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R Sharma

Publications and source records attributed to R Sharma.

At least 127 records · Page 7Linked to original sources
PubMed2001

Multiple copies of the upstream regulatory region of the major capsid protein gene of bacteriophage MB78 inhibit phage morphogenesis.

The 2.311 kb EcoRI F fragment of bacteriophage MB78 has been cloned in multicopy vectors pUC19 and pCR90. Salmonella typhimurium strains carrying such plasmids cannot support development of phage MB78 while other Salmonella phages like P22 and 9NA grow normally. Most of the phage MB78 induced functions are normal in such transformed hosts but proper maturation of the phage particles does not take place. Deletion of 138 bp from the 3' end of the cloned fragment reverses the inhibitory effect. Analysis of nucleotide and the deduced amino acid sequence of a 1.2 kb HindIII-SalI fragment of the phage genome which overlaps the 138 bp confirms that this part contains the upstream regulatory region of the major structural protein gene. It seems that in presence of multiple copies of the upstream regulatory region (which includes a number of promoter like sequence) of the coat protein gene, the maturase gene is down regulated and this is effective only in cis, a situation quite similar to that of Qbeta RNA phages.

Amino Acid Sequence↗
PubMed2001

Inhalable microparticles containing drug combinations to target alveolar macrophages for treatment of pulmonary tuberculosis.

PURPOSE: Drug therapy of tuberculosis (TB) requires long-term oral administration of multiple drugs for curing as well as preventing and/ or combating multi-drug resistance. Persistent, high blood levels of antitubercular drugs resulting from prolonged oral administration of anti-TB drugs may be neither necessary nor sufficient to kill mycobacteria residing in macrophages (M4). Inhalable biodegradable microparticles containing two of the first-line anti-TB drugs, isoniazid (H), and rifampicin (R), were prepared and tested for (i) phagocytosis by mouse Mphi. (ii) administration as a dry powder inhalation to rats, and (iii) targeting alveolar Mphi with high drug doses when administered to rats. METHODS: poly(D-L lactic acid) microparticles were prepared by emulsion methods and their drug content and size distribution determined. These were tested for uptake by murine Mphi in culture and resultant intracellular drug concentrations determined by high performance thin-layer chromatography (HPTLC). Rats were administered an inhalation of microparticles using an inhalation chamber developed in the lab. The extent of microparticle delivery in vivo was examined by flow-cytometry. Drug concentrations in the blood and in alveolar Mphi were estimated by high-performance liquid chromatography after oral, vascular. intratracheal, and inhalation administration. RESULTS: Inhalable microparticles could be prepared and were taken up by cultured Mphi. Large numbers of particles could be delivered to the bronchiopulmonary system through a 2-min exposure to fluidized particles. The intracellular drug concentrations resulting from vascular delivery of soluble drugs were found to be lower than those resulting from particle inhalation. CONCLUSIONS: Inhalable microparticles containing multiple anti-TB drugs offer promises of dose and dosing-frequency reduction, toxicity alleviation, and targeting Mphi-resident persistent mycobacteria.

Administration, Inhalation↗
PubMed2001

Modulation of hepatic and renal glucocorticoid receptors during aging of mice.

The regulation of hepatic and renal glucocorticoid receptors (GRs) in young (4 weeks) and senescent (120 weeks) mice was studied. Significant changes in the level of GRs from liver and kidney were detected, whereas the affinity (Kd) for the hormone [3H]dexamethasone did not change in young and old mice. The concentration of GRs was markedly decreased in liver (25%) and kidney (33%) of old mice as compared to young ones. The magnitude of heat activation of GR complexes was more pronounced in both the tissues at young age compared to old. In addition, we have found changes in the heat activation-inhibition studies of GRs, using polyunsaturated fatty acids (PUFAs) as measured by binding to DNA-cellulose and purified nuclei. Linoleic acid (C18:2) exhibited significant decrease in heat activation of both hepatic and renal hormone-bound GR, with higher magnitude of inhibition in young liver (64%) and kidney (68%) as compared to old (41% and 43%, respectively). Arachidonic acid (C20:4) was also found to be an inhibitor of activation causing significant decrease in hepatic GR activation, with greater inhibition in young liver with respect to old, however, without any such difference in the kidney of young and old mice. Furthermore, DNase I digestion and extraction of nuclear-bound GR-complexes from both the tissues reveal lesser extraction in old liver (26%) and kidney (24%) compared to young tissues, indicating chromatin condensation with aging, thereby controlling the accessibility to such transcription factors as GRs. These findings indicate that the changes in the GR concentration, activation-modulation by PUFAs and chromatin organization, that take place during aging, may contribute to functional changes in glucocorticoid action mechanisms in senescent animals.

