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P V Rao

Publications and source records attributed to P V Rao.

At least 19 recordsLinked to original sources
PubMed2003

Computing P-values for a class of permutation tests of equal survival functions.

Dallas and Rao (Biometrics 56 (2000) 154) proposed a class of permutation tests for testing the equality of two survival distributions based on randomly right censored survival time data consisting of both paired and unpaired observations. Data sets of this type can occur frequently in medical settings. Two members of this class were advocated for use due to their generally high power for detecting scale and location shifts in the exponential and log-logistic distributions for the survival times, and improved power over paired data test procedures that disregard unpaired observations. Because the computations for the tests become quite laborious as the sample sizes increase, computing routines are required for practical implementation of these tests. This paper provides computing routines to execute the tests.

Algorithms↗
PubMed2002

Dietary patterns and glucose intolerance among rural Indian populations.

Dietary data obtained by application of uniform methodology in rural diabetes surveys conducted near Delhi, Ahmedabad, Trivandrum and Cuttack (441 normal persons and 142 subjects ascertained as abnormal following oral glucose tolerance test), at Kalpa (30 normal, 14 abnormal) in Himachal Pradesh state, and near Kottayam (3588 normal, 37 abnormal) in Kerala state, were summarised. Average nutrients intake in rural Indians were between 53% and 69% as carbohydrates, 55% and 70% (of total carbohydrates) as complex carbohydrates, 0% and 8% as free sugars, 11% and 16% as proteins, 16% and 46% (of total proteins) as animal proteins, 17% and 32% as fats and, 30% and 54% (of total fats) as animal fats. There were no consistent differences in the total energy intake and, proportions of total or complex carbohydrates, free sugars, total or animal proteins and total or animal fats between subjects with normal and abnormal glucose tolerance. Complex carbohydrates constituted major source of carbohydrates even in those with abnormal glucose tolerance, and there was also evidence to suggest that animal fat was favoured within India too. Of the Indian dietary habits, it is difficult to identify any specific dietary pattern to relate with diabetes. Qualitative and not quantitative nutrients intake alone needs more detailed analysis for their relationship with glucose tolerance.

Case-Control Studies↗
PubMed2001

Protective effects of amifostine and its analogues on sulfur mustard toxicity in vitro and in vivo.

Sulfur mustard (bis(2-chloroethyl)sulfide, SM) is a highly reactive bifunctional alkylating agent that forms sulfonium ions in the body. SM alkylates DNA, leading to DNA strand breaks and cell death in a variety of cell types and tissues. Although several approaches have been proposed to challenge the toxic action(s) of SM, no satisfactory treatment regimen has evolved. The synthetic aminothiol amifostine, earlier known as WR-2721 (S-2-(3-aminopropylamino)ethyl phosphorothioate), has been extensively used as a chemical radioprotector for the normal tissues in cancer radiotherapy and chemotherapy. SM is known as a radiomimetic agent and this prompted us to evaluate the protective efficacy of amifostine (2.5 mM) and three of its analogues, DRDE-06 (S-2 (3-aminopropylamino) ethyl phenyl sulfide), DRDE-07 (S-2 (2-aminoethylamino) ethyl phenyl sulfide), and DRDE-08 (S-2 (4-aminobutylamino) ethyl phenyl sulfide), against SM toxicity in rat liver slices. Of the four agents tested, a 30-min pretreatment of amifostine and DRDE-07 enhanced the LC50 (a concentration producing 50% leakage of lactate dehydrogenase (LDH) or alanine aminotransferase (ALT)) of SM by 5.9- and 3.3-fold for LDH and 10.2- and 5.5-fold for ALT, respectively. Except DNA fragmentation, both these agents significantly attenuated the loss of intracellular K(+) and mitochondrial integrity (MTT assay), depletion of GSH levels, and histopathology produced by a toxic concentration (80 microM) of SM. However, when amifostine and DRDE-07 were introduced 2 h after SM, no significant protection was observed. SM (77.5 or 155 mg/kg) was also applied dermally on female albino mice and challenged by 0.20 LD50 (po) of amifostine, DRDE-06, DRDE-07, or DRDE-08 at -30 min, 0 min, or +6 h. Protection was observed only when the agents were administered at -30 min or 0 min; posttreatment (+6 h) did not offer any protection. The magnitude of in vivo protection was in the following order: DRDE-07 >or= amifostine > DRDE-08 > DRDE-06. Gas chromatographic analysis showed that there was no direct chemical interaction between SM and the antidotes. The po LD50s of amifostine, DRDE-06, DRDE-07, and DRDE-08 were 1049, 1345, 1248, and 951 mg/kg, respectively. Both in vitro and in vivo data indicate promising roles of amifostine and DRDE-07 as prophylactic agents against SM poisoning.

