Publications by authors named "Applebaum-Bowden D"

Lecithin:cholesterol acyltransferase (LCAT) is an enzyme well known for its involvement in the intravascular metabolism of high density lipoproteins; however, its role in the regulation of apolipoprotein (apo) B-containing lipoproteins remains elusive. The present study was designed to investigate the metabolic mechanisms responsible for the differential lipoprotein response observed between cholesterol-fed hLCAT transgenic and control rabbits. 131I-labeled HDL apoA-I and 125I-labeled LDL kinetics were assessed in age- and sex-matched groups of rabbits with high (HE), low (LE), or no hLCAT expression after 6 weeks on a 0.

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Recent advances in genetics and information emerging from the Human Genome Project make it feasible to examine the importance of dietary-genetic interactions in the development of atherosclerosis. In the opinion of the Working Group, three approaches are necessary to examine this concern. The first approach utilizes animal models to map and identify candidate genes involved in dietary responsiveness and atherogenesis.

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Estrogen replacement therapy reduces the risk of coronary heart disease in women and decreases the extent of atherosclerosis in monkeys. In our previous studies, estrogen treatment decreased arterial LDL degradation and accumulation, thus indicating one mechanism by which estrogen inhibits the progression of atherosclerosis. The influence of progestins on these processes remains nuclear.

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Hepatic lipase (HL) and lipoprotein lipase (LPL) are key enzymes involved in the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins. Despite their similarities, the role that each of these two lipases play in the metabolism of triglyceride-rich lipoproteins and high density lipoproteins is distinct. In order to identify structural domains that may confer the different substrate specificities between HL and LPL, we have utilized a novel approach for performing structure-function analysis of a protein, in vivo, by using recombinant adenovirus vectors to express native and mutant enzymes in an animal model for a human genetic deficiency.

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Hepatic lipase (HL) is an endothelial-bound lipolytic enzyme which functions as a phospholipase as well as a triacylglycerol hydrolase and is necessary for the metabolism of IDL and HDL. To evaluate the feasibility of replacing an enzyme whose in vivo physiologic function depends on its localization on the vascular endothelium, we have infused recombinant replication-deficient adenovirus vectors expressing either human HL (HL-rAdV; n = 7) or luciferase cDNA (Lucif-rAdV; n = 4) into HL-deficient mice with pretreatment plasma cholesterol, phospholipid, and HDL cholesterol values of 176 +/- 9, 314 +/- 12, and 129 +/- 9, respectively. After infusion of HL-rAdV, HL could be detected in the postheparin plasma of HL-deficient mice by immunoblotting and postheparin plasma HL activities were 25,700 +/- 4,810 and 1,510 +/- 688 nmol/min/ml on days 5 and 15, respectively.

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Apolipoprotein E (apoE)-deficient mice develop marked hyperlipidemia as well as atherosclerosis and thus are an excellent animal model for evaluating the potential for gene therapy in human genetic dyslipoproteinemias. Recombinant adenovirus containing either human apoE (rAdv.apoE) or the reporter gene luciferase (rAdv.

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Lipoprotein lipase, hepatic lipase, and lecithin: cholesterol acyltransferase have coordinated enzymatic roles in lipoprotein metabolism. New evidence suggests that the lipases are multifunctional proteins that are able to mediate lipoprotein binding and uptake. The importance of all three enzymes in the control of lipoprotein metabolism can be explored in the future by using the newly generated transgenic animals.

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In previous studies, we have demonstrated a temporal relationship between the postheparin hepatic triglyceride lipase (HTGL) response to sex steroids and the high-density lipoprotein (HDL) cholesterol response. To determine if this relationship is dose-dependent, we compared the effect of three graduated doses of orally administered estradiol and norgestrel in two groups of six postmenopausal women. With estradiol administration, postheparin HTGL activity decreased from 91 +/- 46 to 50 +/- 29 nmol/min/mL, baseline to high dose (P less than .

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Fifty-one hirsute women were randomly treated for nine months with ethinyl estradiol 35 ug plus norethindrone 0.4 mg or 30 ug ethinyl estradiol plus 1.5 mg norethindrone acetate if they needed contraception or spironolactone 200 mg daily if they did not.

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Fifty-one hyperandrogenic women had their lipoprotein lipid profiles determined. Free and albumin-bound testosterone was associated with triglycerides and with high-density lipoprotein cholesterol independent of fasting insulin levels, percent ideal body weight, and waist/hip ratio. To gain insight into mechanisms of these lipid alterations, the women were subgrouped according to apparent source of androgen excess.

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Toward the definition of optimal postmenopausal estrogen replacement we compared the effects of three graduated doses of two oral estrogens, estrone sulfate and 17 beta-estradiol, on the lipid profiles of two groups of six postmenopausal women. Because of metabolic interconversions equivalent serum concentrations of estrone and estradiol were produced with these regimens. However, differential effects were noted in lipoproteins.

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A rapid and inexpensive micro-assay for determining cholesterol in plasma and isolated lipoprotein fractions has been established which utilizes a commercially available enzymatic reagent with semi-automated instruments and microtiter plates. The assay is sensitive, precise, and easy to perform. The color development is linear from 0.

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Concentrations of triglycerides are increased and concentrations of high-density lipoprotein (HDL) cholesterol are low in women with hyperandrogenism. These alterations could be related to excessive androgen or estrogen, to hyperinsulinism, or to a combination of these abnormalities. We examined their independent influences on lipids in 21 women with hyperandrogenism, subgrouped according to apparent source of androgen excess.