Aging↗
PubMed2001

Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection.

3-Hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitors are established anti-lipidemic agents. They also exert immunomodulatory effects. Two recent reports suggest that pravastatin may be useful in decreasing the incidence and severity of acute rejections (ARs) in heart and kidney transplant recipients. We undertook this prospective, randomized, placebo-controlled, double blind trial to investigate the effect of lovastatin on acute renal allograft rejection. Sixty-five consecutive, one-haplotype-matched, living related first renal transplant recipients were randomized to receive either lovastatin 20 mg/d or placebo for 3 months, in addition to cyclosporine, azathioprine, and steroids. Lipid levels, AR episodes, and liver and muscle enzymes were followed for 3 months post-transplant. At the end of the study period, lovastatin had successfully controlled lipid levels. However, there was no effect on AR episodes (15.15% in the treatment group vs. 18.75% in the placebo group).

Adult↗
PubMed2001

Adverse profile of dietary nutrients, anthropometry and lipids in urban slum dwellers of northern India.

OBJECTIVES: The intra-country rural to urban migrant populations undergo radical socio-economic and lifestyle changes in a developing country. Therefore, it is an interesting sample in which to study nutrition pattern, anthropometry and metabolic profile. The aim of this study was to assess nutrient profile and its association with the anthropometry, percentage body fat (%BF) and blood lipids in the urban slum dwellers in northern India. DESIGN: A cross sectional epidemiological descriptive study. SETTINGS: The study was conducted in urban slum colony of Gautam Nagar, situated in a southern area of New Delhi. SUBJECTS: The data was recorded in 227 subjects (52 males and 175 females). RESULTS: The diets averaged approximately 59-60% of energy from carbohydrates, 12-13% energy from protein, and 24-27% energy from dietary total fat. Lower intake of monounsaturated fatty acids (MUFA), a low ratio of n-6/n-3 fatty acids, a high ratio of polyunsaturated and saturated fatty acids, a high intake of erucic acid, and a low consumption of fibre and vitamin E intake were significant observations. Although their mean body mass index (BMI) was in a low range (20.5+/-4.2), %BF was high in females (26.7+/-8.6%; P=0.001), and a high prevalence of abdominal obesity was observed in both males (22%) and females (16%). Moreover, there was high prevalence of hypercholesterolemia, hypertriglyceridemia and, in particular, low levels of high-density lipoprotein cholesterol. Those consuming a high-fat diet (>30%) also consumed high MUFA, n-3 fatty acids, saturated fat and dietary cholesterol. Carbohydrate intake as percentage energy was a significant predictor of the levels of triacylglycerol in males, while in females significant predictors for triacylglycerol include intake of carbohydrate as percentage energy, age, %BF and BMI. CONCLUSION: In this economically deprived population, now constituting approximately 30-50% of the urban population of major cities in India, such adverse dietary, anthropometric and metabolic factors are predictors of early and accelerated atherosclerosis. SPONSORSHIP: This study was fully supported by a financial grant from the Science and Society Division, Department of Science and Technology, Ministry of Science and Technology, Government of India.

Adipose Tissue↗
PubMed2001

High prevalence of diabetes, obesity and dyslipidaemia in urban slum population in northern India.

