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Behavioral versus genetic determination of lipoproteins andidentical twins discordant for exercise

Description: Lipoprotein and weight differences between vigorously active and sedentary MZ twins are used to: (1) estimate the effects of training while controlling for genotype; (2) estimate genetic concordance in the presence of divergent lifestyles.
Date: June 1, 2004
Creator: Williams, Paul T.; Blanche, Patricia J. & Krauss, Ronald M.
Partner: UNT Libraries Government Documents Department

Primate-specific evolution of an LDLR enhancer

Description: Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.
Date: December 1, 2005
Creator: Wang, Qian-Fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles et al.
Partner: UNT Libraries Government Documents Department

Concordant lipoprotein and weight responses to dietary fat changein identical twins with divergent exercise levels

Description: Background/Objective: The purpose of this study is to testthe extent that individual lipoprotein responses to diet can beattributed to genes in the presence of divergent exercise levels.Design:Twenty-eight pairs of male monozygotic twins (one mostly sedentary, theother running an average of 50 km/week more than the sedentary twin) wentfrom a 6-week 40 percent fat diet to a 6-week 20 percent fat diet in acrossover design. The diets reduced fat primarily by reducing saturatedand polyunsaturated fat (both from 14 percent to 4 percent), whileincreasing carbohydrate intake from 45 percent to 65 percent. Results:Despite the twins' differences in physical activity, the dietarymanipulation produced significantly correlated changes (P<0.05) in thetwin's total cholesterol (r=0.56), low-density lipoprotein(LDL)-cholesterol (r=0.70), large, buoyant LDL (Sf7-12, r=0.52), apo A-I(r=0.49), Lp(a) (r=0.49), electrophoresis measurements of LDL-I (LDLsbetween 26 and 28.5 nm diameter, r=0.48), LDL-IIB (25.2-24.6 nm, r=0.54),LDL-IV (22-24.1 nm, r=0.50), and body weights (r=0.41). Replacing fatswith carbohydrates significantly decreased the size and ultracentrifugeflotation rate of the major LDL, the LDL mass concentrations of Sf7-12,LDL-I, high-density lipoprotein (HDL)-cholesterol and apo A-I, andsignificantly increased LDL-IIIA (24.7-25.5 nm diameter) and Lp(a).Conclusions: Even in the presence of extreme exercise difference, genessignificantly affect changes in LDL, apo A-I, Lp(a) and body weight whendietary fats are replaced with carbohydrates.
Date: June 1, 2004
Creator: Williams, Paul T.; Blanche, Patricia J.; Rawlings, Robin & Krauss, Ronald M.
Partner: UNT Libraries Government Documents Department

A common allele on chromosome 9 associated with coronary heartdisease

Description: Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.
Date: March 1, 2007
Creator: McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan; Stewart, Alexandre; Roberts, Robert; Cox, David R. et al.
Partner: UNT Libraries Government Documents Department

Cultured human astrocytes secrete large cholesteryl ester- andtriglyceride-rich lipoproteins along with endothelial lipase

Description: We cultured normal human astrocytes and characterized their secreted lipoproteins. Human astrocytes secreted lipoproteins in the size range of plasma VLDL (Peak 1), LDL (Peak 2), HDL (Peak 3) and a smaller peak (Peak 4), as determined by gel filtration chromatography, nondenaturing gradient gel electrophoresis and transmission electron microscopy. Cholesterol enrichment of astrocytes led to a particular increase in Peak 1. Almost all Peak 2, 3 and 4 cholesterol and most Peak 1 cholesterol was esterified (unlike mouse astrocyte lipoproteins, which exhibited similar peaks but where cholesterol was predominantly non-esterified). Triglycerides were present at about 2/3 the level of cholesterol. LCAT was detected along with two of its activators, apolipoprotein (apo) A-IV and apoC-I. ApoA-I and apoA-II mRNA and protein were absent. ApoJ was present equally in all peaks but apoE was present predominantly in peaks 3 and 4. ApoB was not detected. The electron microscopic appearance of Peak 1 lipoproteins suggested partial lipolysis leading to the detection of a heparin-releasable triglyceride lipase consistent with endothelial lipase. The increased neuronal delivery of lipids from large lipoprotein particles, for which apoE4 has greater affinity than does apoE3, may be a mechanism whereby the apoE {var_epsilon}4 allele contributes to neurodegenerative risk.
Date: December 1, 2003
Creator: Yang, Lin; Liu, Yanzhu; Forte, Trudy M.; Chisholm, Jeffrey W.; Parks, John S. & Shachter, Neil S.
Partner: UNT Libraries Government Documents Department

Relationship of adiposity to the population distribution of plasma triglyceride concentrations in vigorously active men and women

