PubMed Health⌕ Search

Biomedical subjects

R M Krauss

Publications and source records attributed to R M Krauss.

At least 19 recordsLinked to original sources
PubMed1992

Linkage of atherogenic lipoprotein phenotype to the low density lipoprotein receptor locus on the short arm of chromosome 19.

The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a predominance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reductions in high density lipoprotein, and a 3-fold increased risk of myocardial infarction. Significant two-point linkage was found between ALP and the LDL receptor locus on the short arm of chromosome 19 in 51 relatives of nine probands with ALP pattern B. The maximum logarithm of odds (LOD) score of 4.07 was observed at a recombination fraction of 0.04, assuming 100% penetrance of ALP pattern B, and 4.27 at a recombination fraction of zero, assuming 90% penetrance of pattern B. Haplotyping data and multipoint linkage analysis suggest that the gene [named ATHS for atherosclerosis susceptibility (lipoprotein-associated)] responsible for ALP is located distal to D19S76 near or at the LDL receptor locus. This result suggests the possibility that genetic variation at the LDL receptor locus or a closely linked locus on chromosome 19 may be responsible for metabolic alterations in ALP pattern B that account for a substantial proportion of the familial predisposition to coronary artery disease in the general population.

Arteriosclerosis↗
PubMed1992

Bimodality of plasma apolipoprotein B levels in familial combined hyperlipidemia.

To investigate possible genetic influences on plasma apolipoprotein (apo) B levels in familial combined hyperlipidemia (FCHL), commingling analysis was performed on data from seven large kindreds, including 183 individuals. The overall frequency distribution of apo B was skewed and was compatible with the presence of two normally distributed subdistributions (mean values, 117 and 172 mg/dl). The analysis was repeated after stratification of individuals by low density lipoprotein (LDL) subclass phenotype. Among subjects with phenotype A (predominance of large, buoyant LDL), a single apo B distribution was found (mean, 115 mg/dl). Among subjects with phenotype B (predominance of small, dense LDL), the distribution was bimodal, with mean values, 116 and 167 mg/dl, similar to the unstratified data set. Thus the skewing of the overall apo B distribution in FCHL family members may be due to a distinct subset of individuals with phenotype B who are genetically susceptible to even higher elevations of apo B. The higher apo B/phenotype B subjects also showed significantly higher levels of triglyceride and LDL-cholesterol than the lower apo B/phenotype B subjects. The lower apo B/phenotype B subjects had higher triglyceride and lower LDL-cholesterol than the phenotype A subjects. The enhanced information regarding apo B and lipid levels in the three subgroups of individuals identified here may facilitate a better understanding of genetic susceptibility to coronary heart disease.

Adolescent↗
PubMed1992

Differential effects of nicotinic acid in subjects with different LDL subclass patterns.

Twenty-six subjects (20 male, 6 female) at high risk for CAD events were treated with moderate doses of nicotinic acid to investigate whether there was a differential lipoprotein response in patients with different LDL subclass patterns. Subjects were selected to have either pattern A (predominance of large LDL, peak particle diameter greater than 262 A, n = 9) or pattern B (predominance of small LDL, peak particle diameter less than 255 A, n = 17) as assessed by 2-16% gradient gel electrophoresis of plasma. Nicotinic acid dose was similar in pattern A (2111 +/- 651 mg/day) and pattern B subjects (1875 +/- 698 mg/day). Total cholesterol and LDL cholesterol decreased by similar amounts in pattern A (-41 +/- 26 mg/dl and -37 +/- 18 mg/dl) and pattern B (-51 +/- 44 mg/dl and -44 +/- 45 mg/dl) subjects. Triglycerides tended to be reduced more in pattern B subjects (-100 +/- 175 mg/dl) compared to pattern A subjects (-23 +/- 34 mg/dl) although this difference was not statistically significant (P = 0.08 for triglycerides log transformed). HDL cholesterol increased significantly more in the pattern B group (11.9 +/- 14.2 mg/dl) compared to pattern A subjects (0.7 +/- 8.5 mg/dl), (P less than 0.04). Similarly, LDL particle diameter increased significantly more in the pattern B subjects (9.8 +/- 6.9 A) compared to the pattern A subjects (3.6 +/- 3.0 A), (P less than 0.02). All pattern B subjects who achieved a plasma triglyceride less than 140 mg/dl converted to pattern A.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗
PubMed1992

Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size.

