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S Kundu

Publications and source records attributed to S Kundu.

At least 55 records · Page 3Linked to original sources

Denaturation of supercoiled DNA: a Monte Carlo study.

A theoretical investigation of the denaturation characteristics of a supercoiled DNA has been presented employing a Metropolis Monte Carlo algorithm to examine the overall melting profiles of a supercoiled plasmid as the temperature is varied. We show that in contrast to a previously presented algorithm, this much simpler method is sufficient to explain almost all the overall denaturation characteristics and it also correctly calculates the detailed denaturation probabilities of each base pair at various degrees of supercoiling. We also present for the first time a theoretical investigation of the alkaline denaturation of a supercoiled plasmid. Although one can qualitatively reproduce the denaturation profiles using the present Monte Carlo algorithm, the agreement with experiment is not as good as in the case of thermal denaturation. The possible sources of discrepancy between theory and experiment have been discussed.

Algorithms↗

Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction.

BACKGROUND: Patients with mild asthma frequently have only exercise-induced bronchoconstriction, a symptom of inadequate control of asthma. We evaluated the ability of montelukast, a leukotriene-receptor antagonist, to protect such patients against exercise-induced bronchoconstriction. METHODS: We randomly assigned 110 patients (age, 15 to 45 years) with mild asthma and a decrease in the forced expiratory volume in one second (FEV1) of at least 20 percent after exercise on two occasions during a placebo run-in period to receive 10 mg of montelukast (54 patients) or placebo (56 patients) once daily at bedtime for 12 weeks in a double-blind study. Treatment was followed by a two-week, single-blind washout period during which all patients received placebo. Exercise challenges were performed at base line; 20 to 24 hours after dosing at weeks 4, 8, and 12; and at the end of the washout period. The primary end point was the area under the curve for FEV1 (expressed as the percent change from base-line values) in the first 60 minutes after exercise. This measure summarized the extent and duration of bronchoconstriction after exercise. RESULTS: At 12 weeks, montelukast therapy offered significantly greater protection against exercise-induced bronchoconstriction than placebo therapy (expressed as the percentage of inhibition of the end points), as evidenced by the improvement in the area under the FEV1 curve (degree of inhibition, 47.4 percent; P=0.002). Montelukast therapy was also associated with a significant improvement in the maximal decrease in FEV1 after exercise (P=0.003) and the time from the maximal decrease in FEV1 to the return of lung function to within 5 percent of pre-exercise values (P=0.04). The differences between groups in the various measures of lung function were similar at 4, 8, and 12 weeks; there was no evidence of rebound worsening of lung function in the montelukast group after the washout period. After 12 weeks of treatment, patients in the montelukast group were more likely to rate their asthma control as better and less likely to require rescue therapy with a beta-agonist during or after exercise challenge. The rates of adverse events were similar in the two groups. CONCLUSIONS: As compared with placebo, once-daily treatment with montelukast provided significant protection against exercise-induced asthma over a 12-week period. Tolerance to the medication and rebound worsening of lung function after discontinuation of treatment were not seen.

Acetates↗

Utility of electron microscopy in the assessment of transthoracic needle lung biopsy specimens.

RATIONALE AND OBJECTIVES: The authors determine the usefulness of electron microscopy (EM) in the workup of patients with certain intrathoracic masses undergoing transthoracic needle biopsy (TNB). METHODS: Over a 4-year period, 1603 patients underwent TNB at our institution. Of these, 79 had EM examination of the aspirated material. The study is a retrospective review of this latter group. Previous use of EM for TNB had suggested that it may he helpful in those with pleural, chest wall, and mediastinal lesions. The 40 men and 39 women had pulmonary (n = 49), mediastinal (n = 17), pleural (n = 10), and chest wall (n = 3) lesions. RESULTS: The adequate specimen rate was 59% (47 of 79) for light microscopy (LM) and 37% (29 of 79) for EM. Of the 28 patients with satisfactory specimens for both LM and EM, the correct diagnosis was obtained by LM 79% (22 of 28) and EM 96% (27 of 28) of the time. Electron microscopy was most helpful in patients with mediastinal (6 of 6 correct versus 3 of 6 for LM) and pleural (3 of 3 versus 1 of 3) lesions. CONCLUSIONS: In specific circumstances, EM can be a very useful adjunct to LM in patients undergoing TNB. Problems with sample adequacy must be addressed.

Adult↗

Reperfusion edema after lung transplantation: radiographic manifestations.

