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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 217 records · Page 12Linked to original sources

Alloxan diabetes regulates adenosine deaminase activity in mice: tissue- and age-specific correlation.

Effect of alloxan induced diabetes on the activity of adenosine deaminase (ADA) was studied in the liver, spleen, stomach and small intestine of mice at two different postnatal ages (preweaned, 15-day and postweaned, 60-day). Alloxan significantly stimulates (133%) ADA activity in the liver of 15-day old mice, while it has no significant effect in the 60-day old animals. In contrast, ADA activity was moderately increased (25%) in spleen of both the ages. However, no significant influence of alloxan was observed on ADA activity of stomach at either age of mice. On the other hand, alloxan treatment increases (69%) intestinal ADA activity in 15-day old mice, with no significant change in 60-day old animals. Thus, alloxan diabetes increases ADA activity in an age- and tissue-specific manner. Stimulation of ADA activity in diabetic mice might play role in immune and other metabolic dysfunctions in diabetic conditions.

Adenosine Deaminase↗

Dexamethasone induced expression of phosphatase inhibits generation of reactive oxygen species in Ehrlich ascites tumor cells.

Both pre-activated and phorbol ester tetradecanoyl phorbol myristate acetate (TPA) activated reactive oxygen species (ROS) generation were inhibited by dexamethasone in vivo. Time kinetics on influence of dexamethasone on cytosolic phosphoprotein phosphatase activity revealed that, when compared to phosphatase activity in cytosol of control Ehrlich ascites tumor (EAT) cells, a 5-fold increase in specific activity is seen in the cytosol of EAT cells treated (in vivo, 0-90 min. 1 mg/kg body weight) with dexamethasone. Dexamethasone induced phosphatase was partially purified by conventional ion-exchange and gel filtration column chromatographic techniques. Purified phosphatase had a molecular weight of 70 KDa by SDS-PAGE. A dose-dependent inhibition of TPA activated ROS generation by partially purified phosphatase in permeabilized EAT cells suggested that dephosphorylation is a major regulatory mechanism in "switching off" of the respiratory burst. Anti-phosphatase antibodies were raised, purified and were used to quantitate cytosolic phosphatase by ELISA, which revealed that dexamethasone induces 6-fold increase in expression of phosphatase in EAT cells by 120 min. The expression of phosphatase in EAT cell cytosol was further confirmed by immunostaining using anti-phosphatase antibodies, the results of which showed intense blue staining on development with BCIP/NBT.

Animals↗

Stimulus context in hemineglect.

Rightward deviation on bisection of a horizontal line is well described in patients with right brain injury and left hemineglect. Because of the observation that hemineglect patients may bisect very short lines to the left of the true midpoint (the so-called crossover effect), additional models have been proposed to incorporate this finding into existing theories of hemineglect. We investigated a line-length effect in six patients with left hemineglect. When presented with any set of lines of uniform (reference) length, percentage rightward deviation on line bisection remained constant across different line lengths. When lines of a second length were mixed into any uniform set of lines, bisection performance on the reference lines changed. A rightward shift in the perceived midpoint of the reference line occurred if the added lines were shorter than the reference lines; a leftward shift occurred if the added lines were longer. Leftward shifts included shifts across the true midpoint, reproducing the crossover effect. Shifts in the perceived midpoint occurred both on a manual line bisection task and on a line bisection discrimination task in which no manual response was required. We propose that the crossover effect may be part of a more general stimulus-context effect in which the perceived midpoint of a line is related not to absolute length, but to the line's length relative to other lines with which it is presented. Such a context effect has not hitherto been described in the neglect syndrome. A possible mechanism for the effect is a generalization of length estimation produced by the combined influence of the focal stimulus and all stimuli that precede it.

Adult↗

Differentiation of malignant and degenerative benign bone disease using Tc-99m MDP and Tc-99m citrate scintigraphy.