Description: Context and Objective: Vigorous exercise, alcohol and weight loss are all known to increase HDL-cholesterol, however, it is not known whether these interventions raise low HDL as effectively as has been demonstrated for normal HDL. Design: Physician-supplied medical data from 7,288 male and 2,359 female runners were divided into five strata according to their self-reported usual running distance, reported alcohol intake, body mass index (BMI) or waist circumference. Within each stratum, the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles for HDL-cholesterol were then determined. Bootstrap resampling of least-squares regression was applied to determine the cross-sectional relationships between these factors and each percentile of the HDL-cholesterol distribution. Results: In both sexes, the rise in HDL-cholesterol per unit of vigorous exercise or alcohol intake was at least twice as great at the 95th percentile as at the 5th percentile of the HDL-distribution. There was also a significant graded increase in the slopes relating exercise (km run) and alcohol intake to HDL between the 5th and the 95th percentile. Men's HDL-cholesterol decreased in association with fatness (BMI and waist circumference) more sharply at the 95th than at the 5th percentile of the HDL-distribution. Conclusions: Although exercise, alcohol and adiposity were all related to HDL-cholesterol, the elevation in HDL per km run or ounce of alcohol consumed, and reduction in HDL per kg of body weight (men only), was least when HDL was low and greatest when HDL was high. These cross-sectional relationships support the hypothesis that men and women who have low HDL-cholesterol will be less responsive to exercise and alcohol (and weight loss in men) as compared to those who have high HDL-cholesterol.
Date: December 21, 2002
Creator: Williams, Paul T.
Partner: UNT Libraries Government Documents Department

Structure of the LDL receptor extracellular domain at endosomalpH

Description: The structure of the low-density lipoprotein receptor extracellular portion has been determined. The document proposes a mechanism for the release of lipoprotein in the endosome. Without this release, the mechanism of receptor recycling cannot function.
Date: September 5, 2002
Creator: Rudenko, Gabby; Henry, Lisa; Henderson, Keith; Ichtchenko,Konstantin; Brown, Michael S.; Goldstein, Joseph L. et al.
Partner: UNT Libraries Government Documents Department


Description: Epinephrine injection has been shown to produce a two and three fold increase of the higher Sf classes of serum lipoproteins in the rabbit. The previously observed elevation of serum lipids was confirmed. The hyperlipoproteinemia following epinephrine injection appears about the same time as in certain conditions of stress. (auth)
Date: November 21, 1957
Creator: Young, W. & Hayes, T.L.
Partner: UNT Libraries Government Documents Department

An Ultracentrifugal Method for the Determination of Serum Lipoproteins

Description: A convenient method was developed for the ultracentrifugal analysis of all classes of serum lipoproteins which requires a minimum of time, work and materials. The method utilizes the principle of flotation of lipoproteins in a medium of greater density than their own hydrated density. In this procedure the isolation and the analysis of lipoproteins are done in a NaBr mediumn of density 1.20 g/ml. The advantages of this procedure are compared with other available methods, and its application to studies on serum lipoprotein is discussed. (auth)
Date: September 29, 1958
Creator: Del Gatto, L.; Lindgren, F. T. & Nichols, A. V.
Partner: UNT Libraries Government Documents Department

Isolation and Partial Characterization of Lecithin Cholesterol Acyltransferase and High Density Lipoprotein from Hog Plasma

Description: Lecithin:cholesterol acyltransferase (LCAT) was purified 30,000-fold from hog plasma in a homogeneous state as indicated by polyacrylamide gel electrophoresis. The purified enzyme had an apparent molecular weight of 66,000 and was found to contain about 21.4 percent (w/w) carbohydrate. The properties of hog LCAT including amino acid composition were compared with human LCAT. High density lipoprotein (HDL) was isolated from the hog plasma by an immunoaffinity column chromatography. The isolated HDL showed nearly identical lipid-protein composition although it contained additional protein components when it was compared to HDL isolated by a traditional method involving ultracentrifugation.
Date: May 1984
Creator: Park, Yong Bok
Partner: UNT Libraries

Low density lipoprotein subclasses and response to a low-fat diet in healthy men

Description: Lipid and lipoprotein response to reduced dietary fat intake was investigated in relation to differences in distribution of LDL subclasses among 105 healthy men consuming high-fat (46%) and low-fat (24%) diets in random order for six weeks each. On high-fat, 87 subjects had predominantly large, buoyant LDL as measured by gradient gel electrophoresis and confirmed by analytic ultracentrifugation (pattern A), while the remainder had primarily smaller, denser LDL (pattern B). On low-fat, 36 men changed from pattern A to B. Compared with the 51 men in the stable A group, men in the stable B group (n = 18) had a three-fold greater reduction in LDL cholesterol and significantly greater reductions in plasma apoB and mass of intermediate (LDL II) and small (LDL III) LDL subtractions measured by analytic ultracentrifugation. In both stable A and change groups, reductions in LDL-cholesterol were not accompanied by reduced plasma apoB, consistent with the observation of a shift in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid-depleted (LDL III and IV) subfractions, without significant change in particle number. Genetic and environmental factors influencing LDL subclass distributions thus may also contribute substantially to interindividual variation in response to a low-fat diet.
Date: November 1, 1994
Creator: Krauss, R.M. & Dreon, D.M.
Partner: UNT Libraries Government Documents Department

