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Biomedical subjects

R Dahiya

Publications and source records attributed to R Dahiya.

144 records · Page 8Linked to original sources
PubMed1986

The role of sphingomyelin synthetase and sphingomyelinase in 1,2-dimethylhydrazine-induced lipid alterations of rat colonic plasma membranes.

Recently, our laboratory, utilizing the 1,2-dimethylhydrazine model of colonic adenocarcinoma, demonstrated alterations in the 'dynamic component' of fluidity in brush-border membranes prepared from distal colonocytes of rats administered this agent for 5, 10 and 15 weeks, i.e., before the development of colon cancer. Furthermore, changes in the sphingomyelin content and sphingomyelin/phosphatidylcholine molar ratio of these membranes appeared, at least partially, to be responsible for these fluidity alterations. In an attempt to elucidate the mechanism(s) involved in these dimethylhydrazine-induced lipid changes, in the present studies the activities of sphingomyelin synthetase and magnesium-dependent neutral sphingomyelinase, enzymes involved in the synthesis and degradation of this phospholipid, respectively, were examined and compared in distal colonic brush-border membranes prepared from rats after 5, 10 or 15 weeks administration of dimethylhydrazine or diluent. The results of these studies demonstrate that alterations in both these enzymatic activities can be detected after administration of dimethylhydrazine and appear to, at least in part, be responsible for the changes in membrane sphingomyelin composition noted previously. These results as well as a discussion of their possible serve as the basis for the present report.

1,2-Dimethylhydrazine↗
PubMed1986

Glycosphingolipid patterns of fetal and adult small intestinal mucosa in the sheep.

The ganglioside and neutral glycosphingolipid composition of fetal and adult sheep small intestinal mucosa were characterized and compared. Mono- and tetrahexosylceramide were the major neutral glycolipids of both fetal and adult tissue. Fetal mucosa, however, possessed a higher content of monohexosylceramide than its adult counterpart. Similarly, GD1a, GM3 and GM2 were found to be the principal gangliosides in fetal and adult tissue. Adult intestinal mucosa possessed significant amounts of GT1a not present in fetal tissue. Analysis of the hydroxy and nonhydroxy fatty acids as well as the long-chain bases of the major glycosphingolipids revealed differences between these lipophilic components of glycolipids in fetal and adult intestinal mucosa. The results, therefore, indicate that both quantitative and qualitative differences in glycosphingolipid composition exist between fetal and adult sheep small intestinal mucosa.

Animals↗
PubMed1986

Distribution of glycosphingolipids of monkey small and large intestinal mucosa.

The ganglioside and neutral glycosphingolipid composition of adult monkey small and large intestinal mucosa were characterized and compared. GM3, GM2 and GD1A were found to be the principal gangliosides in each of these tissues. Dihexosylceramide was the major neutral glycosphingolipid of both organs. The total content of gangliosides and neutral glycolipids/ceramide, however, was ca. four-fold and two-fold higher, respectively, in small intestinal than colonic mucosa. While all glycosphingolipids examined contained hydroxy and nonhydroxy fatty acids, the former fatty acids accounted for 60-90% of the total fatty acids in both organs. Sphingosine was the predominant long chain base of ceramide, mono-, di-, tri- and tetrahexosylceramide, whereas phytosphingosine was the major base of GM3 in both tissues. The results of these studies demonstrate that while many similarities of monkey small and large intestinal glycosphingolipids exist, qualitative and quantitative differences are present along the length of the monkey gut. These differences may be at least partially responsible for certain of the well-recognized variations in normal physiological and pathological processes that occur in these organs.

Animals↗
PubMed1986

Distribution of glycosphingolipids and ceramide of rat small intestinal mucosa.

