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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 145 records · Page 8Linked to original sources

Lipid peroxidation and vitamin E in ischemic heart disease.

The study was carried on 90 adult cases which were divided into 3 groups of 30 cases each. Group A consisted of 30 normal healthy controls whereas Group B and C comprised of 30 patients each of chronic stable ischaemic heart disease and of acute myocardial infarction (AMI), respectively. Patients in all the 3 groups were age and sex matched. Group C consisted of 17 cases of anterior wall myocardial infarction, 10 of inferior wall, 2 of anterolateral and 1 of antero-inferior MI and they had an average 6.96 +/- 3.39 hours of chest pain before hospitalization. Serum vitamin E in group A, B and C on day 1 was 7.90 +/- 3.23, 5.345 +/- 2.37 and 1.302 +/- 1.090 micrograms/ml, respectively and malondialdehyde (MDA) levels in these groups were 0.759 +/- 0.27, 0.780 +/- 0.334 and 3.092 +/- 1.124 nmol/ml, respectively. Vitamin E and MDA levels in group C on day 3 were 3.382 +/- 1.088 micrograms/ml and 1.492 +/- 0.849 nmol/ml, respectively. In Group C, vitamin E levels were significantly decreased (p < 0.001) as compared to controls and remained low after 2 days. MDA levels were raised more than 3 times in AMI group (p < 0.01) and decreased slightly after 2 days but were elevated compared to controls. Findings suggest that vitamin E deficiency is inversely related to lipid peroxidation and is elevated during AMI. Therefore supplementation of vitamin E in AMI would be beneficial.

Coronary Disease↗

Upper urinary tract stones & Ureaplasma urealyticum.

Extensive culture of stones and of pre-operative and renal pelvic urine for isolation of bacteria and Ureaplasma urealyticum were performed in 70 patients of nephrolithiasis. Stones were subjected to biochemical analysis and scanning electron microscopy. Micro-organisms were isolated from 33 (47%) of 70 renal stones. Of the 38 species of micro-organisms isolated, 14 were urea-splitting (U. urealyticum 2; Klebsiella pneumoniae 8; Morganella morganii 1; Acinetobacter spp 3) and 24 were nonurea splitting. U. urealyticum was cultured from the renal stones of two patients. Pelvic urine, unlike voided urine did reflect the bacteriology of the stone. Biochemically, 55 stones (79%) were calcium oxalate phosphate stones, 10 (14%) were calcium oxalate stones and 5 (7%) were uric acid stones. None of the stones were found to be of struvite composition. These data suggest that infection stones are uncommon in this part of the country. Further, infection of renal stones with fastidious organisms like U. urealyticum and multi-drug resistant bacteria necessitate their removal to ensure complete cure.

Adult↗

Elevated levels of anti-proteus antibodies in patients with active rheumatoid arthritis.

We carried out this study to determine if our patient population with rheumatoid arthritis (RA) has elevated levels of antibodies to gut bacteria. Seventy patients with RA were categorised as being either active or inactive on clinical grounds. Antibodies to the H and O antigens of Proteus mirabilis and Salmonella typhi were determined by tube agglutination method in these patients, 18 patients with osteoarthritis and 82 healthy controls. There was no significant difference in the anti-proteus antibody titres between both the control groups and patients with inactive disease. However, antibody levels among patients with active disease were significantly higher than controls (P < 0.001). There was no significant difference in anti-salmonella antibody titres among the various disease and control groups. Elevated antibody levels could suggest a role for Proteus as an etiological agent in RA.

Adult↗

Postoperative bronchopulmonary complications in stage III lung cancer patients treated with preoperative paclitaxel-containing chemotherapy and concurrent radiation.