Analysis of individual lipoproteins and liposomes

Description: We describe the application of single molecule detection (SMD) technologies for the analysis of natural (serum lipoproteins) and synthetic (liposomes) transport systems. The need for advanced analytical procedures of these complex and important systems is presented with the specific enhancements afforded by SMD with flowing sample streams. In contrast to bulk measurements which yield only average values, measurement of individual species allows creation of population histograms from heterogeneous samples. The data are acquired in minutes and the analysis requires relatively small sample quantities. Preliminary data are presented from the analysis of low density lipoprotein, and multilamellar and unilamellar vesicles.
Date: August 1, 1997
Creator: Robbins, D.L.; Keller, R.A. & Nolan, J.P.
Partner: UNT Libraries Government Documents Department

Isolation, Physical and Chemical Characterization of Lecithin:Cholesterol Acyltransferase from Human Plasma

Description: The physiological role of LCAT has been the subject of a number of recent articles (Glomset, 1979; Nilsson-Ehle et al., 1980). According to most current theories, the enzyme functions in combination with high-density lipoproteins in the reverse cholesterol transport pathway which presumably returns peripheral cholesterol to the liver where cholesterol catabolism takes place. Despite the exciting potential for studies on the catalytic function and the nature of the enzyme-substrate complex, the mechanism of action of LCAT remains largely unexplored. The relatively slow progress in the elucidation of the LCAT reaction mechanism is likely to be due to the difficulties in the isolation of the enzyme in sufficient quantities. Consequently, considerably less is known about the physical and chemical properties of the enzyme. Therefore, the first objective of this investigation was to isolate and purify sufficient amount of enzyme for subsequent characterization studies. The second objective of this investigation was to characterize the physical properties of the enzyme by techniques including analytical ultracentrifugation, ultraviolet spectroscopy, and circular dichroism and fluorescence spectroscopy. The third objective of this investigation was to characterize the chemical properties of the enzyme which deals with the amino acid and carbohydrate composition and with some basic structural features that are related to the chemical composition of LCAT.
Date: December 1981
Creator: Chong, Kui Song
Partner: UNT Libraries

Characterization and Reconstruction of Nanolipoprotein Particles (Nlps) by Cryo-EM and Image Reconstruction

Description: Nanolipoprotein particles (NLPs) are small 10-20 nm diameter assemblies of apolipoproteins and lipids. At Lawrence Livermore National Laboratory (LLNL), they have constructed multiple variants of these assemblies. NLPs have been generated from a variety of lipoproteins, including apolipoprotein Al, apolipophorin III, apolipoprotein E4 22K, and MSP1T2 (nanodisc, Inc.). Lipids used included DMPC (bulk of the bilayer material), DMPE (in various amounts), and DPPC. NLPs were made in either the absence or presence of the detergent cholate. They have collected electron microscopy data as a part of the characterization component of this research. Although purified by size exclusion chromatography (SEC), samples are somewhat heterogeneous when analyzed at the nanoscale by negative stained cryo-EM. Images reveal a broad range of shape heterogeneity, suggesting variability in conformational flexibility, in fact, modeling studies point to dynamics of inter-helical loop regions within apolipoproteins as being a possible source for observed variation in NLP size. Initial attempts at three-dimensional reconstructions have proven to be challenging due to this size and shape disparity. They are pursuing a strategy of computational size exclusion to group particles into subpopulations based on average particle diameter. They show here results from their ongoing efforts at statistically and computationally subdividing NLP populations to realize greater homogeneity and then generate 3D reconstructions.
Date: June 7, 2007
Creator: Pesavento, J B; Morgan, D; Bermingham, R; Zamora, D; Chromy, B; Segelke, B et al.
Partner: UNT Libraries Government Documents Department

Studies of the Interaction of LCAT with Lipoprotein Substrates in HDL Deficient Plasma Systems

