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Biomedical subjects

M Viswanathan

Publications and source records attributed to M Viswanathan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Risk of noninsulin dependent diabetes mellitus conferred by obesity and central adiposity in different ethnic groups: a comparative analysis between Asian Indians, Mexican Americans and Whites.

Epidemiological data from Asian Indians from Madras (AI) and Mexican Americans (MA) and non-Hispanic Whites (NHW) from San Antonio heart study were compared to determine the possible contributions by the anthropometric measurements to the varied prevalence of noninsulin dependent diabetes mellitus (NIDDM) in these ethnic groups. MA had the highest rate of obesity (mean body mass index (BMI) 28.9 +/- 5.9 kg/m2) and the highest prevalence of diabetes (men 19.6%; women 11.8%, P < 0.001 vs other groups). NHW although had high rates of obesity (mean BMI 26.2 +/- 5.2 kg/m2) had low prevalence of diabetes (men 4.4%; women 5.7%) than the AI (men 9.9%; women 5.7%) (Mean BMI 22.3 +/- 4.4 kg/m2, P < 0.001). Although AI had lower BMI than MA, the risk conferred by BMI was similarly high in AI and MA and both the ethnic groups had higher risks than NHW. Impaired glucose tolerance (IGT) was also more prevalent in MA than in AI (men, MA vs AI, 11.8 vs 7.5%, P < 0.003; women 16.1 vs 5.5%, P < 0.001). NHW had lower prevalence of IGT in men (5.7%) and women (6.3%) which were significantly lower (P < 0.001) compared to MA only. Age and BMI were predictive factors of NIDDM in all, while waist to hip ratio (WHR) was significant only in AI and MA, although NHW had high WHR. This may be an indicator of differences in genetic susceptibility. This study also highlights the similarity in risk factors between AI and MA living in urban environment and the significance of distribution of adiposity in the comparatively lean AI.

Adult↗
PubMed1997

Reduction in body weight helps to delay the onset of diabetes even in non-obese with strong family history of the disease.

Of the 1200 non-diabetic offspring of non-insulin-dependent diabetic patients registered under the prevention programme, 262 (M:F 189:73) were available for analysis with greater than or equal to 4 years of follow-up. All of them had been prescribed a calorie restricted diet to suit their body weight, occupation and age, and were advised to restrict the use of refined carbohydrates and fats. Regular exercise was also advised. Compliance with these prescriptions was assessed at each follow up. At the time of analysis, it was noted that only 14.5% had developed diabetes in a period of 8 +/- 4.2 years even though many of them had impaired glucose tolerance at entry in the programme. Multiple regression analysis showed that initial 2 h plasma glucose, initial glucose tolerance and gain in body weight were strong predictors of diabetes. Weight loss occurred in persons who adhered to diet and exercise programmes and conversion to diabetes was lower in them compared to those who gained weight (P < 0.002). Although the rate and degree of obesity is less among Indians, it has been observed in several earlier studies that even a minor increase in body mass index increased the risk of diabetes. This study highlights the fact that measures to control weight helps to delay the onset of diabetes even in the non-obese despite a strong family history of the disorder.

Adult↗
PubMed1997

Increased endothelin ET(A) receptor expression in rat carotid arteries after balloon injury.

Endothelins are vasoactive peptides and are believed to act as vascular smooth muscle mitogens. Vascular injury results in medial smooth muscle migration and proliferation with the formation of a neointima. Using quantitative autoradiography, we examined the expression of endothelin receptor subtypes ET(A) and ET(B) in the rat carotid artery 2, 8, and 16 days after balloon-catheter injury. At two and eight days after balloon catheterization, ET(A) receptor expression was significantly increased in the media of the injured vessel when compared to that in the media of the intact vessel. The enhanced expression of receptors returned to normal levels by 16 days after the injury. Neointimal cells also expressed ET(A) receptors at a lower level than that expressed by the injured media 8 days after injury, and continued to express ET(A) receptors 16 days after the injury. ET(B) receptors were not detectable in the media or the neointima at any time after the injury. Our results suggest the ET(A) receptors may have a significant role in injury induced vascular smooth muscle proliferation and neointima formation.

