Biomedical subjects
S Kumar
Publications and source records attributed to S Kumar.
Spectral parameters of trunk muscles during fatiguing isometric axial rotation in neutral posture.
Axial rotation of the trunk is commonly associated with back injury and pain. However, the behaviour of trunk muscles in axial rotation is poorly understood. The objective of this study was to measure spectral parameters from the EMG of erector spinae at T10 and L3 levels, latissimus dorsi, external and internal oblique, rectus abdominis and pectoralis major muscles bilaterally in a standardized repeatable axial rotation at 60% MVC to fatigue. Twelve young and healthy subjects were recruited after screening for musculoskeletal disorders. Surface electrodes were applied to the named seven trunk muscles bilaterally. Subjects were seated in the device called Axial Rotation Tester and stabilized such that they could rotate only their thoracolumbar spine. Other motions were prevented. Subjects held 60% of their MVC for a period of 2 min. Samples (2.1 s) were obtained at every 10 s interval at a sampling frequency of 1 KHz. Samples were subjected to FFT analysis. The total power and the median frequencies were analyzed. The median frequency for different muscles were different (p < 0.001). The slopes of decline of the median frequencies of the agonists were different for different muscles (p < 0.001). This differential fatiguing rate could conceivably create a force imbalance potentiating back injury.
Small aortic annulus: a functional definition.
BACKGROUND & OBJECTIVE: Small aortic annulus is conventionally associated with poor outcome after aortic valve replacement (AVR). Contrarily, several patients have excellent follow-up results after AVR with 19, 20 or 21 size Medtronic Hall (MH) or Sorin Carbocast (SC) prostheses. This disparity prompted a relook at the semantics of a small aortic annulus. METHODS: Available survivors of isolated AVR with #19, #20 or #21 prostheses - 13 with 19 SC or 20 MH valves (Group A) and 29 with 21 SC or MH valves (Group B) were studied. Disparity between actually implanted prostheses versus predicted prosthetic size (tissue annulus diameter) was analysed according to nomograms of Rowlatt et al, NIH Plehn, Kishimoto formula and Sievers composite criteria. Preoperative and follow-up echocardiographic assessments were used for hemodynamic and prosthetic function indices. RESULTS: Both groups were similar in age, height, weight, BSA, BMI, mean NYHA class, CTR, preoperative peak gradient (PG) (92. 0 +/- 29.55 vs 102.88 +/- 33.65), mean gradient (MG) (56.8 +/- 24.6 vs 61.55 +/- 16.56), LVEDD (50.75 +/- 10.92 vs 56.0 +/- 13.5), LVESD (34.37 +/- 13.32 vs 38.52 +/- 13.85) and LVEF (67.5 +/- 12.5 vs 63.9 +/- 14.3). By developmental indices of Rowlatt et al. and NIH, no valve annulus could be designated as narrow. By Sievers composite nomogram all implanted valves were undersized by echocardiographic parameters, in normal range by angiographic criteria and oversized by anatomic autopsy data. Implanted valves in both groups were bigger than Plehn-predicted size (18.16 +/- 1.48 in GrA, 19.46 +/- 1. 10 in GrB). Valve size indices (VSI) (GrA 16.16 +/- 2.85 GrB 14.24 +/- 1.64) and geometric orifice area indices (VAI: valve area index) (GrA 1.50 +/- 0.28 vs 1.41 +/- 0.19) and postoperative rest PG (GrA 47.2 +/- 18.6 GrB 33.8 +/- 9.9) and MG (GrA 27.2 +/- 12.9 vs 19.0 +/- 9.9) were acceptable. LVEDD and LVESD regressed in both groups. LV mass indices regressed from 218.56 +/- 100.85 to 128.17 +/- 27.7 in GrA and 238.94 +/- 102.5 to 134.22 +/- 34.72 in GrB. Performance indices of implanted valves and postoperative aortic valve resistances were correlative. CONCLUSIONS: The size of the implanted prostheses per se does not denote narrowness. Patient-prosthesis mismatch may be considered if predicted prosthesis has VSI <12 mm/m2, VAI <1.31 cm2/m2 or prosthesis orifice diameter <19 mm which may indicate annular enlargement.
Absence of Helicobacter pylori in oral mucosal lesions.
A prospective study was conducted in 26 patients with benign oral ulcers and oral carcinoma and 26 age and sex matched controls to determine the prevalence of Helicobacter pylori in oral mucosal biopsies. Oral mucosal biopsies were subjected to rapid urease test, campylobacter like organism (CLO) test, histopathological examination and bacteriological culture for demonstration of H pylori. Urease test was positive for H pylori in 3 (11.4%) out of 26 cases and CLO test in 2 (14%) out of 14 cases. On histology, H pylori was identified in 4 (15.38%) out of 26 cases. The spiral organism was universally absent in culture of both patients and controls. These pilot data negate the casual association of H pylori in oral mucosal lesions.