PURPOSE: To characterize the radiographic manifestations of reperfusion edema after lung transplantation and to correlate the severity of the radiographic findings with pulmonary physiology. MATERIALS AND METHODS: Chest radiographs obtained after 45 lung transplantation procedures (20 single, 25 double) were reviewed retrospectively. Physiologic parameters (alveolar-arterial gradient, ratio of partial pressure of oxygen to fraction of inspired oxygen) were noted in patients who underwent intubation. RESULTS: Reperfusion edema appeared on day 1 in 39 transplants and by day 3 in 44. One patient's lungs remained clear. Peak severity occurred by day 4 in 43 of 44 transplants. At peak severity, reperfusion edema appeared as reticular interstitial disease in the upper (19%), middle (33%), and lower (34%) lung zones or air-space disease in the upper (31%), middle (61%), and lower (57%) zones. Reperfusion edema was asymmetric after double-lung transplantation in nine patients. The process cleared by day 10 in five transplants and by day 21 in another seven. There was a poor correlation between the severity of radiographic findings and physiologic measurements. CONCLUSION: Reperfusion edema is almost invariable after lung transplantation and most often appears as air-space disease in the middle and/or lower lung zones. The severity of radiographic findings is a poor indicator of pulmonary physiology.

Adult↗

Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group.

The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.

Acetates↗

Purification and characterization of a highly stable cysteine protease from the latex of Ervatamia coronaria.

A highly stable cysteine protease was purified to homogeneity from the latex of Ervatamia coronaria by a simple purification procedure involving ammonium sulfate precipitation and ion-exchange chromatography. The molecular mass was estimated to be approximately 25,000 Da by SDS-PAGE and gel filtration. The extinction coefficient (epsilon 280 nm 1%) of the enzyme was 24.6. The enzyme hydrolyzed denatured natural substrates like casein, hemoglobin, azoalbumin, and azocasein with a high specific activity but showed low specific activity towards synthetic substrates. The pH and temperature optima were 7.5-8.0 and 50 degrees C respectively. The activity of the enzyme was strongly inhibited by thiol-specific inhibitors like leupeptin, iodoacetamide, PCMB, NEM, and mercuric chloride. The striking property of this enzyme was its stability over a wide pH range (2-12) and other extreme conditions of temperature, denaturants, and organic solvents. The N-terminal sequence showed marked similarity to known cysteine proteases.

Amino Acid Sequence↗

Prevalence and determinants of central obesity and age-specific waist:hip ratio of people in five cities: the Indian Women's Health Study.

OBJECTIVE: To study the prevalence of central obesity and age-specific waist:hip ratio of urban women from five Indian cities. DESIGN AND SETTING: Cross-sectional surveys were conducted in 6-12 urban streets in different parts of India using similar methods of sample selection and criteria of diagnosis. SUBJECTS AND METHODS: We randomly selected 3212 women, aged 25-64 years, from Moradabad (n = 902), Trivandrum (n = 760), Calcutta (n = 365), Nagpur (n = 405), and Bombay (n = 780). Evaluation was by a questionnaire administered by a physician and a dietician, a physical examination, and anthropometric measurements. RESULTS: The overall prevalence of central obesity among the total number of women was 55.0%, with the highest prevalence in Calcutta (62.2%) and the lowest in Bombay (47.4%). Waist:hip ratio was 0.85 +/- 0.13 (mean +/- SD) with the highest ratio for women in Calcutta (0.87 +/- 0.12) and the lowest for women in Moradabad (0.84 +/- 0.16). After pooling of data from all five cities, multivariate logistic regression analysis showed that, regardless of age, body mass index (> 23 kg/m2; odds ratio 1.12), sedentary lifestyle (odds ratio 2.51), and family history of obesity (odds ratio 2.15) were strongly associated with central obesity. Excess intake of fat was weakly associated with central obesity but age was not a risk factor for central obesity, although the prevalence was highest among those aged over 55 years in Moradabad, Calcutta, and Nagpur. CONCLUSIONS: The overall prevalence of central obesity among the urban women of India has increased, more so in Calcutta and Trivandrum. Body mass index, sedentary lifestyle, and family history of excess intake of fat were significant risk factors for central obesity.

Adult↗

Montelukast causes prolonged, potent leukotriene D4-receptor antagonism in the airways of patients with asthma.

