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Search Results: 1 - 10 of 198 matches for " Calambur Narasimhan "
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Genetic variation in exon 5 of troponin - I gene in hypertrophic cardiomyopathy cases
Annapurna S,Reena T,Nallari Pratibha,Calambur Narasimhan
Indian Journal of Human Genetics , 2007,
Abstract: Background: Cardiomyopathies are a heterogeneous group of heart muscle disorders and are classified as 1) Hypertrophic Cardiomyopathy (HCM) 2) Dilated cardiomyopathy (DCM) 3) Restrictive cardiomyopathy (RCM) and 4) Arrhythmogenic right ventricular dysplasia (ARVD) as per WHO classification, of which HCM and DCM are common. HCM is a complex but relatively common form of inherited heart muscle disease with prevalence of 1 in 500 individuals and is commonly associated with sarcomeric gene mutations. Cardiac muscle troponin I (TNNI-3) is one such sarcomeric protein and is a subunit of the thin filament-associated troponin-tropomyosin complex involved in calcium regulation of skeletal and cardiac muscle contraction. Mutations in this gene were found to be associated with a history of sudden cardiac death in HCM patients. Aim: Therefore the present study aims to identify for mutations associated with troponin I gene in a set of HCM patients from Indian population. Materials and Methods: Mutational analyses of 92 HCM cases were carried out following PCR based SSCP analysis. Results: The study revealed band pattern variation in 3 cases from a group of 92 HCM patients. This band pattern variation, on sequencing revealed base changes, one at nt 2560 with G>T transversion in exon-5 region with a wobble and others at nt 2479 and nt 2478 with G>C and C>G transversions in the intronic region upstream of the exon 5 on sequencing. Further analysis showed that one of the probands showed apical form of hypertrophy, two others showing asymmetric septal hypertrophy. Two of these probands showed family history of the condition. Conclusions: Hence, the study supports earlier reports of involvement of TNNI-3 in the causation of apical and asymmetrical forms of hypertrophy.
Ventricular Dyssynchrony Patterns in Left Bundle Branch Block, With and Without Heart Failure
Hygriv B Rao,Raghu Krishnaswami,Sharada Kalavakolanu,Narasimhan Calambur
Indian Pacing and Electrophysiology Journal , 2010,
Abstract: Background: Assessment of ventricular dyssynchrony in patients with heart failure is used for selecting candidates for cardiac resynchronization therapy (CRT). The patterns of regional distribution of dyssynchrony in a population with LBBB with and without heart failure have not been well delineated. This aspect forms the object of the study.Methods: Tissue Doppler Imaging (TDI) data of consecutive patients with heart failure and LBBB (Group A) was compared with those with LBBB and normal LV function (Group B). All patients had standard 2D-echocardigraphic examination and TDI. Tissue velocity curves obtained by placing sample volumes in opposing basal and mid segments of septal, lateral, inferior, anterior and posterior walls were analyzed. Inter ventricular dyssynchrony (IVD) was assessed by the difference between aortic and pulmonary pre ejection intervals. LV dyssynchrony (LVD) was assessed by the difference in times to peak velocity. A delay of ≥ 40 msec was considered significant for presence of IVD and LVD.Results: There were 103 patients in Group A and 25 in Group B. The mean QRS duration and PR intervals respectively were 146 ± 25 vs. 152±20 msec and 182± 47 vs. 165±36 msec. (p=NS) LVEF in the 2 groups were (32 ± 6 % vs. 61± 11%; p< 0.01). Prevalence of dyssynchrony in the HF group compared to Group B was 72% vs. 16%, (P<0.01). Lateral wall dyssynchrony in the 2 groups was 37% vs. 0% (p< 0.01) while septal dyssynchrony was 16% vs. 16% (p- NS).Conclusions: 72% of heart failure patients with LBBB have documented dyssynchrony on TDI, which has a heterogeneous regional distribution. Dyssynchrony may be seen in LBBB and normal hearts but it is does not involve the lateral wall. Septal dyssynchrony in heart failure patients may not have the same significance as lateral wall delay.
Successful Catheter Ablation of Persistent Electrical Storm late Post Myocardial Infarction by Targeting Purkinje Arborization Triggers
Paul S Thoppil,B Hygriv Rao,S Jaishankar,Calambur Narasimhan
Indian Pacing and Electrophysiology Journal , 2008,
Abstract: Drug refractory ventricular tachycardia (VT) occurring as a storm after acute myocardial infarction has grave prognosis. We report a case of a middle-aged lady who presented with drug refractory VT that lead to persistent electrical storm two weeks after an anterior wall myocardial infarction. She underwent a successful catheter ablation of VT followed a few days later by implantation of an AICD. Catheter ablation of the VT could control the persistent electrical storm and the patient was free from a recurrence of VT at three month follow up.
