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Biomedical subjects

P Sharma

Publications and source records attributed to P Sharma.

At least 235 records · Page 13Linked to original sources
PubMed1997

Differential effects of Wilms tumor WT1 splice variants on the insulin receptor promoter.

The Wilms tumor gene WT1 has been implicated in the early development of the kidney. Mutations in WT1 are found in a small fraction of Wilms tumor, a pediatric nephroblastoma, and Denys-Drash syndrome, characterized by genitourinary abnormalities. The WT1 gene product functions as a transcriptional repressor of growth factor-related genes. The kidney is one of the major sites of insulin action in vivo and expresses high levels of insulin receptors (IR). IR expression has been detected during early embryogenesis, suggesting that it may play a role in development. We investigated whether two WT1 splice variants lacking or including a three-amino-acid (KTS) insertion between the third and fourth zinc finger in the DNA-binding domain could repress the IR promoter in vitro. We show that the +KTS variant effectively represses promoter activity under all conditions tested but the -KTS variant was only able to repress in the presence of cotransfected C/EBP beta or a dominant-negative p53 mutation. Deletional mapping indicated that distinct regions of the IR promoter mediated the effects of the two isoforms and DNaseI footprint analysis identified potential WT1 binding sites within these regions.

Alternative Splicing↗
PubMed1997

Consequences of hypoxia on the cell size of neuropeptide-Y neurons and the role of ascorbate in cultured neurons from chick embryo.

The effect of ascorbate on the cell size of neuropeptide-Y neurons (NPY) and ascorbate uptake was studied in hypoxic neuronal cultures from chick embryo. Primary neuronal cultures plated on coverslips or on plastic dishes were switched to the serum free or serum supplemented medium and exposed to the normoxia or hypoxia for 8 h. Vehicle (homocysteine) or L-ascorbic acid was added to the incubation medium at 0 h. Cell size and relative optical density of NPY positive neurons on coverslips were measured by image analysis and ascorbate content in the cell culture on dishes was determined by HPLC. Hypoxia increased the size of NPY neurons in vehicle treated cultures but not in ascorbate supplemented cultures containing serum free or serum supplemented medium. Contrastingly, normoxic NPY neurons were damaged by ascorbate in serum free medium and not by incubation with ascorbate in serum supplemented medium. These results indicate that the inhibition of hypoxic induced neuronal swelling by ascorbate is consistent with its antioxidant properties and presence of ascorbate in serum free medium under normoxic conditions may act as a proxidant for cultured neurons.

Animals↗
PubMed1997

Pressure modulates monocyte migration.

Migration of monocytes into the subendothelial space of the aorta has been considered to be an important event in the development of atherosclerosis. Because hypertension is commonly associated with atherosclerosis, we studied the effect of applied pressure on the migration of monocytes. Direct applied pressure increased the migration (P < .001) of monocytes across a filter when compared with normal atmospheric pressure. The migration of monocytes was found to be directly related to the amount of the applied pressure. Amlodipine, a calcium channel blocker, attenuated the migration of monocytes under normal as well as increased pressure conditions in a dose-dependent manner. These studies provide a basis to speculate on the role of direct pressure in the migration of monocytes into the subendothelial space and the possibility that vasoactive agents may modulate the migration of monocytes independent of their pressure-lowering effect.

Amlodipine↗
PubMed1997

GABA agonists and neurotransmitters metabolizing enzymes in steroid-primed OVX rats.

The effect of intraventricular (IVT) administration of GABAA receptor agonist muscimol and GABAB receptor agonist, baclofen was examined on the activity of acetylcholinesterase (AChE), monoamine oxidase (MAO) and Na+, K(+)-ATPase in discrete areas of brain from estrogen-progesterone primed ovariectomized rats. AChE enzyme activity was increased in two subcellular fractions (soluble and total particulate) studied, with statistically significant changes in cerebral hemispheres (CH), cerebellum (CB), thalamus (TH) and hypothalamus (HT), Na+, K(+)-ATPase enzyme activity was decreased in both these fractions. MAO activity increased significantly in CH, TH and HT. The presented results suggest a functional relationship between GABAergic (inhibitory), cholinergic and monoaminergic (excitatory) systems by affecting the rate of degradation of the excitatory neurotransmitters and Na+, K(+)-ATPase.