Amifostine↗
PubMed2001

A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q.

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores > or =1.18 (P< or =.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest.

Chromosome Mapping↗
PubMed2001

Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom.

Variation in CAPN10, the gene encoding the ubiquitously expressed cysteine protease calpain-10, has been associated with type 2 diabetes in Mexican Americans and in two northern-European populations, from Finland and Germany. We have studied CAPN10 in white subjects of British/Irish ancestry, using both family-based and case-control studies. In 743 sib pairs, there was no evidence of linkage at the CAPN10 locus, which thereby excluded it as a diabetes-susceptibility gene, with an overall sib recurrence risk, lambda(S), of 1.25. We examined four single-nucleotide polymorphisms (SNP-44, -43, -19, and -63) previously either associated with type 2 diabetes or implicated in transcriptional regulation of calpain-10 expression. We did not find any association between SNP-43, -19, and -63, either individually or as part of the previously described risk haplotypes. We did, however, observe significantly increased (P=.033) transmission of the less common C allele at SNP-44, to affected offspring in parents-offspring trios (odds ratio 1.6). An independent U.K. case-control study and a small discordant-sib study did not show significant association individually. In a combined analysis of all U.K. studies (P=.015) and in combination with a Mexican American study (P=.004), the C allele at SNP-44 is associated with type 2 diabetes. Sequencing of the coding region of CAPN10 in a group of U.K. subjects revealed four coding polymorphisms-L34V, T504A, R555C, and V666I. The T504A polymorphism was in perfect linkage disequilibrium with the diabetes-associated C allele at SNP-44, suggesting that the synthesis of a mutant protein and/or altered transcriptional regulation could contribute to diabetes risk. In conclusion, we were not able to replicate the association of the specific calpain-10 alleles identified by Horikawa et al. but suggest that other alleles at this locus may increase type 2 diabetes risk in the U.K. population.

Alleles↗
PubMed2001

Selective expression of the small GTPase RhoB in the early developing mouse lens.

This report describes the expression and distribution pattern of RhoB GTPase in the developing mouse lens. RhoB expression was confirmed by sequencing an reverse transcriptase-polymerase chain reaction-generated DNA fragment of RhoB. Immunohistochemical analysis of RhoB revealed expression in the lens vesicle (both anterior and posterior vesicle) at embryonic day (E) 11.5, and in the epithelium and primary fibers of the E14.5 lens. Compared with the neonatal stage (day 1), where RhoB is detected in the entire lens (epithelium, primary, and secondary fibers), expression of this protein is restricted to the epithelial and outer cortical secondary fibers in postnatal lenses (from day 7 to day18). Interestingly, in E11.5 and E14.5 lenses, RhoB is localized predominantly in the lens, but not detectable in the retina, cornea, or other ocular tissues. RhoB expression appears to be down-regulated in the postnatal lens with concomitant up-regulation in the retina and cornea, compared with earlier stages of development (eyes of E11.5, E14.5, and neonatal mice). This study reveals the selective expression of RhoB in the lens during early eye development and suggests a potential role for this small GTPase in cytoskeletal reorganization associated with lens epithelial cell elongation and differentiation.