Animals↗
PubMed1997

CGP-42112 partially activates human monocytes and reduces their stimulation by lipopolysaccharides.

CGP 42112, a high-affinity ligand for angiotensin II AT2 receptors, binds to rat macrophage/microglia lacking AT2 receptors. Here we report that CGP-42112 binds to human monocytes and exerts specific effects. Binding studies revealed a single site, highly specific for CGP-42112, not displaceable by angiotensin II, angiotensin fragments, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, IL-10, transforming growth factor-beta, or lipopolysaccharide (LPS). Incubation of purified human monocytes in serum-free medium with CGP-42112 enhanced, in a dose-dependent manner, cell attachment to fibronectin and collagen-coated dishes as well as matrix metalloproteinase-9 secretion. CGP-42112 did not promote cytokine secretion. In contrast, when added in the presence of low doses of LPS, CGP-42112 reduced the LPS-stimulated secretion of TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 without affecting IL-10 and decreased the LPS-stimulated matrix metalloproteinase-9 activity. Additionally, CGP-42112 inhibited the increase in protein kinase A activity produced by LPS. Our results indicate that CGP-42112 may modulate monocyte activation through binding to a novel receptor.

Animals↗
PubMed1996

Cloning and transcription factor-binding sites of the human c-rel proto-oncogene promoter.

We report here the cloning, sequencing, functional analysis and DNase I footprinting of the human c-rel promoter region. The results revealed an 824-bp BsaAI-StuI minimal promoter region with a large number of NF-kappa B, Ap2 and Sp1-binding sites, some of them variants of known consensus sequences. This is the first promoter in the Rel/NF-kappa B/I kappa B family to be subjected to a detailed footprinting analysis for the binding of transcription activator proteins. Our finding of 14 Ap2-binding sites may indicate why the human c-rel promoter, unlike the chicken c-rel promoter, has a strong function and is highly responsive to phorbol esters. The presence of five NF-kappa B and six Sp1-binding sites in turn adds to growing evidence that, in mammals, the promoter of the Rel/NF-kappa B/I kappa B family may utilize multiple NF-kappa B- and Sp1-binding sites for their interactive regulation. Furthermore, there are putative binding sites for the PU.1 and Oct 1/2 transcription activator proteins, also present in the mouse c-rel promoter, which may help explain the preferential transcription of the c-rel gene in B- and T-lymphoid cells.

Amino Acid Sequence↗
PubMed1996

Familial aggregation of type 2 (non-insulin-dependent) diabetes mellitus in south India; absence of excess maternal transmission.

The family histories of 976 South Indian Type 2 diabetic patients were recorded in a questionnaire-based survey to establish whether the excess maternal transmission of Type 2 diabetes reported in low prevalence Europid populations was also evident in this medium prevalence population. In 450 families (46.1%), no parental history of diabetes was reported. In 423 families with one parent diabetic, 222 fathers (52.5%) and 201 (47.5%) mothers were diabetic. In the remaining 103 (10.6%) families, both parents were diabetic. In contrast to previous studies, we found no evidence for substantial maternal excess in the transmission of diabetes (325 diabetic fathers vs 304 mothers; p = 0.4; p = 0.07 when compared using life table methods). The age of diagnosis of diabetes in probands was lower than that of their diabetic parents (p < 0.001): furthermore increasing parental history of diabetes was associated with an earlier diagnosis of diabetes in probands (p < 0.001). These results emphasize the extensive familial aggregation of Type 2 diabetes in this population but fail to replicate the evidence for excess maternal transmission evident in lower prevalence Europid populations, suggesting ethnic differences in the extent of this phenomenon.

Adult↗
PubMed1996

Evaluation of the importance of maternal history of diabetes and of mitochondrial variation in the development of NIDDM.

