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Biomedical subjects

B Radhakrishnamurthy

Publications and source records attributed to B Radhakrishnamurthy.

At least 73 records · Page 4Linked to original sources
PubMed1985

Composition of glycosaminoglycans in the lungs of copper-deficient chicks.

Copper deficiency results in defective elastin and collagen maturation in most tissues. A close relationship also exists between these components and proteoglycans in connective tissue. In an effort to obtain information on the nature of proteoglycans in copper deficiency, the composition of glycosaminoglycans in lungs from copper-deficient (1 micrograms/g of diet) or -supplemented (25 micrograms/g diet) chicks was studied. The total glycosaminoglycan concentration in copper-deficient chick lungs did not differ from that in control chick lungs. However, variations in individual glycosaminoglycan concentrations between lungs from copper-deficient and -supplemented chicks were observed. Heparan sulfate and dermatan sulfate concentrations were lower in copper-deficient chick lungs than in controls. The glycosaminoglycans from lungs of copper-deficient chicks also had lower molecular weights than glycosaminoglycans from lungs of control birds.

Animals↗
PubMed1985

Identification of fibronectin and laminin in glycoprotein extracts of human aorta.

Glycoproteins were extracted from human atherosclerotic lesions by a phosphate buffered heparin solution and by 0.15 M NaCl, followed by sequential digestion of the tissue by collagenase and elastase. Proteins obtained from the extracts by fractional precipitation by (NH4)2SO4 at 40%, 60% and 100% saturation of the salt at pH 4.0 were analyzed for total protein and for fibronectin and laminin by immunodiffusion. Greater amounts of proteins were extracted from atherosclerotic lesions than from uninvolved tissue. The buffered heparin solution extracted several-fold more protein than 0.15 M NaCl. Fibronectin was found in most protein fractions from every extract, but the presence of laminin was noted only in the protein fractions precipitated at 40% saturation of (NH4)2SO4 in the extracts of the tissue by heparin.

Aorta↗
PubMed1984

Heterogeneity of heparan sulfate chains in a proteoglycan from bovine lung.

A heparan sulfate proteoglycan from bovine lung gas-exchange tissue was isolated by extraction of the tissue with 4.0 M guanidine HCl in the presence of multiple protein inhibitors. The proteoglycan was purified by precipitation with cetylpyridinium chloride in 0.5 M KCl followed by CsCl isopycnic centrifugation (po = 1.45) in 4.0 M guanidine/HCl. Further purification was achieved by gel filtration on Sepharose CL-2B and by chromatography in DEAE-Sepharose CL-6B column. The proteoglycan had 14.9% protein and 22.4% uronate. Heparan sulfate chains from the proteoglycan were isolated after beta-elimination. Fractionation of heparan sulfate chains was achieved on Dowex-1 Cl- column, eluting with a stepwise increase in the concentration of NaCl, 1.0 to 2.0 M with 0.2 M increments. Of the total heparan sulfate recovered from the column, about 10% eluted by 1.2 M NaCl, 68% by 1.4 M NaCl, 18% by 1.6 M NaCl and 4% by 1.8 M NaCl. The fractions varied in their total and N-sulfate ester contents and iduronic acid to glucuronic acid ratios. The fraction that eluted from the Dowex-1 Cl- column at 1.6 M NaCl had the highest molecular weight, 37000, and the fraction that eluted at 1.8 M NaCl had the lowest molecular weight, 12000, as determined by gel filtration method, and the greatest sulfate content. The core protein, obtained by digestion of proteoglycan by heparan sulfate lyase, showed mostly a single band in SDS-polyacrylamide gel electrophoresis. The observations indicate a heterogeneity of the composition of heparan sulfate chains in the proteoglycan. This heterogeneity likely contributes to variations in biologic properties of different heparan sulfate proteoglycan preparations.

Animals↗
PubMed1984

Dynamics of lipoprotein-glycosaminoglycan interactions in the atherosclerotic rabbit aorta in vivo.