High prevalence of Arginine to Glutamine Substitution at 98, 141 and 162 positions in Troponin I (TNNI3) associated with hypertrophic cardiomyopathy among Indians
Rani Deepa,Nallari Pratibha,Priyamvada Singh,Narasimhan Calambur
BMC Medical Genetics , 2012, DOI: 10.1186/1471-2350-13-69
Abstract: Background Troponin I (TNNI3) is the inhibitory subunit of the thin filament regulatory complex Troponin, which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Mutations (2-7%) in this gene had been reported in hypertrophic cardiomyopathy patients (HCM). However, the frequencies of mutations and associated clinical presentation have not been established in cardiomyopathy patients of Indian origin, hence we have undertaken this study. Methods We have sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in 101 hypertrophic cardiomyopathy patients (HCM), along with 160 healthy controls, inhabited in the same geographical region of southern India. Results Our study revealed a total of 16 mutations. Interestingly, we have observed Arginine to Glutamine (R to Q) mutation at 3 positions 98, 141 and 162, exclusively in HCM patients with family history of sudden cardiac death. The novel R98Q was observed in a severe hypertrophic obstructive cardiomyopathy patient (HOCM). The R141Q mutation was observed in two familial cases of severe asymmetric septal hypertrophy (ASH++). The R162Q mutation was observed in a ASH++ patient with mean septal thickness of 29 mm, and have also consists of allelic heterogeneity by means of having one more synonymous (E179E) mutation at g.4797: G → A: in the same exon 7, which replaces a very frequent codon (GAG: 85%) with a rare codon (GAA: 14%). Screening for R162Q mutation in all the available family members revealed its presence in 9 individuals, including 7 with allelic heterogeneity (R162Q and E179E) of which 4 were severely affected. We also found 2 novel SNPs, (g.2653; G → A and g.4003 C → T) exclusively in HCM, and in silico analysis of these SNPs have predicted to cause defect in recognition/binding sites for proteins responsible for proper splicing. Conclusion Our study has provided valuable information regarding the prevalence of TNNI3 mutations in Indian HCM patients and its risk assessment, these will help in genetic counseling and to adopt appropriate treatment strategies.
An In Silico Analysis of Troponin I Mutations in Hypertrophic Cardiomyopathy of Indian Origin
Gayatri Ramachandran, Manoj Kumar, Deepa Selvi Rani, Venkateshwari Annanthapur, Narasimhan Calambur, Pratibha Nallari, Punit Kaur
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070704
Abstract: Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder of the myocardium which is hypertrophied resulting in arrhythmias and heart failure leading to sudden cardiac death (SCD). Several sarcomeric proteins and modifier genes have been implicated in this disease. Troponin I, being a part of the Troponin complex (troponin I, troponin C, troponin T), is an important gene for sarcomeric function. Four mutations (1 novel) were identified in Indian HCM cases, namely, Pro82Ser, Arg98Gln, Arg141Gln and Arg162Gln in Troponin I protein, which are in functionally significant domains. In order to analyse the effect of the mutations on protein stability and protein-protein interactions within the Troponin complex, an in silico study was carried out. The freely available X-ray crystal structure (PDB ID: 1JIE) was used as the template to model the protein followed by loop generation and development of troponin complex for both the troponin I wild type and four mutants (NCBI ID: PRJNA194382). The structural study was carried out to determine the effect of mutation on the structural stability and protein-protein interactions between three subunits in the complex. These mutations, especially the arginine to glutamine substitutions were found to result in local perturbations within the troponin complex by creating/removing inter/intra molecular hydrogen bonds with troponin T and troponin C. This has led to a decrease in the protein stability and loss of important interactions between the three subunits. It could have a significant impact on the disease progression when coupled with allelic heterogeneity which was observed in the cases carrying these mutations. However, this can be further confirmed by functional studies on protein levels in the identified cases.
A Novel Arginine to Tryptophan (R144W) Mutation in Troponin T (cTnT) Gene in an Indian Multigenerational Family with Dilated Cardiomyopathy (FDCM)
Deepa Selvi Rani, Perundurai S. Dhandapany, Pratibha Nallari, Calambur Narasimhan, Kumarasamy Thangaraj
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101451
Abstract: Cardiomyopathy is a major cause of heart failure and sudden cardiac death; several mutations in sarcomeric protein genes have been associated with this disease. Our aim in the present study is to investigate the genetic variations in Troponin T (cTnT) gene and its association with dilated cardiomyopathy (DCM) in south-Indian patients. Analyses of all the exons and exon-intron boundaries of cTnT in 147 DCM and in 207 healthy controls had revealed a total of 15 SNPs and a 5 bp INDEL; of which, polymorphic SNPs were compared with the HapMap population data. Interestingly, a novel R144W mutation, that substitutes polar-neutral tryptophan for a highly conserved basic arginine in cTnT, altering the charge drastically, was identified in a DCM, with a family history of sudden-cardiac death (SCD). This mutation was found within the tropomyosin (TPM1) binding domain, and was evolutionarily conserved across species, therefore it is expected to have a significant impact on the structure and function of the protein. Family studies had revealed that the R144W is co-segregating with disease in the family as an autosomal dominant trait, but it was completely absent in 207 healthy controls and in 162 previously studied HCM patients. Further screening of the proband and three of his family members (positive for R144W mutant) with eight other genes β-MYH7, MYBPC3, TPM1, TNNI3, TTN, ACTC, MYL2 and MYL3, did not reveal any disease causing mutation, proposing the absence of compound heterozygosity. Therefore, we strongly suggest that the novel R144W unique/private mutant identified in this study is associated with FDCM. This is furthermore signifying the unique genetic architecture of Indian population.
