterogeneity in FCPD with respect to familial factors. Some families show marked familial aggregation of FCPD while in others the disease occurs either sporadically or in association with other family members who have abnormal glucose handling.

Adolescent↗

Thermal and metabolic responses to cold by men and by eumenorrheic and amenorrheic women.

Previous work has suggested that men (M) are more sensitive to cold stress than women. There have also been observations that suggest that amenorrheic women (AW) are less thermally responsive than eumenorrheic women (EW). We investigated the hypothesis that M, EW, and AW would have different responses to cold stress. The subjects (6/group) were tested four times: twice at rest for 60 min (5 and 22 degrees C) and twice in a progressive exercise test (5 and 22 degrees C). At rest at 22 degrees C AW had a lower O2 uptake (VO2) than M and lower rectal (Tre) and finger temperatures than EW. At rest at 5 degrees C both AW and EW had lower skin temperature (Tsk) than M, but there were no group differences in peripheral Tsk sites. M increased VO2 after 10 min and EW after 20 min of cold stress; however, AW did not increase metabolism until 60 min. In the two exercise tests Tre increased in proportion to relative work load; in the 5 degrees C test there was little evidence that exercise increased Tsk sites above rest levels. Few of the metabolic or thermal differences could be accounted for by body fatness, body surface area (BSA), or BSA/kg. The data support the hypothesis that M, EW, and AW have different responses to cold stress.

Adult↗

Exocrine pancreatic function in tropical fibrocalculous pancreatic diabetes.

Exocrine pancreatic function was studied by fecal chymotrypsin test in three groups of diabetic patients seen in southern India. Exocrine pancreatic insufficiency, as shown by low fecal chymotrypsin levels, was seen in 87.5% of patients with fibrocalculous pancreatic diabetes (FCPD), in 23.5% of insulin-dependent diabetes mellitus patients, and in 4.5% of non-insulin-dependent diabetes mellitus patients. There was no correlation between fecal chymotrypsin levels and serum amylase, serum lipase, age, body mass index, duration of diabetes, fasting plasma glucose, or glycosylated hemoglobin levels. The fecal chymotrypsin test is a useful additional investigation for the diagnosis of FCPD found in tropical countries.

Adult↗

Retinopathy in insulin dependent diabetes mellitus (IDDM) in south India.

The prevalence of diabetic retinopathy was assessed by direct and indirect ophthalmoscopy in a group of patients with insulin dependent diabetes mellitus (IDDM). Fourteen percent of patients had retinopathy. Proliferative retinopathy and severe background retinopathy including maculopathy were both seen in four percent of patients. It is possible that the lower prevalence rates for these complications is due to the shorter duration of diabetes in our patients.

Adult↗

Fibrocalculous pancreatic diabetes in the elderly.

Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes seen in tropical countries. It is secondary to chronic, calcific, non-alcoholic pancreatitis. FCPD is usually a disease of youth. This paper reports on two elderly onset cases of FCPD. Macrovascular complications are usually rare in FCPD patients. These two patients had evidence of macrovascular diseases probably due to the older age group of the patients.

Calcinosis↗

Pineal indoleamine metabolism in pyridoxine-deficient rats.

Pyridoxine deficiency causes physiologically significant decrease in brain serotonin (5-HT) due to decreased decarboxylation of 5-hydroxytryptophan (5-HTP). We have examined the effect of pyridoxine deficiency on indoleamine metabolism in the pineal gland, a tissue with high indoleamine turnover. Adult male Sprague-Dawley rats were fed either a pyridoxine-supplemented or pyridoxine-deficient diet for 8 weeks. Pyridoxine deficiency did not alter the pattern of circadian rhythm of pineal 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), N-acetylserotonin (NAS), and melatonin. However the levels of these compounds were significantly lower in the pineal glands of pyridoxine-deficient animals. Pineal 5-HTP levels were consistently higher in the pyridoxine-deficient animals and a conspicuous increase was noticed at 22.00 h. Increase in pineal NAS and melatonin levels caused by isoproterenol (5 mg/kg at 17.00 h) were significantly lower (P less than 0.05) in the pyridoxine-deficient animals. Treatment of pyridoxine-deficient rats with pyridoxine restored the levels of pineal 5-HT, 5-HIAA, NAS, and melatonin to values seen in pyridoxine-supplemented control animals. These results suggest that 5-HT availability could be an important factor in the regulation of the synthesis of pineal NAS and melatonin.