Analysis of human immune response to potential hepatitis C viral epitopes.
A peptide-based enzyme immunoassay (PBEIA) has been developed using synthetic peptides whose sequences were selected from the core, envelope and non-structural regions of the prototype hepatitis C virus (HCV) genome. Results of PBEIA of sera obtained from several patients with various liver disorders were compared to those of commercial enzyme-linked immunosorbent assays (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). A large number of samples, which were repeatedly negative in commercial ELISA, were positive in PBEIA. There was a good correlation between the results of PBEIA and RT-PCR. The developed PBEIA proved to be a sensitive assay that had high specificity and was capable of detecting antibodies in various HCV-related liver disorders including the acute phase of the infection.
Aetiology of nasopharyngeal carcinoma. A review.
The present overview is based on recent available information on nasopharyngeal carcinoma (NPC) from various parts of the world including India. The available data suggests that NPC is a rare tumour in most parts of the world. But the incidence is higher in China and South East Asia and also among the Chinese wherever they have migrated. NPC is also relatively higher especially among the mongoloid group of the people in the North Eastern Region of India as compared to other parts of the country. The distinct geographical and ethnic distribution of NPC have stimulated much research to find out its etiology. The results suggest that Epstein Barr Virus (EBV) infection and genetic susceptibility are the constant aetiological factors for the higher incidence of NPC among various ethnic groups while other factors such as ingestants and inhalants may depend on the distinct dietary practices and living environment adopted by various ethnic groups in different geographical region of the world.
Early development of acute filariasis in a migrant from non-endemic to hyper endemic area: a case report.
A case report of a European woman who contracted filariasis after staying for a few weeks in a filaria endemic area of south India is presented in this paper.
Evaluation and comparison of antibody ELISAs for serodiagnosis of bovine trypanosomosis.
A total of 457 serum samples from cattle kept under moderate tsetse challenge in Mukono County, Uganda, (79 of them with confirmed trypanosomosis) and 86 sera from cattle in Germany were tested for Trypanosoma antibodies using enzyme-linked immunosorbent assay (ELISA) with antigen obtained from blood stream form (BSF) and in vitro cultivated procyclic (PRO) trypanosomes. The BSF and PRO ELISA showed a moderate quantitative correlation. A difference plot revealed a slightly non-linear relation between the two methods. Cut-off values were established using (A) non-exposed controls, (B) exposed negative controls and (C) by mixture distribution analysis of the quantitative ELISA results for the sample from the endemic target population. The diagnostic agreement between both assays was significant (kappa, p < 0.05). The diagnostic accuracy of the two tests relative to standard parasitological detection methods was not markedly different as shown by the areas under the receiver operating characteristic (ROC) plots. In our study, neither non-exposed controls (cut-off A) nor exposed negative controls (cut-off B) were suitable for establishing cut-off values. Based on the cut-off value C, derived from mixture distribution analysis, the proportion of animals with elevated antibody levels in the study population was estimated by both assays at 45% (41-50% binomial 95% confidence interval). This can be regarded as an unbiased estimate of the proportion of 'sero-responders' and not necessarily as a proxy for infection prevalence in the target population. We recommend the PRO ELISA to be used for seroepidemiological surveys, since in vitro cultivation of procyclic trypanosomes allows a continuous and standardised preparation of test antigen.
Comparison of the hemolytic activity and solution structures of two snake venom cardiotoxin analogues which only differ in their N-terminal amino acid.
Cardiotoxin analogues IV (CTX IV) and II (CTX II) isolated from the venom of Taiwan Cobra (Naja naja atra) differ in their amino acid sequence by a single amino acid at the N-terminal end. Leucine at the N-terminal end in CTX II is replaced by arginine in CTX IV. CTX IV is an unique snake venom cardiotoxin as it is the only cardiotoxin isoform known so far which possesses a positively charged residue at the N-terminal amino acid. All other cardiotoxins have a hydrophobic amino acid (leucine or isoleucine) at their N-terminal end. The aim of the present study is to understand the effect(s) of the presence of a cationic residue on the structure and functional properties of cardiotoxin(s). Comparison of the hemolytic activities of CTX IV and CTX II shows that lytic activity of the former is at least twice as that shown by the latter. Comparison of the solution structures of CTX IV and CTX II using two-dimensional NMR spectroscopy and dynamical simulated annealing technique reveals that the backbone fold of both the toxin isoforms is almost similar. The secondary structural elements in these two cardiotoxin isoforms consist of long, triple-stranded, as well as short, double-stranded, antiparallel beta-sheets. Thermal denaturation experiments showed that the structure of CTX IV is more stable than that of CTX II. Critical analysis of the three-dimensional structures of CTX IV and CTX II reveals the presence of a "cationic" cluster comprising of positively charged residues on the concave side of the CTX IV molecule. Similar clusters consisting of positively charged residues are not found in CTX II. The differential erythrocyte lytic activities of these two cardiotoxins are attributed to the difference(s) in the distribution of the positively charged residues in their three-dimensional structures.