Montelukast, a new specific oral cysteinyl LT3-receptor antagonist was evaluated for its activity in attenuating inhaled leukotriene D4 (LTD4) bronchoconstriction in patients with asthma. In two double-blind, placebo-controlled, randomized crossover studies, patients with mild asthma (forced expiratory volume in 1 second [FEV1] > or = 70%) were studied. In trial A, LTD4 challenge began 4 hours (peak plasma concentration) after a single dose of placebo or 5, 20, 100, and 250 mg montelukast. In trial B, and LTD4 challenge was started 20 hours after administration of placebo, 40 mg montelukast, or 200 mg montelukast. During each challenge, twofold increasing concentrations of LTD4 were inhaled until specific airways conductance (sGaw) decreased by at least 50% (PC50) or the highest concentration of LTD4 was inhaled. In trial A with all doses and in trial B with the 200 mg dose, bronchoconstriction was attenuated (50% fall in sGaw was not observed) up to the highest dose of LTD4 administered. In trial B, during the 40 mg period, only two of six patients exhibited a 50% fall in sGaw; PC50 ratios (montelukast 40 mg/placebo) were 18 and 45 in these two patients. These results indicate that montelukast is a highly potent and long-lasting antagonist of LTD4-induced bronchoconstriction in patients with asthma.

Acetates↗

Immunoassays to study prevalence of antibody against GB virus C in blood donors.

Immunoassays were developed to determine the seroprevalence of antibody against human GB virus C (GBV-C). The antigenic target in each assay was a 44.6-kDa glycosylated protein representing the first 315 amino acids encoded by the GBV-C E2 gene. Sera or plasma were assayed for E2 antibody using an anti-human EIA format in which antigen-coated polystyrene beads were reacted with sample, and bound antibody was detected by addition of enzyme labelled goat anti-human IgG. The presence of anti-E2 antibody was confirmed using a sandwich EIA format in which samples were reacted with antigen coated polystyrene beads, followed by addition of solution phase biotinylated antigen. Detection of antibody captured biotinylated E2 was accomplished by addition of enzyme-conjugated anti-biotin antibody. Antibody against the E2 antigen was detected in 7.4 and 7.8% of 500 sera and 500 plasma, respectively, from US volunteers donating to a Wisconsin blood center, and in approximately 10.7% of hepatitis and retrovirus marker-negative volunteer blood donors from a Missouri blood center. The rate in 1018 sera from US commercial donors at multiple US blood centers was 36.7%. These results indicated a relatively high prevalence of GBV-C exposure in US volunteer donors, and particularly in commercial donors. The clinical implication of the high exposure rate is unclear. These immunoassays are being combined with nucleic acid detection to assess prevalence of GBV-C world wide and to determine if GBV-C plays a role as an etiologic agent.

Animals↗

Clarithromycin-induced ventricular tachycardia.

Clarithromycin is a relatively new macrolide antibiotic that offers twice-daily dosing. It differs from erythromycin only in the methylation of the hydroxyl group at position 6. Although the side-effect profile of erythromycin is established, including gastroenteritis and interactions with other drugs subject to hepatic mixed-function oxidase metabolism, experience with the newer macrolides is still being recorded. Cardiotoxicity has been demonstrated after both intravenous and oral administration of erythromycin but has never been reported with the newer macrolides. We report a case of ventricular dysrhythmias that occurred after six therapeutic doses of clarithromycin. The dysrhythmias resolved after discontinuation of the drug.

Adult↗

Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids.

BACKGROUND: Cysteinyl leukotriene release in association with airway inflammation is a feature of clinical asthma. The acute effects of montelukast (MK-0476), a potent, orally administered, specific cysteinyl leukotriene receptor antagonist, on airways obstruction was assessed in patients with mild to moderately severe asthma. METHODS: Twenty two asthmatic subjects were randomised to receive montelukast, 100 mg or 250 mg, or placebo in a double blind, three period, crossover trial. Ten of the patients were using concomitant inhaled corticosteroids. RESULTS: Montelukast increased the forced expiratory volume in one second (FEV1) from predose baseline values compared with placebo, the percentage point differences between montelukast and placebo being 8.6% (95% CI 3.6 to 13.6) and 8.5% (95% CI 3.5 to 13.5) for the 100 mg and 250 mg doses, respectively. CONCLUSION: Single oral doses of montelukast 100 mg and 250 mg produced significant increases in FEV1 irrespective of the concurrent use of inhaled corticosteroids in asthmatic subjects with airflow limitation.

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