Animals↗

Abnormalities in erythrocyte insulin binding in offspring of conjugal non-insulin-dependent diabetic parents.

Insulin binding to erythrocyte insulin receptors was studied in 23 offspring (13 men and 10 women) born of conjugal diabetic parents having type 2 diabetes. Nine of the offspring were obese and 14 were non-obese, but all had normal glucose tolerance. Twenty-three age-, sex- and weight-matched non-diabetic subjects without a family history of diabetes were studied as controls. In the non-obese offspring mean basal plasma immunoreactive insulin (IRI) was elevated (P less than 0.01), but the mean stimulated IRI showed no change in comparison to that of controls. In the obese offspring mean basal plasma IRI was similar, but the mean stimulated IRI was lower than that of obese controls (P less than 0.01). Mean specific insulin binding was decreased in both obese (P less than 0.01) and non-obese (P less than 0.01) offspring when compared with the respective controls. Scatchard analysis of the binding data and the higher insulin concentrations required to achieve 50% inhibition of tracer binding indicated decreased receptor affinity in both obese and non-obese offspring. Analysis by average affinity profiles also indicated decreased receptor affinity, as shown by a lower average affinity constant Kc for the empty sites, in the offspring in comparison to that of controls (P less than 0.001). Abnormalities in insulin binding to its receptor along with decreased affinity in the face of normal glucose tolerance may be an early biochemical marker of potential diabetes in this group at high risk of developing diabetes.

Adult↗

High prevalence of diabetes in an urban population in south India.

An urban population in a township in south India was screened for diabetes with an oral glucose tolerance test, every fifth person aged 20 and over registered at the local iron ore company's hospital being screened. Of 678 people (346 men and 332 women) who were tested, 34 (5%; 20 men and 14 women) had diabetes and 14 (2%; 8 men and 7 women) had impaired glucose tolerance. Thirteen subjects were already known to be diabetic. Diabetes was present in 21% (37/179) of people aged over 40. The peak prevalence (41%; 7/17) was in the group aged 55-64. A family history of diabetes was present in 16 of the 34 subjects with diabetes and nine of the 15 with impaired glucose tolerance. Diabetes was significantly related to obesity in women but not in men (57% (8/14) v 5% (1/20)). The plasma glucose concentration two hours after glucose loading was correlated to body mass index, age, and income in both sexes. The prevalence of diabetes was significantly higher in subjects whose income was above the mean. When the overall prevalence of diabetes was adjusted to the age distribution of the Indians living in Southall, London, and in Fiji it increased to 10% and 9%, respectively. The prevalence of diabetes is high among urban Indians and is comparable with the high prevalence seen in migrant Indian populations.

Adult↗

Prevalence of non-insulin-dependent diabetes mellitus in Asian Indian families with a single diabetic parent.

Offspring of one parent diabetic (OPDR-A) and offspring of one parent diabetic with a first-degree family history on the non-diabetic parental side (OPDR-B) were studied to assess the influence of familial aggregation on the prevalence of non-insulin-dependent diabetes mellitus (NIDDM). All parents and offspring were tested for diabetes by oral glucose tolerance test. All parents had NIDDM. The prevalence of diabetes was 36% and 54% in the OPDR-A and OPDR-B families, respectively. The prevalence rate in OPDR-B was higher compared to OPDR-A families (P less than 0.01). The prevalence of diabetes in OPDR families was not different whether the father or the mother had diabetes. There was a male predominance among the diabetic offspring. The age at diagnosis was lower in the offspring compared to that in their parents in both groups. The expected risk of diabetes was greater in OPDR-B families compared to OPDR-A families. Thus it is seen that there is high prevalence of NIDDM in our population even in families with only one diabetic parent.