Tuberculosis control in India: role of private doctors.
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World Bank's policy of structural adjustment under fire in India.
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Axial rotation strength in seated neutral and prerotated postures of young adults.
STUDY DESIGN: To determine the trunk-twisting capability from neutral and prerotated postures, a study was designed to measure torque generated in isometric and isokinetic activities of 50 young adults. OBJECTIVES: To determine the isometric and isokinetic axial rotation strengths of male and female subjects in neutral and asymmetric postures and to quantify the effect of velocity of rotation on the isokinetic trunk strength profile. METHODS: A specially designed axial rotation tester was employed using specially written modular software for data collection and analysis. The isometric strengths were measured in neutral, 15 degrees, and 30 degrees prerotated trunk postures. The isokinetic strength was measured in activities starting from the neutral position to fully rotated and from a fully rotated position to neutral positions at 10 degrees, 20 degrees, and 40 degrees per second angular velocity. The data obtained were subjected to multivariate and univariate analyses of variances with multiple comparisons and multiple regression analyses. RESULTS: All study participants were significantly stronger in isometric twisting activities than in the isokinetic activities. In isometric activities, participants were 20-25% weaker in prerotated postures when twisting in the direction of prerotation and were approximately 30% stronger in the opposite direction. For isokinetic activities, the trunk rotation from neutral to asymmetric positions produced lesser torques compared with torques from rotated positions to the neutral position. The torque-producing capability declined with increasing velocity of activity. CONCLUSION: This study adds to the data base of rotational strength.
Complete protective immunity induced in mice by immunization with the 19-kilodalton carboxyl-terminal fragment of the merozoite surface protein-1 (MSP1[19]) of Plasmodium yoelii expressed in Saccharomyces cerevisiae: correlation of protection with antigen-specific antibody titer, but not with effector CD4+ T cells.
The 19-kDa carboxyl-terminal fragment of the merozoite surface protein-1 (MSP1) is a leading malaria vaccine candidate but is unable to induce immunity in all monkeys or all strains of mice. The mechanism of immunity is unclear, although data show that cell-mediated immunity plays a critical role following immunization with the larger mature MSP1 protein. We optimized a vaccine protocol using the MSP1(19) fragment of Plasmodium yoelii expressed in Saccharomyces cerevisiae, such that following exposure of mice to parasites, they remained undetectable in peripheral blood, whereas control animals all died at very high parasitemia within 10 days. We then depleted the vaccinated mice of >99% of CD4+ T cells by anti-CD4 mAb treatment and could show that infections in most animals remained subpatent following challenge. Furthermore, mice in which the gene for the mu-chain of Ig had been disrupted could not be immunized with MSP1(19). Immunity in normal mice did not depend on the presence of an intact spleen nor production of nitric oxide, persisting unabated when >70% of splenic macrophages were depleted. Thus, while effector CD4+ T cells may contribute to immunity, neither they nor factors associated with a Th1-type cell mediated immune response appeared to play the major role in MSP1(19)-induced protection in normal mice. Furthermore, T cells were not sufficient for immunity in mice lacking B cells. In normal mice, protection correlated with a very high titer of MSP1(19)-specific Abs (>6,400,000), predominantly G1 and G2b, which may function by merozoite neutralization.
Recombinant caspase-3 expressed in Pichia pastoris is fully activated and kinetically indistinguishable from the native enzyme.
Intracellular cysteine proteinases (caspases) play key roles in inflammation and apoptosis. Recombinant caspases are typically produced in Escherichia coli expression systems with the attendant problems of solubilization, re-folding and activation of the protease. Here we describe the expression of hexahistidine-tagged caspase-3 (CPP32/Yama/Apopain) in the methylotropic yeast Pichia pastoris, and the purification of soluble enzyme from yeast lysates using cobalt affinity chromatography. The recombinant protease is fully activated, stable, and cleaves the synthetic substrate DEVD-AFC (Km 16.8 microM) but not YVAD-AFC. It mediates the cleavage of the apoptotic death substrate poly(ADP-ribose) polymerase in cell extracts, but does not cleave pro-interleukin-1beta. It is inhibited by the peptide DEVD-CHO (Ki 2.2 nM), far less efficiently by YVAD-CMK (Ki 0.3 microM), and not detectably by CrmA. By these criteria, recombinant caspase-3 is indistinguishable from native caspase-3 purified from apoptotic cell extracts. Activation of recombinant caspase-3 occurs in yeast in the absence of any intrinsic caspase activity, suggesting that caspase-3 can auto-activate. However, the purified enzyme was incapable of cleaving pro-caspase-3 indicating that autoactivation of caspase-3 in vivo is not likely to occur unless very high concentrations are achieved.