Previous studies have suggested that glycosphingolipids may be involved in a number of physiological functions of the small intestinal mucosa. Regional variations in many of these processes exist along the length of this organ. In the present studies, the glycosphingolipid and ceramide composition of the proximal, middle and distal thirds of the rat small intestine were characterized and compared. Mono- and trihexosylceramide were the major neutral glycolipids and hematoside (GM3), the principal ganglioside of this organ. Monohexosylceramide was the major glycolipid of the proximal segment, whereas trihexosylceramide predominated in the distal segments. The total content of neutral glycolipids, ceramide and gangliosides as well as the content of the individual glycosphingolipids and ceramide were highest in the distal segment, intermediate in the middle and lowest in the proximal segment. Additionally, regional variations were noted in the fatty acid composition of the major glycosphingolipids. These differences in the composition of glycolipids and ceramide along the length of the intestine may be responsible, at least partially, for the regional functional specialization seen in this organ.

Animals↗
PubMed1986

Premalignant alterations in the lipid composition and fluidity of colonic brush border membranes of rats administered 1,2 dimethylhydrazine.

Dimethylhydrazine (DMH) is a potent procarcinogen with selectivity for the colon. To determine whether alterations in the lipid composition and fluidity of rat colonic brush border membranes existed before the development of DMH-induced colon cancer, rats were injected s.c. with this agent (20 mg/kg body weight per wk) or diluent for 5, 10, and 15 wk. Animals were killed at these time periods and brush border membranes were prepared from proximal and distal colonocytes of each group. The "static" and "dynamic" components of fluidity of each membrane were then assessed, by steady-state fluorescence polarization techniques using limiting hindered fluorescence anisotropy and order parameter values of the fluorophore 1,6 diphenyl-1,3,5-hexatriene (DPH) and fluorescence anisotropy values of DL-2-(9-anthroyl) stearic acid and DL-12-(9-anthroyl) stearic acid, respectively. Membrane lipids were extracted and analyzed by thin-layer chromatography and gas-liquid chromatography. Phospholipid methylation activity in these membranes was also measured using S-adenosyl-L-methionine as the methyl donor. The results of these studies demonstrate that: the lipid composition and both components of fluidity of proximal DMH-treated and control membranes and their liposomes were similar at all time periods examined; at 5, 10, and 15 wk the "dynamic component of fluidity" of distal DMH-treated membranes and their liposomes was found to be higher, similar, and lower, respectively, than their control counterparts; the "static component of fluidity" of distal DMH-treated membranes and their liposomes, however, was similar to control preparations at all three time periods; and alterations in the lipid composition and phospholipid methylation activities appeared to be responsible for these differences in the "dynamic component of fluidity" at these various time periods.

1,2-Dimethylhydrazine↗
PubMed1985

Glycosphingolipids of fetal and adult sheep colonic mucosa.

The ganglioside and neutral glycosphingolipid composition of fetal and adult sheep colonic mucosa were characterized and compared. Mono- and tetrahexosylceramide were the major neutral glycolipids of both fetal and adult colons. Adult, but not fetal, mucosa also possessed di- and trihexosylceramide. Similarly, GD1a, GM3 and GM2 were found to be the principal gangliosides in fetal and adult tissue. Adult colonic mucosa possessed significant amounts of GT1a not present in fetal tissue. Analysis of the hydroxy and nonhydroxy fatty acids as well as of the long chain bases of the major glycosphingolipids revealed differences between these lipophilic components of glycolipids in fetal and adult colonic mucosa. The present results, therefore, indicate that both quantitative and qualitative differences in glycosphingolipid composition exist between fetal and adult sheep colonic mucosa.

Animals↗
PubMed1985

Aggravation of experimental atherosclerosis in vasectomized, cholesterol-fed rabbits.

Rabbits were fed a stock or atherogenic diet for a period of fourteen months. Half of each group of rabbits was bilaterally vasectomized while the other half underwent sham vasectomy. The level of plasma cholesterol was significantly elevated following vasectomy in stock diet-fed rabbits. Atherogenic diet feeding caused marked elevation of plasma cholesterol in both vasectomized as well as sham-vasectomized animals. At the termination of the experiments, aortic cholesterol in stock diet-fed vasectomized rabbits remained unchanged, but this was increased in both vasectomized and sham-vasectomized atherogenic diet-fed animals. Aortic sudanophilia, atherosclerotic plaque size and coronary atherosclerosis index were significantly increased in vasectomized atherogenic diet-fed rabbits as compared to their controls. In stock diet-fed vasectomized rabbits no macroscopic or microscopic lesions were seen even in the presence of mild hypercholesterolaemia.

