Biomedical subjects

J M Hoeg

Publications and source records attributed to J M Hoeg.

118 records · Page 7Linked to original sources

PubMed1983

Presence of two forms of apolipoprotein B in patients with dyslipoproteinemia.

Current information suggests that the major forms of the human B apolipoproteins, B-100 and B-48, are under separate genetic control and are synthesized by the liver and intestine, respectively. The apolipoprotein B composition of plasma lipoproteins has been determined in order to gain insight into the metabolic defects in patients with dyslipoproteinemias. Patients with type I and type V hyperlipoproteinemia can be separated into two groups based on apolipoprotein composition and triglyceride concentration. The first group had markedly elevated plasma triglycerides with B-48 in the 1.006 g/ml density fraction and only B-100 within IDL and LDL. The second group had plasma triglycerides less than 1200 mg % and only B-100 in all density fractions. Patients with type III hyperlipoproteinemia had B-48 in only the density less than 1.006 g/ml with B-100 in IDL and LDL; the type III hyperlipoproteinemic patient with apolipoprotein E deficiency, however, had B-48 in density less than 1.006 g/ml fraction, IDL, and LDL. Patients with type IIa, IIb, and IV hyperlipoproteinemia had only B-100 in all density fractions. These combined results are interpreted as indicating that B-48 is associated with triglyceride-rich lipoproteins synthesized by the intestine and that patients with phenotypes I, III, and V have defects in chylomicron remnant metabolism. In addition, in patients with types I and V hyperlipoproteinemia, mild hypertriglyceridemia appears to be associated with lipoprotein particles of liver origin.

Apolipoproteins↗

PubMed1983

Heterogeneity of lipoprotein electrophoretic patterns in patients with type IIa hyperlipoproteinemia.

Previous evaluations of plasma lipoproteins from patients with type IIa hyperlipoproteinemia have demonstrated quantitative but not qualitative differences from lipoproteins isolated from normal subjects. Using a reproducible, sensitive, high-resolution agarose gel electrophoretic system, we evaluated the plasma lipoprotein of 22 consecutive, untreated, unrelated patients with type IIa hyperlipoproteinemia. Five distinct electrophoretic patterns were observed. This electrophoretic heterogeneity in type IIa hyperlipoproteinemia reflects subtle charge differences in the lipoproteins from these patients, which were not detected with paper electrophoresis or with lipoprotein quantification. There was little, if any, difference in total plasma cholesterol, low- or very-low-density lipoproteins, plasma triglycerides, or concentrations of apolipoproteins A-I, A-II, B, C-II, or E in these subgroups. However, unique clinical features were correlated with the electrophoretic patterns. These findings support the concept that the type IIa hyperlipoproteinemic phenotype includes several molecular defects that are reflected in subtle differences in lipoprotein charge.

Adult↗

PubMed1982

Characterization of neutral and acid ester hydrolase in Wolman's disease.

Wolman's disease is characterized by diffuse cellular accumulation of cholesteryl ester and triacylglycerol, steatorrhea, and death in infancy. Although lysosomal acid ester hydrolase has been reported to be absent in tissues from affected infants, full evaluation of the intracellular ester hydrolases in hepatic and nonhepatic tissues has not been performed previously. Studies on ester hydrolase activity in human liver and skin fibroblasts have permitted the following conclusions. (1) The ester hydrolase activity for cholesteryl oleate and triolein are parallel in human liver and skin fibroblasts. (2) There is a significant loss of activity for both of these substrates at pH 4 in both liver and skin fibroblasts in a subject with Wolman's disease. (3) At pH 7, however, ester hydrolase activity for both substrates in both liver and skin fibroblast preparations from a patient with Wolman's disease is preserved. (4) The patient's mother, an obligate heterozygote, does not demonstrate any loss of activity for either substrate at pH 4. THese data are consistent with the concept that acid and neutral ester hydrolases are different enzymes.

Adult↗

PubMed1982

Analysis of reversible lipoprotein-cell interactions.

Quantitation and characterization of freely reversible ligand-receptor interactions in adherent cell lines grown in vitro have been technically difficult to perform. We report the growth of human fibroblasts on a microcarrier bead system which obviates the limitation of cell adherence in such determinations. This system has been applied to the reversible interaction of low density lipoproteins (LDL) with the fibroblast membrane receptors. Of the 125I-LDL specifically bound to filtered cells, 52.2 +/- 9.8% was reversibly bound. This reversible LDL-cell binding occurred in less than 1 h at 37 degrees C, was specific for LDL, and occurred without significant 125I-LDL degradation. Using these techniques, it is now possible to obtain direct measurement and characterization of lipoprotein-receptor interactions in adherent cell lines of normal subjects and patients with dyslipoproteinemia.

Cell Membrane↗

PubMed1980

Cervical carcinoma and ectopic hyperparathyroidism.

Profound hypercalcemia can impose both diagnostic and therapeutic difficulties. First, profound hypercalcemia can be life-threatening as well as difficult to control. Second, the use of mithramycin in the treatment of severe hypercalcemia is emphasized. Third, hypercalcemia of hyperparathyroidism cannot be absolutely distinguished from that of malignancy. In the present case, the tubular reabsorption of phosphate, serum calcium levels, and measurement of immunoreactive parathyroid hormone (iPTH) suggested primary hyperparathyroidism, yet ectopic iPTH from a cervical carcinoma was the probable cause of the hypercalcemia.

Carcinoma, Squamous Cell↗

PubMed1977

Estrogen attenuation of the development of hypertension in spontaneously hypertensive rats.

