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Biomedical subjects

B Radhakrishnamurthy

Publications and source records attributed to B Radhakrishnamurthy.

At least 55 records · Page 3Linked to original sources
PubMed1987

Atherosclerosis and its evolution in childhood.

Cardiovascular risk factors in childhood are related to arterial wall changes that lead to atherosclerotic coronary artery disease in later life. Atherosclerosis begins early in life. The observations of early arterial wall connective tissue changes and accompanying early lipid deposition show the importance of understanding cardiovascular risk factors in children. Since risk factors found in childhood are potentially predictive of adult coronary heart disease, methods for prevention of atherosclerosis should begin in children. Rational strategies should be directed to removing atherogenic forces that work in a child at high risk. Primary prevention of atherosclerosis has its maximal potential when begun before advanced irreversible lesions can occur. Consideration needs to be directed to how cardiovascular connective tissue changes and lipid and calcium deposition can be modulated in the injury and healing processes. It is important to recognize that adult coronary artery disease is really a major pediatric problem.

Adolescent↗
PubMed1987

Dolichol synthesis in liver slices of streptozotocin diabetic rats.

The rate of dolichol synthesis in normal and diabetic liver slices in the presence or absence of insulin was investigated with radiolabeled acetate and mevalonate as substrates. Cholesterol and dolichol syntheses were found low in diabetic rat liver slices when incubated either with 1-14C-acetate or 2-3H-mevalonate. In the presence of insulin, cholesterol and dolichol synthesis in diabetic rat liver slices returned to normal in nine hours when incubated with 1-14C-acetate; however, with 2-3H-mevalonate, synthesis of cholesterol and dolichol normalized in about three hours. These studies show that dolichol synthesis in rat liver slices is dependent on insulin.

Acetates↗
PubMed1987

Hepatic glycoprotein synthesis in streptozotocin diabetic rats.

In vitro incorporation of 3H-mannose into dolichol phosphate mannose, dolichol pyrophosphate oligosaccharides, and secretory and membrane glycoproteins was investigated in liver slices from streptozotocin diabetic rats. In addition, 14C-leucine incorporation into glycoproteins was studied. 3H-mannose incorporation was significantly less in secretory glycoproteins from diabetic rat liver slices than from control tissues, but 14C-leucine incorporation in these proteins was similar in both groups. Dolichol-phosphate mannose and dolichol-phosphate oligosaccharide synthesis were significantly down-regulated in diabetes. When incubated with insulin, mannosylation of secretory proteins, dolichol-phosphate mannose and dolichol-phosphate oligosaccharides reached control levels in three hours. Dolichol-phosphate mannosyltransferase activity was significantly less in diabetes, while in the presence of insulin, the enzyme activity reached control levels in three hours. These results indicate that key intermediates in glycoprotein biosynthesis are regulated by insulin.

Animals↗
PubMed1986

Organization of glycosaminoglycan chains in a chondroitin sulfate-dermatan sulfate proteoglycan from bovine aorta.

A chondroitin sulfate-dermatan sulfate proteoglycan was isolated from bovine aorta intima by extraction of the tissue by 4 M guanidine hydrochloride. The proteoglycan was purified by CsCl isopycnic centrifugation followed by gel filtration and ion-exchange chromatography. The proteoglycan had 21.9% protein, 22.1% uronate, 21.4% hexosamine and 10.8% sulfate. Glycosaminoglycan chains obtained from the proteoglycan by beta-elimination were resolved by gel filtration into two fractions, one containing chondroitin 6-sulfate with an approximate molecular weight of 49 000 and the other containing chondroitin 4-sulfate and dermatan sulfate in a proportion of 2:1 with an approximate molecular weight of 37 000. Digestion of the proteoglycan by chondroitinase ABC or AC yielded a protein core with similar composition and behavior in gel filtration and SDS-polyacrylamide gel electrophoresis. An approximate molecular weight of 180 000 was estimated for the core protein. Dermatan sulfate chains with an approximate molecular weight of 10 000 were observed only in the digest of chondroitinase AC. Limited trypsin hydrolysis of the proteoglycan yielded three peptide fragments containing chondroitin 6-sulfate, chondroitin 4-sulfate and dermatan sulfate in varied proportions. A tentative structure for the proteoglycan was suggested.