Animals↗
PubMed2001

Effect of perillic acid, a putative isoprenylation inhibitor, on the cultured rat lens.

Previous studies have demonstrated that agents affecting the cholesterol synthetic pathway can have cataractogenic effects. We have suggested that opacification of cultured lenses resulting from exposure to the cholesterol-lowering agent lovastatin is caused by inhibition of isoprenylation of small GTPases. To test that hypothesis we have investigated the effects of perillic acid, an agent reported to inhibit isoprenylation, on rat lenses in organ culture. Perillic acid caused dose and time dependent opacification of cultured lenses. While the opacities appeared grossly similar to those produced by lovastatin, they differed dramatically when analysed histologically. It also produced marked morphological changes to lens epithelial cells in culture. Analysis of small GTPases in the perillic acid treated cells failed to detect any accumulation in the water soluble fraction as would be expected if isoprenylation was inhibited. Further, studies on the isoprenylation of radiolabelled isoprenoids into proteins in cultured lenses showed no significant decrease following perillic acid exposure. It was concluded that perillic acid causes cataract in this system by a mechanism different from lovastatin and that inhibition of isoprenylation is unlikely to be a primary factor in the perillic acid cataract.

Animals↗
PubMed2001

High prevalence of diabetes and impaired glucose tolerance in India: National Urban Diabetes Survey.

AIMS/HYPOTHESIS: There has been no reported national survey of diabetes in India in the last three decades, although several regional studies show a rising prevalence of diabetes. The aim of this study was to assess the prevalence of diabetes and impaired glucose tolerance in six major cities, covering all the regions of the country. METHODS: Using a stratified random sampling method, 11216 subjects (5288 men; 5928 women) aged 20 years or above, representative of all socio-economic strata, were tested by OGTT. Demographic, anthropometric, educational and social details were recorded using a standard proforma. Physical activity was categorised using a scoring system. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Glucose tolerance was classified using the 2-h values (WHO criteria). Prevalence estimations were made taking into account the stratified sampling procedure. Group comparisons were done by t-test or analysis of variance or Z-test as relevant. Univariate and multiple logistic regression analyses were used to study the association of variables with diabetes and impaired glucose tolerance. RESULTS: Age standardised prevalences of diabetes and impaired glucose tolerance were 12.1% and 14.0% respectively, with no gender difference. Diabetes and impaired glucose tolerance showed increasing trend with age. Subjects under 40 years of age had a higher prevalence of impaired glucose tolerance than diabetes (12.8% vs 4.6%, p < 0.0001). Diabetes showed a positive and independent association with age, BMI, WHR, family history of diabetes, monthly income and sedentary physical activity. Age, BMI and family history of diabetes showed associations with impaired glucose tolerance. CONCLUSIONS/INTERPRETATION: This national study shows that the prevalence of diabetes is high in urban India. There is a large pool of subjects with impaired glucose tolerance at a high risk of conversion to diabetes.

Adult↗
PubMed2001

Dor's endoaneurysmorrhaphy in severe heart failure due to giant cell myocarditis.

Giant cell myocarditis is an unusual and frequently fatal form of myocarditis. A 37-year-old woman presented with resistant cardiac failure and left ventricular aneurysm. She underwent Dor's endoaneurymorrhaphy and was histopathologically proved to have giant cell myocarditis. She had significant improvement of symptoms and was alive 13 months after surgery. Dor's endoaneurysmorrhaphy may be a useful therapeutic modality in selected cases of giant cell myocarditis.

Adult↗
PubMed2001

Supernumerary teeth: literature review.