In 79 South Indian nuclear pedigrees ascertained via probands with NIDDM and both parents living, parental diabetic status was established through previously diagnosed NIDDM (n = 97) or oral glucose tolerance testing (n = 61). There was no significant difference between diabetes prevalence in mothers and fathers (60 vs 53 (76% vs 67%), respectively, p = 0.22). 'Age at diabetes diagnosis' survival curves did differ according to parental gender (p = 0.02) but this may reflect gender differences in health provision rather than pathophysiology. No maternal excess effects of the magnitude evident in previous studies were detected, suggesting either ethnic differences or overestimation of the maternal effect when reported histories of parental diabetes have been used. The tRNA(Leu(UUR) gene region was studied for diabetes-associated variation given the role of mutations in this gene in some pedigrees displaying maternal transmission of NIDDM. None of 142 unrelated South Indian NIDDM subjects displayed the MELAS mutation at nt3243. However, sequencing identified two variants of potential importance: (a) at nt3290 in the tRNA(Leu(UUR) gene, seen in 7/142 diabetic and 1/85 control subjects (p = 0.11), (b) at nt3316 in the ND1 gene (4/142 vs 1/85 subjects, respectively (p = 0.51)). Further studies are needed to determine the relevance of these variants to the development of NIDDM.

Adult↗
PubMed1996

Modeling the structure of the combining site of an antisweet taste ligand monoclonal antibody NC10.14.

We report the predicted combining site structure of the monoclonal antibody fragment, NC10.14, which is specific for the superpotent sweetener, N-(p-cyanophenyl-N'-(diphenylmethyl) guanidine acetic acid, using computer-aided molecular modeling and experimental methods, such as fluorescence spectroscopy and circular dichroism. This is the first computer-aided modeling study on a lambda-chain antibody fragment. We have also identified the amino acids that are involved in ligand binding. Aromatic residues, L:91(W), L:96(W), and H:100G(Y) are predicted to make van der Waals contacts with the p-cyanophenyl moiety of the ligand. Residue H:56(K) is predicted to provide a counterion for the acetic acid moiety, and H:50(E) provides the negatively charged potential for interaction with the positive guanidinium group. We also make a comparison of the binding site architecture of NC10.14 with that of a related monoclonal antibody fragment NC6.8.

Acetates↗
PubMed1996

Genetic contribution of polymorphism of the GLUT1 and GLUT4 genes to the susceptibility to type 2 (non-insulin-dependent) diabetes mellitus in different populations.

Polymorphic variation of genes encoding the glucose transporters glycoproteins (GLUT) may contribute to the genetic susceptibility to type 2 (non-insulin-dependent) diabetes. In this study we evaluated the allele and genotype frequencies of GLUT1 and GLUT4 restriction fragment length polymorphism (RFLP), revealed by digestion with XbaI for GLUT1 and KpnI for GLUT4, in Caucasian, Chinese, Japanese, Asian Indian and American black populations. No differences of the KpnI GLUT 4 RFLP were found between control and diabetic subjects in any ethnic group or when all data are combined. In contrast, positive results were found for the XbaI RFLP: (1) most ethnic groups showed an association of allele 1 with type 2 diabetes, and this association was maintained when all groups were analysed together; (2) after stratifying for sex and obesity, this association was significant only for overweight/obese women. This joint analysis suggests that GLUT1 polymorphism may contribute to susceptibility to type 2 diabetes in some populations, and especially in overweight/obese women.

Adult↗
PubMed1996

Diabetic retinopathy at the time of diagnosis of NIDDM in south Indian subjects.

Several studies from the U.K. and the U.S. have shown that retinopathy was present at diagnosis of non-insulin dependent diabetes mellitus (NIDDM) indicating the likelihood of a latent phase of hyperglycaemia for a long period. This study looked for the prevalence of retinopathy at diagnosis of NIDDM in South Indian subjects who have a fairly high prevalence of diabetes and also a high rate of undetected diabetes. One thousand NIDDM subjects with varying duration of diabetes underwent detailed ophthalmoscopic examination for retinopathy. It was noted that the prevalence of retinopathy increased linearly with duration of diabetes. Among the 60 newly diagnosed NIDDM, 4 (6.7%) subjects had background diabetic retinopathy. Using a weighted linear regression analysis with percentage of retinopathy in relation to duration, it was estimated that hyperglycaemia could have been present 4.1 years prior to the diagnosis of NIDDM. Although the prevalence of retinopathy at diagnosis in South Indian NIDDM was lower than the other reported values, in view of the high prevalence of diabetes in Indians, a large number of patients would have the risk of microangiopathy even before diagnosis of diabetes is made.