Oxidative modification of low density lipoproteins (LDL) has been implicated in the sequence of events leading to fatty streak formation in the arterial intima. Increased oxidative modifications of dense versus buoyant LDL particles could contribute to increased atherosclerosis associated with lipoprotein profiles enriched in small, dense LDL. In the present studies, we compared rates of copper-induced oxidative changes for six LDL subfractions ranging in density from 1.023 to 1.053 g/ml and mean particle diameter from 282 +/- 10 to 245 +/- 3. Rates of formation of thiobarbituric acid-reactive substances (TBARS), as indicated by the time required for half-maximal TBARS formation (T1/2max), decreased with increasing density and decreasing particle diameter to a minimum in fraction 5 (d = 1.046 g/ml, diameter = 250 +/- 5) (P = 0.007). In parallel studies using unfractionated LDL (d = 1.019-1.063 g/ml), T1/2max values were inversely correlated with the predominant LDL species diameter as determined by 2-16% gradient gel electrophoresis (P less than 0.05), consistent with the involvement of subclass composition in determining oxidative behavior. In separate experiments, subfraction differences in oxidation rates as assessed by TBARS formation were verified by the finding of similarly dispartate changes in fluorescence intensity and anionic electrophoretic mobility. T1/2max values were not related to LDL contents of alpha-tocopherol, beta-carotene, protein, triglycerides or phospholipids, but were significantly correlated with unesterified cholesterol content (r = 0.46; P less than 0.001) and were inversely associated with cholesteryl ester content (r = 0.28; P less than 0.05). The positive association of T1/2max with unesterified cholesterol suggests that this constituent may impart resistance to oxidative modification, possibly by altering properties of the surface monolayer where it resides.

Adult↗
PubMed1992

Effects of weight-loss by exercise and by diet on apolipoproteins A-I and A-II and the particle-size distribution of high-density lipoproteins in men.

We studied separately the effects of weight-loss by dieting or by running on apolipoprotein (apo) A-I, apo A-II, and high-density lipoprotein (HDL) subfractions in sedentary, moderately overweight men assigned at random into three groups: exercise without calorie restriction, calorie restriction without exercise, and control. The absorbance of protein-stained polyacrylamide gradient gels was used as an index of mass concentrations for five HDL subclasses that have been identified by their particle sizes: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12.9 nm). During the 1-year trial, the exercisers ran (mean +/- SD) 15.6 +/- 9.1 km/wk, and the dieters reported eating 340 +/- 71 fewer calories per day than at baseline. Total body weight and fat weight were both reduced significantly more in dieters (-7.2 +/- 4.1 and -6.2 +/- 4.1 kg, respectively) and in exercisers (-4.0 +/- 3.9 and -4.6 +/- 3.5 kg) than in controls (0.6 +/- 3.7 and -0.7 +/- 2.7 kg). As compared with mean changes in controls, exercisers and dieters each decreased HDL3b and increased HDL2b. Exercisers also significantly increased plasma apo A-I concentrations. Analysis of covariance was used to statistically adjust the mean lipoprotein changes for the effects of weight-loss. The adjustment eliminated the significant reductions in HDL3b and the significant increases in HDL2b in exercisers and dieters, and it eliminated the significant increase in apo A-I in exercisers. When adjusted, the dieters' mean changes in HDL2b had significantly decreased relative to those of both exercisers and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The metabolic impact of oral contraceptives.

