193 results on '"Kwiterovich PO"'
Search Results
152. The association of low levels of HDL cholesterol and arteriographically defined coronary artery disease.
- Author
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Pearson TA, Bulkley BH, Achuff SC, Kwiterovich PO, and Gordis L
- Subjects
- Adult, Aged, Cardiac Catheterization, Cholesterol blood, Coronary Disease diagnostic imaging, Female, Humans, Lipoproteins, LDL blood, Male, Middle Aged, Risk, Triglycerides blood, Coronary Angiography, Coronary Disease blood, Lipoproteins, HDL blood
- Abstract
Epidemiologic studies have found associations between low levels of high density lipoprotein (HDL) cholesterol and increased risk of coronary artery disease, using myocardial infarction or angina pectoris as endpoints. However, since most studies have not correlated HDL cholesterol with the presence, severity, or location of anatomically proven coronary disease, the present study measured HDL cholesterol levels in 483 men and women undergoing coronary arteriography. Consistent and statistically significant trends of decreasing mean HDL cholesterol levels with increasing numbers of diseased coronary arteries were observed in both men and women and in younger and older age groups. Although women without coronary disease had much higher levels of HDL cholesterol than men without coronary disease, the differences between men and women with similar degrees of coronary disease were small. Low levels of HDL cholesterol were associated with left main coronary disease; patients with both triple vessel disease and left main disease had lower levels of HDL cholesterol than did patients with triple vessel disease without left main disease. These results were not explained by the possible associations of low density lipoprotein cholesterol or triglycerides with HDL cholesterol. These findings suggest that low levels of HDL cholesterol are important risk factors for the development of atherosclerosis and that they may be useful for identifying patients at high risk of certain anatomic patterns of coronary artery disease.
- Published
- 1979
- Full Text
- View/download PDF
153. Resolubilization of certain apoprotein components of human plasma high density lipoproteins in TCA-fixed polyacrylamide gels during destaining in acetic acid solutions.
- Author
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Bachorik PS, Kwiterovich PO, and Simon A
- Subjects
- Acrylamides, Apoproteins blood, Apoproteins isolation & purification, Chemical Precipitation, Chymotrypsinogen, Diffusion, Electrophoresis, Polyacrylamide Gel, Humans, Lipoproteins, HDL isolation & purification, Male, Methods, Proteins, Solubility, Spectrophotometry, Ultraviolet, Staining and Labeling, Acetates, Lipoproteins, HDL blood, Trichloroacetic Acid
- Published
- 1974
- Full Text
- View/download PDF
154. Isolation of a porcine liver plasma membrane fraction that binds low density lipoproteins.
- Author
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Bachorik PS, Kwiterovich PO, and Cooke JC
- Subjects
- Animals, Calcium pharmacology, Heparin pharmacology, Manganese pharmacology, Microsomes, Liver metabolism, Phosphatidylcholines pharmacology, Protein Binding, Subcellular Fractions metabolism, Swine, alpha-Fetoproteins pharmacology, Cell Membrane metabolism, Lipoproteins, LDL metabolism, Liver metabolism
- Abstract
Large amounts of injected radiolabeled low density lipoproteins have been found by others to accumulate primarily in the liver and studies in various types of isolated cells, including hepatocytes, have indicated the presence of specific cell membrane recognition sites for lipoproteins. In the present studies, the high affinity binding of radiolabeled low density lipoproteins ([125I]LDL, d 1.020--1.063 g/mL) was measured in the major subcellular fractions of porcine liver homogenates. The nuclear and mitochondrial fractions were 1.9- and 1.4-fold enriched in binding activity with respect to unfractionated homogenates and contained 15% and 12% of the total binding activity, respectively. The microsomes, which contained most of the plasma membranes and endoplasmic reticulum, were approximately 4-fold enriched in binding and contained 73% of the binding activity. Microsomal subfractions obtained by differential homogenization and centrifugation procedures were 5.6--7.0-fold enriched in LDL binding and contained 54--58% of the homogenate binding activity. They were separated by discontinuous sucrose density gradient centrifugation into fractions which contained "light" and "heavy" plasma membranes and endoplasmic reticulum. The heavy membrane fraction was 2--4 fold in binding with respect to the parent microsomes (16--22 fold with respect to the homogenate). There was no enrichment of binding activity in the other two fractions. Two plasma membrane "marker" enzymes, nucleotide pyrophosphatase and 5'-nucleotidase, were also followed. Of the two, binding in the sucrose density gradient subfractions most closely followed nucleotide pyrophosphatase, which was also most highly enriched (3.2--3.3-fold) in the heavy membrane fraction, but did not follow it exactly. The enzyme was 2-fold richer in the light membranes than in the parent microsomes, though the light membrane binding activity was only 0.4--1.4 times that of the parent microsomes. High affinity binding was time and temperature dependent, saturable, and inhibited by unlabeled low density lipoproteins but not by unrelated proteins. Binding was stimulated 2--3 fold Ca2+, was not affected by treatment with Pronase or trypsin and was inhibited by low concentrations of phospholipids and high density lipoproteins (HDL). Heparin-Mn2+ treatment of HDL did not affect its ability to inhibit [125I] LDL binding. The LDL recognition site was distinct from the liver membrane asialoglycoprotein receptor; LDL binding was not inhibited by desialidated fetuin. We conclude that porcine liver contains a high affinity binding site that recognizes features common to both pig low density and high density lipoproteins. Further studies may elucidate the significance of this binding site in lipoprotein metabolism.
- Published
- 1978
- Full Text
- View/download PDF
155. Dyslipoproteinemia and xanthomatosis.
- Author
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Haber C and Kwiterovich PO Jr
- Subjects
- Adolescent, Adult, Apolipoproteins blood, Arteriosclerosis physiopathology, Child, Child, Preschool, Female, Humans, Hyperlipidemias classification, Hyperlipoproteinemia Type II physiopathology, Hyperlipoproteinemia Type III physiopathology, Hyperlipoproteinemias classification, Infant, Infant, Newborn, Lipids blood, Lipoproteins physiology, Male, Xanthogranuloma, Juvenile physiopathology, Xanthomatosis physiopathology, Lipoproteins blood, Skin Diseases blood, Xanthogranuloma, Juvenile blood, Xanthomatosis blood
- Abstract
The cutaneous markers associated with dyslipoproteinemia are reviewed in the context of the current view of lipid and lipoprotein metabolism. The utility of determining the plasma levels of lipoproteins and certain apoproteins in children or adults with xanthomas or xanthelasma is discussed. We hope that early identification and appropriate treatment of such patients will reduce the morbidity and mortality from the two major complications of dyslipoproteinemia--atherosclerotic cardiovascular disease and pancreatitis.