Genetic variability of Aspergillus terreus from dried grapes  [PDF]
Banu Narasimhan, Madhivathani Asokan
Advances in Bioscience and Biotechnology (ABB) , 2010, DOI: 10.4236/abb.2010.14046
Abstract: RAPD was used to examine the genetic variability among five isolates of Aspergillus terreus spp.. Two random primers were selected for the RAPD assay PG01–5’ CAGGTGTTGC 3’ and PG02–5’ CTGGACAGAC 3’ (Progen Technologies). The characterization of Aspergillus terreus species have been mostly applied on the basis of morphology, phenotype and physiology. DNA Polymorphisms are based on differences in DNA sequences and have advantages over protein polymorphisms. But morphological characterization besides molecular tools will remain a basic and powerful key in the identification of Aspergillus terreus species. The objective of the present study was to isolate the fungal contaminants from dried grapes and compare the genomic profile of the Aspergillus terreus speices isolated from the dried grapes, through RAPD analysis. In the present study with primer PG 01 four different discriminations was there among the A. terreus isolates. There was a homology of genotype between the isolates 1 & 3. And with primer PG 02 four different discriminations were there and there was a homology between 1 & 3. The predominant type was type I in primer I & II. The other isolates belonged to 2, 3 and 4. No similarity was detected for isolates 3, 4 and 5 indicating great genomic diversity of A. terreus.
Aflatoxin B1 contamination in sunflower oil collected from sunflower oil refinery situated in Karnataka  [PDF]
Narasimhan Banu, JohnPaul Muthumary
Health (Health) , 2010, DOI: 10.4236/health.2010.28145
Abstract: In the present study, the aflatoxin B1 contamination at various stages of oil refining and in refined oil were carried out. This was subsequently compared with commercial vegetable oil samples. Among the 23 different sunflower oil samples were tested, 10 of them showed posi-tive results to AFB1 and the remaining 13 showed negative results to AFB1. All the refined oil samples were free from AFB1 contamination.
Taxol as chemical detoxificant of aflatoxin produced by aspergillus flavus isolated from sunflower seed  [PDF]
Narasimhan Banu, Johnpaul Muthumary
Health (Health) , 2010, DOI: 10.4236/health.2010.27119
Abstract: Aflatoxins are the potent toxic, mutagenic, heterogenic and carcinogenic metabolites produced by species of A. flavus and A. parasiticus. In the present study, an attempt has been made to prevent aflatoxin production using an anticancerous drug taxol. Taxol (Paclitaxel) is a well known drug for its anticancerous property mainly to treat breast and ovarian cancers. It was obtained from Taxus brevifolia and it was also obtained from the endophytic fungi present in Taxus brefivolia [1]. Therefore, this drug is specifically selected to screen its activity on the control of A. flavus and AFB1 production at various concentrations. Among the 6 concentrations used, 3 μg of taxol was found to be suitable to control the growth and AFB1 production. The content of AFB1 found at this concentration was 6 ppm by TLC and 6.3 ppm by HPTLC. The complete elimination of AFB1 might require higher concentrations of taxol.
Enumeration of microbial contaminants in sachet water: a public health challenge  [PDF]
Narasimhan Banu, Himabindu Menakuru
Health (Health) , 2010, DOI: 10.4236/health.2010.26086
Abstract: Accessibility and availability of fresh clean water is a key to sustainable development and essential element in health, food production and poverty reduction. In the present study, we have collected water sachet containing CM/L number and they were analysed for physical and bacteriological nature. The organisms isolated in this study were Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas vesicularis and Pseudomonas aeruginosae. The harmful effects of these isolates were evidenced by antibiotic resistance, heavy metal tolerance and antibacterial activity. They were resistant to the antibiotics like amoxiclav, methicillin, chloramphenicol and streptomycin. They showed tolerance to the heavy metals at 5 mM conc. except for lead. For antibacterial activity, they were tested against human pathogens Klebsiella pnemoniae, Proteus mirabilis, Micrococcus leuteus and Salmonella paratyphium. But at the same time these organisms could be exploited for the industrial production of amylase, protease and cellulase.
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