The hormonal components of oral contraceptives exert major effects on plasma lipoprotein metabolism. Estrogens may increase production of plasma triglycerides, leading to increased levels of very low-density lipoproteins, but they may also reduce levels of cholesterol-enriched and potentially atherogenic intermediate- and low-density lipoproteins. Furthermore, estrogens increase levels of high-density lipoproteins (HDLs), particularly the HDL2 subspecies, an effect linked to reduced mortality rates from cardiovascular disease in postmenopausal women receiving hormone replacement therapy. All combination oral contraceptives in use in the United States tend to raise levels of plasma triglycerides, low-density lipoprotein, and HDL3 to varying degrees. In contrast, changes in HDL and HDL2 reflect the combined effects of estrogen dose and relative androgenicity of the progestin component. Although in general, the lipoprotein changes are greater in magnitude with higher dose oral contraceptive preparations, they can be significant in lower dose preparations as well. Oral contraceptives also affect carbohydrate metabolism, primarily through the activity of progestin. Studies have demonstrated insulin resistance, rises in plasma insulin, and relative glucose intolerance by means of curve analysis of glucose tolerance tests. These effects are far less pronounced with lower dose preparations and with formulations using the newer progestins.

Blood Vessels↗
PubMed1992

Coordination of knowledge in communication: effects of speakers' assumptions about what others know.

Two pairs of studies examined effects of perspective taking in communication, using a 2-stage methodology that first obtained people's estimates of the recognizability to others of specific stimuli (public figures and everyday objects) and then examined the effects of these estimates on message formulation in a referential communication task. Ss were good at estimating stimulus identifiability but were biased in the direction of their own knowledge. The amount of information in a referring expression varied inversely with the perceived likelihood that addresses could identify the target stimulus. However, effects were less strong than anticipated. Although communicators do take others' knowledge into account, the extent to which they do so involves a trade-off with other sorts of information in the communicative situation.

Adolescent↗
PubMed1992

Familial correlations of HDL subclasses based on gradient gel electrophoresis.

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the familial correlations of high density lipoprotein (HDL) subclasses for 150 offspring in 47 nuclear families. The absorbance of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). Parent-offspring correlations were computed for two different characterizations of the parents: 1) by sex (i.e., mother versus father) and 2) by their relative values (highest versus lowest HDL). Sibling resemblance was assessed by using the intraclass correlations coefficient. Family members were significantly related for the following subclasses: HDL3c (sibling and father-offspring), HDL3b (sibling), HDL3a (sibling and mother-offspring), HDL2a (mother-offspring), and HDL2b (sibling, father-offspring, and mother-offspring). The offsprings' HDL3c and HDL2b values were more strongly related to their fathers' than to their mothers' values, whereas their HDL2a levels were more strongly related to their mothers' than their fathers' values. In addition, fathers' HDL2b levels were inversely correlated with the offsprings' HDL3b. The parents' HDL subclass levels were more strongly related to subclass levels of their younger (< or = 20 years) than their older offspring. Among all subclasses, HDL2b showed the strongest parent-offspring relation, with the parents' HDL values accounting for over 30% of the variance in offsprings' HDL2b.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

LDL subclass phenotypes and triglyceride metabolism in non-insulin-dependent diabetes.

Plasma low density lipoprotein (LDL) comprises multiple discrete subclasses differing in size, density, and chemical composition. A common, heritable phenotype characterized by the predominance of small, dense LDL particles (LDL subclass phenotype B) is associated with relatively increased concentrations of plasma triglycerides, reduced levels of high density lipoprotein, and increased risk of coronary artery disease in comparison with subjects with larger LDL (LDL subclass phenotype A). Population studies have indicated that approximately 20-30% of adult men have phenotype B, and another 15-20% have LDL of intermediate size. The lipid changes in phenotype B are similar to those that have been observed in patients with non-insulin-dependent diabetes mellitus (NIDDM). In the present study, we have assessed LDL subclass phenotypes in normolipidemic men with NIDDM and in age-matched control subjects who had similar lipid levels. There was a greater than twofold increase in the percentage of individuals with the LDL B phenotype in the NIDDM subjects. The LDL B phenotype was associated with higher plasma triglyceride levels and a trend toward lower high density lipoprotein cholesterol levels compared with the LDL A phenotype in the NIDDM subjects, as has been previously observed in control groups. Indices of diabetic control, such as fasting and hemoglobin A1 levels, were similar regardless of LDL phenotype pattern, suggesting that glycemic control was not likely to account for the increase in the LDL B phenotype. In both control and NIDDM subjects, the clearance of triglyceride-rich lipoproteins was slowed in the subjects with the LDL phenotype B compared with those with the A phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women.

