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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 55 records · Page 3Linked to original sources

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

Granular cell ameloblastoma of jaw. A report of rare case and brief review of literature.

Ameloblastoma is an epithelial odontogenic tumour of the jaw and exhibits diverse microscopic patterns which occurs either singly or in combination with other patterns. The rare granular cell variant is seen in combination usually with follicular or plexiform subtypes. The reported case reveals the microscopic patterns characteristic of granular cell variant only, which is uncommon. The tumour was excised and no recurrence has been observed after nineteen months of surgery.

Adult

Hormonal regulation of malate-aspartate shuttle enzymes during postnatal development of mice.

The regulation of malate-aspartate shuttle enzymes by hydrocortisone was studied in the liver and kidney of 15-, 30- and 60-day old mice. It has been observed that adrenalectomy decreases and hydrocortisone treatment to adrenalectomized mice increases the activity of cytosolic and mitochondrial malate dehydrogenase and cytosolic aspartate aminotransferase in the liver of 15-, 30- and 60-day old mice. Per cent decrease following adrenalectomy remained almost similar in all the postnatal ages studied. However, hydrocortisone effect shows age-dependency. In the kidney, adrenalectomy decreases and hydrocortisone treatment increases the activity of these isoenzymes only in 30- and 60-day old mice. These findings entail that the same enzyme in different tissues of developing animals may be regulated differentially by the same physiological stimuli. Our findings on hormonal regulation of malate-aspartate shuttle enzymes show that they are subjected to different physiological control in various tissues during postnatal development of mice.

Adrenalectomy

Severe hypoxic biventricular dysfunction in tetralogy of Fallot: is Blalock shunt the answer?

In a 4-year-old boy with tetralogy of Fallot, a right modified Blalock-Taussig anastomosis was created because of severe myocardial dysfunction and repeated hypercyanotic spells. Post-operatively, systemic oxygen saturation improved and also myocardial function. It is postulated that hypoxia was responsible for myocardial dysfunction previously, and its elimination has resulted in markedly improved cardiac performance.

Child, Preschool

Aortic atherosclerosis and perioperative stroke in patients undergoing coronary artery bypass: role of intra-operative transesophageal echocardiography.

Intra-operative transesophageal echocardiography was performed in 126 patients undergoing coronary artery bypass grafting. Significant protruding atheromas (grade IV and V; Katz et al., 1992) were present in 12 patients (9.5%). Protruding atheromas had significantly higher incidence in patients above 60 years in age. Preoperative assessment with chest roentgenography and angiography, as well as intra-operative assessment by surgical palpation proved to be insensitive in detecting aortic atheromas. Out of four patients with grade V atheromas, two (50%) developed right hemiplegia postoperatively. For the rest, patients with grade V atheromas and eight patients with grade IV atheromas, surgical technique was modified and that helped in preventing occurrence of perioperative stroke.

Adult

A human gene encoding morphine modulating peptides related to NPFF and FMRFamide.

FMRFamide-related peptides have been isolated from both invertebrates and vertebrates and exhibit a wide range of biological effects in rats. We show here that in humans 2 FMRFamide-related peptides are encoded by a single gene expressed as a spliced mRNA. The larger predicted peptide (AGEGLNSQFWSLAAPQRFamide) differs from the peptide isolated from bovines (AGEGLSSPFWSLAAPQRFamide) by the substitutions of 2 amino acids. The shorter predicted peptide (NPSF, SQAFLFQPQRFamide) is 3 amino acids longer than the bovine 8 amino-acid NPFF (FLFQPQRFamide) or the human NPFF peptide isolated from serum [5], suggesting that the encoded protein is subject to cleavage by a tripeptidyl peptidase or by a novel processing mechanism. On rat spinal cord, the larger peptide is indistinguishable in activity from the equivalent bovine peptide whereas the smaller extended peptide is inactive.

Action Potentials

Enhancement of prostate tumor volume definition with intravesical contrast: a three-dimensional dosimetric evaluation.

PURPOSE: To assess the impact of intravesical contrast during computed tomography (CT) simulation on prostate tumor volume definition and dose distribution. METHODS AND MATERIALS: Sixteen patients with localized adenocarcinoma of the prostate underwent CT-based virtual simulation in preparation for definitive radiotherapy. Patients were immobilized with a foam cradle and an initial CT was performed after oral but without intravesical contrast (noncontrast scan). A second scan was performed following administration of intravesical contrast (contrast scan). Beam apertures were designed on the noncontrast scans and digitized into the contrast scan file. Beam apertures were also designed on the contrast scans. Isodose plans were generated for several beam apertures and arrangements. RESULTS: There was enhanced visualization of the prostate at the cephalad portion of the field for 15 of the 16 cases. The mean differences between the noncontrast and contrast volumes was significant (p = 0.0001). The mean percent underdosage to the prostate ranged from 3.9% to 18.6%, depending upon the target volume and beam arrangement. CONCLUSION: This study demonstrates the necessity of using intravesical contrast for defining the location of the prostate during CT simulation. The underestimation of the extent of the prostate when omitting intravesical contrast leads to significant underdosage. The value of intravesical contrast is most evident when small (prostate only) conformal fields are used.

