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V Warty

Publications and source records attributed to V Warty.

51 records · Page 3Linked to original sources
PubMed1988

Regulation of bile acid synthesis. Isolation and characterization of microsomal phosphatases.

In preliminary experiments, we have shown that rat liver microsomes possess phosphatase activity which was inhibited in the presence of sodium fluoride. We have now separated six microsomal phosphatase fractions appearing to be isoenzymes. They all possess different kinetic constants and are not equally inhibited by tartrate and fluoride ions, inhibitors of phosphatase activity. One phosphatase fraction, in fact, is almost completely unaffected by fluoride ion. More pertinent to our interest, these isoenzymes exhibit differing abilities to modulate the activities of hydroxymethylglutaryl CoA reductase, acyl-CoA:cholesterol O-acetyltransferase, and cholesterol 7 alpha-hydroxylase. Interaction of four of the fractions with rat liver microsomes resulted in a decrease in cholesterol 7 alpha-hydroxylase activity; two were without effect.

Animals↗
PubMed1987

Cyclosporin A-induced cholestasis. The mechanism in a rat model.

Cyclosporin A (CyA) causes cholestasis in a significant proportion of transplant patients. Doses of 5, 10, and 15 mg CyA/kg body wt or the Miglyol 812 vehicle were administered intraperitoneally for 1, 2, and 3 wk to separate groups of rats to investigate the mechanism of this cholestasis. At 1 wk a dose-response relationship between serum CyA levels and increasing CyA doses was noted. A maximum CyA blood level was achieved by 2 wk with the 10- and 15-mg/kg doses. Subsequent studies were performed using the smaller (10 mg/kg) dose administered for 3 wk. This dose resulted in a marked increase in serum bile acid levels compared with vehicle-treated controls (24.6 +/- 4.0 vs. 4.3 +/- 1.2 mumol/L, p less than 0.001) without inducing significant changes in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, bilirubin, alkaline phosphatase, and albumin levels or hepatic architectural alterations. With CyA treatment, baseline bile flow decreased by 35% and bile salt secretion decreased by 25% compared with vehicle-treated animals. Cyclosporin A and vehicle-treated rats were infused intravenously with taurocholate (4 mumol/min X kg) for 2 h and then depleted of bile salts over the next 24 h. Bile samples collected over this period were graphed as bile salt secretion versus bile flow. The mean slope of the linear regression for the CyA-treated rats was 62% of the control, demonstrating a decrease in bile salt-dependent flow. Extrapolation of the linear regression to the ordinate demonstrated a 22% decrease in bile-independent flow with CyA treatment. Therefore, in our experimental model of CyA-induced cholestasis, the decrease in flow observed was the result of a decrease in both bile salt-dependent and bile salt-independent flows and occurred in the absence of significant biochemical or histologically evident hepatotoxicity.

Animals↗
PubMed1986

Effect of insulin on low-density-lipoprotein metabolism in human lymphocytes in vitro.

The metabolism of low-density lipoproteins (LDL) in vitro in the presence of insulin was studied in freshly isolated human peripheral-blood lymphocytes. Insulin appeared to decrease the binding affinity of 125I-LDL to its cell-surface receptor, without any change in apparent Vmax or in the number of LDL receptors. As a consequence, the absolute amounts of 125I-LDL internalized and degraded were lower in the presence of insulin than in its abscence, although the fraction of internalized 125I-LDL degraded in either instance was quite similar. 3-Hydroxy-3-methylglutaryl-CoA reductase activity, and hence cholesterol synthesis, were stimulated by insulin. This effect of insulin was independent of the inhibitory effect of LDL on cholesterol synthesis. At the same time, acid cholesterol esterase and acyl-CoA: cholesterol O-acetyltransferase activities were lower in cells incubated with insulin than in controls. The net effect of these metabolic alterations seems to be that cells accumulate greater quantities of free and esterified cholesterol when treated with insulin.

AMP-Activated Protein Kinases↗
PubMed1985

Differences in the binding, internalization and catabolism of low-density lipoprotein between normal human T and B lymphocytes.

Studies in human peripheral blood B and T lymphocytes show that high-affinity binding of low-density lipoprotein (LDL) to the cell surface receptor and the kinetics of binding are comparable between B and T lymphocytes, but the internalization of receptor-bound LDL in B cells appears deficient. Yet, the fraction of internalized LDL degraded by both B and T lymphocytes is of similar magnitude. Moreover, the lysosomal acid cholesterol ester hydrolase and acyl-CoA:cholesterol acyltransferase activities in B cell were about one-third of those in T lymphocytes. These data suggest deficient LDL catabolism in B lymphocytes relative to that in T lymphocytes.