We examined the relations of gender and lipoproteins to subclasses of high density lipoproteins (HDLs) in a cross-sectional sample of moderately overweight men (n = 116) and women (n = 78). The absorbance of protein-stained polyacrylamide gradient gels was used as an index of mass concentrations of HDL at intervals of 0.01 nm across the entire HDL particle size range (7.2-12 nm). At least five HDL subclasses have been identified by their particle sizes: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). Men had significantly higher HDL3b and significantly lower HDL2a and HDL2b than did women. Correlations of HDL subclasses with concentrations of other lipoprotein variables were generally as strong for gradient gel electrophoresis as for analytical ultracentrifugation measurements of HDL particle distributions. In both sexes, high levels of HDL3b were associated with coronary heart disease risk factors, including high concentrations of triglycerides, apolipoprotein B, small low density lipoproteins, intermediate density lipoproteins, and very low density lipoproteins and low concentrations of HDL2 cholesterol and HDL2 mass. Plasma concentrations of HDL3 cholesterol were unrelated to protein-stained HDL3b levels. HDL3 cholesterol concentrations also did not exhibit the sex difference or the relations with lipoprotein concentrations that characterized HDL3b. Thus, low HDL3b levels may contribute in part to the low heart disease risk in men and women who have high HDL cholesterol. Measurements of HDL3 cholesterol may not identify clinically important relations involving HDL3b.

Adult↗
PubMed1992

Reduced HDL2 cholesterol subspecies and elevated postheparin hepatic lipase activity in older men with abdominal obesity and asymptomatic myocardial ischemia.

Silent myocardial ischemia (SI), an asymptomatic manifestation of coronary artery disease (CAD), was identified in 10% of apparently healthy nonsmoking, nondiabetic older (60 +/- 7 years, mean +/- SD) men with normal plasma cholesterol levels. We hypothesized that in the absence of other major risk factors for CAD, the men with SI would have reduced plasma levels of high density lipoprotein (HDL) and HDL2 subspecies due to an upper-body fat distribution (waist-to-hip ratio [WHR]), hyperinsulinemia, and abnormal postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Compared with 47 normal control subjects of similar age, obesity, and maximal aerobic capacity, the 18 men with SI had higher plasma triglyceride (TG) (162 +/- 71 versus 102 +/- 39 mg/dl, p less than 0.001) and lower HDL-C (33 +/- 6 versus 37 +/- 7 mg/dl, p less than 0.02) levels with no difference in low density lipoprotein cholesterol level. The HDL2b and HDL2a subspecies measured by gradient gel electrophoresis were also lower in the men with SI (p less than 0.01). The plasma glucose and insulin responses during an oral glucose tolerance test were the same in both groups. Postheparin plasma HL activity was significantly higher in 12 men with SI than in 41 control subjects (34 +/- 8 versus 27 +/- 10 mumol/ml.hr-1, p less than 0.03) and was correlated with log insulin area (r = 0.36, p less than 0.05) and WHR (r = 0.32, p less than 0.05) in the control subjects but not in the men with SI. In the control group, the percent HDL2b subspecies was correlated inversely with postheparin plasma HL activity (r = -0.46, p less than 0.01, n = 41) as well as WHR (r = -0.49, p less than 0.001, n = 47) and log insulin area (r = -0.37, p less than 0.05, n = 47) but not in the men with SI. Postheparin LPL activity was the same in both groups of men and did not correlate with HDL, WHR, insulin, or plasma TG levels. As the control subjects and men with SI had comparable degrees of abdominal obesity and hyperinsulinemia, these results suggest that the reduced HDL-C levels in men with SI may be related to elevations in HL activity. Thus, abdominal obesity, hyperinsulinemia, elevated TG levels, and low HDL-C and HDL2 subspecies levels may predispose these older men to atherosclerosis.

