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Biomedical subjects

A D Sniderman

Publications and source records attributed to A D Sniderman.

At least 109 records · Page 6Linked to original sources
PubMed1988

Apolipoprotein B and apolipoprotein AI as predictors of coronary artery disease.

The evidence that plasma levels of apolipoprotein B and apolipoprotein AI are important determinants of the risk of premature coronary artery disease (CAD) are reviewed and a metabolic framework for these relations presented. ApoB and apoAI are compared to total cholesterol and to lipoprotein lipids as predictors of CAD. The emphasis is on apoB as this is the particular interest of this laboratory and because a structural basis has been elucidated that may relate the epidemiologic observations about apoB to the metabolic characteristics of low density lipoprotein. The measurement of apoproteins has revealed much that was previously obscure about normal and abnormal lipoprotein metabolism. However, one of the major challenges is the development of an accurate, widely available commercial assay system for apoproteins.

Apolipoprotein A-I↗
PubMed1988

The effect of a plasma protein fraction on lipid synthesis in cultured skin fibroblasts from normals and patients with hyperapobetalipoproteinemia.

Lipid synthesis was measured in cultured skin fibroblasts obtained from normals and patients with Hyperapobetalipoproteinemia (HyperapoB). Using lipoprotein-deficient serum medium, triglyceride synthesis and cholesterol esterification were greater in normals than in HyperapoB due to differences in de novo synthesis, not to differences in re-esterification or to different rates of hydrolysis. When normal and HyperapoB cells were incubated in serum-free medium, however, lipid synthesis was the same. Serum was then fractionated chromatographically and a partially purified protein fraction shown to be responsible for the stimulatory effect in normals.

Adult↗
PubMed1987

Stimulation of fatty acid uptake and triglyceride synthesis in human cultured skin fibroblasts and adipocytes by a serum protein.

Lipoprotein deficient serum has been shown to enhance lipid synthesis in cultured normal human skin fibroblasts incubated in the presence of oleate-albumin. The factor responsible is nondialyzable and trypsin sensitive. The stimulation is proportional to the concentration of lipoprotein deficient serum in the media and is present at all oleate concentrations and incubation times assayed. The protein has been partially purified by column chromatography to yield a Peak II fraction which stimulates triglyceride synthesis in both fibroblasts and isolated human adipocytes. The stimulation is dependent on the concentration of protein fraction and increases to an apparent saturation level of 200% in fibroblasts. Triglyceride synthesis, however, increases to a much greater extent in adipocytes and did not demonstrate saturation at the maximum Peak II protein concentration assayed. These results suggest that human serum contains a protein which stimulates fatty acid uptake and esterification by adipose tissue.

Adipose Tissue↗
PubMed1987

Kinetics of LDL subfractions.

After injecting 125I- or 131I-labeled lipoproteins, plasma was subjected to discontinuous density gradient centrifugation, which separates low-density lipoproteins (LDL) into three subfractions. Analysis of changes in apolipoprotein B-specific activity with time showed that light LDL is normally the product of intermediate-density lipoprotein and the precursor of heavy LDL, which is subsequently converted to heavier LDL. In hyperapobetalipoproteinemia these relationships are maintained but there is overproduction of light and heavy LDL secondary to increased synthesis of very low-density lipoprotein. In familial hypercholesterolemia, light LDL is produced normally but its conversion into heavy LDL is reduced and independent synthesis of the latter is apparent. These observations suggest that the LDL receptor normally plays a role in the conversion of light into heavy LDL. They also provide an explanation for previously documented differences in LDL composition between hyperapobetalipoproteinemia, in which there is a relative increase in cholesterol-depleted heavy and heavier subfractions, and familial hypercholesterolemia, in which there is a relative increase in the cholesterol-enriched light subfraction.

Animals↗
PubMed1986

Metabolic basis of hyperapobetalipoproteinemia. Turnover of apolipoprotein B in low density lipoprotein and its precursors and subfractions compared with normal and familial hypercholesterolemia.