A review of the literature on supernumerary teeth in general and supernumerary molars in particular was carried out on prevalence, aetiology, complications and the treatment of supernumerary teeth. Additional teeth are relatively common and are usually of simple conical shape (supernumerary teeth) but may resemble teeth of the normal size and shape. The aim of this review is to provide reference material for dental practitioners in Zimbabwe.

Female↗
PubMed2001

Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632.

PURPOSE: The goal of this study was to investigate the role of Rho kinase in the modulation of aqueous humor outflow facility. Rho kinase, a critical downstream effector of Rho GTPase is recognized to control the formation of actin stress fibers, focal adhesions, and cellular contraction. METHODS: Expression of Rho GTPase, Rho kinase, and other downstream targets of Rho GTPase were determined in human trabecular meshwork (HTM) and Schlemm's canal (SC) primary cell cultures by Western blot analysis. The Rho kinase-specific inhibitor (Y-27632)-induced changes in actin stress fibers, focal adhesions, and protein phosphotyrosine status were evaluated by staining with rhodamine-phalloidin, anti-paxillin, and anti-phosphotyrosine antibodies, respectively. Myosin light-chain phosphorylation was determined by Western blot analysis. Y-27632-induced changes in SC cell monolayer permeability were quantitated using a colorimetric assay to evaluate horseradish peroxidase diffusion through SC cell monolayers grown in transwell chambers. Aqueous humor outflow facility was measured using enucleated porcine eyes and a constant-pressure perfusion system. RESULTS: Treatment of HTM and SC cells with Y-27632 (10 microM) led to significant but reversible changes in cell shape and decreases in actin stress fibers, focal adhesions, and protein phosphotyrosine staining. SC cell monolayer permeability increased (by 80%) in response to Y-27632 (10 microM) treatment, whereas myosin light-chain phosphorylation was decreased in both HTM and SC cells. Aqueous humor outflow facility increased (40%-80%) in enucleated porcine eyes perfused with Y-27632 (10-100 microM), and this effect was associated with widening of the extracellular spaces, particularly the optically empty area of the juxtacanalicular tissue (JCT). The integrity of inner wall of aqueous plexi, however, was observed to be intact. CONCLUSIONS: Based on the Rho kinase inhibitor-induced changes in myosin light-chain phosphorylation and actomyosin organization, it is reasonable to conclude that cellular relaxation and loss of cell-substratum adhesions in HTM and SC cells could result in either increased paracellular fluid flow across Schlemm's canal or altered flow pathway through the JCT, thereby lowering resistance to outflow. This study also suggests Rho kinase as a potential therapeutic target for the development of drugs to modulate intraocular pressure in glaucoma patients.

Actins↗
PubMed2001

Lovastatin-induced cytoskeletal reorganization in lens epithelial cells: role of Rho GTPases.

PURPOSE: To understand the involvement of isoprenylated small guanosine triphosphatases (GTPases) in lovastatin-induced cataractogenesis, Rho- and Rac-mediated cell adhesion and actin cytoskeletal reorganization were investigated in lovastatin-treated lens epithelial cells. METHODS: The effects of lovastatin on F-actin reorganization (phalloidin staining), focal adhesion formation (paxillin or vinculin), cell-cell adhesions (cadherin and beta-catenin), and protein tyrosine phosphorylation were evaluated in human and porcine lens epithelial cells by immunocytochemical staining with specific antibodies. To explore the involvement of the Rho and Rac GTPases in lovastatin-mediated effects, changes in distribution of Rho and Rac GTPases were analyzed by Western blot analysis, and the effects of C3-exoenzyme on lovastatin-induced cytoskeletal changes were evaluated by immunocytochemical analysis. RESULTS: Lovastatin induced drastic changes in cell shape in both human and porcine lens epithelial cells, including a profound loss of actin stress fibers, focal adhesions, protein phosphotyrosine, and cell-cell adhesions. Lovastatin treatment also led to the accumulation of nonisoprenylated Rho and Rac GTPases in cytosolic fraction. Supplementation of culture media with geranylgeranyl pyrophosphate dramatically reversed the lovastatin-induced morphologic and cytoskeletal changes, whereas farnesyl pyrophosphate was ineffective. Treatment of cells with C3-exoenzyme (a Rho GTPase-specific inhibitor), however, abolished the geranylgeranyl-supplementation-induced recovery from the morphologic and cytoskeletal effects of lovastatin. CONCLUSIONS: This study demonstrates that inhibition of protein prenylation by lovastatin leads to disruption of actin cytoskeletal organization, and to loss of integrin-mediated focal adhesions and cadherin-mediated cell-cell adhesions in lens epithelial cells. Based on isoprenoid supplementation studies, it could be concluded that impairment of geranylgeranylated Rho and Rac GTPase function is most likely responsible for lovastatin-induced cytoskeletal changes in lens epithelial cells.

