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Biomedical subjects

K Sharma

Publications and source records attributed to K Sharma.

At least 109 records · Page 6Linked to original sources
PubMed1996

An epidemiological study of obesity in Shimla Town.

A cross sectional study of 888 randomly selected subjects in Shimla town was done to determine prevalence of obesity, its relation to age and physical activity. The prevalence of obesity was 21.5% using cut off levels of BMI 25. The prevalence of obesity rose significantly with age. Obesity was less in those having moderate physical activity as compared to those with low and high activity. Primary prevention is required to tackle this disease risk factor through health education focussing on promotion of moderate regular physical activity.

Adult↗
PubMed1995

Growth arrest of a murine mesangial cell line by transforming growth factor beta 1 is associated with inhibition of mitogen-induced Ca2+ mobilization.

Transforming growth factor-beta (TGF beta) is a multifunctional cytokine showing growth effects on many cell types. In the present study effects of TGF beta 1 on mitogen-induced Ca2+ responses were investigated in an immortalized murine mesangial cell line where TGF beta 1 effects on growth are inhibitory. TGF beta 1 was found to inhibit intracellular Ca2+ mobilization induced by platelet-derived growth factor (PDGF). This effect was completely reversed by previous addition of the non-specific serine/threonine kinase inhibitor H-7, but was unaffected by GF 109203X, a specific inhibitor of protein kinase C (PKC). These findings suggest that inhibition of mitogen-induced Ca2+ mobilization by TGF beta 1 appears not to involve prior activation of PKC, but may participate in the mechanisms whereby mesangial cell growth is inhibited by TGF beta 1.

Animals↗
PubMed1995

Enhanced expression of inducible nitric oxide synthase in murine macrophages and glomerular mesangial cells by elevated glucose levels: possible mediation via protein kinase C.

Increased blood flow and vascular permeability of early diabetes have been associated with increased nitric oxide formation in diabetic rats, but the specific nitric oxide synthase responsible is unknown. We examined the modulation of the induction and activity of the inducible NOS isoform by high glucose concentration in a murine macrophage cell line, RAW 264.7, and murine glomerular mesangial cells. Culturing both cell types in high glucose concentration led to significant increases in nitrite production and the mRNA encoding iNOS upon stimulation with LPS plus interferon-gamma, as compared with normal glucose concentration. High glucose also modestly enhanced LPS/IFN-gamma-induced stimulation of the iNOS promoter in transient transfection experiments in mesangial cells. Protein kinase C activation led to enhanced mRNA expression of iNOS, and inhibitors of protein kinase C blocked nitrite accumulation in mesangial cells. These findings suggest that high glucose in combination with stimulation by LPS plus IFN-gamma enhances iNOS expression, and protein kinase C activation may be playing a role in this enhancement.

Amino Acid Oxidoreductases↗
PubMed1995

Primary brain lymphoma. A brief review of clinical aspects and management.

Primary C.N.S. lymphoma is a rare tumor. Five such cases were treated in our clinic between January, 1991, and October, 1993. Four patients had tumor decompression and one had total resection. All of them received radiotherapy (radiation dose 40 Gy) and chemotherapy. One patient expired during the immediate postoperative period. Four patients showed a disappearance of the tumor on CT scan after the complete course of therapy of 9 months. Three patients showed recurrence intracranially at 15, 12, and 10 months. All patients died during follow up except one, who has been alive without recurrence for 10 months. Median survival was 13 months.

Adolescent↗
PubMed1995

Late-migrating neuroepithelial cells from the spinal cord differentiate into sensory ganglion cells and melanocytes.

During embryonic development, neural crest cells give rise to many structures in peripheral tissues. Other neural tube cells are thought to contribute only to structures within the CNS. In contrast to this idea, we report a second wave of migration of cells away from the spinal cord occurring after the emigration of crest cells is complete. Neuroepithelial cells from spinal cords in E5 chicken embryos migrate into the periphery and differentiate into neurons and satellite cells within sensory ganglia and into melanocytes in skin and feathers. These results show that some cell types previously considered to be the descendants exclusively of neural crest cells are also derived from neuroepithelial cells in the spinal cord.

Animals↗
PubMed1995

Prevention of diabetic nephropathy in db/db mice with glycated albumin antagonists. A novel treatment strategy.

