Biomedical subjects

M Paidi

Publications and source records attributed to M Paidi.

7 recordsLinked to original sources

PubMed1996

Binding affinity and particle size of LDL in subjects with moderate hypercholesterolemia: relationship with in vivo LDL metabolism.

The aim of this study was to examine relationships between low density lipoprotein (LDL) metabolism, in vitro binding, and particle size. Twenty four study subjects, 17 men and 7 women, had elevated plasma total cholesterol (TC), ranging from 174 to 232 mg/dl, and LDL cholesterol (LDLC) ranging from 113 to 195 mg/dl after 12 weeks on a Step I diet. The fractional clearance rate (FCR) for LDL ranged from 0.233 to 0.619 pools/day (0.366 +/- 0.021) and was significantly correlated with plasma triglycerides (TG) (P < 0.05). Although there was no relation between FCR and binding in the study group as a whole, those subjects with an FCR within the normal range (< 0.45, n = 20), showed a significant negative correlation between FCR and the KD for LDL binding, (r = 0.52). A subset of four subjects with an elevated FCR (> 0.45) had higher production rate (PR) (P < 0.005) and a significant positive correlation between the KD for LDL binding and FCR (P < 0.05). LDL size varied from 240.0 to 265.8 A and was significantly inversely correlated with plasma TG (P < 0.001) but there was no relation between LDL size and metabolism or binding affinity. Thus, there appears to be a correlation between binding affinity and clearance for subjects who had normal LDL production and clearance rates. On the other hand, mechanisms other than binding affinity appear to influence clearance in subjects with elevated rates of production and clearance.

Adult↗

PubMed1994

Greater effect of diabetes on LDL size in women than in men.

OBJECTIVE: Coronary heart disease (CHD) is increased two- to fourfold in subjects with NIDDM compared with normoglycemic subjects. This excess risk is only partially explained by conventional risk factors. We studied the effect of non-insulin-dependent diabetes mellitus (NIDDM) on the size of low-density lipoproteins (LDL). RESEARCH DESIGN AND METHODS: We examined the effect of NIDDM on LDL size and subclass pattern B (LDL size < 253.5 A) in 95 diabetic subjects and 371 nondiabetic subjects from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. RESULTS: LDL size (A) was significantly lower in diabetic subjects (men: 252.2 +/- 1.8; women: 254.7 +/- 1.3) than in nondiabetic subjects (men: 256.1 +/- 0.8; women: 259.7 +/- 0.7) (P = 0.007). After the use of analysis of covariance to adjust for triglyceride and high-density lipoprotein cholesterol, LDL size was still significantly lower in diabetic women than in nondiabetic women. In men, however, diabetes was no longer significantly associated with LDL size after similar adjustments. Fasting glucose was more strongly correlated with LDL size in women (r = -0.30) than in men (r = -0.18). CONCLUSIONS: We conclude that LDL size is significantly lower in diabetic subjects of both sexes than in nondiabetic subjects, but that diabetic dyslipidemia accounts for the association in diabetic men. The stronger association between LDL size and diabetes in women than in men may partially explain the greater relative risk of CHD observed in women with NIDDM in some studies.

Adult↗

PubMed1994

Simplified isoelectric focusing/immunoblotting determination of apoprotein E phenotype.

We developed a rapid, accurate method for phenotyping apoprotein E that can be used for large-scale population studies. In this method, adapted from the method of Kamboh et al. (J Lipid Res 1988;29:1535-43), 10-microL plasma samples are incubated with dithiothreitol and Tween-20 for 15 min and then applied to 5% polyacrylamide gels containing ampholyte (pH 4.5-8) and urea (3 mol/L). After 2 h of isoelectric focusing, the apoprotein E bands are made visible by immunoblotting. Utilizing whole plasma, this method does not require time-consuming ultracentrifugation, delipidation of samples, or dialysis. Small amounts of plasma are required, electrofocusing time is short, and as many as 160 samples can be processed per day. Identification of phenotype is easily accomplished by noting the location and number of protein bands instead of their intensity. Because identification of phenotype is not affected by sialylation, neuraminidase treatment is not necessary. Agreement in identification of 301 individuals from blinded duplicates was 96%, and there was 98% concordance of results for 431 samples that had undergone genetic typing. This method is thus well suited for large-scale population studies.

Apolipoproteins E↗

PubMed1993

ApoE4 polymorphism increases the risk for exercise-induced silent myocardial ischemia in older men.

The apolipoprotein (apo) E4 polymorphism is associated with increased risk for symptomatic coronary artery disease (CAD). This study examines whether the apo epsilon allele is associated with an increased risk for exercise-induced silent myocardial ischemia (SI) in healthy, older (62 +/- 7 years; mean +/- SD), normocholesterolemic, nonsmoking male volunteers. The apo epsilon 4 allele was present in 20 of 45 (44%) men with SI on graded exercise treadmill testing compared with 22 of 127 (17%) men of comparable age with normal exercise tests (P < .001), resulting in a crude relative risk of 2.57 (95% confidence limits, 1.57 to 4.23) for SI in men with the apo epsilon 4 allele compared with those without the epsilon 4 allele. Although the lipoprotein lipid levels did not differ between men with normal exercise tests and those with SI, the men with the apoE 4/3 phenotype had higher total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels than those with the apoE 2/3 and 3/3 phenotypes (P < .05). Men with SI and the apoE 4/3 phenotype were older (64 +/- 5 versus 57 +/- 8 years, P < .01) and leaner (P < .01) than the normal non-SI men with the apoE 4/3 phenotype. The older age of the men with SI and the apoE 4/3 phenotype is consistent with a progression of atherosclerosis over time. Men with SI and the apoE 3/3 phenotype were of comparable age and body composition to apoE 3/3 phenotype men with normal exercise tests. Thus, even in the presence of normal LDL-C levels, the apo epsilon 4 allele may predispose older men to SI.