The turnover of apolipoprotein B (apo B) in very low density, intermediate density, and low density lipoproteins (VLDL, IDL, and LDL) and in the light and heavy fractions of LDL was determined in seven patients with hyperapobetalipoproteinemia (hyperapo B), six normolipidemic subjects, and five patients with heterozygous familial hypercholesterolemia (FH). After receiving an injection of 125I-VLDL, hyperapo B patients were found to have a higher rate of synthesis of VLDL-apo B than controls (40.1 vs. 21.5 mg/kg per d, P less than 0.05) but a reduced fractional catabolic rate (FCR) (0.230 vs. 0.366/h, P less than 0.01). After receiving an injection of 131I-LDL, hyperapo B patients had higher rates of LDL-apo B synthesis than controls (23.1 vs. 13.0 mg/kg per d, P less than 0.001), as did FH patients (22.7 mg/kg per d). The FCR of LDL was similar in hyperapo B patients and controls (0.386 vs. 0.366/d) but was markedly decreased in FH patients (0.192/d). Most subjects exhibited precursor-product relationships between VLDL and IDL, and all did between IDL and light LDL; an analogous relationship between light and heavy LDL was evident in most hyperapo B patients and controls but not in FH patients. Simultaneous injection of differentially labeled LDL fractions and deconvolution analysis showed increased light LDL synthesis with normal conversion into heavy LDL in hyperapo B, whereas in FH conversion of light LDL was reduced and there was independent synthesis of heavy LDL. These data show that the increased concentration of LDL-apo B in hyperapo B is solely due to increased LDL synthesis, which is secondary to increased VLDL synthesis; in contrast, in FH there is both an increase in synthesis of LDL (which is partly VLDL-independent) and reduced catabolism.

Apolipoproteins B↗
PubMed1986

Tendon xanthomas associated with cholestanolosis and hyperapobetalipoproteinemia.

Large Achilles tendon xanthomas of the type found in severe familial hypercholesterolemia were the first manifestation of cholestanolosis (cerebrotendinous xanthomatosis) in our patient, an otherwise asymptomatic normolipidemic 21-year-old woman. Extensive laboratory investigation disclosed the presence of hyperapobetalipoproteinemia which did not resolve with the administration of probucol. Immunofluorescent studies revealed marked accumulation of apolipoprotein B in a xanthoma excised from the tricipital area. This was in contrast to the spotty and weak fluorescence observed in a tuberous xanthoma, from the same anatomical area and histologically otherwise identical, obtained from a patient with heterozygous familial hypercholesterolemia. Hyperapobetalipoproteinemia has been reported before in association with sitosterolemia but not with cholestanolosis. We suggest that cholestanol, like sitosterol, may interfere with the normal uptake and degradation of low-density lipoproteins by peripheral cells.

Adult↗
PubMed1985

Improvement in resting ventricular performance following coronary bypass surgery.

To assess the changes in resting left ventricular (LV) function following coronary bypass surgery, technetium 99m-labeled multiple equilibrated blood pool gated scans were performed in 53 consecutive patients at rest, before operation, and at 24 hours and 1 week after operation. Left ventricular ejection fraction (LVEF) and end-diastolic volume (EDV) were measured. The LVEF increased significantly from a preoperative value of 49 +/- 2% to 56 +/- 2% at 24 hours after operation (p less than 0.05) and 56 +/- 2% at 1 week following operation (p less than 0.05 compared with the preoperative value). The EDV also exhibited significant changes, decreasing from a preoperative value of 148 +/- 8 ml to 91 +/- 11 ml at 24 hours (p less than 0.001) and 114 +/- 9 ml at 1 week (p less than 0.01 compared with the preoperative value). When the patients were divided into two groups according to the preoperative LVEF (Group 1, LVEF of greater than or equal to 50%; Group 2, LVEF of less than 50%), the observed changes were similar. This study demonstrates significant improvement in resting LV function 24 hours following coronary bypass surgery. This improvement persists at 1 week and is not related to the degree of preoperative impairment. We conclude that the combination of successful revascularization and optimal myocardial protection can result in significant improvement of LV function at rest.

Adult↗
PubMed1985

Effect of dietary treatment on the plasma levels of lipids, lipoprotein cholesterol and LDL B protein in children with type II hyperlipoproteinemia.

These data confirm the effectiveness of therapeutic diets in children with type II hyperlipoproteinemia in conventional terms. However, the decrease in LDL cholesterol was not accompanied by a significant decrease in LDL B (suggesting only a small change in the number of LDL particles in plasma), and a fall in HDL cholesterol occurred, with no significant improvement in the LDL to HDL cholesterol ratio. These findings indicate that further research is needed to develop diets with more optimal effects. Finally, our hypothesis that such diets may produce an LDL particle of altered composition, needs to be confirmed using additional physical-chemical measurements of the size, composition and molecular weight distribution of LDL in plasma before and after dietary intervention.