- Published
- 1984
- Full Text
- View/download PDF
156. Determination of high density lipoprotein-cholesterol in human plasma stored at -70 degrees C.
- Author
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Bachorik PS, Walker RE, and Kwiterovich PO Jr
- Subjects
- Cholesterol, HDL, Freezing, Heparin pharmacology, Humans, Plasma analysis, Triglycerides blood, Cholesterol blood, Lipoproteins, HDL blood
- Abstract
We determined the effect of storage at -70 degrees C on the determination of plasma high density lipoprotein (HDL)-cholesterol. Plasma from 106 subjects was stored for 1, 6, and 12 months, then treated with heparin and MnCl2 to remove other lipoproteins, and HDL-cholesterol was measured. The mean HDL-cholesterol level decreased by 2.9% after 1 month, and by 5.1% after 12 months. The magnitude and direction of the changes were not constant, but were correlated primarily with HDL-cholesterol concentration. After 1 month, samples with HDL-cholesterol levels below 40 mg/dl tended to increase, and those above this value tended to decrease. By 12 months, only those samples with HDL-cholesterol below 22 mg/dl tended to increase. Linear regression analysis indicated changes of 0.9-1.5 mg/dl for each 10 mg/dl initial HDL-cholesterol concentration. Storage of heparin-MnCl2 supernatants, rather than unfractionated plasma, minimized these changes. The mean HDL-cholesterol of stored heparin-MnCl2 supernatants was 3.3% lower after 12 months, and the change was constant regardless of lipoprotein concentration. The findings suggest the possible occurrence of changes in the heparin-MnCl2 precipitability of lipoproteins during storage, which produce errors in HDL-cholesterol analyses, and indicate that samples can be stored more satisfactorily if the other lipoproteins are removed first.
- Published
- 1982
157. Hyperapobetalipoproteinaemia in two families with xanthomas and phytosterolaemia.
- Author
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Kwiterovich PO Jr, Bachorik PS, Smith HH, McKusick VA, Connor WE, Teng B, and Sniderman AD
- Subjects
- Adolescent, Adult, Coronary Disease genetics, Female, Heterozygote, Homozygote, Humans, Male, Pedigree, Hyperlipoproteinemia Type II genetics, Lipoproteins, LDL blood, Phytosterols blood, Xanthogranuloma, Juvenile genetics
- Abstract
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.
- Published
- 1981
- Full Text
- View/download PDF
158. Use of robust variance components models to analyse triglyceride data in families.
- Author
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Beaty TH, Self SG, Liang KY, Connolly MA, Chase GA, and Kwiterovich PO
- Subjects
- Humans, Phenotype, Statistics as Topic, Triglycerides blood, Genetic Variation, Models, Genetic, Triglycerides genetics
- Abstract
A robust approach for analysis of variance components models is presented which does not rely on the assumption of multivariate normality for its validity. This approach uses the multivariated normal distribution as a 'working model' but obtains standard errors for the final estimators which do not depend on this underlying distribution. By using the observed variance in the first derivatives of the multivariate normal 'working model' to modify the conventional score test, hypotheses regarding specific components can also be tested without relying directly on the assumption of multivariate normality. A special case is presented where both the modified score test and the likelihood ratio test are equally robust, and simulated data are used to illustrate this situation. Measurements of triglyceride levels in 391 individuals in 60 families randomly selected from the membership of a health maintenance organization are used to illustrate this robust approach to variance components.
- Published
- 1985
- Full Text
- View/download PDF
159. Reversible high affinity uptake of apo E-free high density lipoproteins in cultured pig hepatocytes.
- Author
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Bachorik PS, Franklin FA Jr, Virgil DG, and Kwiterovich PO Jr
- Subjects
- Animals, Apolipoproteins E metabolism, Cells, Cultured, Iodine Radioisotopes, Liver metabolism, Swine, Lipoproteins, HDL metabolism, Liver cytology
- Abstract
We examined the high affinity binding, uptake, and degradation of apo E-free 125I-high density lipoprotein (HDL) in cultured pig hepatocytes. At steady state, the cells degraded 9.4% of cell-associated 125I-HDL/hour, compared with 41.7%/hour for 125I-LDL. Pulse-chase experiments at 4 degrees C revealed that high affinity 125I-HDL binding was reversible. Similar experiments at 37 degrees C revealed that about 70% of the cell-associated 125I-HDL was released as a macromolecule; the remainder was degraded to acid-soluble products. In contrast, over 75% of the 125I-LDL that was released had been degraded to acid soluble products. The amount of macromolecular 125I-HDL released at 37 degrees C was similar to the amount that was bound to the cell surface, as estimated from measurements of trypsin-releasable radioactivity. Density gradient ultracentrifugation and SDS-polyacrylamide gel electrophoretic analysis of macromolecular 125I-HDL released to the medium revealed an increase in density, and the apparent partial proteolysis of apo A-I (Mr 25,000) to products of apparent Mr 12,000-14,000. The findings suggest that high affinity 125I-HDL uptake had a reversible component in which HDL was concentrated temporarily at the cell surface, modified, and then released as a somewhat denser lipoprotein particle. Measurement of 125I-HDL and 125I-LDL degradation in cell homogenates revealed no difference in the inherent susceptibility of the two lipoproteins to proteolysis by lysosomal enzymes. The overall slower rate of degradation of 125I-HDL compared to 125I-LDL was therefore due in part to the smaller fraction of HDL that was committed to irreversible catabolism. The rate of catabolism of this fraction, however, was considerable. Cells pulsed at 4 degrees C and subsequently warmed to 37 degrees C released one-half the acid-soluble products from 125I-HDL within about 4 hours, compared with 2 hours for cells pulsed with 125I-LDL. These findings indicate that HDL was internalized, transported to lysosomes, and degraded at about one-half the rate of LDL.
- Published
- 1985
- Full Text
- View/download PDF
160. Localization of urinary lactosylceramide in cytoplasmic vesicles of renal tubular cells in homozygous familial hypercholesterolemia.
- Author
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Chatterjee S, Kwiterovich PO Jr, Gupta P, Erozan YS, Alving CR, and Richards RL
- Subjects
- Adolescent, Adult, Cell Survival, Child, Female, Fluorescent Antibody Technique, Homozygote, Humans, Hyperlipoproteinemia Type II genetics, Kidney Tubules enzymology, Male, Microscopy, Electron, gamma-Glutamyltransferase analysis, Glycosphingolipids urine, Hyperlipoproteinemia Type II urine, Kidney Tubules cytology, Lactosylceramides urine
- Abstract
An average 15-fold increase in lactosylceramide (LacCer) in the sediment of receptor-negative, familial hypercholesterolemic (FH) homozygotes has been reported [Chatterjee, S., Sekerke, C.S. & Kwiterovich, P.O., Jr. (1982) J. Lipid Res. 23, 513-522]. We report here the abnormal urinary excretion of significant numbers of renal tubular cells in eight FH homozygotes. The mean activity of gamma-glutamyltransferase, a marker for renal tubular cells, was twice as high in urinary sediment of FH homozygotes as in normals. Membrane-enclosed cytoplasmic vesicles that stained strongly positive with a fluorescein-labeled antibody against LacCer were found in the renal tubular cells of all homozygotes except two who had undergone a portacaval shunt. These two had normal urinary levels of LacCer, and the cytoplasmic vesicles were vacuolated. In the other six, most of the fluorescent antibody label was intracellular and perinuclear. The cytoplasmic vesicles stained strongly with polychromatic Papanicolaou stain, periodic acid/Schiff reagent, and oil red O. Electron microscopy revealed perinuclear membrane-enclosed lipid and free lipid droplets. When two FH homozygotes, who excreted increased LacCer, underwent plasma exchange, the cytoplasmic vesicles became empty, and the urinary LacCer level decreased into the normal range. We conclude that the increased urinary excretion of LacCer in FH homozygotes occurs in renal tubular cells and that the intracellular locatin of LacCer is within cytoplasmic vesicles. The presence of LacCer within these vesicles can be modulated by treatment with plasma exchange.