Adult↗
PubMed1996

Increased non-angiotensin II [125I]CGP 42112 binding in rat carotid artery after balloon injury.

In this study, [125I]CGP 42112, a ligand of high affinity and selectivity for the angiotensin II AT2 receptor, was used to detect and quantify a non-angiotensin II binding site in the balloon-injured carotid artery of the rat. The amount of [125I]CGP 42112 binding was significantly enhanced in the adventitia of the injured arteries. Localization of the binding site using emulsion autoradiography and immunocytochemistry suggests that the binding sites may be expressed by macrophages in the inflamed tissue surrounding the injured artery.

Angiotensin II↗
PubMed1996

An association in non-insulin-dependent diabetes mellitus subjects between susceptibility to retinopathy and tumor necrosis factor polymorphism.

In IDDM an association between diabetic retinopathy and polymorphic markers of MHC has been described. However, these associations are complicated by a primary association between the MHC and IDDM. Because the pathogenesis of retinopathy is likely to be the same in IDDM and NIDDM, NIDDM subjects with retinopathy would be the ideal population to study for an association with MHC markers. The following South Indian subjects were therefore studied: unselected NIDDM (n = 76), unselected IDDM (n = 99), non-diabetic controls (n = 96), NIDDM subjects with maculopathy (MAC), n = 55, NIDDM subjects with proliferative retinopathy (PR), n = 53, and without retinopathy (LTD), n = 46. DNA was amplified and studied using a microsatellite polymorphism located 3.5 kb upstream of TNF-beta within the MHC class III region on the short arm of chromosome 6. No differences in allelic distribution were observed between the random NIDDM subjects and controls (p = 0.17). Differences in allelic distribution were found between unselected IDDM and controls (P = 0.016) and between the NIDDM subjects with maculopathy and/or proliferative retinopathy and no retinopathy (P = 0.006). This association could be accounted for by those patients with proliferative retinopathy (MAC vs LTD, p = 0.23; MAC vs PR, p = 0.07; and PR vs LTD, p = 0.002).

Alleles↗
PubMed1996

An association between type 1 diabetes and the interleukin-1 receptor type 1 gene. The DiMe Study Group. Childhood Diabetes in Finland.

The polygenic susceptibility to type 1 diabetes is well established and recent studies have demonstrated linkage of a further locus on chromosome 2q to disease. We have studied a polymorphism of the interleukin-1 receptor type 1 gene (IL1R1) on chromosome 2q in type 1 diabetic and control subjects from Finland, the United Kingdom, South India: three populations in which the risk of disease varies from very high to very low. In the medium-risk U.K. population we find a very strong association of IL1R1 with type 1 diabetes (p = 0.0002) but we find no overall association in either the high-risk Finnish or low-risk South-Indian populations. However, we do find heterogeneity of risk at IL1R1 amongst Finnish diabetic subjects according to the possession of HLA-DR associated susceptibility (p = 0.0001); there is an association with IL1R1 in only those Finnish diabetic subjects who do not possess high-risk HLA-DR4 or DR3 haplotypes (p = 0.006), as recently demonstrated for the insulin gene region in this population. We find no such heterogeneity of risk in either the U.K. or South-Indian populations. This study further demonstrates the genetic heterogeneity of disease susceptibility between and within populations and also supports the hypothesis of an interaction of the IL1R1 locus with genes within the HLA and insulin gene regions in the susceptibility to type 1 diabetes.

Adolescent↗
PubMed1996

Antioxidant status and lipid peroxidation in type II diabetes mellitus with and without complications.