DNA containing 4'-thio-2'-deoxycytidine inhibits methylation by HhaI methyltransferase.
4'-Thio-2'-deoxycytidine was synthesized as a 5'- protected phosphoramidite compatible with solid phase DNA synthesis. When incorporated as the target cytosine (C*) in the GC*GC recognition sequence for the DNA methyltransferase M. HhaI, methyl transfer was strongly inhibited. In contrast, these same oligonucleotides were normal substrates for the cognate restriction endonuclease R. HhaI and its isoschizomer R. Hin P1I. M. HhaI was able to bind both 4'-thio-modified DNA and unmodified DNA to equivalent extents under equilibrium conditions. However, the presence of 4'-thio-2'-deoxycytidine decreased the half-life of the complex by >10-fold. The crystal structure of a ternary complex of M. HhaI, AdoMet and DNA containing 4'-thio-2'-deoxycytidine was solved at 2.05 A resolution with a crystallographic R-factor of 0.186 and R-free of 0.231. The structure is not grossly different from previously solved ternary complexes containing M. HhaI, DNA and AdoHcy. The difference electron density suggests partial methylation at C5 of the flipped target 4'-thio-2'-deoxycytidine. The inhibitory effect of the 4'sulfur atom on enzymatic activity may be traced to perturbation of a step in the methylation reaction after DNA binding but prior to methyl transfer. This inhibitory effect can be partially overcome after a considerably long time in the crystal environment where the packing prevents complex dissociation and the target is accurately positioned within the active site.
Modulation of cytochrome P450 by 5,5'-bis-trifluoromethyl-2,2'-dichlorobiphenyl, a unique environmental contaminant.
5,5'-Bis-trifluoromethyl-2,2'-dichlorobiphenyl (5,5'CF3-2,2'PCB) is representative of a unique class of trifluoromethyl polychlorinated biphenyls (CF3-PCBs) found in sediments and fish of Lake Ontario, the Niagara river, and their tributaries. The potential hazard of 5,5'CF3-2,2'PCB was assessed by exposing male Wistar rats to this agent in corn oil at a dose of 1 mg/kg/day or 75 mg/kg/day or corn oil alone (control) by oral intubation for 7 consecutive days. No lethality occurred during the course of exposure. A significant increase in liver weight and liver/body weight ratio and significant decrease in body weight gain were observed following exposure to the high dose of CF3-PCB, relative to control. Exposure to the CF3-PCB also resulted in a dose-related increase in the total hepatic cytochrome P450 content. This was associated with a dose-related increase in the O-deethylation of ethoxycoumarin, an activity which is mediated by several cytochrome P450s and thus provides a general representation of cytochrome P450 status. Specifically, a dose-dependent induction of the cytochrome P450s 1A1 and 1A2 (CYP1A1 and CYP1A2) proteins and their respective activities was observed, with significant induction occurring in both the low and high dose CF3-PCB groups, compared to control. Additionally, CYP2B1 and CYP2B2 proteins and activities were induced following treatment with the high dose of 5,5'CF3-2,2'PCB. Since, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds selectively induce CYP1A1 and CYP1A2. the results suggest that 5,5'CF3-2,2'PCB has significant dioxin-like activity. Furthermore, 5,5'CF3-2,2'PCB appears to be acting as a mixed-type inducer since phenobarbital-like induction of CYP2B1 and 2B2 was also associated with exposure.
A pilot study of idiotypic vaccination for follicular B-cell lymphoma using a genetic approach. CRC NO: 92/33. Protocol NO: PH1/027.
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Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli.
ST2/T1 is an orphan receptor highly homologous to the IL-1 receptor. Using ST2 cDNA, ST2 specific primers, and a polyclonal antibody generated against ST2, the expression of mRNA and protein corresponding to both the soluble and membrane anchored forms of ST2 was studied. ST2 mRNAs were ubiquitously expressed in all the human tissues examined and were induced by cytokines and phorbol esters. Three different species of mRNAs were observed in different human cells and tissues. In contrast, only two species of ST2 mRNAs were observed in murine Balb/c-3T3 cells and no ST2 mRNA was seen in most tissues of normal mice. However, in a murine model where mouse ears are exposed to UVB irradiation leading to inflammation, ST2 mRNA was expressed 48 h post UV exposure. Similarly, in Balb/c-3T3 cells, the expression of soluble ST2 mRNA and protein was induced by pro-inflammatory stimuli such as TNF, IL-1alpha, IL-1beta and PMA in both exponentially growing and quiescent cells. The expression of the membrane ST2, however, remained constant. These data suggest a role for ST2 in inflammation.