Actins↗
PubMed2000

Antithrombin III, a serpin family protease inhibitor, is a major heparin binding protein in porcine aqueous humor.

Our hypothesis is that the proteins in aqueous humor may be involved in the regulation of outflow facility through the trabecular meshwork and uveoscleral meshwork. In this study, we analyzed the profile of heparin-binding proteins present in porcine aqueous humor to identify and characterize secretory proteins with a binding affinity for heparin. A single step involving heparin-sepharose affinity chromatography of porcine aqueous humor yielded a approximately 60 kDa protein as the major heparin-binding species. This protein was specifically eluted from the column by heparin. The N-terminal sequence and immunological cross reactivity of this protein confirmed its identity as antithrombin III. Aqueous humor from different species, as well as cells from human trabecular meshwork, Schlemm's canal, and lens epithelium, contained detectable amounts of antithrombin III. Based on its known anticoagulative function in endothelial cells and effects on the production of prostacyclin, it is reasonable to speculate that antithrombin III present in aqueous humor might influence the physiology of the trabecular and uveoscleral meshwork and thereby regulate intraocular pressure.

Amino Acid Sequence↗
PubMed2000

Effects of ethanol on the changes in renal fluid and electrolyte handling and kidney morphology induced by long-term chloroquine administration to rats.

This study investigated the effects of long-term chloroquine and ethanol administration on renal fluid and electrolyte handling and kidney structure. Male Sprague-Dawley rats were orally administered with chloroquine diphosphate (20 microg kg(-1) bw) and/or ethanol (1.6 g kg(-1) bw) every third consecutive day for 4 weeks. Urine volume and total urinary outputs of Na+ and K+ were determined from 24-h samples. For detailed renal studies, rats were subsequently anaesthetised and challenged with a continuous jugular infusion of 0.077 M NaCl at 150 microl min(-1) 24 h after the last treatment. After a 3-h equilibration period, urine flow, Na+ and K+ excretion rates were determined over a 4-h period. Plasma concentrations of AVP and aldosterone were measured in unanaesthetised rats and in anaesthetised rats after hypotonic saline infusion. In separate groups, the rats were anaesthetised with an overdose of ether after 4 weeks of treatment and part of the right kidney was quickly collected and routinely processed for light microscopy. Chloroquine decreased Na+ excretion and increased plasma aldosterone concentrations in anaesthetised rats. Ethanol alone did not alter urinary Na+ outputs or aldosterone levels. Combined chloroquine and ethanol increased renal Na+ excretion, but did not affect plasma aldosterone levels. In unanaesthetised animals all treatments increased aldosterone levels by comparison with control rats. Urinary Na+ excretion was decreased by separate administration of either chloroquine or ethanol, but increased by combined treatment. Microscopic studies showed that concurrent chloroquine and ethanol administration induced extensive damage of the proximal tubule and collecting ducts cells. The results of this study suggest that alcohol consumption and chloroquine administration could result in diminished renal function possibly due to alteration of renally active hormones or kidney morphology.

Aldosterone↗