B-Lymphocytes↗
PubMed1983

Differential suppression of lymphocyte cholesterol synthesis by low density lipoprotein and erythrocyte insulin receptors in normolipidemic subjects.

The rates of cholesterol synthesis from acetate were studied in freshly isolated peripheral blood lymphocytes in 41 age- and sex-matched subjects with essentially normal serum lipid profiles. Insulin binding to erythrocytes obtained from the same blood samples was also studied simultaneously. From the data on lymphocyte cholesterol synthesis in the absence or presence of low density lipoprotein in the medium, an index, LDL50, was calculated for each subject. This is the concentration of LDL cholesterol (nmol/ml) in the medium necessary to reduce cholesterol synthesis to 50% of that in the absence of LDL. On the basis of LDL50, the subjects could be segregated into three distinct groups, I, II, and III, with LDL50 of 6.5, 23.3, and 77.0 nmol/ml, respectively. This grouping was independent of the serum lipid profiles, age or sex. Insulin binding studies showed that the amount of insulin specifically bound and the number of insulin receptors per cell were inversely correlated with LDL50. LDL50 was also determined for 4 subjects with clinically manifested consequences of familial hypercholesterolemia. The LDL50 values for these individuals corresponded to values obtained for subjects in group III. The number of insulin receptors and the amount of insulin bound in these patients were correspondingly low. These results suggest that LDL50 may be useful in discerning abnormal cellular cholesterol metabolism in subjects with or without accompanying hyperlipidemias.

Adult↗
PubMed1981

On the differential suppression of cholesterol synthesis by low density lipoprotein in B and T lymphocytes.

Cholesterol synthesis and its suppression by low density lipoprotein cholesterol were measured in purified B and T peripheral blood lymphocytes. After preincubation for 53 h in lipoprotein-deficient serum, both B and T cells exhibited increased cholesterol synthesis as compared with synthesis measured in cells immediately after their isolation from blood and without preincubation with lipoprotein-deficient serum. The magnitude of this increase was far greater in T cells in comparison with that in B cells in all subjects studied. But, whereas there was an immediate and progressive suppression of cholesterol synthesis in lipoprotein-deficient serum-incubated T cells as the concentration of low density lipoprotein cholesterol in the medium was increased, synthesis in lipoprotein-deficient serum-incubated B cells remained insensitive to the presence of low density lipoprotein in the medium. Hydroxymethylglutaryl-CoA reductase activity was observed also to follow a similar pattern in both cell types. These observations may imply that one or more events, including binding of low density lipoprotein to its receptor, internalization and degradation of low density lipoprotein receptor complex finally leading to suppression of hydroxymethylglutaryl-CoA reductase activity and cholesterol synthesis, fail to take place in B cells.

Adult↗
PubMedDate not supplied

Monitoring of acute lung rejection and infection by bronchoalveolar lavage and plasma levels of hyaluronic acid in clinical lung transplantation.

Local immunological injury caused by acute lung rejection leads to fibroblast proliferation. Hyaluronate is a product of activated fibroblasts and possibly an indicator of fibroblast proliferation. One hundred thirty-six bronchoalveolar lavage and plasma hyaluronate assays were performed in 57 lung transplant recipients. Pulmonary endothelial cell function was assessed by measuring bronchoalveolar lavage levels of purine nucleoside phosphorylase. Presence of acute cellular rejection was monitored by transbronchial biopsy histologic evaluation and was classified as minimal to mild (acute rejection I, II) and moderate to severe (acute rejection III, IV). Infection was confirmed by bronchoalveolar lavage culture and antibiotic sensitivity. Bronchoalveolar lavage hyaluronate levels in clinically stable recipients were 33.5 +/- 4.69 micrograms/L and were significantly higher than with clinically stable recipients (p = 0.0001), infection (p = 0.008), or mild rejection (p = 0.001). Levels were highest in recipients with diffuse alveolar damage (392.4 +/- 60.6 micrograms/L). Diffuse alveolar damage also resulted in significant elevations of plasma HA as compared with stable recipients (p = 0.001) and mild rejection. We conclude that clinically significant injury to the allograft from rejection or diffuse alveolar damage can be assessed by bronchoalveolar lavage hyaluronate assays and suggest that the source of hyaluronate in these instances are activated fibroblasts.

Acute Disease↗