Accelerated protein glycation in diabetes has been mechanistically linked to the pathogenesis of diabetic nephropathy. Because glycated albumin induces abnormalities in cultured mesangial cells that resemble those characterizing the glomerular mesangium in diabetes, and monoclonal antibodies (A717) specific for Amadori-modified glycated albumin prevent these abnormalities, we postulated that in vivo administration of A717 could retard the progression of diabetic nephropathy. To test this hypothesis, diabetic db/db mice and their nondiabetic db/m littermates were treated with eight consecutive weekly injections of 150 micrograms of A717 (Fab fragments) to reduce the elevated plasma glycated albumin concentration, or with irrelevant murine IgG (MIg). Relative to nondiabetics, diabetic mice (MIg treated) manifested proteinuria (3.35 +/- 0.15 vs 0.87 +/- 0.1 mg albumin/mg creatinine), 3.8-fold increase in mesangial matrix fraction, and renal cortical overexpression of mRNAs encoding alpha 1(IV) collagen (2.6-fold increase) and fibronectin (3.8-fold increase). Treatment of db/db mice with A717 significantly reduced the proteinuria (1.52 +/- 0.3 mg/mg creatinine), inhibited mesangial matrix expansion, and attenuated overexpression of matrix mRNAs. The nephropathic protective effects of A717 were independent of any change in blood glucose concentrations. Antibodies unreactive with glycated albumin did not duplicate the beneficial effects of A717. Thus, abrogating the biologic effects of increased glycated albumin with A717 has a salutary influence on the pathogenesis of diabetic nephropathy and has novel therapeutic potential in its management.

Albuminuria↗
PubMed1995

Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator.

Renal cells are a rich source of transforming growth factor (TGF)-beta, and they serve as targets for its actions. Our hypothesis that activation of the TGF-beta system in the kidney is implicated in the development of diabetic renal disease stems from the close similarity of actions of TGF-beta and high ambient glucose on renal cell growth and extracellular matrix metabolism. Proximal tubule cells and glomerular mesangial cells cultured in high glucose concentration express increased TGF-beta 1 mRNA and protein levels, and treatment with anti-TGF-beta antibodies results in prevention of the effects of high glucose to induce cellular hypertrophy and stimulate collagen biosynthesis. Several in vivo studies by different groups of investigators have reported overexpression of TGF-beta in the glomeruli in human and experimental diabetes. We have also observed that the development of renal hypertrophy in the insulin-dependent diabetic BB rat and NOD mouse is associated with increased expression of TGF-beta 1 in the kidney and that short-term administration of antibodies capable of neutralizing the activity of TGF-beta in the streptozotocin mouse model of diabetes results in attenuation of whole kidney and glomerular hypertrophy and overexpression of mRNAs encoding matrix components. Together, these findings are consistent with the hypothesis that the diabetic state stimulates TGF-beta expression in the kidney and that in turn this growth factor may mediate, in an autocrine/paracrine manner, some of the principal early manifestations of diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Visual status in suprasellar pituitary tumours.

A retrospective analysis of 29 cases of pituitary tumours with suprasellar extension that had undergone surgery by transsphenoidal or transcranial route, was done. The correlation between age, duration of symptoms, pre- and post-operative visual acuity, visual field and suprasellar height of the tumour were analyzed. The age and duration of visual loss were found to have a bearing on the final postoperative visual outcome.

Adenoma↗
PubMed1994

Three ARS elements contribute to the ura4 replication origin region in the fission yeast, Schizosaccharomyces pombe.

The ura4 replication origin region, which is located near the ura4 gene on chromosome III of the fission yeast, Schizosaccharomyces pombe, contains multiple initiation sites. We have used 2D gel electrophoretic replicon mapping methods to study the distribution of these initiation sites, and have found that they are concentrated near three ARS elements (stretches of DNA which permit autonomous plasmid replication). To determine the roles of these ARS elements in the function of the ura4 origin region, we deleted either one or two of them from the chromosome and then assessed the consequences of the deletions by 2D gel electrophoresis. The results suggest that each of the three ARS elements is responsible for the initiation events in its vicinity and that the ARS elements interfere with each other in a hierarchical fashion. It is possible that the large initiation zones of animal cells are similarly composed of multiple mutually interfering origins.