Abdomen↗
PubMed1992

Development of a proton nuclear magnetic resonance spectroscopic method for determining plasma lipoprotein concentrations and subspecies distributions from a single, rapid measurement.

We are developing a method for quantifying plasma lipoproteins by proton nuclear magnetic resonance (NMR) spectroscopy that offers advantages over existing clinical methods. We showed that the major lipoproteins have distinct NMR properties sufficient to permit their concentrations to be extracted from a computer lineshape analysis of the plasma lipid methyl resonance envelope (Clin Chem 1991; 37:377-86). We have now discovered that the spectra of the subspecies within each lipoprotein class are different enough to influence the composite spectrum of that class and hence the spectrum of whole plasma. By including spectra representative of these subspecies as additional components in the lineshape-fitting analysis, a complete concentration profile of very-low-density, low-density (LDL), and high-density (HDL) lipoproteins plus the subspecies distributions within these classes can be simultaneously generated. A pilot study of 30 plasma samples of widely varied composition demonstrated good agreement between NMR-derived values and lipoprotein lipid concentrations and LDL and HDL subspecies distributions determined by gradient-gel electrophoresis.

Feasibility Studies↗
PubMed1992

Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes.

Lp(a) is a unique lipoprotein consisting of an LDL-like particle and a characteristic protein, apo(a). Increased levels of Lp(a) constitute a risk factor for coronary heart disease. Variation in the size of the apo(a) protein is a phenotype controlled by the apo(a) gene on chromosome 6 and is related to Lp(a) plasma levels. Based on 169 MZ and 125 DZ adult female twin pairs, this study's purpose was to estimate the proportion of the variation in Lp(a) levels that is due to genetic influences and to determine the extent to which the apo(a) locus explains this heritability. Lp(a) levels were significantly more similar in MZ twins than in DZ twins: mean co-twin differences were 3.9 +/- 5.7 mg/dl and 16.0 +/- 19.9 mg/dl (P less than .001), respectively. Intraclass correlations were .94 in MZ twins and .32 in DZ twins, resulting in a heritability estimate of .94 (P less than .001). Heritability was then calculated using only co-twins with the same apo(a) phenotype: the heritability estimate decreased to .45 but was still highly significant (P less than .001). Therefore, on the basis of heritability analysis of women twins, Lp(a) levels are almost entirely genetically controlled. Variation at the apo(a) locus contributes to this heritability, although other genetic factors could be involved.

Adult↗
PubMed1992

Production of polyacrylamide gradient gels for the electrophoretic resolution of lipoproteins.

We describe a protocol to cast nondenaturing polyacrylamide gradient gels (SFBR3/31) for the size resolution of lipoproteins. The protocol yields gels with minimal lot-to-lot variation in length and electrophoretic properties. Absorbance profiles of cholesterol-stained lipoproteins in baboon sera were used to estimate the relative amounts of stain in four lipoprotein size classes (VLDL+LDL, HDL1, HDL2, and HDL3). When compared with gels from a commercial source, the SFBR3/31 gels gave very similar results in terms of precision (coefficients of variation) and of estimated amounts of lipoproteins in the four size classes. In other studies, we estimated peak diameters of protein-stained human lipoproteins after calibrating the gels with size standards. Peak diameters estimated using SFBR3/31 gels were highly correlated (r2 = 0.99, n = 33) with those estimated using gels from a commercial source. We conclude that the protocol reliably produces gradient gels that are suitable for the analysis of lipoprotein phenotypes.