Animals↗
PubMed1982

Altered lipid profile, postheparin lipolytic activity, and xanthoma of choroid plexus in vasectomized rabbits fed an atherogenic diet.

Plasma and erthrocyte lipid profile and lipoprotein lipase activity in postheparin plasma on vasectomized rabbits were studied and also the incidence of atherosclerosis in different arterial beds. Four groups of animals were studied, sham-vasectomized and vasectomized animals fed stock diet (groups A1, A2) and sham-vasectomized and vasectomized animals fed atherogenic diet (groups B1, B2). Elevated levels of neutral lipids and phospholipids in plasma and in erythrocytes of the vasectomized rabbits were observed. This elevation of blood lipids was the result of an increase in all fractions, however, phosphatidylcholine increased more than other phospholipid fractions in plasma. In erythrocytes the increase of phosphatidylethanolamine was greater than that of phosphatidylcholine. The accumulation of triglyceride-rich plasma lipids in all the vasectomized rabbits may be the result of a relatively decreased stimulation of postheparin lipolytic activity. The vasectomized animals given atherogenic diet revealed a significantly greater aortic sudanophilia and extensive occluding coronary atherosclerosis as compared to lesions seen in sham-vasectomized rabbits fed the same diet. Two rabbits of group B2 had xanthomatous lesions in choroid plexus of brain.

Animals↗
PubMedDate not supplied

Phosphorus metabolite characterization of human prostatic adenocarcinoma in a nude mouse model by 31P magnetic resonance spectroscopy and high pressure liquid chromatography.

A series of experiments were conducted to identify and quantify the phosphorus metabolites of DU 145 xenografts (a human prostatic adenocarcinoma cell line grown in nude mice) using 31P MRS and HPLC. The 31P spectral characteristics of DU 145 xenografts were compared to perfused DU 145 cells and to in situ human prostatic adenocarcinomas. These studies demonstrated that both DU 145 xenografts and perfused DU 145 cells exhibited reduced levels of phosphocreatine relative to spectra of in situ human prostatic adenocarcinomas. Elevated levels of phosphomonesters (PMEs) were observed in 31P spectra of both DU 145 xenografts and in situ human prostatic adenocarcinomas. The major components of the PME resonance of DU 145 xenografts were identified as phosphocholine and phosphoethanolamine. High levels of diphosphodiesters (DPDEs) were consistently observed for both DU 145 xenografts and perfused DU 145 cells, but were absent in 31P spectra in in situ primary human adenocarcinomas. In agreement with spectroscopic results, high pressure liquid chromatographic analyses of human tissue removed at surgery contained insignificant amounts of DPDEs while DU 145 xenografts had high levels of DPDEs consisting mainly of uridine-5'-diphospho-N-acetylgalactosamine (22.4 nmol/mg protein) and uridine-5'-diphospho-N-acetylglucosamine (7.4 nmol/mg protein).

Adenocarcinoma↗
PubMedDate not supplied

Frequent genotype changes at -308 of the human tumor necrosis factor-alpha promoter region in human uterine endometrial cancer.

This study was designed to test the hypothesis that genotypic changes of tumor necrosis factor alpha (TNF-alpha) promoter region are associated with endometrial cancer. TNF-alpha gene encodes a cytokine involved in angiogenesis and oncogenesis of several cancers. Some uncommon alleles are reported to be associated with increased production of TNF-alpha and the onset of various cancers. Studies of such alleles are lacking in endometrial cancer. In this study, we examined the genetic changes at the polymorphic 3 loci of TNF-alpha promoter regions (-238, -308 and 488) in 41 Japanese patients with uterine endometrial carcinomas (UEC). Nine of 41 UEC samples (22%) had genotype changes from GA to A at -308 promoter region of the TNF-alpha gene. There were no genotype changes at -238 and 488 regions of TNF-alpha in UEC samples. The results of our study demonstrate for the first time that genotype changes from GA to A in UEC patients. We conclude that the genotype changes at -308 promoter region of TNF-alpha may play an essential role in the malignant transformation of endometrial cells.

Cell Transformation, Neoplastic↗