Adolescent↗

Clinical features of diabetes in the young as seen at a diabetes centre in south India.

This study reports on the clinical pattern of 545 consecutive young diabetic patients with age at onset below 30 years attending a diabetes centre in Southern India. Three hundred and fourteen patients (57.7%) were classified as having non-insulin-dependent diabetes of the young (NIDDY), 119 (22%) as insulin-dependent diabetes (IDDM) and 28 (5%) as malnutrition-related diabetes (MRDM); 4% fibrocalculous pancreatic diabetes and 1% protein-deficient pancreatic diabetes. The remaining 84 patients could not be classified into any of the above categories. A positive family history of diabetes was more common in NIDDY compared to the other groups (P less than 0.001). While 40.3% of patients with IDDM had age at onset below 15 years, the other types of diabetes were rarely seen in patients younger than this. Body mass index (BMI) did not reliably indicate the MRDM forms of diabetes as 70% of patients with IDDM also had a BMI of less than 18, one of the criteria recommended for the diagnosis of MRDM. C-peptide levels in MRDM were intermediate between the IDDM and NIDDY groups. Microvascular complications were present in all the groups of young diabetics. The frequency was higher in NIDDY patients who also had a longer duration of diabetes. There was an increasing prevalence of complications with increasing duration of diabetes.

Adult↗

Flight effects on plasma levels of free fatty acids, growth hormone and thyroid hormones in homing pigeons.

Significant increases in circulating levels of free fatty acids (FFA) and growth hormone (GH), were observed in homing pigeons after a flight of 48 km, lasting 60-80 min. No significant change in plasma levels of thyroxine (T4) and triiodothyronine (T3) was observed. Nor was there any change in T3/T4 ratio. The increase in plasma FFA is attributed to the increased release into circulation of at least one adipokinetic hormone, GH. It may be concluded that in free sustained homing flight under normal weather conditions and within the specific distance and duration, metabolic fuel and hormonal homeostasis is maintained.

Animals↗

Erythrocyte insulin binding abnormalities in fibro calculous pancreatic diabetes.

Insulin binding to erythrocyte insulin receptors was studied in 17 patients (13 men and 4 women) with fibrocalculous pancreatic diabetes mellitus (FCPD) and compared with that of 14 newly diagnosed NIDDM patients matched for age, sex and severity of hyperglycemia, and 14 age and sex-matched non-diabetic control subjects. In the uncompensated diabetic state, mean (+/- S.D.) specific binding of insulin was lower in both FCPD and NIDDM patients, compared with non-diabetic controls (P less than 0.001). Control of diabetes with short term therapy (2-6 weeks) resulted in a significant improvement in the mean specific insulin binding in both FCPD and NIDDM patients (P less than 0.001) due to increased binding affinity in the former, and increased affinity and the number of binding sites in the latter. As compared to short term therapy, chronic therapy (5-8 months) in FCPD patients resulted in a marginal decrease in specific insulin binding. However, this was still significantly higher than the basal value (P less than 0.05). FCPD patients had an initial low mean basal plasma IRI and a much lower mean stimulated IRI response as compared to NIDDM and non-diabetic controls.

Adult↗

Insulin resistance in Fibrocalculous (tropical) pancreatic diabetes.

Insulin resistance was assessed by Insulin Tolerance Test (ITT) in 12 patients with FCPD, 10 with NIDDM and 12 age and sex matched control subjects. The mean BMI of the FCPD was lower than the NIDDM and control groups (P less than 0.001). There was no significant difference between the mean fasting plasma glucose or HbA1 between the FCPD and NIDDM patients. The mean fasting C-peptide of the FCPD group was significantly lower than the NIDDM and control groups (P less than 0.001). The mean glucose disposal rate (KITT) was 5.57 +/- 2.28 in the control group, 2.15 +/- 2.00 in the FCPD and 1.77 +/- 0.91 in the NiDDM group (P less than 0.001, control vs FCPD and NIDDM). The difference in KITT between FCPD and NIDDM groups was not significant statistically. The data suggests that patients with FCPD have evidence of insulin resistance and this is similar to that seen in NIDDM patients.

Adult↗