The authors present a prospective analysis of Tc-99m MDP and Tc-99m citrate scintigraphy in 108 patients with known malignant or degenerative benign bone disease. Of 108 patients, 59 (group A) had malignant bone disease. The other 49 patients (group B) had degenerative benign bone disease for which the results of Tc-99m MDP scans were positive. In both groups the Tc-99m citrate scan was performed 1 week after the Tc-99m MDP scan. The Tc-99m citrate/Tc-99m MDP lesion-to-background radioisotope uptake ratio (RUR) was calculated for each lesion 3 hours after radionuclide administration. The mean RUR for the malignant lesions was 1.0 +/- 0.484; for the benign lesions, the RUR was 0.29 +/- 0.250. Static imaging was also done for 10 lesions each from the malignant and benign groups at 1, 3, and 24 hours to study the kinetics of Tc-99m citrate. Time-activity curves for malignant lesions showed that the RUR remained high for 24 hours, whereas benign lesions showed a drastic decrease at 3 and 24 hours compared with the 1-hour images. The ratio of Tc-99m citrate to Tc-99m MDP is a promising parameter to differentiate malignant from benign degenerative lesions seen as areas of increased activity on Tc-99m MDP bone scans. The sensitivity and specificity of this technique were 97.8% and 95%, respectively.

Adult↗

Giant cell phlebitis as a cause of large intestinal stricture.

Although arteritis of the gastrointestinal tract is well known, an isolated phlebitis without associated arteritis of the colon and cecum is rare. We describe a distinct form of giant cell phlebitis in a 16-year-old girl causing ischemic stricture of the large intestine. She presented with subacute intestinal obstruction and was suspected of suffering from tuberculosis. However, histopathologic examination showed giant cell phlebitis, the arterioles and arteries being spared. Although this is an extremely rare form of nonprogressive vasculitis, it should be considered in the differential diagnosis of strictures in the large intestine, especially in the young.

Adolescent↗

Leptomeningeal carcinomatosis from carcinoma of the palatine tonsil.

Distant metastases from carcinoma of the palatine tonsil are very uncommon. We encountered a case of a carcinoma involving the tonsillar region that resulted in subarachnoid mestastases following local radical radiotherapy. Metastases were diagnosed following magnetic resonance imaging and spinal fluid cytology. The patient succumbed to the disease after a rapid downhill course, 1 month following diagnosis of the secondary deposit. The present paper describes the rare site of distant metastasis and reviews the relevant literature.

Carcinoma, Squamous Cell↗

Chest wall tuberculosis simulating breast carcinoma: imaging appearance.

Tuberculosis of the breast is a rare disease. Tubercular abscesses predominantly affecting the soft tissues are also very infrequent. A case of chest wall tuberculosis secondarily involving the breast presenting as a hard, fixed lump simulating mammary carcinoma is presented here. There was no evidence of pleural or pulmonary tuberculosis.

Breast Diseases↗

The external and internal anatomy of human mandibular canine teeth with two roots.

This study investigated the internal anatomy of 65 human mandibular canines with two well-defined roots. The teeth were decalcified and injected with gelatin coloured with india ink. Diaphanization was carried out using clear resin to allow permanent preservation. It was found that all mandibular canines with two roots had two root canals. Lateral canals were found in 68.9% of teeth and 19.7% had lateral canals at the bifurcation. The results of the external measurements (cusp tip to root apex) showed that the average buccal root length was 23.0 mm and the average lingual root length was 22.7 mm. The maximum and minimum buccal lengths were 26.7 mm and 17.9 mm respectively and the maximum and minimum lingual lengths were 27.2 mm and 17.1 mm respectively. The buccal root was the larger of the two in 47.7% of teeth and 43.1% had roots of equal size. The lingual root was larger than the buccal root in 9.2% of cases. Clinicians should be aware of the anatomical variation that exists for mandibular canines.

Cuspid↗

Regulation of Na-K-ATPase gene expression by hyperoxia in MDCK cells.

Na-K-ATPase plays a central role in a variety of physiological processes, including ion transport and regulation of cell volume. Our previous data showed that hyperoxia increased the expression of Na-K-ATPase alpha 1 and beta 1 mRNA in lung type II cells. We similarly show that hyperoxia (> or = 95% O2 for 24-48 h) increased steady-state mRNA levels in both Na-K-ATPase subunits in Madin-Darby canine kidney (MDCK) cells. The mechanism of gene regulation by hyperoxia was assessed. Stability of the Na-K-ATPase mRNA levels of both subunits was unchanged in hyperoxia-exposed MDCK cells. To determine whether gene transcription was augmented by hyperoxia, MDCK cells were transfected with a beta 1-subunit promoter-reporter construct. Transfection with the wild-type promoter (beta 1-817) revealed a 1.9 +/- 0.2-fold increase in promoter activity. Transfection with 5' deletion constructs identified a 61-base pair (bp) region between -102 and -41 that was necessary for this increase in promoter activity by hyperoxia. Incorporation of this 61-bp region into a minimal promoter (mouse mammary tumor virus) similarly increased promoter activity 2.3-fold in the presence of hyperoxia. This increase in promoter activity was not seen when MDCK cells were incubated with various concentrations of hydrogen peroxide. In summary, hyperoxia increased Na-K-ATPase beta 1-subunit mRNA steady-state level due to increased transcription in MDCK cells. A region necessary for this hyperoxic effect on beta 1 transcription is located between base pairs -102 and -41 on the promoter.