Acrylic Resins↗
PubMed1992

Correlations of plasma lipoproteins with LDL subfractions by particle size in men and women.

Nondenaturing gradient gel electrophoresis of plasma low density lipoprotein (LDL) has been used to identify major LDL subclasses that are influenced by genetic and other factors. In the present paper, this technique has been extended by measuring absorbance of lipid- or protein-stained gels as an index of concentration at intervals of 0.05 nm across the entire LDL particle size range (21.8-30 nm) in moderately overweight men (n = 115) and women (n = 78). When LDL absorbance levels were correlated with other lipoprotein variables, we found that the strengths of the correlations with each of triglycerides, apolipoprotein (apo) B, high density lipoprotein (HDL)2, and apoA-I achieve relative maximum values for two regions within the small LDL range (21-26 nm), one within LDL-IVB (22-23.2 nm) and a second within LDL-III (24.2-25.5 nm). We also found that the increase in LDL accompanying higher triglyceride levels occurs below 25.5 nm in men and between 24.5 and 26.5 nm in women, suggesting either that triglycerides are related to different LDL subclasses in men and women, or that particle sizes of metabolically homologous LDL subclasses may differ in men and women. As compared to analytic ultracentrifuge measurements, gradient gel measurements of LDL absorbance by the procedure described here provide greater resolution of LDL subclasses but less precision in estimating LDL levels.

Adult↗
PubMed1991

Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI.

Epidemiological surveys have identified a strong inverse relationship between the amount in the plasma of high density lipoproteins (HDL), apolipoprotein AI (ApoA-I), the major protein component of HDL, and the risk for atherosclerosis in humans. It is not known if this relationship arises from a direct antiatherogenic effect of these plasma components or if it is the result of other factors also associated with increases in ApoA-I and HDL levels. Because some strains of mice are susceptible to diet-induced formation of preatherosclerotic fatty streak lesions, and because of available techniques for the genetic manipulation of this organism, the murine system offers a unique setting in which to investigate the process of early atherogenesis. To test the hypothesis that induction of a high plasma concentration of ApoA-I and HDL would inhibit this process, we studied the effects of atherogenic diets on transgenic mice expressing high amounts of human ApoA-I. We report that transgenic mice with high plasma ApoA-I and HDL levels were significantly protected from the development of fatty streak lesions.

Animals↗
PubMed1991

The tangled web of coronary risk factors.

Although epidemiologic, genetic, and pathophysiologic studies have shown that low-density lipoproteins (LDLs) are involved in the development of coronary artery disease, the standard measurement of LDL cholesterol comprises a number of separate components that may contribute in different ways to the disease process. Some of these components appear to be of particular pathologic importance. Intermediate-density lipoproteins (IDLs) and lipoprotein (a) are highly atherogenic species that each normally account for up to 10% to 15% total LDL cholesterol but may be disproportionately elevated in pathologic states and may therefore contribute disproportionately to coronary disease risk in certain patients. Recently, another subclass of LDL, characterized by relatively small particle size and increased density, also has been found to be associated with relatively increased risk of coronary disease. Furthermore, levels of this subclass, designated LDL-III, are linked to a number of interrelated hormonal and metabolic factors, each of which have also been associated with risk of coronary artery disease. These include male gender, postmenopause, abdominal adiposity, elevated triglyceride levels, increased levels of apolipoprotein B, and reductions in high-density lipoproteins (HDLs), particularly in the HDL2 subclass. Other studies have demonstrated that many of these factors are also commonly associated with relative insulin resistance and hyperinsulinemia. Thus, a lipoprotein profile characterized by a relative increase in LDL-III and a reduction in HDL2 is indicative of a constellation of metabolic features that defines a high-risk state and that makes it extremely difficult to single out one or more factors that are most directly involved in the disease process. Combinations of genetic and environmental factors acting on this "tangled web" of risk factors may account for much of the variation in coronary disease susceptibility found in the general population.

Androgens↗