- Published
- 1983
- Full Text
- View/download PDF
161. Coronary risk factor statement for the American public. A statement of the nutrition committee.
- Author
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Grundy SM, Arky R, Bray GA, Brown WV, Ernst ND, Kwiterovich PO Jr, Mattson F, Weidman WH, Schonfeld G, and Strong JP
- Subjects
- American Heart Association, Coronary Disease complications, Coronary Disease prevention & control, Diabetes Complications, Humans, Hypercholesterolemia complications, Hypertension complications, Life Style, Obesity complications, Physical Examination, Risk, Smoking, Stress, Psychological complications, United States, Coronary Disease etiology
- Published
- 1985
162. Genetics of the hyperlipidemias and cardiovascular implications.
- Author
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Kwiterovich PO Jr
- Subjects
- Arteriosclerosis etiology, Child, Coronary Disease etiology, Genes, Dominant, Humans, Hyperlipidemias classification, Hyperlipidemias epidemiology, Phenotype, Hyperlipidemias complications, Hyperlipidemias genetics
- Published
- 1977
- Full Text
- View/download PDF
163. Familial hypercholesterolemia (one form of familial type II hyperlipoproteinemia). A study of its biochemical, genetic and clinical presentation in childhood.
- Author
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Kwiterovich PO Jr, Fredrickson DS, and Levy RI
- Subjects
- Adult, Cholesterol blood, Coronary Disease epidemiology, Female, Humans, Hypercholesterolemia epidemiology, Lipoproteins, HDL blood, Lipoproteins, LDL blood, Male, Middle Aged, Triglycerides blood, United States, Xanthomatosis epidemiology, Hypercholesterolemia genetics
- Abstract
Primary hyperbetalipoproteinemia (type II hyperlipoproteinemia) is a common disorder associated with premature vascular disease. It is frequently due to genetic abnormalities, some of which are expressed in childhood. We have examined the manner in which that form of hyperbetalipoproteinemia known as familial hypercholesterolemia may be expressed in 236 children aged 1-19 born of 90 matings in which one parent had hyperbetalipoproteinemia of this variety and one parent did not.Two Gaussian populations were fitted to the distribution of both low density lipoprotein cholesterol (C(LDL)) and plasma cholesterol (C) in these children and a likelihood ratio test strongly favored a two over a one population model for both C(LDL) (X(2) = 18.41, P < 0.0005) and C (X(2) = 7.81, P < 0.025). 45% of the children were in the population identified as affected; their mean C(LDL) was 229. The remaining 55% were in the normal population with a mean C(LDL) of 110 which was indistinguishable from that of an unrelated control population, aged 1-19. On the basis of an assumed frequency of hyperbetalipoproteinemia in the general population of 5%, the Edwards' test indicated that a polygenic model of inheritance was highly unlikely (expected, 22%; observed, 45%). The segregation ratio obtained from the derived intersection between the two population curves (C(LDL), 164 mg/100 ml; C, 235 mg/100 ml) was 45/55 (abnormal/normal). The percentage of abnormal children in the first decade (52%) significantly exceeded that in the second (39%) (P < 0.01). The ratios (II/N) were 50/47 and 55/84 in the offspring of affected female and male parents, respectively (X(2) = 3.819, 0.05 < P < 0.10). Only 10% of hyperbetalipoproteinemic children were considered to have hyperglyceridemia. These children, frequently, but not invariably, had a parent with hyperglyceridemia in addition to hyperbetalipoproteinemia (P < 0.05). None of the affected children who were examined had ischemic heart disease (IHD) and 7% had tendon xanthomas. Half of the parents (mean age, 37.4 yr) who were examined had IHD and three-quarters had xanthomas. The data agree well with the hypothesis that hyperbetalipoproteinemia is inherited as a monogenic trait with early expression in these children. More than one genetic defect within the group is not excluded, but retrospective analyses of the 345 first-degree adult relatives of the affected parents indicated that most of the abnormal parents probably represented familial hypercholesterolemia, rather than combined hyperlipidemia, the other most generally recognized form of familial hyperbetalipoproteinemia.
- Published
- 1974
- Full Text
- View/download PDF
164. Immunohistochemical localization of glycosphingolipid in urinary renal tubular cells in Fabry's disease.
- Author
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Chatterjee S, Gupta P, Pyeritz RE, and Kwiterovich PO Jr
- Subjects
- Adolescent, Adult, Child, Preschool, Cholesterol blood, Fabry Disease pathology, Female, Fluorescent Antibody Technique, Globosides blood, Globosides urine, Glycosphingolipids blood, Histocytochemistry, Humans, Kidney Tubules ultrastructure, Male, Middle Aged, Triglycerides blood, Fabry Disease urine, Glycosphingolipids urine, Kidney Tubules metabolism, Trihexosylceramides
- Abstract
Although the accumulation of neutral glycosphingolipid (GSL), principally globotriaosylceramide ( GbOse3Cer ), in the kidney of patients with Fabry's disease is well documented, little is known about the type and quantity of lipid present in the renal tubular cells shed in the urine. Using a variety of cytologic technics, the authors examined exfoliated cells found in the urine specimens of patients hemizygous and heterozygous for alpha-galactosidase A deficiency. Renal tubular cells contained periodic acid- Shiff positive material that could be identified easily by Papanicolaou stain. A fluorescein-labeled antibody specific for GbOse3Cer localized this lipid to the cytoplasm. Electron microscopy showed numerous electron-dense multilamellar membranous inclusions within phagolysosomes and electronlucent material within lysosomes of tubular cells. Based on immunofluorescence, heterozygote individuals had similar distribution but less quantity of cytoplasmic GSL. The authors conclude that in Fabry's disease GSL accumulates probably in lysosomes of renal tubular cells. These cells are exfoliated and can be identified specifically in voided urine specimens. Examination of renal tubular cells in urine using the fluorescein antibody technic described here affords a noninvasive means of diagnosing and following the effect of therapy in patients with Fabry's disease.