Animals↗

Documentation of angiotensin II receptors in glomerular epithelial cells.

Angiotensin II decreases glomerular filtration rate, renal plasma flow, and glomerular capillary hydraulic conductivity. Although angiotensin II receptors have been demonstrated in mesangial cells and proximal tubule cells, the presence of angiotensin II receptors in glomerular epithelial cells has not previously been shown. Previously, we have reported that angiotensin II caused an accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured glomerular epithelial cells. Current studies were conducted to verify the presence of angiotensin II receptors by immunological and non-peptide receptor ligand binding techniques and to ascertain the activation of intracellular signal transduction in glomerular epithelial cells in response to angiotensin II. Confluent monolayer cultures of glomerular epithelial cells were incubated with angiotensin II, with or without losartan and/or PD-123,319 in the medium. Membrane vesicle preparations were obtained by homogenization of washed cells followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins followed by multiscreen immunoblotting was used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2 (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells was studied by measuring the levels of cAMP, using radioimmunoassay. Results obtained in these experiments showed the presence of both AT1 and AT2 receptor types in glomerular epithelial cells. Angiotensin II was found to cause an accumulation of cAMP in glomerular epithelial cells, which could be prevented only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2, respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP indicate that glomerular epithelial cells respond to angiotensin II in a manner distinct from that of mesangial cells or proximal tubular epithelial cells. Our results suggest that glomerular epithelial cells participate in angiotensin II-mediated control of the glomerular filtration barrier.

Angiotensin Receptor Antagonists↗

Lectin histochemistry reveals the appearance of M-cells in Peyer's patches of SCID mice after syngeneic normal bone marrow transplantation.

Peyer's patches in the intestinal mucosa are characterized by the presence of several lymphatic follicles and interfollicular T-cell regions. Luminal antigens are transported across the intestinal epithelium to stimulate the Peyer's patch pre-B-cells in the follicles that proliferate and migrate to distant sites. Evidence suggests that antigen priming of B-lymphocytes is responsible for the number and location of Peyer's patches during postnatal life, but little is known about the histogenesis of Peyer's patches and their overlying membranous (M) cells. To examine whether T- and B-lymphocytes in Peyer's patches have an influence on M-cell generation, we studied the development of Peyer's patches and M-cells in severe combined immunodeficient (SCID) mice reconstituted with bone marrow cells from normal syngeneic mice. Our experiments demonstrate that the donor bone marrow cells in the host scid mice repopulate to form single (primary) follicles and aggregates of lymphoid nodules, the Peyer's patches. Use of the lectins Anguilla anguilla (AAA) and Ulex europaeus I (UEA-I) as positive markers of mouse Peyer's patch M-cells revealed that M-cells develop in the dome epithelium overlying the single primary follicles and Peyer's patches of reconstituted scid mice. This experimental system therefore allows the study of the histogenesis of Peyer's patches and M-cells.

Animals↗

Oxidant effects on epithelial Na,K-ATPase gene expression and promoter function.

The lung epithelium resorbs alveolar fluid through combined action of sodium channels and the sodium pump, Na,K-ATPase. The lung often is exposed to hyperoxia in disease states and hyperoxia generates a mixture of reactive oxygen species. In vivo and in vitro exposure of rat lung and alveolar type II cells, respectively, increases gene expression of both alpha-1 and beta-1 subunits of the sodium pump. In contrast to the primary type II cells, several type II cell lines did not increase sodium pump gene expression with hyperoxia, but the renal tubular epithelial MDCK cell line did. Using promoter-receptor constructs transfected into MDCK cells, hyperoxia did not markedly increase transcription of the alpha-1 subunit but doubled transcription of the beta-1 subunit gene. Using 5'-deletion constructs, the region required for the beta-1 increase was localized to a 40-base pair region from -44/-84. The hyperoxic responsiveness of this region was confirmed using constructs with one or two copies of this region placed in minimal promoter-luciferase reporters. This 5' promoter region contains a consensus binding sequence for SP-1, a basal transcription factor but not for binding of other known transcription factors. Thus, hyperoxia induces Na,K-ATPase beta-1 promoter transcription, likely acting through a novel mechanism.