1. This study was conducted on 467 cases of non-insulin-dependent diabetes mellitus and 180 healthy controls. Lipid peroxidation products in plasma and erythrocytes were assayed as thiobarbituric acid reactive substances, along with the erythrocyte antioxidant enzymes, namely superoxide dismutase, catalase and glutathione peroxidase. In addition, scavenger vitamins A, C and E and reduced glutathione levels in blood were also measured. 2. Lipid peroxidation was significantly raised within the first 2 years of diagnosis, and superoxide dismutase, catalase, reduced glutathione and vitamins C and E were significantly lowered. 3. These changes were correlated with the duration of the disease and were of a higher magnitude with the development of complications. 4. The results suggest that the antioxidant deficiency and excessive peroxide-mediated damage may appear early on in non-insulin-dependent diabetes mellitus, before the development of secondary complications.

Adult↗
PubMed1996

Smooth muscle DNA replication in response to angiotensin II is regulated differently in the neointima and media at different times after balloon injury in the rat carotid artery. Role of AT1 receptor expression.

We have reported that angiotensin II (Ang II) infusion to rats during the third and fourth weeks after vascular injury stimulates DNA replication in a larger proportion of smooth muscle cells (SMCs) in the arterial neointima than in the underlying media or the normal arterial media. Whether this increased responsiveness to Ang II is a transient or stable property of neointimal cells after vascular injury remained unclear. The present study examined smooth muscle DNA replication in response to Ang II infusion (250 ng.kg-1.min-1 for 2 weeks) at 3 to 4, 9 to 10, or 27 to 28 weeks after balloon injury to the rat carotid artery. Control rats received Ringer's lactate. BrdU (0.8 mg.kg-1.d-1) was coinfused to label replicating DNA. The increased replicative response to Ang II in the neointima versus the normal arterial media did not persist beyond the period of rapid lesion growth shortly after injury, even in neointimal areas without endothelial regeneration. By 9 to 10 weeks after injury, replication frequencies were comparable in the neointima and the normal arterial wall. In the presence of a regenerated endothelium, neointimal DNA replication was lowered but not abolished. After the early period, however, the most marked difference may be the loss of ability of medial SMCs to respond mitogenically to systemic Ang II. As a consequence, Ang II-induced DNA replication in injured arteries was greater in the neointima than in the underlying media at all times studied after injury. DNA replication levels correlated with AT1 receptor levels in the injured artery neointima but not media, as shown by receptor binding in vascular sections at 3 and 10 weeks after injury. The growth response to systemic Ang II is differentially regulated in adjacent smooth muscle layers in the injured arterial wall in vivo via mechanisms that include, but are not restricted to, the regulation of AT1 receptor expression in SMCs.

Angiotensin II↗
PubMed1995

Expression of a novel angiotensin II receptor subtype in gerbil brain.

Angiotensin II receptors are highly localized in adult gerbil brain. Apparent receptor number is high in subfornical organ, vascular organ of the lamina terminalis, nucleus of the solitary tract, hippocampus, and in the anterior pituitary gland. In the hippocampus, binding is localized to the stratum oriens, radiatum, the lacunar molecular layers of the CA1 subfield, and the molecular layer of the gyrus dentatus, with a medial to lateral and anterior to posterior gradient in receptor expression. Binding is absent from the pyramidal layer of the CA1 subfield and from the granular cell layer of the gyrus dentatus, areas rich in angiotensin IV binding. Characterization in the hippocampus revealed the presence of a high affinity receptor, sensitive to incubation with the guanine nucleotide GTP gamma S, and displaced by angiotensin II = angiotensin III < Sar1-Ile8-angiotensin II, but not by angiotensin IV or other angiotensin fragments, the AT1 receptor antagonist losartan, or the AT2 ligands CGP 42112 or PD 123177. In other brain areas, binding was equally insensitive to displacement by AT1 or AT2 ligands, with the exception of binding in the olfactory bulb, which was totally displaced by CGP 42112 and PD 123177, but not by losartan. In the gerbil, most of the brain and pituitary angiotensin II receptors are different from the AT1, AT2 and AT4 subtypes, and should be considered 'atypical' until further characterization.

Angiotensin II↗