Acetylcholine↗
PubMed1997

Comparison of immunomodulation by cyclosporin A and azathioprine on pancreatic xenograft survival.

Prolonged survival of pancreatic xenografts in the muscles of diabetic rabbits under the immunomodulation of cyclosporin A and azathioprine was achieved. The mean graft survival time (as assessed by euglycemic status and histopathological findings) in Group A (azathioprine treated) was 36 days, in Group B (cyclosporin A treated) it was 69 days, and the difference was significant (p < 0.001). Adequate immunosuppression helps the pancreatic xenograft to normalize the blood glucose level (BGL) by prolonging its survival time. Our study demonstrates that xenotransplanted islet cells in a natural environment (pancreatic tissue in the form of thin slices) survive and function adequately in immunosuppressed recipients, and addition of cyclosporin A significantly prolongs survival of the xenograft. This discordant xenotransplantation model may be useful for future xenotransplantation studies.

Adjuvants, Immunologic↗
PubMed1997

HIV-1 gp160 envelope protein modulates proliferation and apoptosis in mesangial cells.

Mesangial cell (MC) hyperplasia and accumulation of extracellular matrix are the predominant features of HIV-associated nephropathy (HIVAN). Since mice transgenic for HIV-1 genes show renal lesions mimicking HIVAN, we studied the effect of HIV-1 gp160 protein on cultured murine MC (MMC) proliferation and apoptosis. HIV-1 gp160 protein stimulated (p < 0.001) MMC proliferation when compared with control MMCs. This effect of gp160 protein peaked at a concentration of 0.01 microg/ml. MMCs treated with a higher concentration of gp160 protein (0.1 microg/ml) or for a prolonged period of time (72 h) showed apoptosis rather than cell proliferation. These studies were further confirmed by DNA fragmentation and end labeling assays. gp160 also enhanced apoptosis in human MCs. Tumor necrosis factor (TNF)-alpha enhanced (p < 0.001) MMC apoptosis, and anti-TNF-alpha antibodies inhibited gp160-induced MMC apoptosis. In addition, gp160 protein attenuated MMC expression of Bcl-2 mRNA expression. These results suggest that gp160-induced apoptosis may be affected in part by the release of TNF-alpha and associated with attenuated mRNA expression of Bcl-2 by MMCs.

AIDS-Associated Nephropathy↗
PubMed1997

Effect of morphine on renomedullary interstitial cell proliferation and matrix accumulation.

Renal interstitial scarring is an important feature of heroin-associated nephropathy. We studied the effect of morphine, an active metabolite of heroin, on cultured rat renal medullary interstitial cell (RMIC) proliferation and matrix accumulation. Morphine (10(-12) M) enhanced (p < 0.001) the proliferation of RMIC (control, 15.0+/-0.5 vs. morphine, 20.4+/-1.1 x 10(4) cells/ml). This effect of morphine was dose and time dependent. [3H]thymidine and bromodeoxyuridine incorporation studies confirmed the mitogenic effect of morphine on RMIC. Morphine also enhanced mRNA expression for c-jun and c-myc on RMIC. However, nalbuphine, a non-addicting alkaloid did not modulate the proliferation of RMIC. Morphine enhanced the accumulation of collagen type I in a dose-dependent manner and also increased (p < 0.001) the accumulation of collagen type III at a high concentration (control, 1,291+/-55.8 vs. morphine, 10(-4) M, 2,697.6+/-257.8 ng/microg protein). Morphine did not modulate the accumulation of laminin or fibronectin. Neutralizing antibody to IL-6 inhibited the effect of morphine on RMIC. H7, a protein kinase C inhibitor, also attenuated the morphine-induced RMIC proliferation. The present study provides a basis for a hypothesis that morphine may be playing a role in the development of renal interstitial pathology in patients with heroin addiction.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

In vitro ammonia utilization and urea synthesis by rat liver after portacaval shunt.