Animals↗

TNF-alpha increases albumin permeability of isolated rat glomeruli through the generation of superoxide.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that plays a central role in inflammation. Glomerular levels of TNF-alpha are elevated in human and experimental glomerulonephritis. Glomerular cells produce and respond to TNF-alpha. One of the mechanisms by which these cells respond to TNF-alpha is through generation of reactive oxygen species. In this study, the effect of TNF-alpha on albumin permeability (P(albumin)) of isolated rat glomeruli and the possible mechanism of this effect were examined. Isolated rat glomeruli were incubated with TNF-alpha (0.4 ng/ml), TNF-alpha with anti-TNF-alpha antibodies, and TNF-alpha with the reactive oxygen species scavengers superoxide dismutase, catalase, DMSO, or dimethylthiourea for 12 min at 37 degrees C, and P(albumin) was calculated. TNF-alpha increased P(albumin) of isolated glomeruli compared with control (0.70 +/- 0.02, n = 25 versus 0.00 +/- 0.05, n = 26), and this effect was abrogated by anti-TNF-alpha antibodies (-0.18 +/- 0.05, n = 23). Superoxide dismutase abolished the increase in P(albumin) (-0.04 +/- 0.11, n = 23), whereas catalase (0.73 +/- 0.08, n = 30), DMSO (0.64 +/- 0.03, n = 10), or dimethylthiourea (0.51 +/- 0.08, n = 10) did not alter the effect of TNF-alpha. These results indicate that TNF-alpha increased P(albumin+)++ of isolated glomeruli and that the mediator of the increased P(albumin) is superoxide. It is concluded that TNF-alpha derived from glomerular or extraglomerular sources can increase glomerular P(albumin) through generation of superoxide and may lead to proteinuria.

Administration, Topical↗

Prostaglandin E1 in infants with congenital heart disease: Indian experience.

BACKGROUND: E-type prostaglandins (PGE1) can effectively maintain the patency of the ductus arteriosus in neonates. Its use, therefore and be life saving in infants born with ductus dependent congenital heart disease. Although PGE1 is available for over two decade in western world, it has been introduced in India only since April, 1995. OBJECTIVE: To assess the efficacy of PGE1 at our center. SETTING: Hospital based. METHOD: 65 infants with ductus dependent congenital heart disease were included. Age at time of starting PGE1 infusion ranged from 18 hours to 39 days. Forty two of these were more than a week of age, 19 were more than 14 days, and two were above one month. PGE1 was started in an initial dose of 0.05 microgram/kg/min, decreased to 0.005-0.01 microgram/kg/min for maintenance. The indications for use of PGE1 were to increase pulmonary blood flow in 33 cases with pulmonary atresia, tricuspid atresia or critical pulmonic stenosis (Group I); to increase systemic blood flow in 15 cases with coarctation of aorta, hypoplastic left heart and interruption of aortic arch (Group II); to improve mixing in 13 cases of transposition of great arteries (Group III) and for improving the left ventricular volumes by keeping the duct open in 4 cases of transposition of great arteries with intact ventricular septum (Group IV). The efficacy of the drug was assessed by a rise on PaO2 and SaO2% determined for Group I & III, and by appearance of lower limbs pulses in Group II. Left ventricular volumes were serially measured by echocardiography in Group IV cases. RESULTS: The drug was successful in 62 of the 65 cases. There were two failures. One was a 39 days old baby with Ebstein's anomaly of tricuspid valve and pulmonary atresia and other was an eight days old baby with coarctation of aorta and renal failure. In addition, PGE1 could not be continued in another baby due to development of a linear skin rash locally. Side effects included apnea in 5 (9%) of 56 spontaneously breathing patients. Necrotizing enterocolitis, hyperpyrexia and jitteriness was sent in one case each. Six patients died. Two were related to PGE1, one due to failure, another due to its side effects. Definitive procedure were performed in 51 cases electively. PGE1 was used upto 13 days with sustained benefit. CONCLUSIONS: PGE1 is an effective drug for keeping the ductus open in infants with ductus dependent congenital heart disease. It can be used for neonates beyond the first week of life with efficacy. Apnea is a major side effect and close monitoring is essential.

Age Factors↗