Description: Enzymatic and lipid transfer reactions involved in reverse cholesterol transport were studied in HDL deficient plasma systems. Fasting plasma samples were obtained from control and cholesterol fed guinea pigs as well as from a fish eye disease patient and were used to localize the enzyme LCAT among plasma lipoproteins (VLDL, LDL, and HDL). In both guinea pig and fish eye disease patient plasma, the LCAT activity was found in association with the HDL type particles. Cholesterol feeding in guinea pigs altered the properties of lipoprotein substrates for LCAT resulting in some changes, specifically: 1) decreased fractional rate of plasma cholesterol esterification and, 2) lower transfer of free cholesterol (FC) and esterified cholesterol (CE) within the lipoprotein fractions.
Date: August 1989
Creator: Paranjape, Sulabha
Partner: UNT Libraries

The use of transgenic animals to study lipoprotein metabolism

Description: The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.
Date: December 1, 1993
Creator: Rubin, E.M. & Plump, A.S.
Partner: UNT Libraries Government Documents Department

Studies on Lipoprotein Specificity of Human Plasma Lecithin Cholesterol Acyltransferase

Description: Huian plasma high-density lipoprotein (HDL) were isolated by a procedure employing polyanion precipitation and column chromatography. Lipid and protein composition of the HDL isolated by this method was found to be similar to another HDL preparation isolated by ultracentrifugation. However, minor differences were noted, including a higher phospholipid and apoproteinE content and lower triglyceride content of the HDL isolated by column chromatography. Four subfraction of HDL were obtained following chromatography on an anion exchange column. The subfraction four had the highest esterified to free cholesterol ratio, the second highest phospholipid to unesterified cholesterol, and the lowest molecular weight. In addition it was consistently coincided with lecithin: cholesterol acyltransferase (LCAT) activity and found to be the best substrate for the enzyme.
Date: May 1981
Creator: Jahani, Mehrnoosh
Partner: UNT Libraries

Ernest Orlando Berkeley National Laboratory - Fundamental and applied research on lean premixed combustion

Description: Ernest Orland Lawrence Berkeley National Laboratory (Berkeley Lab) is the oldest of America's national laboratories and has been a leader in science and engineering technology for more than 65 years, serving as a powerful resource to meet Us national needs. As a multi-program Department of Energy laboratory, Berkeley Lab is dedicated to performing leading edge research in the biological, physical, materials, chemical, energy, environmental and computing sciences. Ernest Orlando Lawrence, the Lab's founder and the first of its nine Nobel prize winners, invented the cyclotron, which led to a Golden Age of particle physics and revolutionary discoveries about the nature of the universe. To this day, the Lab remains a world center for accelerator and detector innovation and design. The Lab is the birthplace of nuclear medicine and the cradle of invention for medical imaging. In the field of heart disease, Lab researchers were the first to isolate lipoproteins and the first to determine that the ratio of high density to low density lipoproteins is a strong indicator of heart disease risk. The demise of the dinosaurs--the revelation that they had been killed off by a massive comet or asteroid that had slammed into the Earth--was a theory developed here. The invention of the chemical laser, the unlocking of the secrets of photosynthesis--this is a short preview of the legacy of this Laboratory.
Date: July 7, 1999
Creator: Cheng, Robert K.
Partner: UNT Libraries Government Documents Department

Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

Description: This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.
Date: June 14, 2006
Creator: Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F. & Forte, Trudy M.
Partner: UNT Libraries Government Documents Department

INEL BNCT Research Program annual report 1994

Description: This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1994. Contributions from the principal investigators about their individual projects are included, specifically, chemistry (pituitary tumor studies, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, ICP-AES analysis of biological samples), physics (treatment planning software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (small and large animal models tissue studies and efficacy studies). Information on the potential toxicity of BSH and BPA is presented and results of 21 spontaneous tumor bearing dogs that have been treated with BNCT at Brookhaven National Laboratory (BNL) are discussed. Several boron carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors is presented. Highlights from the First International Workshop on Accelerator-Based Neutron Sources for BNCT are included. Selected papers have been indexed separately for inclusion in the Energy Science and Technology Database.
Date: November 1, 1995
Creator: Venhuizen, J.R.
Partner: UNT Libraries Government Documents Department

A prominent large high-density lipoprotein at birth enriched in apolipoprotein C-I identifies a new group of infancts of lower birth weight and younger gestational age

Description: Because low birth weight is associated with adverse cardiovascular risk and death in adults, lipoprotein heterogeneity at birth was studied. A prominent, large high-density lipoprotein (HDL) subclass enriched in apolipoprotein C-I (apoC-I) was found in 19 percent of infants, who had significantly lower birth weights and younger gestational ages and distinctly different lipoprotein profiles than infants with undetectable, possible or probable amounts of apoC-I-enriched HDL. An elevated amount of an apoC-I-enriched HDL identifies a new group of low birth weight infants.
Date: October 1, 2003
Creator: Kwiterovich Jr., Peter O.; Cockrill, Steven L.; Virgil, Donna G.; Garrett, Elizabeth; Otvos, James; Knight-Gibson, Carolyn et al.
Partner: UNT Libraries Government Documents Department