BACKGROUND AND AIMS: In this study, a prevalence survey of various atherosclerosis risk factors was carried out on hitherto poorly studied rural-urban migrants settled in urban slums in a large metropolitan city in northern India, with the aim of studying anthropometric and metabolic characteristics of this population in socio-economic transition. DESIGN: A cross-sectional epidemiological descriptive study. SUBJECTS: A total of 532 subjects (170 males and 362 females) were included in the study (response rate approximately 40%). METHODS AND RESULTS: In this study, diabetes mellitus was recorded in 11.2% (95% CI 6.8-16.9) of males and 9.9% (95% CI 7.0-13.5) of females, the overall prevalence being 10.3% (95% CI 7.8-13.2). Based on body mass index (BMI), obesity was more prevalent in females (15.6%; 95% CI 10.7-22.3) than in males (13.3%; 95% CI 8.5-19.5). On the other hand, classifying obesity based on percentage body fat (%BF), 10.6% (95% CI 6.4-16.2) of males and 40.2% (95% CI 34.9-45.3) of females were obese. High waist-hip ratio (WHR) was observed in 9.4% (95% CI 5.4-14.8) of males and 51.1% (95% CI 45.8-56.3) of the females. All individual skinfolds and sum of skinfolds were significantly higher in females (P<0.001). In both males and females above 30 y of age, there was a steep increase in the prevalence of high WHR, and in females, %BF was very high (particularly in %BF quartile>30%). Furthermore, total cholesterol and low-density lipoprotein cholesterol were high in both males and females. Stepwise multiple linear regression analysis showed that for both males and females BMI, WHR and %BF were positive predictors of biochemical parameters, except for HDL-c, for which these parameters were negatively associated. CONCLUSIONS: Appreciable prevalence of obesity, dyslipidaemia, diabetes mellitus, substantial increase in body fat, generalised and regional obesity in middle age, particularly in females, need immediate attention in terms of prevention and health education in such economically deprived populations.

Adolescent↗
PubMed2001

Univentricular repair in children under 2 years of age: early and midterm results.

BACKGROUND: Encouraging results have been obtained from early univentricular repair. Our study was designed to assess the impact of young age (less than 2 years) on the outcome of univentricular repair. PATIENTS AND METHODS: Between January 1992 and December 1998, 65 out of 311 patients undergoing univentricular repair at the All India Institute of Medical Sciences, New Delhi, were less than 2 years of age. We compared these 65 carefully selected patients (group 1) with the 246 patients who were more than 2 years of age (group 2). Since 1994, all patients of both groups had a fenestration of the intra-atrial baffle. RESULTS: The early mortality rate was 9.2% in group 1 and 7.7% in group 2. The overall Fontan failure rate was 12.3% in group 1 and 12.2% in group 2. In group 1, a higher incidence of Fontan failure was noted in patients with suboptimal weight, non-tricuspid atresia morphology, nonfenestrated Fontan and those who did not comply with more than two of Choussat's criteria, but the values were not statistically significant. Aortic cross-clamp time of more than 60 min was the only and highly significant predictor of Fontan failure (P < 0.01). The overall effusion rate was 24.05% in group 1 and 27.98% in group 2. In group 1, patients weighing less than 10 kg (P = 0.0007), without fenestration of the atrial baffle (P < 0.05) and with systemic ventricular dysfunction (P < 0.001), systemic ventricular end-diastolic pressure of more than 12 mmHg (P < 0.001), mean pulmonary artery pressure of more than 15 mmHg (P < 0.001) and aortic crossclamp time of more than 60 min (P < 0.01), were all found to be significant risk factors of pleural effusion. Pulmonary artery distortion needing reconstruction did not increase the Fontan failure or effusion rates. Oxygen saturation ranged from 85 to 94% (mean 89%) in patients having a functioning fenestration at a mean follow-up period of 30 months. The actuarial survival at 84 months was 90 +/- 0.04% in group 1 and 88 +/- 0.02% in group 2. CONCLUSIONS: Our results suggest that carefully selected patients under 2 years of age are suitable candidates for one-stage univentricular repair and that survival is not significantly different from that of older patients. Routine fenestration of the intra-atrial baffle is an option available to ameliorate morbidity and obviate mortality. Non-compliance with more than two of Choussat's criteria appears to be additive in unsatisfactory outcome.

