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Biomedical subjects

M W Baumstark

Publications and source records attributed to M W Baumstark.

At least 37 records · Page 2Linked to original sources
PubMed1997

Homozygous familial defective apolipoprotein B-100. Enhanced removal of apolipoprotein E-containing VLDLs and decreased production of LDLs.

Familial defective apolipoprotein B-100 (FDB) is a frequently inherited disorder of lipoprotein metabolism. The glutamine-for-arginine substitution at position 3500 of apolipoprotein (apo) B-100 leads to defective binding of apo B-100 to the low density lipoprotein (LDL) receptor and accumulation of LDL in the plasma. We recently identified a patient homozygous for this mutation. His LDL cholesterol and apo B concentrations were approximately twice normal, whereas his apo E plasma level was low. Using a stable-isotope labeling technique ([2H3]leucine-primed constant infusion), we studied lipoprotein turnover in vivo in the fasting state in this patient and three clinically healthy, normolipidemic individuals not carrying the FDB mutation. The residence time of LDL apo B-100 was prolonged 3.6-fold in the FDB homozygote (8.3 vs 2.3 days). The production rate of LDL apo B-100 was decreased (7.4 vs 15 mg per kg per day). In FDB the residence time of very low density lipoprotein (VLDL) apo B-100 was longer (2.6 vs 1.3 hours), whereas the residence time of VLDL apo E was shorter (2.6 vs 4.5 hours) than normal. These data show that the in vivo metabolism of apo B-100-containing lipoproteins in FDB is different from that in familial hypercholesterolemia, in which LDL receptors are defective. In both conditions the residence times of LDL apo B-100 appear to be increased to approximately the same degree. This contrasts with the LDL apo B-100 synthetic rate, which is increased in familial hypercholesterolemia and decreased in FDB. The decreased production of LDL apo B-100 in FDB may originate from enhanced removal of apo E-containing LDL precursors by LDL receptors, which may be upregulated in response to the decreased flux of LDL-derived cholesterol into hepatocytes.

Apolipoprotein B-100↗
PubMed1997

Crystallization and preliminary X-ray diffraction data of two different human low-density lipoprotein (LDL) subfractions.

Human LDL subfractions LDL-2 (d = 1.031-1.034 g/ml) and LDL-5 (d = 1.040-1.044 g/ml) were crystallized in two different crystal forms by using polyethylene glycol as a precipitant. Both fractions were from one donor. Crystals of LDL-5 were yellow, hexagonal, and showed no dichroism. Crystals of LDL-2 were of the same color, had a rodlike shape with notches at both ends, and were highly dichroitic. LDL-2 crystals diffracted to a resolution of 29 A by using synchrotron radiation. Indexing in P1 resulted in preliminary parameters for the reduced cell of a = 171 A, b = 438 A, c = 519 A, alpha = 102 degrees, beta = 99 degrees, gamma = 91. These dimensions are consistent with the size of LDL particles. Using Fourier transform infrared spectroscopy (FTIR) and agarose gel electrophoresis, we could further confirm that the crystals consist of LDL. The FTIR spectrum showed bands characteristic for lipids and protein. Dissolved crystals exhibited a mobility similar to native LDL in agarose gels and could be stained with anti-human apolipoprotein B (apoB).

Crystallization↗
PubMed1997

Small, dense LDL particle concentration correlates with plasminogen activator inhibitor type-1 (PAI-1) activity.

The relation between LDL subfractions and fibrinolytic activity was studied in 150 men aged 53 to 63 years. Apolipoprotein B (apoB) concentration in the most dense LDL-5 (r = 0.39, p <0.001) and LDL-6 (r = 0.43, p <0.001) subfractions associated with plasminogen activator inhibitor type-1 (PAI-1) activity. Subjects in the highest LDL-6 apoB tertile had higher PAI-1 (24.7 vs. 13.1 AU/ml, p <0.001) and lower t-PA (0.26 vs. 0.54 IU/ml, p <0.001) activities than men in the lowest tertile. The difference in PAI-1 remained after adjusting for either triglycerides (p = 0.039) or insulin (p = 0.015) with cardiorespiratory fitness as an additional covariate, and history of cardiovascular disease and smoking as factors. In a regression analysis, plasma insulin and LDL-6 apoB, but not plasma triglycerides and body mass index, entered the model, and explained 30.6 and 3.9% of the variance in PAI-1 activity, respectively. The novel finding of the present study was the independent association between small, dense LDL particles and PAI-1 activity in middle-aged men.

Analysis of Variance↗
PubMed1996

Lipoprotein(a) in endurance athletes, power athletes, and sedentary controls.