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To test whether estrogen can modulate the cholesterolemic response to an Occidental diet, six healthy postmenopausal women were studied for 84 days while ingesting a solid food diet of constant composition high in cholesterol content (995 mg/d). In the middle of the study, estrogen (17 alpha-ethinyl estradiol, 1 microgram/kg per day) was administered orally. Ingestion of the diet for the initial 28 days did not alter lipoprotein lipid or apolipoprotein (apo) levels.

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1. Exogenous sex steroids appear to influence lipoproteins in a manner that is a caricature of the effects of endogenous sex steroids: Estrogens raise HDL (selectively HDL2) and lower LDL; Androgens lower HDL (selectively HDL2), while raising LDL. 2.

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To assess the effect of glycemic control on triglyceride (TG) and apoprotein E (apo E) metabolism, plasma levels of TG and apo E were studied in nine nonobese subjects with insulin-dependent diabetes mellitus (IDDM) following acute ingestion of polyunsaturated fat. Each subject was studied twice: before and after ten days of continuous subcutaneous insulin infusion (CSII). Each subject ingested identical meals on both study days.

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Administration of the androgenic anabolic steroid, stanozolol, is associated with decreased high density lipoprotein (HDL) cholesterol (primarily due to decreased HDL2 cholesterol) and increased levels of postheparin plasma hepatic triglyceride lipase (HTGL) activity. Since HTGL appears to play a role in HDL metabolism, we examined the temporal relationship between these changes. HDL cholesterol remained stable during the first two days of stanozolol administration, but decreased 14% (P less than .

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The increased incidence of atherosclerotic coronary artery disease in patients with systemic lupus erythematosus (SLE) may be due to a dyslipoproteinemia caused by corticosteroid administration. To determine whether lipoprotein lipid levels are abnormal in SLE and the relation of lipoprotein levels to corticosteroid use, lipid and apolipoprotein levels were measured in 46 female patients with SLE and 30 matched control subjects. The patients with SLE had higher levels of plasma triglyceride (134 versus 73 mg/dl; p less than 0.

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Hepatic triglyceride (HTGL) and lipoprotein lipase (LPL) probably have major roles in the removal of triglyceride from triglyceride-rich lipoprotein and in the formation of high density lipoprotein (HDL). However, no population-based study of their activity and relationship to lipoprotein lipid levels has been reported. To determine these relationships, we recalled 33 men and 17 women of a randomly selected sample of the Lipid Research Clinics Pacific Northwest Bell Telephone Company Health Survey.

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Recent data suggest that the protection against ischemic heart disease afforded by high density lipoprotein (HDL) cholesterol (C) may be concentrated in the HDL2 subfraction. To examine the behavioral correlates of the HDL subfractions, we recalled 33 men and 17 women of a random sample from the Pacific Northwest Bell Telephone Company Health Survey. Adiposity and very low density lipoprotein (VLDL) triglyceride were negatively correlated with HDL2C.

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Circulating triglyceride is cleared by a combination of hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL). Although LPL has been extensively studied in diabetes, the effect of insulinization on H-TGL activity has not been well characterized. To determine whether H-TGL activity is altered in insulin-deficient diabetes, postheparin plasma was obtained from eight beagle dogs: three normal (nondiabetic) control dogs and five pancreatectomized diabetic dogs were studied acutely in poor diabetic control (underinsulinized), and again in short-term good control (well insulinized).

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Studies of simultaneous autologous 131I-chylomicron (Sf greater than 400) and 125I-very low density lipoprotein (VLDL) (Sf 20 to 400) apolipoprotein B (apo B) were performed both before (triglyceride level c 1500 mg/dL) and during treatment with stanozolol, a 17 alpha-methyl anabolic androgenic steroid (triglyceride level c 750 mg/dL) in a 74-year-old woman with a past history of recurrent chylomicronemic pancreatitis. Both before and during stanozolol treatment chylomicron apo B disappeared rapidly and directly, little appearing in VLDL and virtually none in intermediate (IDL) or low density lipoproteins (LDL). Multicompartmental analysis indicated that the great majority of chylomicron apo B was removed via an extremely rapid compartment (estimated fractional catabolic rate [FCR], 5.

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The effects of the anabolic steroid stanozolol (17-methyl-2H-5 alpha-androst-2-eno-(3,2-c)pyrazol-17 beta-ol) on lecithin-cholesterol acyltransferase, apolipoproteins B and D and the Lp(a) lipoprotein were determined in a prospective study of ten normolipidemic women with postmenopausal osteoporosis. Lecithin-cholesterol acyltransferase was reduced approx. 30% by 6 weeks of treatment with stanozolol (off treatment 5.

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To investigate the effects of estrogens and androgens on the metabolism of high density lipoproteins (HDL) and low density lipoproteins (LDL), a normolipidemic postmenopausal woman was studied under the following conditions: (1) during supplementation with ethinyl estradiol (0.06 mg/d); (2) without sex steroid therapy; (3) during treatment with stanozolol, an androgenic, anabolic steroid (6 mg/d). During these manipulations HDL and LDL cholesterol levels fluctuated widely but reciprocally: during estrogen supplementation HDL increased while LDL decreased; during stanozolol HDL-C decreased while LDL-C increased.

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To determine the effect of dietary cholesterol on the low-density lipoprotein (LDL) receptor of circulating mononuclear cells, nine adults (six men, three women) consumed a natural diet consisting of 45% of the calories as carbohydrate, 40% as fat, and 15% as protein, polyunsaturated/saturated fatty acid ratio 0.80 to 0.84, and either 137 +/- 25 mg cholesterol per day (low cholesterol phase) or 1034 +/- 25 mg cholesterol per day (high cholesterol phase).

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