We previously observed encouraging results and acceptable toxicity in phase II trials testing preoperative split-course thoracic radiation and simultaneous cisplatin, etoposide, and 5-fluorouracil in stage III non-small cell lung cancer patients. We decided to delete 5-fluorouracil and to incorporate paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into our combined-modality treatment. The first group of patients received carboplatin dosed at an area under the concentration-time curve of 4 on day 2, etoposide 50 mg orally days 1 to 5 and 8 to 12, cisplatin 50 mg/m2 on day 21, and paclitaxel 35 mg/m2 escalated to 45 mg/m2 on days 1 and 8. Group 2 patients received carboplatin dosed at an area under the concentration-time curve of 4 on day 1, etoposide 45 mg/m2 intravenously daily on days 2 to 5, and paclitaxel 80 mg/m2 (escalating to 120 mg/m2) on day 1. Patients in group 3 received carboplatin dosed at an area under the concentration-time curve of 4 on day 1 and paclitaxel 120 mg/m2 (escalating to 140 mg/m2) on day 1. Each patient received radiation 2 Gy daily on days 1 to 5 and 8 to 12, and a total of two cycles was given at 28-day intervals. Twenty-one patients received preoperative chemoradiotherapy: group 1, five patients; group 2, 11 patients; and group 3, five patients. Thoracotomy was not done in five patients due to cerebrovascular accident in one and progressive tumor in four. The remaining 16 patients had the following procedures: pneumonectomy, eight; lobectomy, six; chest wall resection, one; and no resection, one. Postoperative complications included bronchopleural fistula in one patient each in groups 1 and 3, hypoxia in one patient in group 1, pulmonary hypertension in one patient in group 2, pneumonia in one patient in group 2, and adult respiratory distress syndrome in one patient in group 3, which proved lethal. Thus, six of 16 patients had serious postoperative complications. The relatively high incidence of postoperative bronchopulmonary complications suggests that the use of preoperative paclitaxel-containing chemotherapy and simultaneous thoracic radiation may not be feasible.

Antineoplastic Combined Chemotherapy Protocols↗

Evaluation of efficacy of standard haemodialysis and verapamil added peritoneal dialysis.

The study was carried out on 30 adult subjects of acute renal failure who were randomly divided into two groups of 15 patients each. Group A patients were subjected to standard haemodialysis (HD) for 4 hours using holofibre dialyser and group B patients received 36 hours of peritoneal dialysis (PD) where Verapamil was added intraperitonealy in the dose of 10 mg/ L/cycle in the clearance periods III, V, VII, IX and XI (Total dose 150 mg). The 36 hours of PD consisted of 36 cycles of one hour duration each and these were divided into 12 clearance periods (CP) of 3 cycles each. Following both the forms of dialytic treatments, there was significant improvement in the signs of uraemia with fall in the blood urea and serum creatinine levels. The peritoneal clearances, percentage fall of urea and creatinine, and protein loss were similar in the two groups (p > 0.5). However, ultrafiltration was significantly higher in the group B. No untoward effects were noticed in group B however group A patients had episodes of hypotension (5)] disequilibrium (6) and cardiac arrhythmias (1). It can be concluded that both clinically and biochemically, 36 hours of Verapamil added PD and 4 hours of hemodialysis are comparable and therefore, peritoneal dialysis may be used more frequently in acute renal failure specially in situations where trained dialysis staff is not available and patients are not haemodynamically stable.

Adult↗

Physiological perspectives of copper.

Living organisms are composed of only 30 elements, nine of which are required in traces (1:20,000), hence called "Trace elements". The family of trace elements comprises of selenium, chromium, manganese, iron, cobalt, copper, zinc, molybdenum and iodine. Each element has specific associations referred as metalloenzymes.

Animals↗

Rubiadin, a new antioxidant from Rubia cordifolia.

Rubiadin, a dihydroxy anthraquinone, isolated from alcoholic extract of Rubia cordifolia, possesses potent antioxidant property. It prevents lipid peroxidation induced by FeSO4 and t-butylhydroperoxide (t-BHP) in a dose dependent manner. The per cent inhibition was more in the case of Fe2+ induced lipid peroxidation. The antioxidant property of the preparation has been found to be better than that of EDTA, Tris, mannitol, Vitamin E and p-benzoquinone.

Animals↗

Mechanism of photosensitization of glioblastoma and neuroblastoma cells by merocyanine 540: a lipid peroxidation study.

Mechanism of merocyanine 540 (MC540) mediated photosensitization in glioblastoma (U-87MG) and neuroblastoma (Neuro 2a) cells was investigated. Photoinduced lipid peroxidation was measured in the presence of mechanistic probes-deuterium oxide (D2O), sodium azide, superoxide dismutase (SOD), mannitol and sodium benzoate. In both the types of cells, the photoinduced lipid peroxidation was enhanced in D2O whereas it showed inhibition in the presence of sodium azide. SOD also inhibited the lipid peroxidation while sodium benzoate and mannitol had no effect. These results suggest that photosensitization of U-87MG and Neuro 2a cells by MC 540 involves both type I (free radical mediated) and type II (singlet oxygen mediated) mechanisms.