Animals↗
PubMed1986

Nonenzymatic glycosylation of proteins and protease activities in granulation tissues in experimental diabetes.

Serum proteins and hemoglobins show increased nonenzymatic glycosylation in diabetes mellitus. The measure of glycosylated proteins, particularly hemoglobin, is considered to be a preferred indicator in the control of diabetes. In a study of diabetes and inflammation, we assessed the extent of nonenzymatic glycosylation of proteins of granulation tissue from diabetic rats. Five, seven, and ten days after carrageenan injection, the granuloma proteins were extracted. Nonenzymatic glycosylation was measured in soluble and insoluble granuloma proteins by thiobarbituric acid assay. Protease activities and free amino groups were assayed in soluble extracts. Nonenzymatic glycosylation in soluble proteins of both groups reached a maximum on the seventh day. However, nonenzymatic glycosylation in soluble proteins of the diabetic granulomas was significantly greater than the controls on days five and seven. During the days after granuloma induction, nonenzymatic glycosylation in the insoluble granuloma tissue proteins gradually decreased without any significant differences between controls and diabetics. Significant decreases in the free amino groups in soluble proteins of the diabetic tissues were noted. Greater activities of cathepsins B and D were noted in diabetic tissues over controls. These observations suggest that, in addition to increased proteolysis, increased nonenzymatic glycosylation of tissue proteins could be associated with the impaired process of wound healing in diabetics.

Animals↗
PubMed1986

Studies of chemical and biologic properties of a fraction of sulodexide, a heparin-like glycosaminoglycan.

The chemical composition and biologic properties of a fraction (f) of Sulodexide, a heparin-like GAG, were studied and compared with those of two sulfated GAG preparations and heparin from intestinal mucosa. f-Sulodexide and the sulfated GAG preparations were fractionated on a Dowex-1Cl- column and subsequently on an antithrombin III affinity column. Low affinity and high affinity fractions had similar chemical composition and lipoprotein lipase releasing ability, but they varied in anticoagulant activity. Low affinity fractions from f-Sulodexide had negligible anticoagulant activity while high affinity fractions had one-half the activity of mucosal heparin. When compared to heparin, both fractions had one third amount of lipoprotein lipase releasing activity. The low anticoagulant activity of f-Sulodexide suggests a suitability for long-term use as an antiatherogenic agent.

Animals↗
PubMed1986

Low density lipoprotein retention by aortic tissue. Contribution of extracellular matrix.

We compared in vitro heparin binding activity and in vivo intravascular clearance and aortic uptake in rabbits of native, reductively methylated and heparin-complexed low density lipoprotein (LDL) in order to explore the extracellular matrix binding vs cellular metabolism of LDL. Reductively methylated LDL formed soluble and insoluble complexes with heparin which was comparable to native LDL. Reductive methylation of LDL produced only 30% reduction in aortic uptake vs 60% reduction in plasma clearance, reflecting the relatively smaller contribution of receptor-mediated pathway in aortic tissue vs whole animal. The intravascular clearance of native and heparin-complexed LDL remained essentially the same, indicating similarities in cellular metabolism of LDL in both cases. But the aortic uptake of the heparin bound LDL was 30% less than the native LDL, suggesting an inhibition in binding of heparin-complexed LDL to tissue proteoglycans. Saline extraction accounted for only part (53-66%) of the LDL preparations that were retained by the tissue while subsequent collagenase and elastase treatments extracted 3-5% and 17-22% of the materials respectively. These results favor the contribution of arterial extracellular matrix components to the retention of LDL.

Animals↗
PubMed1986

Fasting plasma glucose and insulin levels and their relationship to cardiovascular risk factors in children: Bogalusa Heart Study.