Chromosome Mapping↗
PubMed1994

Transdermal delivery of buprenorphine through cadaver skin.

The skin permeation of buprenorphine base and HCl salt through cadaver skin was investigated. The octanol-water partition coefficient and solubilities of both buprenorphine free base and HCl salt were determined at 32 degrees C. As expected, buprenorphine free base was more lipophilic than its HCl salt and was practically insoluble in aqueous buffer at pH 8.7. The drug solubility decreased exponentially as the pH of the solution increased, whereas the permeability coefficient increased as the donor solution pH decreased. The skin flux of buprenorphine.HCl was significantly higher than that of the free base from propylene glycol/lauric acid vehicle mixtures. Buprenorphine base permeation through tape-stripped epidermis suggested that in addition to stratum corneum, viable epidermis presented a significant diffusion barrier because of the very low aqueous solubility of the free base observed. The mean steady-state skin fluxes of buprenorphine.HCl were 20.3 and 29.7 micrograms/cm2/h from propylene glycol:lauryl alcohol: ethanol (80:15:5) and propylene glycol: propylene glycol monolaurate: water (80:15:5) vehicle mixtures, respectively. The skin flux of buprenorphine.HCl from various monolithic matrix patches was also evaluated. When capric acid, lauric acid, and lauryl alcohol were separately incorporated into an adhesive matrix, the skin flux of buprenorphine.HCl was enhanced by a factor of 2 to 3.5. Finally, based on the total body clearance and minimum effective concentration of buprenorphine, a transdermal delivery rate of 2.5 micrograms/cm2/h from a 20-cm2 patch was estimated. The in vitro skin permeation data clearly suggest that transdermal delivery of buprenorphine is feasible to achieve a desired systemic analgesic effect.

Administration, Cutaneous↗
PubMed1994

Maternal serum human chorionic gonadotrophin and pregnancy-associated plasma protein A, markers for fetal Down syndrome at 8-14 weeks.

Maternal serum levels of human chorionic gonadotrophin and its subunits (intact, alpha, and free beta h CG) and pregnancy-associated plasma protein A (PAPP-A) were measured in 279 women between 8 and 14 weeks' gestation. This group included 23 pregnancies in which the fetus had Down syndrome (DS), diagnosed either at birth or during the second trimester (n = 17) or from chorionic villus sampling (CVS) (n = 6). Normal medians were determined from the 258 apparently normal pregnancies. The median levels of intact hCG (1.4 MOM) and free beta hCG (2.1 MOM) were significantly raised, whereas the median level of PAPP-A (0.39 MOM) was significantly lower in the DS pregnancies when compared with the control group. Levels of alpha hCG were similar in both the control and the DS pregnancies. Analysis of samples taken prior to 14 weeks' gestation demonstrated that only PAPP-A (0.34 MOM) was significantly altered in DS pregnancies. However, after the exclusion of DS cases diagnosed at CVS, the median intact hCG (1.56 MOM), free beta hCG (2.27 MOM), and alpha hCG (1.8 MOM) were all raised in DS pregnancies. This emphasizes the problem of the interpretation of biochemical markers when DS cases are diagnosed at CVS.

Biomarkers↗
PubMed1994

Comparison of the two major ARS elements of the ura4 replication origin region with other ARS elements in the fission yeast, Schizosaccharomyces pombe.

We have previously reported that the replication origin region located near the ura4 gene on chromosome III of the fission yeast, Schizosaccharomyces pombe, contains three closely spaced origins, each associated with an autonomously replicating sequence (ARS) element. Here we report the nucleotide sequences of two of these ARS elements, ars3002 and ars3003. The two ARS elements are located on either side of a transcribed 1.5 kb open reading frame. Like 11 other S. pombe ARS elements whose sequences have previously been determined in other laboratories, the 2 new ARS elements are unusually A+T-rich. All 13 ARS elements contain easily unwound stretches of DNA. Each of the ARS elements contains numerous copies, at a higher than expected frequency, of short stretches of A+T-rich DNA in which most of the Ts are on one strand and most of the As are on the complementary strand. We discuss the potential significance for ARS function of these multiple asymmetric A+T-rich sequences.