Animals↗

Cyclosporine protects glomeruli from FSGS factor via an increase in glomerular cAMP.

Cyclosporine (CsA) administration to patients with recurrent focal segmental glomerulosclerosis (FSGS) after transplantation results in remission of proteinuria. We have shown that sera from patients with recurrent FSGS can increase the glomerular albumin permeability (Palbumin) and that increase in glomerular cAMP levels can alter the permeability characteristics of glomeruli in vitro. The purpose of this study was to determine if the increased glomerular levels of cAMP were related to the protective effects of CsA on an increase in Palbumin by FSGS sera. Glomeruli from Sprague-Dawley rats following intraperitoneal administration of CsA (25 mg/kg/day), cremophore (25 mg/kg/day), or saline for 5 days were incubated with 1:50 dilution of serum from three FSGS patients or with pooled normal human serum prior to calculation of Palbumin. Glomerular cAMP was measured by radioimmunoassay. Glomerular ultrastructural changes were assessed by transmission electron microscopy (TEM). Serum from three FSGS patients markedly increased Palbumin of glomeruli from saline or cremophore treated rats (saline, 0.68+/-0.08; 0.72+/-0.07; 0.70+/-0.07; and cremophore, 0.79+/-0.05; 0.81+/-0.02; 0.79+/-0.01; n=25 glomeruli in each group). In contrast Palbumin of glomeruli from CsA treated rats was not increased by any of the three FSGS sera tested (0.03+/-0.02; 0.04+/-0.05; 0.02+/-0.07, n=25 glomeruli in each group). Glomerular cAMP (pmol/mg of protein) increased 5 fold in CsA treated rats (328+/-26; 5 rats) compared with cremophore or saline treated rats (87+/-24 and 65+/-23, P<0.01; 5 rats in each group). The glomerular basement membrane appeared to be thickened and the lamina densa had an irregular appearance after treatment with CsA. No ultrastructural changes of glomerular epithelial or endothelial cells were evident. We conclude that CsA may have a direct protective effect on the glomerular filtration barrier in FSGS. We postulate that increased levels of glomerular cAMP by CsA may play an important role in protecting the glomerular Palbumin effect of the FSGS factor and may contribute to remission of proteinuria in FSGS patients.

Albumins↗

A single-step immunochromatographic test for the detection of Entamoeba histolytica antigen in stool samples.

A rapid, single step, sensitive and specific immunochromatographic test for the detection of E. histolytica antigens in the stool samples is described. Monoclonal antibody AC55 specific for E. histolytica was used as capture antibody on nitrocellulose sheet. The same antibody was conjugated to colloidal gold to detect the presence of antigen. In this test, multiple steps of washing, incubation, etc. are not required and there is no need for secondary colour development as gold particles produce a typical reddish, purple colour, when they bind to the solid phase at the site of immune reaction. 151 stool samples from patients with suspected amoebiasis were screened by this assay. Sensitivity of the test was found to be 97.6% and specificity 92.6%. 25 polyxenic E. histolytica cultures and other cultures were also tested. The test did not show positive reaction with other intestinal parasites.

Animals↗

Sex differences in estrogen receptor and progestin receptor induction in the guinea pig hypothalamus and preoptic area.

Quantitative in vitro autoradiography was used to determine if regional sex differences in estrogen receptor (ER) content and/or estrogen responsiveness, as indicated by an increase in progestin receptor (PR), are present in the adult guinea pig brain. Adult male and female guinea pigs were gonadectomized 1 week before subcutaneous injection of 25 micrograms estradiol benzoate (EB)/kg body wt or the sesame oil vehicle. Animals were killed by decapitation 44 h after injection. Unoccupied PRs, and unoccupied and occupied ERs, were measured in discrete brain regions by quantitative in vitro autoradiography using [3H]R5020 and [3H]estradiol as ligands, respectively. In vehicle-injected controls, a higher level of ER was found in the arcuate nucleus (ARC), dorsal medial nucleus (DMN) and ventrolateral nucleus (VLN) of females as compared to males. At 44 h after EB injection, 32-55% of the ERs were occupied; however, EB treatment caused a marked down-regulation of total receptor (calculated as occupied+ unoccupied receptor) in most of the brain regions examined, including the periventricular preoptic area (PVP), medial preoptic area (MPO), bed nucleus of the stria terminalis, paraventricular nucleus, ARC, ventrolateral hypothalamus (VLH), VLN, and DMN. In EB-treated animals, PR binding was detectable in the PVP, MPO, ARC, VLH, and VLN, with higher levels of binding observed in the PVP, MPO, and VLN of the female as compared to the male. No PR binding was observed in oil-injected control animals. These results demonstrate region-specific sex differences in ER as well as estrogen-induced regulation of progestin and ERs in the guinea pig brain. The discordance between the regional distributions of sex differences in ER and estrogen-induced PR implies that sex differences in ER and estrogen-induced PR implies that sex differences in estrogen response may not be clearly linked to a sex difference in receptor number. Instead, sex differences in response may involve differences in receptor number within specific subpopulations of estrogen target cells or may involve differences in ER dynamics.