- Published
- 1984
- Full Text
- View/download PDF
165. Modulation of apolipoprotein B antigenic determinants in human low density lipoprotein subclasses.
- Author
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Teng B, Sniderman A, Krauss RM, Kwiterovich PO Jr, Milne RW, and Marcel YL
- Subjects
- Antibodies, Monoclonal, Cholesterol, LDL analysis, Electrophoresis, Polyacrylamide Gel, Female, Humans, Male, Middle Aged, Protein Conformation, Radioimmunoassay, Apolipoproteins B immunology, Epitopes analysis, Lipoproteins, LDL analysis
- Abstract
To investigate the effect of low density lipoprotein (LDL) heterogeneity on the conformation of LDL apolipoprotein B (apo-B), the immunoreactivities of 6 monoclonal antibodies against LDL apo-B were measured in 3 LDL subfractions isolated by equilibrium density gradient ultracentrifugation. To ensure a broad range of LDL particles, the LDL subfractions were prepared from normal subjects and patients with hyperapobetalipoproteinemia. With 3 of the antibodies, 1D1, 5E11, and 3A10, LDL fractions 1 (the most buoyant), 2 (the intermediate), and 3 (the densest) were equally immunoreactive and competed similarly with reference whole LDL. In contrast, with 3 other antibodies, 2D8, 3F5, and 4G3, fraction 1 was significantly more reactive than fraction 3; that is for each in turn, 290, 250, and 150% more of the densest LDL protein was required to achieve the same displacement as with fraction 1. Further, the immunoreactivities of the 3 LDL fractions with antibodies 2D8, 3F5, and 4G3 were negatively correlated with their LDL cholesterol to LDL protein ratio with r values of 0.727, 0.898, and 0.870, respectively, suggesting that as LDL particle size decreases, the conformation of the LDL apo-B changes progressively. It is of interest that the antigenic determinants recognized by 3F5 and 4G3 are close to the LDL receptor recognition site on LDL apo-B. Therefore, it is possible that the reduced immunoreactivity of these determinants in dense LDL may be the in vitro correlate of the reduced fractional catabolics rate of dense LDL compared to buoyant LDL previously observed in vivo.
- Published
- 1985
166. Distribution of antithrombin III and glucosylceramide in human plasma lipoproteins and lipoprotein deficient plasma.
- Author
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Chatterjee S, Bell WR, and Kwiterovich PO Jr
- Subjects
- Humans, Male, Reference Values, Antithrombin III analysis, Cerebrosides blood, Glucosylceramides blood, Lipoproteins blood
- Abstract
We have investigated the distribution of antithrombin-III and glucosylceramide (Glc-Cer) in human plasma, plasma lipoproteins and lipoprotein-deficient plasma. Antithrombin III activity was measured employing immunochemical and biological assays. Glc-Cer was quantified by gas liquid chromatography (GLC). Whole plasma contained 145 micrograms antithrombin III/ml plasma, all of which was associated with the lipoprotein-deficient plasma (d greater than 1.25 g/ml). Whereas, most if not all the plasma GlcCer was associated with plasma low density lipoproteins (LDL) (d-1.022-1.055 g/ml) and high density lipoproteins (HDL) (d-1.063-1.25). GlcCer was not found in the lipoprotein-deficient plasma. We conclude that GlcCer on lipoproteins does not contribute to antithrombin III activity. Moreover, the absence of GlcCer in lipoprotein-deficient plasma does not impair antithrombin-III activity.
- Published
- 1984
- Full Text
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167. The East Baltimore study. I. plasma cholesterol and triglyceride levels in an inner city black population.
- Author
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Kwiterovich PO Jr, Jenkins JA, Van Natta P, Bachorik PS, and Chase GA
- Subjects
- Adolescent, Adult, Age Factors, Aged, Child, Child, Preschool, Coronary Disease epidemiology, Female, Humans, Infant, Infant, Newborn, Male, Maryland, Middle Aged, Risk, Seasons, Sex Factors, Socioeconomic Factors, Statistics as Topic, Black or African American, Black People, Cholesterol blood, Triglycerides blood
- Published
- 1980
168. Detection of dyslipoproteinemia with the use of plasma total cholesterol and triglyceride as screening tests. The Lipid Research Clinics Program Prevalence Study.
- Author
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Kwiterovich PO Jr, Stewart P, Probstfield JL, Stinnett S, Chambless LE, Chase GA, Jacobs DR, and Morrison JA
- Subjects
- Adolescent, Adult, Age Factors, Child, Diagnostic Errors, Female, Humans, Lipoproteins blood, Male, Middle Aged, Regression Analysis, Sex Factors, Cholesterol blood, Hyperlipoproteinemias diagnosis, Hypolipoproteinemias diagnosis, Triglycerides blood
- Abstract
The efficiency of screening for dyslipoproteinemias associated with hyperlipoproteinemia or with hypolipoproteinemia was examined in 8449 white examinees from the Lipid Research Clinics Prevalence Study. A two-stage lipid screening approach was used. A positive screening test for hyperlipidemia was defined as an elevated level of plasma total cholesterol or triglyceride at both visit 1 and visit 2. A positive screening test for hypolipidemia was defined as a reduced plasma total cholesterol level at both visits. The syndromes of dyslipoproteinemia were defined according to the lipoprotein pattern present at visit 2. When hyperlipidemia was used as a screening tool, generally only about one-half or less of the cases of hyperlipoproteinemia were detected (high proportion of false-negative results). Of all the hyperlipidemic participants, more than 80% had hyperlipoproteinemias (type I, IIa, IIb, III, IV, or V), and such lipid screening therefore provided a lower proportion of false-positive than false-negative results. Most of the participants (greater than 98%) without hyperlipoproteinemia were correctly identified (true negatives). The efficiency of screening for hypolipoproteinemia was in general poorer than that found for hyperlipoproteinemia. Our results were found to be related, in part, to the marked regression to the mean of plasma cholesterol and triglycerides at the extremes of the distributions and to the wide variety of dyslipoproteinemias that can be present within a given range of plasma cholesterol or triglyceride values. The results emphasize the importance of measuring plasma lipoproteins in the patient who is being evaluated for dyslipoproteinemia.
- Published
- 1986
169. Hyperapobetalipoproteinemia: the major dyslipoproteinemia in patients with chronic renal failure treated with chronic ambulatory peritoneal dialysis.
- Author
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Sniderman A, Cianflone K, Kwiterovich PO Jr, Hutchinson T, Barre P, and Prichard S
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Kidney Failure, Chronic therapy, Lipids blood, Lipoproteins blood, Male, Middle Aged, Renal Dialysis, Apolipoproteins B blood, Hyperlipoproteinemia Type III diagnosis, Hyperlipoproteinemias diagnosis, Kidney Failure, Chronic blood, Peritoneal Dialysis, Continuous Ambulatory
- Abstract
In the present study, plasma cholesterol, triglyceride, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, and the major protein in LDL, apoB, were measured in 28 patients with chronic renal failure treated with hemodialysis and in 28 patients with chronic renal failure treated with chronic ambulatory peritoneal dialysis (CAPD). Elevated plasma triglycerides and reduced HDL cholesterol were frequent in both the hemodialysis and CAPD patients. However LDL levels were significantly higher in the CAPD patients as evident both by LDL cholesterol and LDL apoB. Even so, only one of the CAPD patients was hypercholesterolemic whereas 14 (or 50%) had hyperapobetalipoproteinemia (HyperapoB). Insulin-dependent diabetes was more frequent in the CAPD group but only 2 of the 9 insulin-dependent diabetics in this group had HyperapoB, and therefore, diabetes mellitus cannot account for the difference between the 2 groups. Thus HyperapoB appears to be a prevalent dyslipoproteinemia in CAPD patients and as such might be another factor which places CAPD patients at particularly increased risk of atherosclerosis.
