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Biomedical subjects

M Vijayakumar

Publications and source records attributed to M Vijayakumar.

At least 37 records · Page 2Linked to original sources

Free radical scavenging potential of Picrorhiza kurrooa Royle ex Benth.

For assessing free radical scavenging potential of P. kurrooa, the antioxidant activity of P. kurrooa extract was studied by lipid peroxidation assay using rat liver homogenate. The extract (1 mg/ml) showed marked protection (up to 66.68%) against peroxidation of liver phospholipids. Besides, reduced glutathione showed very encouraging activity. The extract also exhibited significant scavenging activity. Thus augmenting the wide use of plant in the indigenous system of medicine, which may partly be due to antioxidant and free radical scavening activity of the extract.

Animals↗

Acute and crescentic glomerulonephritis.

Acute nephritic syndrome is clinically characterized by hematuria, proteinuria, oliguria, and volume overload with or without azotemia and histologically be acute proliferative glomerulonephritis. Acute post streptococcal glomerulonephritis is the commonest cause in children. There is a preceding infection prior to this condition in majority. This is one of the comonest causes of renal edema in children. Early recognition, prompt and aggressive therapy and adequate follow-up are mandatory. Prognosis is usually good unless associated with severe renal failure and crescentic glomerulonephritis where the outcome is relatively poor unless treatment is early and adequate. Pathologically acute proliferative nephritis is with diffuse proliferative glomerulonephritis with or without crescents. Immunosuppressive therapy is not needed in simple acute proliferative glomerulonephritis but is essential in modifying the outcome of crescentic glomerulonephritis. Delayed resolution, severe renal failure at onset, progressive renal failure and associated systemic features like skin rashes, joint pains, hepatosplenomegaly and persistent fever are the indications for biopsy. Overall the prognosis in classical post streptococcal acute proliferative glomerulonephritis is good.

Acute Disease↗

Left ventricular mass and arterial compliance: relation to coronary heart disease and its risk factors in South Indian adults.

BACKGROUND: Rates of coronary heart disease (CHD) in India are rising, and are now similar to those in Western countries. The prevalence of conventional CHD risk factors such as hypercholesterolaemia, hypertension, smoking and obesity, tend to be lower in Indian than Western populations, and fail to explain these high rates of disease. Increased left ventricular (LV) mass and decreased arterial compliance predict a higher risk of CHD in Western populations, but there are no published data from India. We have measured LV mass and arterial compliance, and examined their relation to CHD and other known risk factors, in men and women living in Mysore, South India. METHODS: We examined 435 men and women born in Mysore during 1934-1953. LV mass was measured by echocardiography and arterial compliance (derived from pulse wave velocity, PWV) was measured by a non-invasive optical method in three arterial segments. RESULTS: The mean LV mass was 149 g (S.D. 37) in men and 125 g (S.D. 32) in women. The mean PWV was 4.14 m/s in the aorto-radial, 3.28 m/s in the aorto-femoral and 13.59 m/s in the femoro-popliteal-posterior tibial segments. LV mass and PWV were positively correlated with each other and with systolic and diastolic blood pressures, non-insulin dependant diabetes mellitus, fasting plasma glucose, insulin, proinsulin concentrations and serum triglyceride concentrations (p<0.05 for all), independently of age, sex and body size. In addition, LV mass correlated negatively with fasting serum HDL-cholesterol (p=0.02). Higher LV mass was associated with an increased risk of CHD (p=0.05). CONCLUSIONS: The mean LV mass in this Indian population is low compared with Western populations, though as in the West, increased LV mass is associated with an increased risk of CHD. Greater LV mass and reduced arterial compliance are associated with higher levels of many known CHD risk factors especially with those which form the Insulin Resistance Syndrome.

Adult↗

Blood pressure, arterial compliance, and left ventricular mass: no relation to small size at birth in south Indian adults.

OBJECTIVE: To determine whether reduced fetal growth leads to raised blood pressure, reduced arterial compliance, and increased left ventricular mass in an Indian population. DESIGN: A retrospective cohort study of men and women (age range 40-61 years) whose weight, length, and head circumference at birth were recorded. SETTING: The Holdsworth Memorial Hospital, Mysore, South India. SUBJECTS: 435 men and women born in the hospital between 1934 and 1953. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures; compliance in four arterial segments derived from pulse wave velocity, measured by a non-invasive optical method; and left ventricular mass measured using M mode echocardiography. RESULTS: Small size at birth was not associated with increased adult blood pressure or left ventricular mass, or with reduced arterial compliance. Systolic blood pressure and left ventricular mass were higher in subjects who were greater in length at birth, rising by 1.64 mm Hg (95% confidence interval (CI) -0.08 to +3.37 mm Hg) and 1.63 g/m(2) (95% CI 0.13 to 3.13 g/m(2)), respectively, per one inch (2.5 cm) increase in birth length, independently of adult size. Arterial compliance was reduced in people whose mothers were lighter and had smaller pelvic (external conjugate) diameters. CONCLUSIONS: The higher prevalence of coronary heart disease in Indian men and women of lower birth weight, shown in an earlier study of the same cohort, cannot be explained by changes in blood pressure, arterial compliance, and left ventricular mass. The association of raised blood pressure and left ventricular mass with longer birth length suggests that the way in which the intrauterine environment influences coronary heart disease differs between Indian and Western populations.