Dynamics of lipoprotein-glycosaminoglycan interactions in aortas were studied in vivo using the atherosclerotic rabbit model. Severe hypercholesterolemia and atherosclerosis were produced by relatively long-term feeding of a high cholesterol diet. [35S]Sulfate uptake by aorta was measured to assess the sulfated glycosaminoglycan metabolism while the plasma and aorta distribution of 125I-labeled LDL after intravascular injection was determined to monitor aortic LDL uptake and complex formation with glycosaminoglycans. The retention and distribution of LDL as lipoprotein-glycosaminoglycan complexes in different extracellular connective tissue elements were evaluated by extracting the tissues with saline, collagenase and elastase. Hypercholesterolemia with atherosclerosis resulted in a several-fold increase in the uptake of LDL by aorta despite a marked reduction of 125I-labeled LDL in the plasma compartment and in a significant increase in glycosaminoglycan content of aorta coupled with an increased 35S incorporation into glycosaminoglycans. Elastase-solubilized fractions from normal aortas and collagenase-solubilized fractions from atherosclerotic aortas contained maximum labeled and nonlabeled glycosaminoglycan, suggesting alterations in the make-up of fibrous structures of connective tissue matrix in atherosclerosis. Saline extraction and collagenase and elastase digestions solubilized varied proportions of lipoprotein-cholesterol and 125I-labeled LDL, thereby representing different pools of extracellular matrixbound lipoproteins. A tendency for 125I-labeled LDL to increase in collagenase- and elastase-solubilized fractions with time (4 h vs. 24 h) was noted. The occurrence of both lipoproteins and glycosaminoglycan (labeled and nonlabeled) in the ultracentrifugal floating fraction at solvent density 1.063 g/ml demonstrated that the lipoproteins solubilized by different extraction procedures occur in part as lipoprotein-glycosaminoglycan complexes. The specific activities of glycosaminoglycan in the complexes obtained by different extraction procedures differed markedly (elastase greater than collagenase greater than saline), emphasizing the presence of different pools of complexes. Thus, besides arterial cell-mediated processes, extracellular matrix components are important in affecting the retention and accumulation of LDL in atherosclerosis.

Animals↗
PubMed1984

Variability in blood pressure response to dietary sodium intake among African green monkeys (Cercopithecus aethiops).

Since salt-sensitivity to blood pressure (BP) response is a species-related phenomenon, the response of BP to dietary sodium was examined in 14 adult male African green monkeys (Cercopithecus aethiops). The animals were exposed to graded increase of dietary NaCl at 0 (control), 3.0, 4.5, and 6.0%, respectively for 45, 139, 37, and 90 days. Systolic and diastolic BP and body weights were measured twice weekly. Body weight did not differ significantly between successive diets. The mean (+/- SD) systolic/diastolic BP for control, 3.0, 4.5, and 6.0% NaCl diets were 88.8 +/- 15.4/65.9 +/- 13.7, 101.9 +/- 17.6/72.1 +/- 13.0, 90.5 +/- 20.9/62.2 +/- 16.2, and 115.3 +/- 22.6/81.0 +/- 16.4, respectively. BP changes between successive diets were significant (p less than 0.05). Monkeys with high or low initial mean arterial BP levels on control diet tended to maintain the same order with significantly high correlations between BP levels for successive diet periods (r = 0.88 to 0.95, p less than 0.0001). Thus as a group, this nonhuman primate species responds to increased NaCl intake with elevated mean systolic and diastolic BP. Individual variations in salt sensitivity and consistency in persistence of BP levels in this species has bearing on human hypertension.

Animals↗
PubMed1984

Serum lipoprotein lipid and apoprotein (B and A-I) responses to saturated fat-rich diet in cynomolgus monkeys: effects of carbohydrate type and cholesterol.

