Biomedical subjects

Y Arad

Publications and source records attributed to Y Arad.

23 records · Page 2Linked to original sources

PubMed1990

Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipidemia by reducing the production of apoB-containing lipoproteins: implications for the pathophysiology of apoB production.

We investigated the metabolism of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) apolipoprotein B (apoB) in seven patients with combined hyperlipidemia (CHL), using 125I-labeled VLDL and 131I-labeled LDL and compartmental modeling, before and during lovastatin treatment. Lovastatin therapy significantly reduced plasma levels of LDL cholesterol (142 vs 93 mg/dl, P less than 0.0005) and apoB (1328 vs 797 micrograms/ml, P less than 0.001). Before treatment, CHL patients had high production rates (PR) of LDL apoB. Three-fourths of this LDL apoB flux was derived from sources other than circulating VLDL and was, therefore, defined as "cold" LDL apoB flux. Compared to baseline, treatment with lovastatin was associated with a significant reduction in the total rate of entry of apoB-containing lipoproteins into plasma in all seven CHL subjects (40.7 vs. 25.7 mg/kg.day, P less than 0.003). This reduction was associated with a fall in total LDL apoB PR and in "cold" LDL apoB PR in six out of seven CHL subjects. VLDL apoB PR fell in five out of seven CHL subjects. Treatment with lovastatin did not significantly alter VLDL apoB conversion to LDL apoB or LDL apoB fractional catabolic rate (FCR) in CHL patients. In three patients with familial hypercholesterolemia who were studied for comparison, lovastatin treatment increased LDL apoB FCR but did not consistently alter LDL apoB PR. We conclude that lovastatin lowers LDL cholesterol and apoB concentrations in CHL patients by reducing the rate of entry of apoB-containing lipoproteins into plasma, either as VLDL or as directly secreted LDL.

Adult↗

PubMed1990

Nonuniform radiolabeling of VLDL apolipoprotein B: implications for the analysis of studies of the kinetics of the metabolism of lipoproteins containing apolipoprotein B.

Radiolabeling of whole lipoproteins or individual apolipoproteins has been an essential tool for the determination of the kinetics of apolipoprotein metabolism in vivo. Mathematical analysis of specific radioactivity (SA) or total radioactivity data has demonstrated the existence of significant complexity in the plasma decay curves of several apolipoproteins. Results obtained during development of methods to study the metabolism of apolipoprotein B (apoB) in very low density lipoprotein (VLDL) subclasses isolated according to flotation (Sf) rates from whole radiolabeled (d less than 1.006 g/ml) VLDL suggested nonuniform radiolabeling of apoB in the three Sf subclasses being studied. We therefore determined apoB SA in VLDL Sf subclasses in ten hypertriglyceridemic and five normal subjects. After radioiodination of apoB in whole VLDL, different apoB SA were found in Sf 400-100, Sf 100-60, and Sf 60-20. The pattern of labeling was quite variable among subjects. On average, apoB SA in the VLDL tracer was greatest in Sf 400-100, and least in Sf 60-20. Nonuniform labeling could also be demonstrated in five studies in which samples were obtained 3 min after intravenous injection of the tracer into subjects with a wide range of plasma triglycerides. Nonuniform labeling of apoB in whole VLDL was also demonstrated in two of the subjects by isolating subclasses of their VLDL that did not bind to an anti-apolipoprotein E immunoaffinity column. These results indicate that the usual assumption of homogeneous labeling of apoB may be erroneous. We have derived a simple mathematical formula to study the consequences of this assumption in estimating kinetic parameters. It is shown that an erroneous assumption of homogeneous tracer labeling may significantly underestimate or overestimate the true production rate, even in a simple two-pool model. Identification of labeling characteristics and incorporation of this information into the mathematical analysis of the plasma radioactivity data can improve the accuracy of the analysis as well as the sensitivity of compartmental models generated by such data.

Apolipoproteins B↗

PubMed1981

Isoelectric focusing of hemoglobins on thin-layer agarose.

Isoelectric focusing on thin layers of agarose was used to separate several human hemoglobin variants in narrow pH range (pH 6-9). Problems with gel flooding and distortions due to electroendosmotic flow were solved by altering the casting and processing of the gel, by modifying the focusing apparatus, and by utilizing commercial agarose that had been chemically modified to reduce electroendomosis. Hemoglobins C, O-ARAB, A2, and E were distinguished from one another, as were hemoglobins S, D-LOS ANGELES, G-PHILADELPHIA, F. A, I, and J. The technic is rapid, simple, and relatively inexpensive. The agarose is nontoxic, has excellent gelling properties, and possesses large pores, yet gives resolution equivalent or superior to that obtained on thin layers of polyacrylamide gel, making it preferable to polyacrylamide for thin-layer isoelectric focusing.

Genetic Variation↗

PubMedDate not supplied

Correlations between vascular calcification and atherosclerosis: a comparative electron beam CT study of the coronary and carotid arteries.

PURPOSE: Electron beam CT (EBCT)-derived coronary artery calcium scores correlate with the extent of atherosclerosis, but there is a substantial variance about the general relationship between coronary calcification and coronary atherosclerosis. The relationship between calcification and atherosclerosis may also differ in various arteries. This study was designed to evaluate whether the relation between carotid artery intima-media thickness (IMT) and carotid artery calcium could be used as a correction factor to improve the correlation between coronary calcification and coronary atherosclerosis. METHOD: We measured atherosclerosis in the coronary and carotid arteries by angiography and ultrasonography, respectively, and quantified coronary and carotid calcium deposition with EBCT in 50 subjects. The correlation between the findings in the carotid and coronary arteries was investigated. RESULTS: Coronary artery calcium score correlated with coronary angiography and with carotid calcium score. Coronary stenosis correlated with carotid IMT. There was no meaningful correlation of carotid IMT and carotid calcium. CONCLUSION: There is an intraindividual variation in the relationship of plaque mass to calcification among different vessels. The relation between carotid artery calcification and carotid IMT is not predictive of the relation between coronary artery calcification and coronary obstruction.

Aged↗

PubMedDate not supplied

Dehydroepiandrosterone feeding prevents aortic fatty streak formation and cholesterol accumulation in cholesterol-fed rabbit.

The concentration of dehydroepiandrosterone sulfate (DHEA-S) in human plasma is higher than any other steroid. Recent evidence has suggested an inverse relationship between plasma DHEA levels and the development of coronary atherosclerosis in humans. We used the cholesterol-fed rabbit model to investigate whether DHEA feeding would diminish aortic fatty streak formation in this model. Fifteen New Zealand White rabbits were fed rabbit chow supplemented with 0.5% cholesterol (wt/wt). Seven animals were, in addition, fed DHEA, 0.5% of diet (wt/wt). Animals were sacrificed after 2 months, and the aortic involvement with fatty streaks was evaluated by computerized planimetry of Sudan IV-stained aortas and by chemical analysis of aortic wall lipids. Compared to controls, DHEA-fed animals had similar plasma levels of total, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol, corticoids, and estrogens. DHEA-fed animals had higher plasma levels of total, VLDL, and LDL triglycerides and lower HDL triglycerides than did controls. DHEA feeding resulted in 30% and 40%, respectively, inhibition of fatty streak formation by chemical analysis and planimetry. We conclude that DHEA feeding inhibits the development of aortic fatty streaks in cholesterol-fed rabbits, independent of changes in plasma total and LDL cholesterol levels of DHEA conversion to estrogens or corticoids.

Animals↗