To examine the effects of estrogen on the development of high blood pressure in rats with a genetic predisposition toward hypertension, we administered to rats of the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) strains 0.05 mg mestranol daily from ages 4 to 13 wks. Control animals of each strain received corn oil placebos. Systolic blood pressure was measured by a microphonic tail-cuff technique twice a week after the rats were 6 wks of age. Estrogen treatment in SHR was associated with a significant reduction in the level of hypertension attained, but estrogen treatment had no effect on blood pressure in WKY. Estrogen prevented normal growth in SHR and WKY, but this effect (reproduced in another group of SHR and WKY by restriction of food intake) was not related to the lower blood pressures seen in estrogen-treated SHR. Thus, it appeared that estrogen administration attenuated the rise in blood pressure normally seen in SHR and that this attenuation was independent of the estrogenic effect on body weight.

Animals↗

PubMedDate not supplied

Nephrocalcinosis in homozygous familial hypercholesterolemia: ultrasound and CT findings.

An association between homozygous familial hypercholesterolemia (FH) and nephrocalcinosis has not, to our knowledge, been previously reported. Evaluation in 10 cases of homozygous FH revealed evidence of nephrocalcinosis in 7 cases. Fine, uniform calcifications in the renal papillae were demonstrated by renal ultrasound or CT. Renal papillary necrosis was demonstrated by intravenous pyelogram in one case. No renal function impairment was noted in these seven patients. There was no evidence of hypercalcemia. These findings may have implications for the use of a potentially nephrotoxic drug for the treatment of this disease--in particular, when an immunosuppressive agent is required following liver transplantation.

Adolescent↗

PubMedDate not supplied

Characterization of a human hepatic receptor for high density lipoproteins.

Characterization of the membrane receptor for the low density lipoproteins (LDL) has led to insights into cellular receptor physiology as well as mammalian lipid transport. Result with LDL have stimulated the search for specific receptors for other plasma lipoproteins. Receptors for high density lipoproteins (HDL) have been identified in human fibroblasts and smooth muscle cells. Specificity for this receptor has been difficult to define since normal HDL contains several apolipoproteins, and particles containing apolipoproteins B and E have been shown to compete for HDL binding. In the present study, we demonstrate that HDL isolated from a patient devoid of apolipoprotein E was bound specifically by human hepatic membranes. This binding reached saturation within 2 hours and was EDTA-resistant. Assuming a single receptor model, we found that 2.9 x 10(15) receptors/mg membrane protein bound with an affinity KD = 3.5 x 10(-7) M at 0 to 4 degrees C and KD = 1.9 x 10(-7) M at 37 degrees C. The binding was effectively competed with intact HDL3, with HDL3 that had undergone selective arginine and lysine residue modification, and with antibodies to apolipoproteins A-I and A-II. However, LDL, asialofetuin, and HDL3 which had undergone tyrosine modification by nitration, and anti-apolipoprotein B did not compete with apo A-I HDL binding. In contrast to LDL binding, the human hepatoma cell line, HEPG2, increased HDL binding with cholesterol loading that was specific for HDL3. Thus, hepatic tissue can modulate its recognition of HDL. Finally, hepatic membranes from a patient lacking normal hepatic LDL receptors bound apo A-I HDL normally. These data indicate that a saturable, specific regulatable receptor for apo E-free HDL is present in human liver.

Apolipoprotein A-I↗

PubMedDate not supplied

Enhanced apolipoprotein E production with normal hepatic mRNA levels in the Watanabe heritable hyperlipidemic rabbit.

The Watanabe heritable hyperlipidemic rabbit (WHHL) provides an experimental animal model for the low density lipoprotein (LDL) receptor defect present in patients homozygous for familial hypercholesterolemia (FH). Both WHHL rabbits and FH patients have a four- to sevenfold increase in plasma levels of apolipoprotein E (apo E). To determine the etiology for the elevated apo E concentrations, kinetic studies of radiolabeled apo E were conducted in WHHL and control New Zealand White (NZW) rabbits. The sites of apo E synthesis in the WHHL rabbit were evaluated by quantitating apo E mRNA levels in 12 tissues by dot-blot analysis of total RNA from each tissue with an apo E cDNA probe. Compared to the NZW rabbit, the WHHL rabbit had a twofold increase in the plasma apo E residence time, a fourfold increase in apo E production rate, and normal apo E mRNA levels in the liver and all other major apo E synthetic tissues. However, a fivefold increase in WHHL aortic apo E mRNA levels was observed. The elevated level of aortic apo E mRNA indicated a potential role for apo E in modulating atherogenesis in the WHHL rabbit. These results established that the increased plasma apo E in the WHHL rabbit was due to increased synthesis and delayed catabolism. Moreover, the fourfold increase in apo E synthesis with normal tissue apo E mRNA levels may reflect a translational or posttranslational regulation of apo E synthesis.

Animals↗

PubMedDate not supplied

An approach to the management of hyperlipoproteinemia.

Recent clinical trials indicate that reduction of plasma cholesterol concentrations in individuals with increased levels of low-density lipoproteins reduces their risk of myocardial infarction and death. Therefore, the question of "whether to treat" should be shifted to "whom to treat" and "how best to treat". The understanding of normal lipid transport via the plasma lipoproteins has grown to a sophisticated level over the past 20 years. Plasma cholesterol, required for cellular membrane integrity, and plasma triglycerides, the primary mammalian energy source, are carried in lipoprotein particles that vary in size, density, lipid composition, and apolipoprotein content. Some lipoprotein particles (low-density lipoproteins) play a causal role in the atherosclerotic process, while other particles (high-density lipoproteins) appear to prevent this process. Utilizing this understanding of the plasma lipoproteins, a systematic approach to the management of the patient with hyperlipoproteinemia has been developed which may lead to the normalization of plasma lipoprotein concentrations in the majority of hyperlipoproteinemic patients.

Anticholesteremic Agents↗