Plasma glucose and insulin levels were determined in a total biracial community of 3313 children, ages 5-17 years. Black children have significantly higher insulin and lower glucose levels than white children of comparable age and sex. Children of diabetic parents have elevated levels of age- and weight-adjusted fasting cholesterol. Moderate tracking (r = 0.31) of glucose levels over a 3-year period was seen. Insulin levels, however, track well (r = 0.36) only in older children (ages 9-14 years at initial examination). Fasting insulin levels are positively related to measures of obesity, systolic and diastolic blood pressure, triglyceride, beta-lipoprotein cholesterol and pre-beta-lipoprotein cholesterol levels. In addition, insulin levels are negatively related to alpha-lipoprotein cholesterol levels. Fasting glucose levels are positively related to systolic and diastolic blood pressure, triglycerides, pre-beta-lipoprotein cholesterol, and obesity levels. The relationship of plasma glucose and insulin levels to the traditional cardiovascular risk factors in children emphasizes the importance of subtle abnormalities in carbohydrate metabolism in the early natural history of cardiovascular disease.

Adolescent↗
PubMed1986

Effect of dietary carbohydrate type on lipoprotein lipase, hepatic lipase, and lecithin:cholesterol acyltransferase activities in cynomolgus monkeys.

The effects of dietary sucrose and starch with and without exogenous cholesterol on postheparin plasma lipoprotein lipase (PHLA) and hepatic lipase (HLA) were studied in cynomolgus monkeys. Serum triglyceride levels were higher in sucrose-fed animals than starch and exogenous cholesterol lowered serum triglyceride levels when added to sucrose diet but not starch diets. Sucrose markedly increased insulin levels, more so than starch; however, dietary cholesterol lowered insulin levels in sucrose diet but increased the levels in starch diet. PHLA activity was increased two- to threefold greater in sucrose than in starch diets. Exogenous cholesterol lowered PHLA activity in sucrose diet but increased PHLA activity in starch diet. HLA activity was increased with sucrose more than starch. Lecithin:cholesterol acyltransferase (LCAT) activity was significantly higher in sucrose diets than in the starch diet. Addition of cholesterol to either of these diets lowered the LCAT activity. These results indicate that PHLA, HLA, and LCAT activities not only are affected by the nature of carbohydrates, but also are related to triglyceride metabolism. The interaction of carbohydrates and cholesterol in the diet by influencing these selected enzymes plays an integrated role in lipoprotein particle interconversion processes.

Animals↗
PubMed1985

Complexes of low-density lipoproteins and arterial proteoglycan aggregates promote cholesteryl ester accumulation in mouse macrophages.

We studied the effect of complexes of low-density lipoproteins (LDL) and different proteoglycan preparations from bovine aorta on LDL degradation and cholesteryl ester accumulation in mouse peritoneal macrophages. Native proteoglycan aggregate containing proteoglycan monomers, hyaluronic acid and link protein was isolated by associative extraction of aortic tissue, while proteoglycan monomer was obtained by dissociative isopycnic centrifugation of the native proteoglycan aggregate. In vitro proteoglycan aggregates were prepared by reaction of the proteoglycan monomer with exogenous hyaluronic acid. 125I-labeled LDL-proteoglycan complexes were formed in the presence of 30 mM Ca2+ and incubated with macrophages. At equivalent uronic acid levels in the proteoglycans the degradation of 125I-labeled LDL contained in the native proteoglycan aggregate complex was 3.7-7.5-fold greater than the degradation of the lipoprotein in the proteoglycan monomer complex. Degradation of 125I-LDL in the in vitro aggregate complex, while higher than that in the monomer complex, was markedly less than that in the native aggregate complex. The larger size and the greater complex-forming ability of the native proteoglycan aggregate might account for the greater capacity of the aggregate to promote LDL degradation in macrophages. The proteoglycan-stimulated degradation of LDL produced a marked increase in cholesteryl ester synthesis and content in macrophages. The LDL-proteoglycan complex was degraded with saturation kinetics, suggesting that these complexes are internalized through high-affinity receptors. Degradation was inhibited by the lysosomotropic agent, chloroquine. Acetyl-LDL, but not native LDL, competitively inhibited the degradation of the 125I-LDL component of the complex. Polyanionic compounds such as polyinosinic acid and fucoidin, while completely blocking the acetyl-LDL-stimulated cholesteryl ester formation, had no effect on the proteoglycan aggregate-stimulated cholesterol esterification. This suggests that LDL-proteoglycan complex and acetyl-LDL are not entering the cells through the same receptor pathway. These results demonstrate that the interaction of LDL with arterial wall proteoglycan aggregates results in marked cholesteryl ester accumulation in macrophages, a process likely to favor foam cell formation. A role for arterial proteoglycans in atherosclerosis is obvious.