Adenocarcinoma

A thermostable D-hydantoinase isolated from a mesophilic Bacillus sp.AR9.

A thermostable hydantoinase has been characterized from a mesophilic Bacillus sp.AR9. The hydantoinase produced by this Bacillus sp.AR9 is strictly D-specific and is constitutively produced with high yields (4500 U/ml) in this strain. The enzyme is not only alkalo- and thermostable but has a pH and temperature optimum of 9.5 and 65 degrees C, respectively, which is advantageous for the bioconversion of DL-5-monosubstituted-hydantoin derivatives. The enzyme has a half life of 80 minutes at 70 degrees C and loses only 33% of its activity in 4 hr at 60 degrees C. The enzyme has a broad substrate specificity with a maximum of 100% with hydantoin and about 26% with dihydrouracil. Co+ + ions enhance the activity of the enzyme by more than 60%.

Amidohydrolases

The unusual imaging appearance of primary retroperitoneal teratoma: report of a case.

Primary retroperitoneal (RP) teratoma is a rare entity which has a distinctive imaging appearance. We describe herein the case of a 25-year-old man in whom a RP teratoma was found to have an extremely unusual imaging morphology by ultrasound and computed tomography (CT). The tumor was resected and histopathological examination confirmed the diagnosis of primary benign RP teratoma.

Adult

The influence of diet on the mucin carbohydrates in the chick intestinal tract.

The presence of nutrients in the intestinal lumen is a major factor influencing bacterial colonization in poultry. This study was conducted to investigate the effects of poultry feed on viscosity of intestinal contents and on mucin carbohydrates by comparing jejunal supernatants and the histochemical composition of goblet cells in chicks reared to 5 weeks of age on either a conventional maize-based diet or a wheat-based diet or a wheat diet supplemented with 0.1% xylanase. Regional differences in the distribution of the neutral, carboxylated and sulphated mucins were demonstrated using conventional histochemical techniques, while a panel of lectins was used to study alterations in glycoconjugate synthesis of mucins in chicks fed different diets. 1) Feeding a diet supplemented with xylanase lowered the viscosity but increased the amount of neutral, carboxylated and sulphated mucins in the jejunum. 2) In chicks fed a maize-based diet, neutral mucins increased in the surface and upper crypt goblet cells of the small and large intestines but decreased in the caecum. 3) Feeding a diet supplemented with xylanase modified crypt-surface glycosylation of N-acetylglucosamine residues and resulted in loss of sialic acid residues in the small and large intestines. These results indicate that the constituents of poultry feed, in particular the consumption of a diet supplemented with xylanase, lead to changes in intestinal viscosity and mucin composition which are associated with alterations in the goblet cell glycoconjugates of the chick intestinal tract.

Animal Feed

Clinical observation of the temporal association between crack cocaine and duodenal ulcer perforation.

HYPOTHESIS: To determine if a cause-effect relationship exists between crack cocaine use and duodenal ulcer perforation (DUP). PATIENTS AND METHODS: A retrospective study was conducted of all patients undergoing emergency surgical management for peptic ulcer disease over a 6-year period at a large inner-city municipal teaching hospital. The hospital records of 78 consecutive patients presenting with complications of peptic ulcer disease between April 1990 and April 1996 were reviewed. Group A (n = 24) consisted of patients with confirmation of crack cocaine usage within 8 hours of clinical presentation; group B (n = 54) consisted of patients with no antecedent history of crack cocaine use. Demographic data, timing of drug use, clinical presentation, laboratory and radiographic findings, toxicology screening, operative findings, and postoperative course were compared between the two groups. RESULTS: Both groups revealed a similar gender distribution, tobacco use, prior peptic ulcer symptoms, and laboratory findings. Group A patients were younger (t test, P = 0.01) and more likely to present with perforation, whereas patients in group B presented with a combination of symptoms (chi square, P = 0.03). Duodenal ulcer perforation was present in 75% of patients in group A compared with 46% of patients in group B (chi square, P = 0.04). Group B patients had a significantly longer hospital stay compared with those in group A (t test, P = 0.01). Both crack cocaine and alcohol are independent predictors of duodenal ulcer perforation. CONCLUSIONS: Patients with recent use of crack cocaine and/or alcohol are more likely to present with duodenal perforations. Although a temporal association between crack cocaine use and duodenal ulcer perforation was demonstrated, this study does not confirm a cause-effect relationship. A prospective cohort study is needed to clarify the pathogenesis of this potential cause-effect relationship.

Adult