- Published
- 1987
- Full Text
- View/download PDF
170. Effects of genetic mechanisms on plasma lipoprotein metabolism and the pathogenesis of atherosclerosis.
- Author
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Kwiterovich PO Jr, Bachorik PS, and Chatterjee S
- Subjects
- Apolipoproteins blood, Arteriosclerosis etiology, Arteriosclerosis physiopathology, Cholesterol blood, Gangliosides metabolism, Homozygote, Humans, Hypercholesterolemia genetics, Hyperlipidemias blood, Hyperlipoproteinemias genetics, Lipoproteins, HDL blood, Phospholipids metabolism, Triglycerides blood, Arteriosclerosis genetics, Lipoproteins blood
- Published
- 1979
171. Increased plasma cholestanol and 5 alpha-saturated plant sterol derivatives in subjects with sitosterolemia and xanthomatosis.
- Author
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Salen G, Kwiterovich PO Jr, Shefer S, Tint GS, Horak I, Shore V, Dayal B, and Horak E
- Subjects
- Adolescent, Adult, Child, Cholesterol analogs & derivatives, Cholesterol blood, Cholestyramine Resin therapeutic use, Female, Humans, Male, Middle Aged, Xanthomatosis drug therapy, Cholestanols blood, Phytosterols blood, Sitosterols blood, Xanthomatosis blood
- Abstract
We have measured plasma sterol composition in 14 subjects with sitosterolemia and xanthomatosis. In addition to elevated plasma phytosterol (campesterol 16 +/- 7 mg/dl and sitosterol 35 +/- 16 mg/dl) and normal to moderately high cholesterol levels (258 +/- 96 mg/dl), concentrations of 5 alpha-saturated stanols, cholestanol, 5 alpha-campestanol, and 5 alpha-sitostanol were at least 10 times greater than controls. Diets contained plentiful quantities of cholesterol and plant sterols, but only trace amounts of cholestanol (less than 2 mg/day) and no detectable 5 alpha-campestanol and 5 alpha-sitostanol, which indicated that the 5 alpha-saturated stanols were formed endogenously. Treatment with cholestyramine reduced plasma cholesterol and phytosterol levels by 45% and 5 alpha-saturated stanols by 55%. These results indicate that abnormally high plasma concentrations of cholestanol, 5 alpha-campestanol, and 5 alpha-sitostanol are found in subjects with sitosterolemia and xanthomatosis, and that treatment with cholestyramine effectively reduced elevated plasma sterol levels.
- Published
- 1985
172. Hyperlipidemia: clinical clues in the first two decades of life.
- Author
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Neill CA, Ose L, and Kwiterovich PO Jr
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Humans, Hypercholesterolemia diagnosis, Hyperlipidemias genetics, Infant, Infant, Newborn, Medical History Taking, Physical Examination standards, Hyperlipidemias diagnosis
- Published
- 1977
173. Pediatric implications of heterozygous familial hypercholesterolemia. Screening and dietary treatment.
- Author
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Kwiterovich PO Jr
- Subjects
- Adolescent, Adult, Age Factors, Apolipoproteins B analysis, Child, Child, Preschool, Cholesterol blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Coronary Disease complications, Follow-Up Studies, Heterozygote, Humans, Hyperlipoproteinemia Type II drug therapy, Hyperlipoproteinemia Type II genetics, Infant, Infant, Newborn, Pedigree, Polymorphism, Restriction Fragment Length, Receptors, LDL deficiency, Triglycerides blood, Xanthomatosis complications, Hyperlipoproteinemia Type II diagnosis
- Abstract
Heterozygous familial hypercholesterolemia (FH) is completely expressed at birth and in childhood by significant elevations of plasma total and low density lipoprotein (LDL) cholesterol levels. High density lipoprotein cholesterol levels can be low in FH. Screening of children for FH using a LDL cholesterol level is efficient in families with known FH, while for general population screening, the LDL cholesterol level is too nonspecific. Newer cellular and molecular biologic approaches of screening for FH promise to be more specific. A diet low in cholesterol (less than 200 mg/day), total fat (30% of calories), and saturated fat (less than 10% of calories) but moderately enriched in polyunsaturated fat (up to 10% of calories) will lower the total and LDL cholesterol levels about 10% to 15% in most heterozygous FH children. Many children will eventually require the addition of a drug to achieve satisfactory lowering of the LDL cholesterol level. The early detection and treatment of FH offers the optimal approach to the prevention of premature coronary artery disease.
- Published
- 1989
174. Fenofibrate for the treatment of type IV and V hyperlipoproteinemias: a double-blind, placebo-controlled multicenter US study.
- Author
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Goldberg AC, Schonfeld G, Feldman EB, Ginsberg HN, Hunninghake DB, Insull W Jr, Knopp RH, Kwiterovich PO, Mellies MJ, and Pickering J
- Subjects
- Adolescent, Adult, Aged, Cholesterol blood, Clinical Trials as Topic, Double-Blind Method, Female, Fenofibrate adverse effects, Humans, Male, Middle Aged, Random Allocation, Time Factors, Triglycerides blood, United States, Fenofibrate therapeutic use, Hyperlipoproteinemia Type IV drug therapy, Hyperlipoproteinemia Type V drug therapy, Propionates therapeutic use
- Abstract
The results of a randomized, double-blind, placebo-controlled multicenter trial of fenofibrate in the treatment of type IV/V hyperlipoproteinemia are reported. Ten study centers in the United States recruited 147 adults with a history of type IV or V hyperlipoproteinemia. After a six- to 12-week dietary stabilization period and a four-week placebo period, patients whose 12-hour fasting total plasma triglyceride levels ranged from 350 to 1,500 mg/dl were continued in the study; 55 patients with levels of 350 to 499 mg/dl were placed in group A and 92 with levels of 500 to 1,500 mg/dl in group B. Patients in each group were randomly assigned to receive 100 mg of fenofibrate or placebo three times daily for eight weeks. In both groups A and B fenofibrate-treated patients showed statistically significant reductions in levels of total cholesterol, very-low-density lipoprotein cholesterol, total triglycerides, and very-low-density lipoprotein triglycerides, and significant increases in high-density lipoprotein cholesterol; patients in group B also showed a significant increase in low-density lipoprotein cholesterol levels. Sixteen of the 75 fenofibrate-treated patients and 11 of the 72 placebo patients reported adverse events that were potentially drug related; most of these were gastrointestinal and a few reported musculoskeletal and skin reactions. It is concluded that fenofibrate is an effective and safe agent in the treatment of type IV/V hyperlipoproteinemia.