Journal Article↗
PubMed2001

Subaortic membrane excision: mid-term results.

BACKGROUND: Subaortic membrane (SAM) is a form of fixed subaortic obstruction in which a fibrous membrane is located below the aortic valve. AIM: To determine the role of surgical treatment for patients with a discrete SAM. PATIENTS AND METHODS: The hospital records of 45 patients (age range: 2-23 years; median 8 years) undergoing surgery for SAM between 1990 and 1998 at the All India Institute of Medical Sciences, New Delhi, India, were analysed. Preoperative echocardiographically calculated gradients across the left ventricular outflow tract ranged from 50 to 154 mmHg (mean: 86.5 +/- 33.2 mmHg). Nine patients had trivial aortic regurgitation (AR), 10 had mild AR and five had moderate-severe AR. The left ventricular ejection fraction (LVEF) ranged from 20 to 68% (mean 48 +/- 15%). Nineteen patients had significant left ventricular dysfunction (LVEF <50%). Transaortic resection of SAM was done in all patients along with excision of a wedge-shaped segment of septal muscle underlying the membrane. RESULTS: There were no early or late postoperative deaths. On follow up (up to 113 months), only four patients had gradients >30 mmHg. LVEF improved to 45-70% (mean 58 +/- 7.7%). AR reduced to mild in four patients and trivial in four patients, and did not progress further. CONCLUSION: Resection of SAM carries long-term benefits. Routine septal myectomy appears to be associated with a low risk of recurrence.

Journal Article↗
PubMed2001

Dipole localization for identification of neuronal generators in independent neighboring interictal EEG spike foci.

PURPOSE: We evaluated dipole localizations of independent neighboring interictal spike foci using scalp electroencephalogram (EEG) to identify neuronal generators of epileptic discharges. METHODS: Three pediatric patients with extratemporal lobe epilepsy who had two independent neighboring interictal spike foci on scalp EEG were studied. Prolonged video EEG was digitally recorded from 19 scalp electrodes, whose positions were registered using a three-dimensional digitizer. Interictal spikes were visually selected based on negative phase reversals on bipolar montages. We analyzed the dipole position and moment of each spike using a single moving dipole and three-shell spherical head model. The dipoles were overlaid onto magnetic resonance (MR) images and divided into two groups based on two spike foci. RESULTS: The dipoles of the two groups were oriented either tangentially or radially to the scalp in close proximity to each other. The dipoles oriented radially were located underneath the electrode with a negative peak; those oriented tangentially were between electrodes with a negative and positive peak. The positions of tangential dipoles were more concentrated than those of radial dipoles. The epileptogenic regions corresponded to the dipole localizations. Surgical excisions were performed based on the results of electrocorticography. After surgery, two patients were seizure free, and one had rare seizures (follow-up period, 13-31 months). CONCLUSIONS: We showed that dipoles in close proximity but with different orientations projected two negative maxima on scalp EEG in three patients with extratemporal localization-related epilepsy. Equivalent current dipole analysis of individual interictal spikes can provide useful information about the epileptogenic zone in these patients.

Adolescent↗
PubMed2001

Uric acid in cachectic and noncachectic patients with chronic heart failure: relationship to leg vascular resistance.