Animals↗
PubMed1985

Isolation and characterization of a link protein from bovine aorta proteoglycan aggregate.

Proteoglycan aggregates were isolated from bovine aorta by extraction with 0.5 M guanidine hydrochloride in the presence of proteinase inhibitors and purified by isopycnic CsCl centrifugation. The bottom two-fifths (A1) of the gradient contained 30% of proteoglycans in the aggregated form. The aggregate had 14.8% protein and 20.4% hexuronic acid with hyaluronic acid, dermatan sulfate and chondroitin sulfates in a proportion of 18:18:69. A link protein-containing fraction was isolated from the bottom two-fifths by dissociative CsCl isopycnic centrifugation. The link protein that floated to the top one-fifth of the gradient was purified by chromatography on Sephadex G-200 in the presence of 4 M guanidine hydrochloride. It moved as a single band in SDS-polyacrylamide gel electrophoresis with a molecular weight of 49 000. The amino acid composition of link protein resembled that of link protein from cartilage, but was strikingly different from that of the protein core of the proteoglycan monomer. The neutral sugar content of link protein was 3.5% of dry weight. Galactose, mannose and fucose constituted 21, 62 and 16%, respectively of the total neutral sugars. In aggregation studies the link protein was found to interact with both proteoglycan monomer and hyaluronic acid. Oligosaccharides derived from hyaluronic acid decreased the viscosity of link protein-free aggregates of proteoglycan and hyaluronic acid but not of link-stabilized aggregates, demonstrating that the link protein increases the stability of proteoglycan aggregates.

Animals↗
PubMed1985

Glycoprotein biosynthesis during inflammation in normal and streptozotocin-induced diabetic rats.

Extracellular glycoproteins play an important role in wound healing; yet little is known about glycoprotein biosynthesis and its regulation by insulin in inflammation. Using [1-14C] fucose as a marker, glycoprotein biosynthesis was studied in carrageenan-induced granuloma from diabetic and control rats. Fucose incorporation into glycoproteins was followed for 24 h after an intraperitoneal injection of the label. Radioactivity in trichloroacetic acid precipitable serum glycoproteins and saline-soluble and insoluble glycoproteins was assessed in five-, seven-, and ten-day-old granuloma tissues. Fucose incorporation was higher in soluble glycoproteins (P less than 0.01) at all points in controls than in diabetic granulomas, and peak incorporation was reached in both groups on the seventh day. Incorporation of fucose into insoluble glycoproteins was higher in normals on the seventh day than in diabetics. Liver-, kidney-, and intestine-soluble glycoproteins showed a maximum incorporation on the seventh day, but no difference was noted between diabetic and normal rats. Incorporation of fucose in insoluble glycoproteins showed a gradual decline with the age of granuloma in all tissues from both groups, with the exception of the kidney. In the kidney, fucosylation of insoluble glycoproteins was decreased (P less than 0.01) in diabetics compared to controls. These results indicate an active phase of biosynthesis, with an increase in glycosylation during inflammation that is probably insulin dependent.

Animals↗
PubMed1985

Relationship of carbohydrate intolerance to serum lipoprotein profiles in childhood. The Bogalusa Heart Study.