- Published
- 1989
175. Fat and cholesterol intakes of white adults in Columbia, Maryland. Upper-middle socioeconomic level subjects.
- Author
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Salz KM, Haigh NZ, Chase GA, and Kwiterovich PO Jr
- Subjects
- Adult, Age Factors, Diet standards, Energy Intake, Fats, Unsaturated administration & dosage, Female, Humans, Male, Maryland, Middle Aged, Sex Factors, Socioeconomic Factors, White People, Cholesterol, Dietary administration & dosage, Diet trends, Dietary Fats administration & dosage
- Abstract
In a cross-sectional study of white adults with upper-level socioeconomic status (in Columbia, Maryland), intakes of total, saturated, and polyunsaturated fat and of cholesterol were assessed. The intakes were compared with dietary recommendations made by the Inter-Society Commission for Heart Disease Resources, the American Heart Association, and the Senate Select Committee. Only moderate dietary changes were needed for a menu modification that conforms to the dietary recommendations for men. If the group studied reflects the impact of public health nutrition education, areas in need of attention seem to be a reduction in the amount and a change in the quality of dietary fat.
- Published
- 1982
176. Evaluation of urinary cells in acid cholesteryl ester hydrolase deficiency.
- Author
-
Chatterjee S, Castiglione E, Kwiterovich PO Jr, Hoeg JM, and Brewer HB
- Subjects
- Fibroblasts enzymology, Humans, Kidney Tubules enzymology, Leukocytes enzymology, Lipid Metabolism, Lipid Metabolism, Inborn Errors metabolism, Lipids urine, Liver metabolism, Xanthomatosis metabolism, Xanthomatosis urine, Carboxylic Ester Hydrolases deficiency, Cholesterol Esters metabolism, Lipid Metabolism, Inborn Errors urine, Sterol Esterase deficiency
- Abstract
Deficiency in the lysosomal enzyme responsible for cholesteryl ester hydrolysis, acid cholesteryl ester hydrolase (E.C. 3.1.1.13), leads to two clinically recognized diseases: Wolman disease and cholesteryl ester storage including leukocytes, fibroblasts and liver. Analysis of urinary sediment from well characterized cases of Wolman disease and CESD also revealed the shedding of lipid enriched renal tubular cells. Morphologic, enzymic and lipid compositional studies of these cells indicate that the enzyme deficiency observed in fibroblasts and leukocytes from these individuals are reflected in these cells shed in the urine. These findings in renal tubular cells confirm and extend those made in other cell types. These studies indicate that analysis of urinary sediment in suspected cases of acid cholesteryl ester deficiency may provide a meaningful approach for monitoring therapeutic attempts involving enzyme infusion and gene therapy.
- Published
- 1986
- Full Text
- View/download PDF
177. Effect of low-dose alcohol use versus abstention on apolipoproteins A-I and B.
- Author
-
Moore RD, Smith CR, Kwiterovich PO, and Pearson TA
- Subjects
- Adult, Apolipoprotein A-I, Clinical Trials as Topic, Coronary Disease prevention & control, Humans, Male, Middle Aged, Prospective Studies, Random Allocation, Alcohol Drinking, Apolipoproteins A blood, Apolipoproteins B blood, Beer, Lipoproteins, HDL blood, Sexual Abstinence, Sexual Behavior
- Abstract
An inverse association between low to moderate alcohol consumption and coronary heart disease has been demonstrated in epidemiologic studies of diverse design. An attempt was made to determine if this association might be due to an effect of alcohol on apolipoproteins A-I and B and to determine if low-dose alcohol intake might have a potentially protective effect by this mechanism in persons at increased risk for coronary heart disease. To address this, an eight-week prospective randomized clinical trial of abstention versus low-dose alcohol consumption, defined as one beverage per day, was conducted in white men, aged 21 to 60 years, most of whom were patients of a preventive cardiology program. Apolipoprotein A-I levels had a mean increase of 9 mg/dl in the 28 participants who drank alcohol compared with a mean decline of 5 mg/dl in the 28 participants who abstained (p less than 0.005). This association was independent of other cardiovascular risk factors. Low-density lipoprotein (LDL)-B levels had a mean increase of 7 mg/dl in both arms of the trial (NS). However, the ratio of apolipoprotein A-I to LDL-B increased by 4 percent in the drinkers and decreased 10 percent in the abstainers (p less than 0.03). No significant changes in mean levels of total high-density lipoprotein (HDL)-, HDL2-, or HDL3-cholesterol were observed with this low dose of alcohol. This effect on apolipoprotein A-I suggests a possible mechanism by which low-dose alcohol may lower the risk of coronary heart disease.
- Published
- 1988
- Full Text
- View/download PDF
178. Effects of tunicamycin on the binding and degradation of low density lipoproteins and glycoprotein synthesis in cultured human fibroblasts.
- Author
-
Chatterjee S, Kwiterovich PO Jr, and Sekerke CS
- Subjects
- Cells, Cultured, Fibroblasts drug effects, Fibroblasts metabolism, Glucosamine metabolism, Humans, Kinetics, Leucine metabolism, Protein Binding, Glucosamine analogs & derivatives, Glycoproteins biosynthesis, Lipoproteins, LDL metabolism, Tunicamycin pharmacology
- Published
- 1979
179. Stimulation of fatty acid uptake and triglyceride synthesis in human cultured skin fibroblasts and adipocytes by a serum protein.
- Author
-
Cianflone K, Kwiterovich PO, Walsh M, Forse A, Rodriguez MA, and Sniderman AD
- Subjects
- Adipose Tissue metabolism, Biological Transport, Active drug effects, Blood Proteins metabolism, Cells, Cultured, Fibroblasts metabolism, Humans, Skin metabolism, Blood Proteins pharmacology, Fatty Acids, Nonesterified metabolism, Triglycerides biosynthesis
- Abstract
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.