Base Composition↗
PubMed1994

Serum levels of erythropoietin and selected other cytokines in patients with anemia of chronic disease.

Serum levels of erythropoietin and five other cytokines potentially operational in erythropoiesis were determined in patients with anemia of chronic disease. No correlation between erythropoietin levels and severity of anemia was found. A spectrum of abnormality was encountered among patients in whom there was less than expected erythropoietin response to increased levels of erythropoietin and among others in whom the erythropoietin levels were subnormal for their degree of anemia. Increased serum levels of interleukin-3, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were encountered in limited numbers of patients, especially those with increased erythropoietin levels. Deficient erythropoietin production is concluded to be the major cause of anemia of chronic disease.

Aged↗
PubMed1994

Detection of site of air entry in venous air embolism: role of Valsalva maneuver.

Venous air embolism in posterior fossa surgery is a well-documented complication. Various highly sensitive devices help in early detection of air embolism. In management of air embolism, sealing the site of air entry is an important step in preventing further episodes. Here we discuss the importance of inspiratory hold after lung inflation (Valsalva maneuver) in helping to localize the site of air entry and its role in the management of venous air embolism observed in two cases of posterior fossa mass, operated in sitting position.

Astrocytoma↗
PubMed1994

The emerging role of transforming growth factor-beta in kidney diseases.

Transforming growth factor-beta (TGF-beta) is a prototypical multifunctional cytokine, with growth being only one of its many functions. Its receptors and actions are germane to almost every cell in the body involved in tissue injury and repair, and its effects are best understood in the context of a cellular response to a changing environment. The broad areas in which TGF-beta plays a crucial role include cell proliferation and extracellular matrix production. TGF-beta is a key regulatory molecule in the control of the activity of fibroblasts and has been implicated in several disease states characterized by excessive fibrosis. In the kidney, TGF-beta promotes tubuloepithelial cell hypertrophy and regulates the glomerular production of almost every known molecule of the extracellular matrix, including collagens, fibronectin, tenascin, and proteoglycans, as well as the integrins that are the receptors for these molecules. Furthermore, TGF-beta blocks the destruction of newly synthesized extracellular matrix by upregulating the synthesis of protease inhibitors and downregulating the synthesis of matrix-degrading proteases such as stromelysin and collagenase. As will be discussed, there is a strong body of in vitro and in vivo evidence suggesting that persistent overproduction of TGF-beta 1 in glomeruli after the acute inflammatory stage of glomerulonephritis causes glomerulosclerosis. TGF-beta may also be important in a variety of other chronic renal disorders characterized by hypertrophy and sclerosis, such as diabetic nephropathy. In this review we will attempt to offer a basic understanding of the cellular and molecular biology of TGF-beta and its receptors, with special focus on the role of the TGF-beta system in the kidney during development, growth, and disease.

Animals↗
PubMed1994

Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse.

Renal hypertrophy is an early feature of diabetes, and it may predispose the kidney to the eventual development of parenchymal dysfunction. Since we have previously demonstrated that short-term culture in high glucose concentration stimulates production of transforming growth factor-beta 1 (TGF-beta 1) in proximal tubular and glomerular mesangial cells, we postulated that this cytokine, which has potent regulatory effects on cellular growth and extracellular matrix production, is important in mediating diabetic renal disease. In this study we evaluated the gene and protein expression of TGF-beta 1 in the kidney of two rodent models of spontaneous insulin-dependent diabetes mellitus [the biobreeding (BB) rat and the nonobese diabetic (NOD) mouse]. In association with the appearance in both models of significant renal hypertrophy, TGF-beta 1 mRNA levels were increased threefold in the kidney of the diabetic BB rat after 3 days of diabetes and also threefold after 7-9 days in the NOD mouse. There was no increase in TGF-beta 1 transcripts in the livers of the diabetic animals, suggesting that this response is tissue specific. Immunohistochemical studies revealed that TGF-beta 1 protein is concordantly elevated in the cortical tubular cells of the diabetic kidney in both models. These results suggest that the stimulated expression of renal TGF-beta is an early manifestation of the involvement of the kidney by diabetes. Whether increased TGF-beta production in the diabetic kidney is a key promoter of diabetic renal manifestations (e.g., hypertrophy) deserves additional studies.

Animals↗