Adolescent↗
PubMed1984

Surgery for postinfarction left ventricular aneurysm: prognosis and long-term follow-up.

To identify preoperative indicators of outcome following surgery for postinfarction left ventricular aneurysm, the authors have analysed the clinical course of 67 consecutive patients who underwent operation from 1970 to 1982. Follow-up extended to 12 years (mean 4.6 years) and was 97% complete. Postoperative mortality was 8.9%. Factors that were associated with a significantly (p less than 0.05) increased risk of early death included emergency surgery, the presence of ventricular arrhythmias preoperatively and a left ventricular end-diastolic pressure of more than 25 mm Hg on cardiac catheterization. Patients who underwent myocardial revascularization concomitantly had a lower mortality (7.1% v. 18.2% for aneurysmectomy alone), decreased postoperative morbidity and increased longevity. Marked functional improvement was noted in all groups. Actuarial survival (including operative mortality) was 66% at 6 years, and was significantly (p less than 0.05) better in patients operated upon for angina (83.6% +/- 8.1%) than in those operated upon for congestive heart failure (53% +/- 13%). The authors conclude that the most important predictor of outcome following postinfarction aneurysm surgery is the preoperative hemodynamic status of the left ventricle. Since functional recovery and prognosis after operation have been excellent, an aggressive surgical approach to symptomatic left ventricular aneurysms is warranted.

Adult↗
PubMed1984

Salvage of a severely ischemic limb by arteriovenous revascularization: a case report.

Severe ischemia in a limb that cannot be revascularized almost inevitably leads to gangrene and eventual amputation. For decades, surgeons have considered utilizing the venous system to revascularize ischemic tissue in numerous areas, including the lower limb, but with very limited success. This report documents the successful revascularization of a severely ischemic pregangrenous limb with a bypass graft from the femoral artery to a tibial vein. The authors believe this is the first clinical report of salvage of an ischemic limb by this approach.

Aged↗
PubMed1983

Early recognition of the patient at late high risk: incomplete infarction and vulnerable myocardium.

The process of identifying patients with myocardial infarction (MI) at high risk after hospital discharge should begin at admission. By using basic clinical and laboratory information, enhanced by a wide variety of noninvasive tests, not only can individual patients at risk be recognized, but also the processes that determine risk can, at least in part, be appreciated. Outcome is affected by the extent of damaged tissue and, apparently, by the amount of potentially ischemic muscle. MI may change the coronary circulation such that a new and fragile balance between supply and demand results, both within and outside the infarct zone; that is, the infarct may be incomplete and the viable muscle within it may then be vulnerable to later ischemia. Muscle outside the infarct zone may be left in much the same precarious state. Also, coronary spasm may not be infrequent in the weeks after MI. These factors together may underlie recurrent post-MI myocardial ischemia.

Aged↗
PubMed1983

Atherosclerosis and apoproteins B and A-I.

The lipid hypothesis stipulates that the risk of developing CAD is related to the cholesterol levels of various lipoprotein fractions, the risk increasing with either a higher LDL cholesterol level or a lower HDL cholesterol level. The data reviewed here indicate that the measurement of the plasma level of the major apoproteins of LDL and HDL, apoB and apoA-I, respectively, provide additional information in the assessment of a patient at risk for CAD. In the case of LDL B, two "normocholesterolemic" groups with CAD are detected, those with normotriglyceridemic HyperapoB and those with hypertriglyceridemic HyperapoB . In all of these syndromes associated with premature CAD, HyperapoB , FCH, and FH, the common denominator is an increased number of LDL particles. A low level of apoA-I may indicate that one of the subfractions of HDL (HDL2) is decreased. HDL2 is generally decreased in disorders where LDL B is elevated, a combination that may be particularly atherogenic. Conversely, elevated apoA-I and HDL cholesterol levels, or decreased LDL cholesterol and LDL B protein levels, are associated with a low prevalence of CAD and longevity. Thus, LDL and HDL levels may be metabolically linked, a relation which is more evident if apoproteins are measured and which may be obscured if apoproteins are not determined. The assessment of dyslipoproteinemia in a patient at risk for CAD might optimally include measurement of LDL B and apoA-I levels, in addition to LDL cholesterol and HDL cholesterol levels.