- Published
- 1987
- Full Text
- View/download PDF
180. The clinical, biochemical, and familial presentation of type V hyperlipoproteinemia in childhood.
- Author
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Kwiterovich PO Jr, Farah JR, Brown WV, Bachorik PS, Baylin SB, and Neill CA
- Subjects
- Adult, Amine Oxidase (Copper-Containing) blood, Child, Female, Humans, Hyperlipidemias diet therapy, Lipase blood, Lipoprotein Lipase blood, Lipoproteins, HDL blood, Male, Chylomicrons blood, Hyperlipidemias blood, Hyperlipidemias genetics, Lipoproteins, VLDL blood, Triglycerides blood
- Abstract
Primary type V hyperlipoproteinemia was identified in two preadolescent children. The propositus (kindred N) was a 10-year-old girl with severely creamy plasma, lipemia retinalis, hypertriglyceridemia (triglyceridelevel, 6,800 mg/100 ml), and ypercholesterolemia (cholesterol level, 490 mg/100 ml). Her parents and an 8-year-old sister all had endogenous hypertriglyceridemia (type IV hyperlipoproteinemia). In kindred A, an 11-year-old boy had triglyceride levels as high as 1,100 mg/100 ml and recurrent abdominal pain. His father had type V hyperlipoproteinemia; his mother was normal. All three of his older teenage siblings had type IV hyperlipoproteinemia. The enzymatic activities of lipoprotein lipase (LPL), hepatic triglyceride lipase (HTL), and histaminase (H) were studied in postheparin plasma. The LPL level was low in the children and both parents in kindred N. LPL level in kindred A was normal, except for one child with type IV hyperlipoproteinemia. HTL level was normal to above normal in both kindreds. Most patients had a normal H level, but one parent (kindred N) had no preheparin H and very low levels of postheparin H. There was a strong correlation (r = 0.58, significant at less than 1% level) between release of LPL and H but not between HTL and H (r= 0.22). The mean (+/- 1 S.D.) levels of the enzymes were as follows: LPL, 2.8 +/- 0.7 micronmol/ml/hr in kindred N and 5.4 +/- 2.2 micronmol/ml/hr in kindred A; H, 13.4 +/- 6.8 units/ml in kindred N and 22.0 +/- 11.9 units/ml in kindred A; and HTL, 18.0 +/- 7.1 micronmol/ml/hr in kindred N and 14.9 +/- 6.3 micronmol/ml/hr in kindred A. The enzymatic activities of kindreds N and A were significantly different for LPL (P less than .001) and H (.025 less than P less than .05) but not for HTL. All but one child had at least one high insulin level, which was accompanied by hyperglycemia in two children. The hypertriglyceridemia in all but one child was ameliorated on therapeutic diets. These data suggest that the genetic basis of the hypertriglyceridemia in these two families is different and that hyperchylomicronemia in childhood is not confined to the rara type I hyperliporproteinemia.
- Published
- 1977
181. Apolipoprotein B gene haplotypes. Association between Ag and DNA polymorphisms.
- Author
-
Ma YH, Ladias JA, Bütler R, Schumaker VN, Antonarakis SE, Lusis AJ, Heinzman C, and Kwiterovich PO
- Subjects
- Apolipoproteins B blood, Blotting, Southern, Cholesterol blood, Codon, Deoxyribonucleases, Type II Site-Specific, Female, Genetic Linkage, Humans, Male, Middle Aged, Phenotype, Polymorphism, Restriction Fragment Length, Triglycerides blood, Apolipoproteins B genetics, Arteriosclerosis genetics, DNA genetics, Epitopes genetics, Haplotypes, Polymorphism, Genetic
- Abstract
Berg et al. (Clin Genet 1986;30:515-520) have reported that an Xba I DNA polymorphic site in exon 26 of the apolipoprotein (apo) B gene is associated both with the Ag(x/y) immunochemical polymorphism and with elevated serum lipoprotein levels. Ma et al. (Arteriosclerosis 1987;7:301-305) have reported that the same Xba I polymorphism is associated with a different immunochemical polymorphism, Ag(c/g). To extend and clarify these observations, we have determined the Ag and Xba I polymorphism for 106 individuals. We find that the Xba I restriction fragment length polymorphism is in linkage disequilibrium with both Ag(x/y) and Ag(c/g) loci; thus, all 31 Xba I(X1/X1) genotypes observed in this study are also Ag(y/y). All but one of 22 Xba I(X2/X2) genotypes are also Ag(g/g). For individuals homozygous at either two or three of these loci, it was possible to determine the haplotypes for 128 apo B alleles. Of the eight possible apo B haplotypes, only four were represented in this unambiguous subpopulation, although other minor haplotypes were present in the total population from which it was derived. The identification of major apo B haplotypes in human populations may simplify the search for significant correlations between certain apo B alleles and lipid levels and atherosclerosis.
- Published
- 1988
- Full Text
- View/download PDF
182. Apoproteins B and A-I and coronary artery disease in humans.
- Author
-
Brunzell JD, Sniderman AD, Albers JJ, and Kwiterovich PO Jr
- Subjects
- Adult, Apolipoprotein A-I, Apolipoproteins B, Arteriosclerosis blood, Arteriosclerosis genetics, Coronary Disease blood, Coronary Disease genetics, Humans, Hyperlipidemias complications, Hyperlipidemias genetics, Hyperlipoproteinemias complications, Hyperlipoproteinemias genetics, Lipoproteins, HDL blood, Middle Aged, Apolipoproteins blood, Arteriosclerosis etiology, Coronary Disease etiology
- Published
- 1984
- Full Text
- View/download PDF
183. Neonatal screening for hyperlipidemia.
- Author
-
Kwiterovich PO Jr
- Subjects
- Arteriosclerosis etiology, Cholesterol blood, Humans, Hyperlipidemias genetics, Infant, Infant, Newborn, Lipoproteins, LDL blood, Mass Screening, Hyperlipidemias diagnosis, Infant, Newborn, Diseases diagnosis
- Published
- 1974
184. The Columbia population study. I. Plasma cholesterol and triglyceride levels.
- Author
-
Kwiterovich PO Jr, Chase GA, and Bachorik PS
- Subjects
- Adolescent, Adult, Age Factors, Aged, Child, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Cholesterol blood, Triglycerides blood
- Published
- 1978
185. The lipid hypothesis. Genetic basis.
- Author
-
Glueck CJ and Kwiterovich PO Jr
- Subjects
- Cholesterol blood, Chylomicrons blood, Coronary Disease blood, Coronary Disease genetics, Humans, Hypercholesterolemia genetics, Hyperlipidemias classification, Hyperlipidemias genetics, Hyperlipidemias metabolism, Lipids blood, Lipoproteins, HDL blood, Lipoproteins, HDL metabolism, Lipoproteins, LDL blood, Lipoproteins, LDL metabolism, Lipoproteins, VLDL blood, Lipoproteins, VLDL metabolism, Models, Biological, Triglycerides blood, Coronary Disease etiology, Hyperlipidemias complications
- Published
- 1978
- Full Text
- View/download PDF
186. Uptake and metabolism of lactosylceramide on low density lipoproteins in cultured proximal tubular cells from normal and familial hypercholesterolemic homozygotes.