BACKGROUND: The objective of this study was to study in vitro ammonia utilization and urea synthesis by the rat liver after portacaval shunt (PCS) in comparison to controls. This study is part of a series of experiments to investigate metabolic derangements in the liver following PCS. METHODS: Sixteen male Wistar rats weighing 150-230 g were used. PCS was performed on 8 and the rest served as sham-operated controls. The experiments were performed 4 weeks postoperatively. The usually monitored postoperative parameters after PCS like body weight, rise in ammonia levels in the peripheral blood, atrophy of mesenteric fat, atrophy of the liver, etc., were comparable to other PCS series. Liver slices (1 x 2 x 1 mm) were prepared from each rat liver and incubated in Krebs-Henseleit buffer. RESULTS: After incubation, ammonia utilization in the controls was 162.88+/-20.12 micromol/g dry weight/h while in PCS rats it was 81.35+/-2.64 micromol/g dry weight/h (p < 0.0001). The rate of urea synthesis in controls was 122.54+/-12.93 micromol/g dry weight/h whereas in the PCS group it was 14.99+/-2.21 micromol/g dry weight/h (p < 0.0001). CONCLUSION: These results indicate a significant decline in the capacity of the liver for ammonia utilization as well as urea synthesis after PCS.

Ammonia↗
PubMed1997

Effect of silver leaf on circulating lipids and cardiac and hepatic enzymes.

About 50 mg of silver leaf (metallic silver) was given daily by mouth to 30 healthy volunteers for 20 days. A statistically significant hypophospholipidemic, hypotriglyceridemic, hypocholesterolemic and hypoglycemic effect was observed. This was accompanied by a less marked fall in total lipids and significant rise in HDL-cholesterol. In addition, a decrease in plasma enzymes - alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatine phosphokinase (CPK), gamma glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH) was noted. This was statistically significant for all enzymes except CPK. The safety of ingested silver foil is indicated by absence of pathology in urine and unaltered levels of protein and albumin in the plasma. These observations suggest that silver could be beneficial in conditions like diabetes mellitus, obesity and atherosclerosis.

Female↗
PubMed1997

Normalization of esophageal pH with high-dose proton pump inhibitor therapy does not result in regression of Barrett's esophagus.

OBJECTIVE: The importance of esophageal acid control in the management of Barrett's esophagus is controversial. The objective of this study was to assess the impact of esophageal acid control on the symptoms of reflux disease, healing of erosive esophagitis, change in length of Barrett's epithelium, and the appearance of squamous islands. METHODS: Thirteen of 27 patients on 60 mg lansoprazole underwent ambulatory 24 h esophageal pH monitoring while on therapy. Symptoms were recorded, and the length of Barrett's epithelium was measured, photographed, and biopsied every 6 months over an average of 5.7 yr. RESULTS: Eight of 13 patients had a normal 24 h pH (group I, mean pH < 4, 0.8%), five patients had abnormal results (group II, mean pH < 4, 10.6%). Symptoms improved in all patients, and there was complete healing of erosive esophagitis in all patients. An increase in the number of squamous islands was noted in 62.5% of patients in group I and in 80% of patients in group II. The mean length of Barrett's epithelium at baseline and study completion in group I was 5.6 and 5.0 cm, respectively (mean decrease, 0.6 cm), and for group II was 4.2 and 4.2 cm, respectively (mean decrease, 0 cm). There was no significant difference in the change in length between the two groups (p = 0.494). CONCLUSIONS: Although symptoms improved, erosive esophagitis healed, and squamous islands increased, there was no significant decrease in the length of Barrett's esophagus. Control of esophageal pH alone is not sufficient for the reversal of Barrett's esophagus.

2-Pyridinylmethylsulfinylbenzimidazoles↗