Adult↗

Hydrogen bonds between short polar side chains and peptide backbone: prevalence in proteins and effects on helix-forming propensities.

A survey of 322 proteins showed that the short polar (SP) side chains of four residues, Thr, Ser, Asp, and Asn, have a very strong tendency to form hydrogen bonds with neighboring backbone amides. Specifically, 32% of Thr, 29% of Ser, 26% of Asp, and 19% of Asn engage in such hydrogen bonds. When an SP residue caps the N terminal of a helix, the contribution to helix stability by a hydrogen bond with the amide of the N3 or N2 residue is well established. When an SP residue is in the middle of a helix, the side chain is unlikely to form hydrogen bonds with neighboring backbone amides for steric and geometric reasons. In essence the SP side chain competes with the backbone carbonyl for the same hydrogen-bonding partner (i.e., the backbone amide) and thus SP residues tend to break backbone carbonyl-amide hydrogen bonds. The proposition that this is the origin for the low propensities of SP residues in the middle of alpha helices (relative to those of nonpolar residues) was tested. The combined effects of restricting side-chain rotamer conformations (documented by Creamer and Rose, Proc Acad Sci USA, 1992;89:5937-5941; Proteins, 1994;19:85-97) and excluding side- chain to backbone hydrogen bonds by the helix were quantitatively analyzed. These were found to correlate strongly with four experimentally determined scales of helix-forming propensities. The correlation coefficients ranged from 0.72 to 0.87, which are comparable to those found for nonpolar residues (for which only the loss of side-chain conformational entropy needs to be considered).

Asparagine↗

Alterations in the levels of monoamines in discrete brain regions of clomipramine-induced animal model of endogenous depression.

It has been hypothesized that the dysfunction of the serotonergic and catecholaminergic neurotransmission is involved in the pathogenesis of depression. These hypotheses are being tested in a novel rat model of depression developed by the treatment of antidepressant-clomipramine neonatally from postnatal day 8 to 21. After the attainment of adulthood, these rats mimicked the features of the human endogenous depression showing significant decrease in the aggressive behavior and food intake. Biogenic amine estimations in these rats revealed that the levels of serotonin and noradrenaline were decreased significantly (P < 0.001) in frontal cortex, hippocampus, brain stem, septum and hypothalamus, while the levels of dopamine were decreased significantly (P < 0.001) only in the hippocampus compared to normal control and vehicle treated groups of rats. Our results demonstrate the dysfunction of serotonergic and noradrenergic neurotransmission, with lesser involvement of dopaminergic neurotransmission in the clomipramine induced experimental model of depression.

Aggression↗

Variation at the MJD locus in the major psychoses.

Expansion of triplet repeats has been seen to underlie several disorders that manifest anticipation. Clinical evidence suggests that anticipation occurs in the major psychoses. We studied the distribution of repeat sizes at the Machado-Joseph disease (MJD) locus in a group of patients with the major psychoses. We did not find any large expansions, though 2 patients had alleles that were two repeats larger than in our controls. The difference in allele sizes was larger in the patient sample as compared to the controls. The effect of such large differences might be of functional significance.

Adult↗

Electrostatic enhancement of diffusion-controlled protein-protein association: comparison of theory and experiment on barnase and barstar.

The electrostatic enhancement of the association rate of barnase and barstar is calculated using a transition-state theory like expression and atomic-detail modeling of the protein molecules. This expression predicts that the rate enhancement is simply the average Boltzmann factor in the region of configurational space where association occurs instantaneously in the diffusion-controlled limit. Based on experimental evidence, this "transition state" is defined by configurations in which, relative to the stereospecifically bound complex, the two proteins are shifted apart by approximately 8 A (so a layer of water can be accommodated in the interface) and the two binding surfaces are rotated away by 0 degrees to 3 degrees. The values of the average Boltzmann factor, calculated by solving the Poisson-Boltzmann equation, for the wild-type complex and 16 complexes with single mutations are found to correlate well with experimental results for the electrostatic rate enhancement. The predicted rate enhancement is found to be somewhat insensitive to the precise definition of the transition state, due to the long-range nature of electrostatic interactions. The experimental ionic strength dependence of the rate enhancement is also reasonably reproduced.