- Author
-
Chatterjee S, Clarke KS, and Kwiterovich PO Jr
- Subjects
- Biological Transport, Homozygote, Humans, Iodine Radioisotopes, Kinetics, Reference Values, Tritium, Glycosphingolipids metabolism, Hyperlipoproteinemia Type II metabolism, Kidney Tubules, Proximal metabolism, Lactosylceramides metabolism, Lipoproteins, LDL blood
- Abstract
The metabolism of low density lipoproteins (LDL), and LDL modified by reductive methylation (M-LDL) of lysine residues, was studied in proximal tubular (PT) cells both from normal human kidney and from urine of patients with homozygous (LDL receptor-negative) familial hypercholesterolemia (FH). LDL and M-LDL was labeled either in the protein moiety with 125I or in the lactosylceramide moiety with 3H. The binding and degradation of 125I-LDL in normal cells was saturable and displaced by unlabeled LDL but not by M-LDL. The uptake of [3H]lactosylceramide (LacCer) low density lipoprotein in normal renal cells was saturable, and time and temperature-dependent. Exogenously derived [3H]LacCer on LDL was rapidly taken up and catabolized to monoglycosylceramide, or it was utilized for the endogenous synthesis of globotriaosylceramide (trihexosylceramide) and globotetraosylceramide (tetraglycosylceramide). [3H]LacCer M-LDL was taken up less avidly and metabolized less extensively than [3H]LacCer-LDL in normal cells. In homozygous FH renal cells the binding of 125I-LDL was not saturable and not displaced by unlabeled LDL. 125I-LDL degradation did not occur in FH cells. The homozygous FH PT cells took up a 2-fold greater amount of exogenously derived [3H]LacCer on LDL than normal cells. Yet, most of the [3H]LacCer taken up by FH PT cells accumulated as LacCer, and only small amounts were metabolized to monoglycosylceramide, globotriaosylceramide (trihexosylceramide), or globotetraosylceramide (tetraglycosylceramide). When normal and FH PT cells were preincubated with LDL (0-100 micrograms/ml medium), there was a 5-fold increase in cellular LacCer levels in FH cells at saturating levels of LDL, whereas there was about a 50% decrease in LacCer levels in normal cells. While the high affinity binding of LDL was not essential for the delivery of LacCer to cells, the data support the conclusion that LDL binding to the LDL receptor facilitates further LacCer processing and metabolism in normal renal cells. We speculate that [3H] LacCer is taken up by FH homozygous cells via a LDL receptor-independent mechanism and accumulates in the cells without significant metabolism. LacCer taken up by this mechanism contributes to the storage of LacCer in FH PT cells.
- Published
- 1986
187. Glycosphingolipids of human plasma lipoproteins.
- Author
-
Chatterjee S and Kwiterovich PO
- Subjects
- Female, Humans, Hypercholesterolemia blood, Lipoproteins, HDL blood, Lipoproteins, LDL blood, Lipoproteins, VLDL blood, Male, Glycosphingolipids blood, Lipoproteins blood
- Published
- 1976
- Full Text
- View/download PDF
188. Genetic influences on susceptibility to atherosclerosis in the young.
- Author
-
Kwiterovich PO
- Subjects
- Adolescent, Adult, Age Factors, Arteriosclerosis etiology, Arteriosclerosis physiopathology, Child, Child, Preschool, Humans, Hyperlipoproteinemia Type II complications, Hyperlipoproteinemia Type II physiopathology, Infant, Lipoproteins, LDL metabolism, Receptors, LDL metabolism, Risk Factors, Arteriosclerosis genetics, Hyperlipoproteinemia Type II genetics
- Published
- 1989
189. Cholestyramine in type II hyperlipoproteinemia. A double-blind trial.
- Author
-
Levy RI, Fredrickson DS, Stone NJ, Bilheimer DW, Brown WV, Glueck CJ, Gotto AM, Herbert PN, Kwiterovich PO, Langer T, LaRosa J, Lux SE, Rider AK, Shulman RS, and Sloan HR
- Subjects
- Adult, Age Factors, Body Weight, Cholesterol blood, Cholesterol, Dietary, Cholestyramine Resin pharmacology, Clinical Trials as Topic, Female, Humans, Hypercholesterolemia complications, Hyperlipidemias complications, Lipids blood, Lipoproteins antagonists & inhibitors, Male, Middle Aged, Obesity, Placebos, Sex Factors, Triglycerides blood, Xanthomatosis drug therapy, Cholestyramine Resin therapeutic use, Hyperlipidemias drug therapy, Hyperlipidemias genetics, Lipoproteins blood
- Published
- 1973
- Full Text
- View/download PDF
190. Glycolipids and other lipid constituents of normal human liver.
- Author
-
Kwiterovich PO Jr, Sloan HR, and Fredrickson DS
- Subjects
- Adolescent, Adult, Amino Alcohols analysis, Child, Child, Preschool, Cholesterol analysis, Chromatography, Gas, Chromatography, Thin Layer, Fatty Acids analysis, Gangliosides analysis, Glycols analysis, Glycosides analysis, Humans, Liver Diseases classification, Middle Aged, Phospholipids analysis, Sphingomyelins analysis, Triglycerides analysis, Glycolipids analysis, Lipids analysis, Liver analysis
- Abstract
An analysis of the lipids in normal human liver is presented which is particularly designed to assist in the classification and study of lipid-storage diseases. Special emphasis has been given to a determination of the quantity and composition of the neutral glycolipid classes and predominant ganglioside (Gm(3)). The neutral glycolipid content of 0.19 (sd +/- 0.11) micro moles per g wet tissue, represented 0.4% of the total lipid in liver. Ceramide dihexoside was the most abundant neutral glycolipid. The mean contents of cholesterol, glycerides, and total phospholipids were 3.9, 19.5, and 25.1 mg/g wet weight, respectively. The relative amounts of seven different phospholipid classes were also determined; these included cardiolipin (diphosphatidylglycerol), which constituted 3.9% of the liver phospholipids.
- Published
- 1970
191. The National Heart Institute Twin Study.
- Author
-
Feinleib M, Havlik RJ, Kwiterovich PO, Tillotson J, and Garrison RJ
- Subjects
- Adult, Anthropometry, Epidemiology, Female, Humans, Male, Middle Aged, National Institutes of Health (U.S.), Pregnancy, Twins, United States, Heart Diseases genetics
- Published
- 1970
- Full Text
- View/download PDF
192. Neonatal diagnosis of familial type-II hyperlipoproteinaemia.
- Author
-
Kwiterovich PO Jr, Levy RI, and Fredrickson DS
- Subjects
- Child, Preschool, Cholesterol blood, Diet Therapy, Electrophoresis, Paper, Follow-Up Studies, Humans, Hyperlipidemias therapy, Infant, Infant, Newborn, Lipoproteins, HDL blood, Lipoproteins, LDL blood, Lipoproteins, VLDL blood, Pedigree, Ultracentrifugation, Umbilical Arteries, Umbilical Veins, Hyperlipidemias diagnosis, Hyperlipidemias genetics, Infant, Newborn, Diseases diagnosis
- Published
- 1973
- Full Text
- View/download PDF
193. Type IV hyperlipoproteinaemia.
- Author
-
Kwiterovich PO Jr and Margolis S
- Subjects
- Child, Cholesterol blood, Chylomicrons blood, Clofibrate therapeutic use, Diagnosis, Differential, Diet Therapy, Dietary Carbohydrates, Humans, Hyperlipidemias complications, Hyperlipidemias diagnosis, Hyperlipidemias drug therapy, Insulin metabolism, Lipoproteins, HDL blood, Lipoproteins, LDL blood, Lipoproteins, VLDL blood, Norethindrone therapeutic use, Pancreatitis complications, Phenotype, Triglycerides blood, Triglycerides metabolism, Uric Acid blood, Vascular Diseases complications, Xanthomatosis complications, Hyperlipidemias blood, Hyperlipidemias genetics
- Published
- 1973
- Full Text
- View/download PDF
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