Animals↗

Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis.

BACKGROUND: Heavy proteinuria and progressive renal injury recur after transplantation in up to 40 percent of patients with renal failure caused by idiopathic focal segmental glomerulosclerosis. A circulating factor may be responsible for this recurrence. METHODS: To determine whether patients with focal segmental glomerulosclerosis have a circulating factor capable of causing glomerular injury, we tested serum samples from 100 patients with the disorder in an in vitro assay of glomerular permeability to albumin. Of the 56 patients who had undergone renal transplantation, 33 had recurrences. Sixty-four patients, many of whom had undergone transplantation, were being treated with dialysis. Thirty-one patients with other renal diseases and nine normal subjects were also studied. RESULTS: The 33 patients with recurrent focal segmental glomerulosclerosis after transplantation had a higher mean (+/-SE) value for permeability to albumin (0.47+/-0.06) than the normal subjects (0.06+/-0.07) or the patients who did not have recurrences (0.14+/-0.06). After plasmapheresis in six patients with recurrences, the permeability was reduced (from 0.79+/-0.06 to 0.10+/-0.05, P = 0.008), and proteinuria was significantly decreased. Patients with corticosteroid-sensitive nephrotic syndrome or with membranous nephropathy after transplantation had low levels of serum activity. The circulating factor bound to protein A and hydrophobic-interaction columns and had an apparent molecular mass of about 50 kd. CONCLUSIONS: A circulating factor found in some patients with focal segmental glomerulosclerosis is associated with recurrent disease after renal transplantation and may be responsible for initiating the renal injury.

Adult↗

Characterization of pre-transcription complexes made at a bacteriophage T4 middle promoter: involvement of the T4 MotA activator and the T4 AsiA protein, a sigma 70 binding protein, in the formation of the open complex.

Bacteriophage T4 middle promoters have excellent matches to the -10 consensus sequence for the sigma 70 subunit of Escherichia coli RNA polymerase, but a binding site for the T4 transcriptional activator MotA replaces the sigma 70 -35 consensus. E. Coli RNA polymerase transcribes from middle promoters with or without the activator. In contrast, transcription by T4-modified E. coli RNA polymerase, which is present during T4 infection, requires NotA. We show that transcription by unmodified polymerase from the T4 middle promoter P uvsx is independent of the specific sequences within the -35 region, and the Dnase I footprint obtained with unmodified polymerase and P uvsx resembles those seen previously with E. coli extended -10" promoters. In contrast, although T4-modified polymerase alond binds P uvsx, promoter unwinding and detection of a Dnase I footprint requires MotA. This footprint is significantly different from that obtained with unmodified polymerase, starting upstream of around position -20. Previous work has indicated that the T4 AsiA protein, which binds tightly to sigma 70, is the phage modification required for MotA activation. We show that in the presence of AsiA, MotA, and otherwise unmodified polymerase, Dnase I protection of P uvsx is now similar to that obtained with the fully modified polymerase and MotA up to around position -40. However, protection upstream of -40 is still similar to that seen with unmodified polymerase. Our results support the idea that MotA-dependent activation requires AsiA binding to sigma 70 to achieve specific protein-DNA contacts within the -20 to -40 region of a middle promoter.

Bacteriophage T4↗

Entamoeba invadens: characterization of cysteine proteinases.