BACKGROUND: Chronic heart failure (CHF) is a hyperuricemic state, and capillary endothelium is the predominant site of xanthine oxidase in the vasculature. Upregulated xanthine oxidase activity (through production of toxic free radicals) may contribute to impaired regulation of vascular tone in CHF. We aimed to study the relationship between serum uric acid levels and leg vascular resistance in patients with CHF with and without cachexia and in healthy control subjects. METHODS: In 23 cachectic and 44 noncachectic patients with CHF (age, 62 +/- 1 years, mean +/- SEM) and 10 healthy control subjects (age, 68 +/- 1 years), we assessed leg resting and postischemic peak vascular resistance (calculated from mean blood pressure and leg blood flow by venous occlusion plethysmography). RESULTS: Cachectic patients, compared with noncachectic patients and control subjects, had the highest uric acid levels (612 +/- 36 vs 459 +/- 18 and 346 +/- 21 micromol/L, respectively, both P <.0001) and the lowest peak leg blood flow and vascular reactivity (reduction of leg vascular resistance from resting to postischemic conditions: 83% vs 88% and 90%, both P <.005). In all patients, postischemic vascular resistance correlated significantly and independently of age with uric acid (r = 0.61), creatinine (r = 0.47, both P <.0001), peak VO2 (r = 0.34), and New York Heart Association class (r = 0.33, both P <.01). This correlation was not present in healthy control subjects (r = -0.04, P =.9). In multivariate and stepwise regression analyses, serum uric acid emerged as the strongest predictor of peak leg vascular resistance (standardized coefficient = 0.61, P <.0001) independent of age, peak VO2, creatinine, New York Heart Association class, and diuretic dose. CONCLUSIONS: Hyperuricemia and postischemic leg vascular resistance are highest in cachectic patients with CHF, and both are directly related independent of diuretic dose and kidney function. The xanthine oxidase metabolic pathway may contribute to impaired vasodilator capacity in CHF.

Adult↗
PubMed2001

Both subtype 1 and 2 receptors of angiotensin II participate in regulation of intracellular calcium in glomerular epithelial cells.

We have documented that both receptors of angiotensin II (ANG II) (AT1 and AT2) are involved in regulation of intracellular signals in glomerular epithelial cells (GECs). We studied the role of these receptors in regulation of intracellular ionized calcium [Ca2(+)]i in GECs. Cells were loaded with Indo-1 (Ca2(+)) and SNARF-1 (pH) fluorescent dyes and then incubated with or without ANG II for 1 hour at 37 degrees C. In some experiments AT(1) and AT(2) receptor blockers (Losartan and PD 12339, respectively) were added. In additional experiments cells were incubated with thapsigargin (Tg) and bradykinin (BK) as well as ANG II. A four-channel fluorescence videomicroscope system was used to measure real-time [Ca2(+) ]i in individual cells. Levels of inositol triphosphate (IP(3)) were measured with radioimmunoassay. An amount of 100 nmol/L of ANG II caused a maximal increase in [Ca2(+)]i in calcium-containing buffer. ANG II had no effect on intracellular pH of GECs. Increase in [Ca2(+)]i by ANG II was prevented by the concurrent use of Losartan and PD 123319. BK caused a transient increase in [Ca2(+)]i, which was significantly decreased by ANG II; concurrent addition of Losartan and PD 123319 prevented ANG II effect. ANG II prevented the accumulation of Ca2(+) in intracellular stores. ANG II caused a significant but transient increase in levels of IP(3). In summary, ANG II increases extracellular/intracellular calcium dependent bidirectional Ca2(+) transport in GECs, inhibits BK induced release of Ca2(+) from IP(3) sensitive stores, and, in addition, reduces refilling of endoplasmic reticulum [Ca2(+)] depleted by repeated BK stimulation. Both receptor subtypes appear to be important in ANG II mediated physiologic responses of GECs and may participate in modulation of glomerular function in vivo.

Angiotensin II↗
PubMed2001

Remote superficial femoral artery endarterectomy: Multicenter medium-term results.