Three hundred-eighty-eight children were selected from a total community and biracial (black-white) population for a special in-depth study related to serum lipoproteins and carbohydrate metabolism. Based on two previous serum lipoprotein determinations of high and/or low beta and pre-beta-lipoprotein cholesterol, they were stratified into four groups. A glucose tolerance test was performed for fasting, 30-minute, and one-hour glucose, insulin, free fatty acids, calcium, and magnesium. Observations of height, weight, and triceps skinfold were also obtained on the children. Children in the high beta-lipoprotein cholesterol groups tended to have higher glucose levels and were more obese than the other groups, while children in the high pre-beta-lipoprotein cholesterol group tended to have high insulin levels following the glucose load. Fasting blood levels were not appreciably different in the various groups, but after the glucose load an unusually high insulin secretory response occurred in black children, especially black girls. Black girls also demonstrated somewhat lower blood sugars than the other race-sex groups. The insulin/glucose ratios were dramatically different in the black children, especially black girls. These differences were particularly noted in the groups with the high pre-beta-lipoprotein. Black children also tended to have higher insulin/free fatty acid ratios during the glucose tolerance test. These differences persisted even after adjusting for obesity. Although not significant, calcium levels consistently decreased in all groups following a glucose load. The observation of racial contrasts in glucose and insulin responses are interesting. While black girls appear to show low glucose and high insulin responses to a glucose load, low and delayed insulin response along with high glucose response occur in whites, especially white girls. Since white children have greater body fat content, these observations suggest more insulin resistance in white children. Even at low levels of obesity, subtle carbohydrate lipid metabolic aberrations are found in children having high levels of serum lipoproteins. A persistence of these conditions could contribute to accelerated atherosclerosis and subsequent coronary artery disease.

Adolescent↗
PubMed1985

Proteoglycans from lungs of rabbits treated with pronase and cadmium chloride.

The composition of proteoglycans was studied in lungs from rabbits treated intratracheally with pronase, CdCl2, or saline. Proteoglycans were extracted from the lungs by 0.5 M and 4.0 M guanidine hydrochloride (GdnHCl) in sequence. Proteoglycans were isolated from the extracts by CsCl isopycnic centrifugation and fractionated by gel filtration on a Sepharose CL-4B column. The lungs from pronase-treated rabbits had approximately 33% greater total uronate than did lungs from saline-treated control animals, whereas CdCl2-treated rabbit lungs had 28% less uronate than did control lungs. Pronase-treated animal lungs had a greater proportion of hyaluronic acid and dermatan sulfate than did the control animal lungs. Relatively greater amounts of uronate were extracted by 0.5 M GdnHCl from the enzyme-treated rabbit lungs than from the CdCl2- or saline-treated animal lungs. The concentrations of hyaluronic acid and heparan sulfate in 0.5 M GdnHCl extract and dermatan sulfate in 4.0 M GdnHCl extract were greater in pronase-treated animal lungs than in control lungs. Gel filtration of proteoglycans sedimented at q greater than 1.45 revealed that pronase-treated animal lungs had proteoglycans smaller in molecular size than those in control lungs. The observations indicate that intratracheal treatment with pronase and CdCl2 alters the composition of proteoglycans in the lung, and such alterations are likely important in the pathogenesis of emphysema.

Animals↗
PubMed1985

Composition of glycosaminoglycans from aortas from deoxycorticosterone-induced hypertensive pigs.

Hypertension was induced in young male pigs by subcutaneous implantation of deoxycorticosterone acetate in a Silastic rubber carrier. Hemodynamic variables were periodically monitored. Six to eight weeks after implantation, the animals were necropsied and aortas were dissected. Glycosaminoglycans (GAG) were isolated from aortas from hypertensive pigs and from normotensive controls. Individual glycosaminoglycans in mixtures were fractionated and quantitated by chromatography on Dowex 1 Cl- column. No differences were noted in total glycosaminoglycan concentration between hypertensive and control animal aortas; the differences in individual GAG in aorta media-adventitia between the groups were not statistically significant. The relative proportions of heparan sulfate and dermatan sulfate in aorta intima were significantly greater (p less than 0.05) in hypertensive aortas than in normotensive intima. These two glycosaminoglycans increased in hypertensive animals at the expense of chondroitin 4-sulfate and hyaluronic acid. There was no difference in chondroitin 6-sulfate between the groups. A possible explanation of changes of glycosaminoglycans in hypertension because of altered lysosomal activity is suggested.

Animals↗