Cysteine proteinases have a number of important functions in the life cycle of protozoan parasites. Based on our previous studies demonstrating the role of cysteine proteinases in invasion by Entamoeba histolytica, we evaluated the cysteine proteinases of E. invadens, a related protozoan which causes invasive disease of reptiles. E. invadens readily encysts in axenic culture and provides a model to investigate the role of cysteine proteinases in encystation. Broad bands of approximately 130-230, 55, and 35 kDa were detected on gelatin substrate gels and were inhibited with specific cysteine proteinase inhibitors. Maximal enzymatic activity was detected with peptide substrates containing arginine in the P2 position. A 567-bp fragment containing the active site of an E. invadens cysteine proteinase gene was amplified by PCR and had 37.7, 79.1, and 67.9% identity to the derived amino acid sequences of the acp 1, 2, and 3 genes, respectively, of E. histolytica. The PCR product hybridized with a single band of 1.1 kb on a Southern blot of EcoRI-restricted E. invadens genomic DNA. Long-term inhibition of cysteine proteinase activity during encystation resulted in significantly fewer cysts (P < 0.02); however, this effect appeared to be secondary to decreased trophozoite cell division. No difference in chitin synthase activity was detected between controls and encysting cells with inhibited cysteine proteinases, suggesting that these proteinases are not critical for activation of a zymogen form of chitin synthase. These studies demonstrate that cysteine proteinases may be critical for the survival of E. invadens, and specific inhibition may ultimately interrupt transmission.

Amino Acid Sequence↗

Expression and purification of anthrax toxin protective antigen from Escherichia coli.

Anthrax toxin consists of three separate proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF). PA binds to the receptor on mammalian cells and facilitates translocation of EF or LF into the cytosol. PA is the primary component of several anthrax vaccines. In this study we expressed and purified PA from Escherichia coli. The purification of PA from E. coli was possible after transporting the protein into the periplasmic space using the outer membrane protein A signal sequence. The purification involved sequential chromatography through hydroxyapatite, DEAE Sepharose CL-4B, followed by Sephadex G-100. The typical yield of purified PA from this procedure was 500 microg/liter. PA expressed and purified from E. coli was similar to the PA purified from Bacillus anthracis in its ability to lyse a macrophage cell line (J774A.1). The present results suggest that a signal sequence is required for the efficient translocation of PA into E. coli periplasmic space.

Amino Acid Sequence↗

Inhibition of human HT-29 colon carcinoma cell adhesion by a 4-fluoro-glucosamine analogue.

Cell surface glycoconjugates play an important role in cellular recognition and adhesion. Modification of these structures in tumour cells could affect tumour cell growth and behaviour, including metastasis. 2-Acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-alpha-D-glycopyranose (4-F-GlcNAc) was synthesized as a potential inhibitor and/or modifier of tumour cell glycoconjugates. The effect of this sugar analogue on the adhesive properties of human colon carcinoma HT-29 cells was evaluated. Treatment of HT-29 cells with 4-F-GlcNAc led to reduced cell surface expression of terminal lactosamine, sialy-Le(x) and sialyl-Le(a), as determined by Western blotting and flow cytometry. The aberrant expression of these oligosaccharide structures on the HT-29 cell surface resulted in: (1) decreased E-selectin mediated adhesion of human colon cells to human umbilical cord endothelial cells (HUVEC); (2) impaired adhesion of HT-29 cells to beta-galactoside binding lectin, galectin-1; and (3) reduced ability to form homotypic aggregates. After exposure to 4-F-GlcNAc, lysosomal associated membrane proteins (lamp) 1 and 2, and carcinoembryonic antigen (CEA) detected in HT-29 cells were of lower molecular weight, probably due to impaired glycosylation. These results strongly suggest that modification of tumour cell surface molecules can alter tumour cell adhesion and that tumour cell surface oligosaccharides may be suitable targets for therapeutic exploitation.

Blotting, Western↗

The voluntary community health movement in India: a strengths, weaknesses, opportunities, and threats (SWOT) analysis.

There has been a prolific growth of voluntary organizations in India since independence in 1947. One of the major areas of this growth has been in the field of community health. The purpose of this article is to historically trace the voluntary movement in community health in India, analyze the current status, and predict future trends of voluntary efforts. A review of the literature in the form of a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was the method of this study. Some of the key trends which emerged as the priority areas for progress and for strengthening voluntary organizations in the future were enhancing linkages between health and development; building upon collective force; greater utilization of participatory training; establishing egalitarian and effectual linkages for decision making at the international level; developing self-reliant community-based models; and the need for attaining holistic empowerment at individual, organizational, and community levels through "duty consciousness" as opposed to merely asking for rights.

Community Health Services↗