OBJECTIVE: The results of percutaneous transluminal angioplasty, atherectomy, and laser angioplasty for the treatment of long-segment (>10 cm) superficial femoral artery (SFA) occlusive disease have proved disappointing. Remote superficial femoral artery endarterectomy (RSFAE) is a minimally invasive procedure, performed through a single limited groin incision that may offer patency rates comparable with those of above-knee femoropopliteal (AKFP) bypass graft. In this retrospective multicenter study the medium-term results of RSFAE are examined. METHODS: Sixty patients were included in this study. Indications for the procedure were claudication in 52 patients and limb salvage in eight patients. RSFAE was performed with the MollRing Cutter device through a femoral arteriotomy. The distal "flap" of atheroma was anchored by balloon/stent angioplasty through the femoral arteriotomy. All patients underwent a follow-up examination with serial color flow ultrasound scanning. RESULTS: Ten patients with heavily calcified SFAs failed as "intentions to treat"; these patients underwent AKFP bypass grafting. The mean length of the endarterectomized SFAs was 22.3 cm (range, 8-37 cm). The primary cumulative patency rate by means of life-table analysis was 61.4% +/- 9% (SE), (mean, 12.9 months; range, 3-36 months). During follow-up, percutaneous transluminal angioplasty was necessary in 14 patients, for a primary-assisted patency rate of 82.6% +/- 8%. The locations of the restenoses after RSFAE were evenly distributed along the endarterectomized SFAs. There were no deaths and one wound complication (hematoma), and the mean hospital length of stay was 1.4 days +/- 0.8 days. CONCLUSIONS: RSFAE is a safe and moderately durable procedure. If long-term patency rates are similar to those of AKFP bypass graft, RSFAE may prove to be a minimally invasive adjunct for the treatment of SFA occlusive disease that will lower operative morbidity, reduce hospital LOS, and shorten recuperation.

Aged↗
PubMed2001

Factors associated with delays in accessing HIV primary care in rural Arkansas.

While debate continues at what stage of human immunodeficiency virus (HIV) disease to begin combination antiretroviral therapy, a number of clinical and public health benefits are linked to early entry into primary care soon after first testing HIV positive. However, HIV-infected patients continue to test late and delay entry into care. We used routinely collected demographic and clinical information to examine which factors are associated with delays in seeking care in a predominantly rural, economically poor area of Arkansas. The study population is 75% African American and male and 70% lack health insurance; nearly one fourth were referred from prison. At diagnosis, two thirds of the population had CD4 counts below 500 cells per microliter. Days from initial HIV diagnosis to entry into care declined from a median of 178 in 1994 to 24 in 1998. In 1998, 75% of the population entered into primary care within 2 months of diagnosis. However, CD4 counts at HIV diagnosis also declined in this period, from a median of 427 in 1995 to 208 cells per microliter in 1998. More recent year of diagnosis was associated with a shorter delay in seeking care; males, and individuals lacking health insurance took significantly longer to enter into care than females and those with insurance, respectively. Our univariate finding of extensive delays in seeking care in the prison population did not hold in the multivariate analysis. We found significant delays in time to initial HIV diagnosis, and further considerable delays in males and those lacking health insurance in the time taken to enter into primary care.

Adolescent↗
PubMed2001

Tc-99m Infecton scan in possible pelvic inflammatory disease.

Tc-99m Infecton imaging was used to examine patients thought to have pelvic inflammatory disease (PID) based on clinical and sonographic findings. Twenty-one patients with PID had Tc-99m Infecton scans. Eleven patients underwent a second radionuclide scan after 1 month of antibiotic treatment. The diagnosis of PID was confirmed by laparoscopy in one patient who was later found to have a tubercular infection. In the remaining patients, the diagnosis was based on uterine tenderness, fever and lower abdominal pain that responded to antibiotics, and ultrasound findings. These patients had infection of the uterus, fallopian tubes, the cul-de-sac, or all of these. The Tc-99m Infecton scan appears to be useful in the diagnosis of possible PID and is recommended after a complete course of antibiotics for monitoring treatment response.

Adult↗
PubMed2001

Hemiagenesis of the thyroid associated with chronic lymphocytic thyroiditis.

The authors report a case of hemiagenesis of the left thyroid lobe indicated on Tc-99m pertechnetate scan and later confirmed on ultrasonography. The patient was clinically hypothyroid with a right-sided goiter. The cytopathologic diagnosis was made by fine-needle aspiration cytologic analysis, which indicated chronic lymphocytic thyroiditis in the right lobe of the thyroid gland. Later the patient's condition was stabilized with thyroxine replacement therapy. The association of hemiagenesis of the thyroid with chronic lymphocytic thyroiditis has not been reported in the literature.

Adult↗