Adult↗
PubMed1983

Composition and distribution of low density lipoprotein fractions in hyperapobetalipoproteinemia, normolipidemia, and familial hypercholesterolemia.

Hyperapobetalipoproteinemia is defined as the combination of a normal low density lipoprotein (LDL) cholesterol in the face of an increased LDL apolipoprotein B (apoB) protein. To examine the physical basis for the apparent disproportion between LDL cholesterol and apoB characteristic of this syndrome, we used density gradient ultracentrifugation to isolate LDL fractions from 10 normal subjects, from 20 patients with hyperapobetalipoproteinemia (10 normotriglyceridemic and 10 hypertriglyceridemic), and from 7 patients with familial hypercholesterolemia. In familial hypercholesterolemia, more LDL was in fraction 1--"light" LDL--and this LDL was relatively enriched in cholesterol and poor in protein. By contrast, it was fraction 2--"heavy" LDL--that differed in hyperapobetalipoproteinemia, being denser, depleted of cholesterol (particularly cholesteryl ester), and relatively enriched in apoB. These findings were more pronounced in the hypertriglyceridemic patients than in the normotriglyceridemic patients with hyperapobetalipoproteinemia. Thus this study confirms that considerable heterogeneity exists between LDL subfractions within individuals but, in addition, indicates there are also marked--and apparently characteristic--differences in LDL composition amongst normal subjects and patients with hyperapobetalipoproteinemia or familial hypercholesterolemia.

Apolipoproteins↗
PubMed1982

Association of hyperapobetalipoproteinemia with endogenous hypertriglyceridemia and atherosclerosis.

Researchers disagree on whether plasma triglyceride levels are an independent risk factor for atherosclerotic coronary artery disease. We hypothesized that patients with endogenous hypertriglyceridemia would differ: Some would have normal values of plasma low-density lipoprotein (LDL) B protein; others, despite their normal level of LDL cholesterol, would have increased levels of LDL B protein. We believe the latter patients--those with hyperapobetalipoproteinemia--would be the ones at risk for atherosclerosis. We studied two populations. Group 1, consisting of 162 patients with type IV lipoprotein patterns, was divided into two groups. One subgroup (A), which included 38 patients with elevated plasma LDL B atherosclerotic disease than the other subgroup (B) of 36 patients with normal levels of plasma LDL B protein (10 patients versus two, p less than 0.02). Group 2 consisted of 100 patients who had had myocardial infarction. Eighty-one percent of the 47 hypertriglyceridemic and 70% of the 53 normotriglyceridemic patients had elevated plasma LDL B protein levels (129 mg/dL or greater)--a proportion significantly higher than that in Group 1 (p less than 0.001). Thus, an elevated plasma level of LDL B protein not only identifies subgroups of patients with type IV lipoprotein patterns, but also may be an important marker for atherosclerotic disease.

Adult↗
PubMed1981

Hyperapobetalipoproteinaemia in two families with xanthomas and phytosterolaemia.

The death of a 13-year-old boy from coronary atherosclerosis prompted the study of an Amish family. Five of his twelve sibs had tendon and tuberous xanthomas, and increased plasma plant sterols, particularly beta-sitosterol. The plasma level of the major apoprotein of low density lipoprotein (LDL), the B protein, was very high (mean 173 mg/dl) in these five sibs, while the LDL cholesterol level was moderately increased (209 mg/dl). Four other sibs and both parents had an increased LDL B protein level with a normal or mildly raised plasma total and LDL cholesterol level (hyperapobeta-lipoproteinaemia). Evidence for coronary artery disease was found in both parents and three xanthomatous sibs. The original family with beta-sitosterolaemia and xanthomatosis, described in 1974, was re-examined. The proband and her sister had persistent phytosterolaemia and normocholesterolaemia but increased LDL B protein levels. Both parents, two uncles, and three of four grandparents had increased LDL B protein levels and normal total and LDL cholesterol levels. The proband's father had atypical angina pectoris. People with the full syndrome (phytosterolaemia, xanthomas, and hyperapobetalipoproteinaemia) are most probably homozygous for a mutant allele. An increased LDL B protein level permits the identification of heterozygotes in these families, even though in the fasting state they show no phytosterolaemia. The homozygote and probably the heterozygote are at increased risk for cardiovascular atherosclerotic disease.

Adolescent↗