The effects of carbohydrate type and cholesterol in a high saturated fat diet (40% cal) on serum lipoprotein lipid and apoprotein responses were studied in 12 male cynomolgus monkeys (Macaca fascicularis). For 6 wk each monkey was fed one of four semipurified diets that provided by calorie 49% as starch or sucrose without and with 1 mg/kcal cholesterol. Starch and sucrose diets without added cholesterol resulted in similar levels of serum total cholesterol and apoB; whereas starch produced significantly higher values for these variables than sucrose when cholesterol was added to these diets. Starch diet, irrespective of dietary cholesterol, yielded significantly lower apoA-I levels than sucrose diet. Carbohydrate type did not affect serum triglyceride levels. Cholesterol-enriched starch diet resulted in relatively higher intermediate- and low-density lipoproteins and lower high-density lipoproteins in comparison to similar sucrose diet. Thus, the magnitude of responses of serum lipoproteins can be affected by the type of carbohydrate.

Animals↗
PubMed1983

Hemostatic properties and serum lipoprotein binding of a heparan sulfate proteoglycan from bovine aorta.

The biologic properties of two major proteoglycans of bovine aorta, heparan sulfate proteoglycan and chondroitin sulfate-dermatan sulfate proteoglycan were compared. The heparan sulfate proteoglycan was isolated either by elastase digestion or by 4.0 M guanidine hydrochloride extraction, of aorta tissue, fractionated by CsCl isopycnic centrifugation and purified by chondroitinase ABC treatment. The first method resulted in considerably greater yield (about 70% of the total heparan sulfate proteoglycan of the tissue) than the second procedure (12% of total). The chondroitin sulfate-dermatan sulfate proteoglycan was obtained by 4.0 M guanidine-HCl extraction of aorta tissue followed by CsCl isopycnic centrifugation. The chemical composition of both heparan sulfate proteoglycan preparations was similar. Unlike the chondroitin sulfate-dermatan sulfate proteoglycan, which eluted in the void volume of Sepharose CL-6B column, the heparan sulfate proteoglycan preparations were each resolved into a high molecular weight fraction (kav = 0.18 and 0.13) and a low molecular weight fraction (kav = 0.47 and 0.36). The heparan sulfate proteoglycan preparations exhibited significantly more potent anticoagulant and platelet aggregation inhibitory activities than the chondroitin sulfate-dermatan sulfate proteoglycan. The protein core of the proteoglycan molecules did not seem to be essential for their hemostatic properties. The complex forming ability of the heparan sulfate proteoglycan with serum low density lipoproteins (LDL) was much less than that of chondroitin sulfate-dermatan sulfate proteoglycan in the presence and absence of Ca2+. Interaction between heparan sulfate proteoglycan and LDL was also much more sensitive to changes in the ionic strength of the medium than that of chondroitin sulfate-dermatan sulfate proteoglycan and the lipoprotein. Since the total sulfate content of both proteoglycans is almost similar, the smaller molecular size and hence the lower overall charge density of the heparan sulfate proteoglycan appears to be partly responsible for its low affinity for LDL. The differences in biologic properties of the two proteoglycans might have implications in the pathophysiology of cardiovascular diseases.

Animals↗
PubMed1983

Serum lecithin:cholesterol acyltransferase activities of cynomolgus monkeys fed different carbohydrate diets.

Although serum lecithin:cholesterol acyltransferase (LCAT) activity is known to be modulated by nutritional factors, little is known about the effects of dietary carbohydrate on this enzyme. Therefore, LCAT activities were assessed in cynomolgus monkeys fed diets for 6 weeks on 4 diets containing 77% of calories as sucrose or starch and cholesterol at 0 and 1 mg/kcal. Three different assay conditions were used in order to measure the overall LCAT activity and to differentiate enzyme activity from the effect of serum substrate and end-product lipoprotein alterations by diet on this enzyme. Molar rate of serum total LCAT activity was higher in sucrose than starch diets (P less than 0.01). Use of sera from sucrose-fed animals, either as substrate or enzyme source, increased the fractional rate of cholesterol esterification (P less than 0.01). Exogenous cholesterol lowered serum total LCAT activity only in sucrose diet (P less than 0.01). Use of sera from sucrose + cholesterol-fed animals as substrate significantly lowered the fractional rate of cholesterol esterification (P less than 0.01); whereas no such alterations were noted when this serum was used as enzyme source. The differential effect of starch and sucrose diets on LCAT activity suggests that the nature of dietary carbohydrates may affect LCAT activity in association with triglyceride metabolism by altering the amount of enzyme in terms of its activity and/or the nature of substrate and cholesterol ester acceptor lipoproteins.