Bacterial Proteins↗

Sacral chordomas: a 10-year study.

A retrospective analysis of 14 cases of sacral chordoma seen between 1984 and 1993 at the Kidwai Memorial Institute of Oncology is reported. The mean patient age was 54 years, with 13 males and one female. Seventy-one per cent of patients presented with symptoms related to a painful sacral mass. Eight patients underwent radical surgery and two had adjuvant radiotherapy. One patient had a partial tumour resection. Three patients received radical radiotherapy. Two patients were offered only pain relief medication. The median follow-up was 33 months. The actuarial overall survival (OS) at 5 years was 48%. In the 12 patients in whom curative therapy was attempted, the 5-year OS was 56% and progression-free survival was 36%. Four patients developed local recurrence and three developed distant metastasis.

Chordoma↗

Design of fast enzymes by optimizing interaction potential in active site.

The diffusional encounter between substrate and enzyme, and hence catalytic efficiency, can be enhanced by mutating charged residues on the surface of the enzyme. In this paper we present a simple method for screening such mutations. This is based on our earlier result that electrostatic enhancement of the enzyme-substrate binding rate constant can be accounted for just by the interaction potential within the active site. Assuming that catalytic and structural integrity is maintained, the catalytic efficiency can be optimized by surface charge mutations which lead to stronger interaction potential within the active site. Application of the screening method on superoxide dismutase shows that only charge mutations close to the active site will have practical effect on the catalytic efficiency. This rationalizes a large number of findings obtained in previous simulation and experimental studies.

Animals↗

Modeling of protein conformational fluctuations in pKa predictions.

A method is presented to account for conformational fluctuations of a protein in predicting the pK(a) values of its titrating groups. Conformations of the protein are generated by conventional molecular dynamics or Monte Carlo simulations, in which the protonations of the titrating groups are fixed. For each protein conformation, the electrostatic free energies required to add a proton charge to a titrating group while other groups are either unprotonated or protonated are calculated within a dielectric continuum model. These are used to determine the mean protonations of the titrating groups in the conformation at a series of pH values. The mean protonations are then used to determine the relative weight of the particular conformation with the titrating groups having all possible protonations. A conformationally averaged mean protonation for each titrating group is finally obtained by the weighted sum of the group's mean protonations in all the conformations. This method is applied to yeast iso-1-ferricytochrome c. The predicted pK(a) values are in general agreement with experimental results.

Computer Simulation↗

Echocardiographic evaluation of patients with acute rheumatic fever and rheumatic carditis.

BACKGROUND: Cardiac involvement is the most important component of acute rheumatic fever. The role of echocardiography in the evaluation of rheumatic carditis has not been adequately defined. We used echocardiography in a large sample of patients with acute rheumatic fever to describe morphological abnormalities associated with rheumatic carditis and to assess its role in the diagnosis of rheumatic carditis. METHODS AND RESULTS: Cross-sectional and color Doppler echocardiographic examination was performed in 108 consecutive patients with acute rheumatic fever within 24 to 48 hours of diagnosis. Twenty-eight patients had acute rheumatic fever without clinical evidence of carditis (group 1). Thirty-five patients had a presumed first episode of rheumatic carditis (group 2), and 45 patients had a recurrence of carditis (group 3). Patients in group 1 did not demonstrate any evidence of valvular regurgitation. Mitral regurgitation was the most common Doppler echocardiographic feature in groups 2 (94%) and 3 (84%). Valvular thickening with or without restriction of leaflet mobility was frequently seen in rheumatic carditis. One of every 4 patients with rheumatic carditis demonstrated echocardiographic presence of focal valvular nodules. These nodules were found on the body and the tips of the mitral valve leaflets and disappeared on follow-up. Ventricular dilatation (group 2, 54%; group 3, 74%) and restriction of leaflet mobility (group 3, 37%) were common mechanisms of mitral regurgitation in rheumatic carditis; valve prolapse (group 2, 9%; group 3, 16%) and annular dilatation (group 2, 12%; group 3, 21%) were infrequent. The majority of patients with rheumatic carditis had normal left ventricular systolic function. Congestive heart failure (group 2, 17%; group 3, 40%) was invariably associated with the presence of hemodynamically significant valve lesions. On follow-up, no patient in group 1 developed valvular regurgitation. In group 2 patients, a progressive decrease in left ventricular dimensions was observed without any change in ventricular fractional shortening. Valvular regurgitation remained unchanged in 69% of patients, decreased in 22%, and disappeared in 9%. CONCLUSIONS: In patients with rheumatic carditis, the mitral valve is most often involved and mitral regurgitation is the most common finding on color flow imaging. Mitral regurgitation in rheumatic carditis is related to ventricular dilatation and/or restriction of leaflet mobility. Rheumatic carditis does not result in congestive heart failure in the absence of hemodynamically significant valve lesions. In a quarter of patients with rheumatic carditis, we observed valve nodules that may represent echocardiographic equivalents of rheumatic verrucae. Our study failed to reveal any incremental diagnostic utility of echocardiography and Doppler color flow imaging in rheumatic fever without clinical evidence of carditis.