Aged↗

PubMed1993

LDL size and subclass pattern in a biethnic population.

Recently, the presence of small, dense low-density lipoprotein (LDL) has been recognized as a risk factor for coronary heart disease. There has been little work on correlates of LDL size in population-based studies and none in Mexican Americans. We examined the relationship of LDL size and pattern to anthropometric and metabolic variables in 466 Mexican Americans and non-Hispanic whites in the San Antonio Heart Study. LDL size in Angstrom units was significantly lower in Mexican Americans (255.8 +/- 0.6) than in non-Hispanic whites (257.9 +/- 0.7) (P = 0.041) after adjustment for gender and age. The percentage of subjects with pattern B tended to be higher in Mexican Americans than in non-Hispanic whites (40.0% versus 34.4%, respectively), although this difference did not reach statistical significance. In univariate analysis, LDL size was significantly associated with glucose (r = -.20), insulin (r = -.19), male gender (r = -.20), total cholesterol (r = -.22), high-density lipoprotein cholesterol (HDL-C) (r = .53), and triglyceride concentrations (r = -.63). In multivariate analyses, higher triglyceride, insulin, and glucose concentrations, lower HDL-C, and male gender were independent correlates of smaller, denser LDL. Correlates of LDL size were similar in Mexican Americans and non-Hispanic whites. Our results confirm previous reports that triglyceride and HDL-C concentrations are the most important variables associated with LDL size. The additional findings of independent effects of male gender, glucose, and insulin concentrations suggest that sex hormones and the insulin resistance syndrome may also play an important role.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1989

Low-density lipoprotein (LDL) distribution shown by 99mtechnetium-LDL imaging in patients with myeloproliferative diseases.

STUDY OBJECTIVE: To image and identify by noninvasive methods the sites of low-density lipoprotein (LDL) catabolism in patients with myeloproliferative disease in whom chronic hypocholesterolemia was previously reported. STUDY DESIGN: The 99mTechnetium-LDL (Tc-LDL) distribution in patients with myeloproliferative diseases was compared with that in normal subjects. The Tc-LDL distribution was also compared with the distribution and organ uptake of a macrophage-seeking radiotracer. 99mTc-sulfur colloid (Tc-SC). SETTING: Major metropolitan referral center and institutional practice. PATIENTS: Three normal subjects, two patients with polycythemia vera, two with post polycythemia myeloid metaplasia, and one with agnogenic myeloid metaplasia. The patients were being managed with hydroxyurea or phlebotomy. INTERVENTION: Ten mCi of Tc-LDL (homologous) was injected intravenously. MEASUREMENTS AND MAIN RESULTS: Gamma camera images of Tc-LDL biodistribution and organ uptake were obtained 4 hours after injection of the tracer. In normal subjects, the Tc-LDL was predominantly taken up by the liver, with relative nonvisualization of spleen and central or peripheral marrow. Patients with myeloproliferative disease showed marked splenic uptake of Tc-LDL. Peripheral bone marrow uptake extended to the lower tibia in two patients with post-polycythemia myeloid metaplasia. Splenic and bone marrow uptake paralleled that of Tc-SC. Hypercellularity of central and peripheral marrow at the sites of Tc-LDL uptake was confirmed by biopsy specimens. The Tc-LDL uptake, however, was not correlated with collagen fibrosis. CONCLUSIONS: These results indicate that spleen and bone marrow are sites of LDL catabolism in patients with myeloproliferative disease and suggest the role of macrophages in the hypocholesterolemia and accelerated LDL catabolism of myeloproliferative disease.

Adult↗

PubMed1988

Radiotracers for low density lipoprotein biodistribution studies in vivo: technetium-99m low density lipoprotein versus radioiodinated low density lipoprotein preparations.

In an attempt to characterize the in vivo behavior of [99mTc] low density lipoprotein (LDL), biodistribution studies were performed in normal and hypercholesterolemic (HC) rabbits. In normal rabbits, 24 hr after the injection of [99mTc]LDL, 99mTc activity accumulated mainly in adrenal glands, spleen, liver, and kidney. In HC rabbits, however, there was a marked reduction of 99mTc activity in these organs. In both normal and HC rabbits, less than 17% of 99mTc activity appeared in the 24-hr urine following injection of [99mTc]LDL, suggesting that in vivo, [99mTc]LDL is trapped and accumulated within the tissues. Direct comparison of [99mTc]LDL, 125I-native-LDL and [131I]tyramine cellobiose-LDL (the previously validated trapped radioligand) in normal rabbits, demonstrated that the biodistribution of [99mTc]LDL was similar to that of [131I]tyramine cellobiose-LDL. The adrenal glands, liver, and spleen accumulated significantly greater quantities of 99mTc and 131I activity per gram of tissue than 125I (from native-LDL). In addition, imaging studies in monkeys, showed that the hepatic uptake and retention of [99mTc] LDL was similar to that of [131I]tyramine cellobiose LDL. In contrast, radioiodine from native-LDL was deiodinated in liver with subsequent excretion into the intestine. These results suggest that [99mTc]LDL acts as a trapped ligand in vivo and should therefore, be a good tracer for noninvasive quantitative biodistribution studies of LDL.

Animals↗