Animals↗
PubMed1983

Glycosaminoglycan composition of germfree dog lungs.

Connective tissue of the lung is fundamentally important to pulmonary function. Exposure to foreign materials such as environmental toxins and microorganisms alters the connective tissue composition of pulmonary structures. In an effort to obtain information on the nature of complex carbohydrates in lungs unexposed to foreign materials, the composition of glycosaminoglycans from germfree dogs was studied. The total glycosaminoglycan concentration in germfree dog lungs was 47% greater than that in conventional dog lungs. Variations in individual glycosaminoglycan concentrations between germfree dog lungs and conventional dog lungs were noted. Heparan sulfate and heparin concentrations were lower in germfree dog lungs than in conventional dog lungs. Heparan sulfate fractions from germfree dog lungs had lower total sulfate content than heparan sulfate fractions from conventional dog lungs. The differences in glycosaminoglycan composition between germfree dog lungs and conventional dog lungs are likely due to exposure of conventional animals to a "normal" microbial flora and other environmental factors.

Animals↗
PubMed1982

Studies of arterial wall glycosaminoglycans and collagen during experimental regression of atherosclerotic lesions in cynomolgus monkeys.

The effect of various antiatherogenic regimens on glycosaminoglycan and collagen concentrations in aortas from cynomolgus monkeys with diet-induced atherosclerosis was studied. The drugs and materials that were studied included d-thyroxine, [4-chloro-6-(2,3-xylidino)-2-pyrimidinyl]thioacetic acid, cholestyramine, alfalfa, and glucophage. The treatments resulted in varied degrees of regression of lesions. The mean hydroxyproline concentration in aortas among groups of animals treated with different regimens was significantly different within the groups (p less than 0.001) and correlated with the severity of the lesions (p less than 0.01). The mean total glycosaminoglycan concentration among different groups did not differ significantly but correlated positively (p less than 0.05) with the severity of lesions. Heparan sulfate and hyaluronic acid increased with regression and decreased with increasing severity of lesions, whereas chondroitin sulfates followed an opposite trend. These observations show connective tissue components are intimately involved in remodeling the aorta during regression of diet-induced atherosclerosis.

Animals↗
PubMed1981

Interaction of serum lipoproteins and a proteoglycan from bovine aorta.

The interactions of a chondroitin sulfate-dermatan sulfate proteoglycan with serum very low (VLDL), low (LDL), and high density (HDL3) lipoproteins were studied with special reference to the nature of the interaction of LDL and the proteoglycan. The proteoglycan formed insoluble complexes with VLDL and LDL, but no complex was formed with HDL3. The proteoglycan (40 micrograms/ml) converted 98% of added LDL (150 micrograms of cholesterol/ml) into insoluble complex at a Ca2+ concentration of 30 mM. Physiologic concentrations of albumin inhibited insoluble complex formation with VLDL and LDL by 61.5 and 40.7%, respectively. The proteoglycan formed soluble complexes with LDL even in the absence of Ca2+. Optimum soluble complex formation occurred when the medium contained 66.6 micrograms of proteoglycan and 166.6 micrograms of LDL cholesterol/ml. Specific modifications of the lysine and/or arginine residues of LDL prevented complex formation with the proteoglycan, thus indicating the requirement of the positive charges of the protein moiety of LDL in the interaction. Removal of the protein core or the glycosaminoglycan chains of the proteoglycan prevented interaction with LDL. Desulfation of the proteoglycan molecule also inhibited complex formation with LDL. Thus, the native state of the arterial proteoglycan molecule confers optimum charge density for specific interaction with serum apoprotein B-containing lipoproteins.

Amino Acids↗