Acute Disease↗

Weight in infancy and prevalence of coronary heart disease in adult life.

OBJECTIVE: To determine whether low birth weight and low weight at 1 year are followed by an increased prevalence of coronary heart disease in adult life. DESIGN: A follow up study of men born during 1920-30 whose birth weights and weights at 1 year were recorded. SETTING: Hertfordshire, England. SUBJECTS: 290 men born and still living in East Hertfordshire. MAIN OUTCOME MEASURE: The prevalence of coronary heart disease, defined by the Rose/WHO chest pain questionnaire, standard electrocardiographic criteria, or history of coronary artery angioplasty or graft surgery. RESULTS: 42 (14%) men had coronary heart disease. Their mean birth weight, 7.9 lb (3600 g), was the same as that of the other men. Their mean weight at 1 year, 21.8 lb (9.9 kg), was 1 lb (454 g) lower (95% confidence interval 0.1 to 1.8, P = 0.02). Percentages of men with coronary heart disease fell from 27% in those who weighed 18 lb (8.2 kg) or less at 1 year to 9% in those who weighed more than 26 lb (11.8 kg) (P value for trend = 0.03). This trend occurred in both smokers and non-smokers and within each social class. CONCLUSION: These findings add to the evidence that coronary heart disease is "programmed" during early growth.

Birth Weight↗

Birth weight, weight at one year, and left ventricular mass in adult life.

OBJECTIVE: To examine how fetal and infant growth are related to left ventricular mass in adult life. DESIGN: A follow up study of men born during 1920-30 whose birth weights and weights at 1 year were recorded. SETTING: Hertfordshire, England. SUBJECTS: 290 men born and still living in East Hertfordshire, England. MAIN OUTCOME MEASURE: Left ventricular mass calculated from measurements of interventricular septal thickness and left ventricular posterior wall thickness and left ventricular internal diameter at end diastole measured by M mode echocardiography. RESULTS: Left ventricular mass was highest in men with the lowest weight at 1 year and fell with increasing weight at 1 year (r = 0.18, P = 0.01). Left ventricular mass was not related to birth weight. The relation with weight at 1 year was independent of factors in adult life known to influence left ventricular mass, including body size, systolic blood pressure, and age. The enlarged left ventricular mass associated with reduced growth in infancy was concentric, affecting both the interventricular septum and the left ventricular posterior wall. Concentric left ventricular hypertrophy is known to be associated with increased death rates from coronary artery disease. CONCLUSION: Low weight at 1 year is associated with concentric enlargement of the left ventricle in adult life. This is consistent with a previous finding of higher mortality from cardiovascular disease in men of low weight at 1 year, and provides further evidence that cardiovascular disease may be partly programmed in early life. The left ventricular enlargement may be a long term result of haemodynamic changes in utero or of persisting changes in growth factor concentrations.

Aged↗

Scalp flap--a utility and reconstructive option for head and neck surgeons.

Regional scalp flaps are invaluable in resurfacing defects resulting from resections in the area of the upper face, orbit and scalp itself. The tissue lies adjacent to the defect, is easy to harvest, and can be termed as a 'durable one-stage' procedure. Scalp defects posterior to the vertex lend themselves to resurfacing by a posterior flap based on the occipital arteriovenous system. Anterior scalp defects including upper face and orbit can be resurfaced by an anterior scalp flap based on the superficial temporal arteriovenous system. While large areas can be resurfaced and the donor site effectively camouflaged, this flap finds less of an acceptance amongst patients with defects in the upper facial region when compared to the scalp defects. We recount our experience with these flaps and describe the high points of the reconstructive procedure and the results obtained in ten consecutive cases carried out over a three year period at the Department of Head and Neck Surgery, Kidwai Memorial Institute of Oncology, Bangalore, India. The short healing time and minimal morbidity make this reconstructive option an attractive one for the practising Head and Neck Surgeon.

Carcinoma, Squamous Cell↗