Elevated concentrations of lipoprotein(a) [Lp(a)] have been shown to be an independent risk factor for atherosclerotic disease. Physical activity and physical fitness have been shown to improve lipoprotein metabolism and reduce the risk of coronary artery disease. Studies on the influence of physical activity and physical fitness on Lp(a) levels including a large number of endurance as well as power athletes have not been performed before. Therefore, we determined parameters of physical fitness (maximal oxygen consumption), physical activity, and lipoproteins in 105 endurance athletes, 57 power athletes, and 87 sedentary young men. As expected, we found that endurance athletes with a good physical fitness had significantly higher concentrations of high-density lipoprotein cholesterol than power athletes and sedentary controls. Regarding mean Lp(a) levels (rocket immunoelectrophoresis), however, there were no significant differences between endurance athletes, power athletes, and sedentary controls. Even when including only those with Lp(a) values > 10 mg.dl-1, no differences were observed between the groups. These findings indicate that intensive training over years and good aerobic fitness improve the ratio of low-density lipoprotein to high-density lipoprotein cholesterol but have no or only minor effects on Lp(a) concentrations.

Adult↗
PubMed1996

Association between serum fibrinogen concentrations and HDL and LDL subfraction phenotypes in healthy men.

Hyperfibrinogenemia and a dyslipoproteinemia characterized by reduced HDL2 cholesterol and elevated levels of small, dense LDL particles are risk factors for coronary artery disease. However, the relationship between fibrinogen and lipoproteins, in particular LDL subfractions, is uncertain. We therefore measured serum fibrinogen levels and serum concentrations of cholesterol and apolipoproteins of VLDL, IDL, six LDL, and two HDL subfractions by using the technique of density-gradient ultracentrifugation in 132 nonsmoking men without evidence of coronary artery disease or infection. Dividing the individuals into quartiles according to their fibrinogen values showed that men within the highest fibrinogen quartile (fibrinogen 2.90 to 4.34 g/L) had significantly higher concentrations of small, dense LDL (d > 1.044 g/mL) apolipoprotein B and cholesterol and lower concentrations of HDL2 cholesterol than men within the lower fibrinogen quartiles (fibrinogen < 2.55 g/L). Multivariate regression analysis revealed that the association between fibrinogen and small, dense LDL particles was independent of serum triglycerides, cholesterol, body mass index, and age. In contrast, the relationship between fibrinogen and HDL2 cholesterol was primarily influenced by triglycerides and cholesterol and not independently influenced by fibrinogen. There were no significant differences between the quartiles in terms of insulin, glucose, insulin resistance, free fatty acids, lipoprotein(a), and blood pressure. This study showed that fibrinogen is associated with the expression of a more atherogenic LDL subfraction phenotype independent of body mass index, age, other serum lipids, and insulin resistance in a healthy male nonsmoking population. The reason for this association is uncertain. These findings reinforce the evidence that fibrinogen should be determined when assessing coronary risk.

Aging↗
PubMed1995

Relationship between obesity and concentration and composition of low-density lipoprotein subfractions in normoinsulinemic men.

Obesity, insulin resistance (IR) with hyperinsulinemia, and a dyslipoproteinemia characterized by reduced high-density lipoprotein 2 (HDL2) cholesterol and elevated levels of small, dense low-density lipoprotein (LDL) particles are risk factors for coronary artery disease (CAD). The impact of obesity independent of hyperinsulinemia on the concentration and composition of small, dense LDL subfractions is uncertain. The aim of this study was to investigate the relationship between obesity indices, namely body mass index (BMI), skinfold measurements (SF), and waist to hip ratio (WHR), and LDL-subfraction particle concentration and composition in 200 healthy men without evidence of IR. A precise analysis of the concentration of lipids and apolipoproteins and the composition of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and two HDL- and six LDL-subfraction particles was obtained using the technique of density-gradient ultracentrifugation. Dividing the individuals according to BMI showed that those with a BMI greater than 27 kg/m2 had significantly lower HDL2 cholesterol and apolipoprotein (apo) A-I and higher VLDL and IDL cholesterol and apo B concentrations than those with a BMI less than 25 kg/m2. Regarding LDL particles, we found that men with a BMI above 25 kg/m2 had significantly more small, dense LDL particles (d 1.044 to 1.063 g/mL) and correspondingly fewer medium, dense LDL particles (d 1.031 to 1.037 g/mL) than leaner men; those with a BMI above 27 kg/m2 had the highest concentration of circulating small, dense LDL particles. These findings were not influenced by fasting insulin concentrations, IR, or WHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Decreased binding of apolipoprotein (a) to familial defective apolipoprotein B-100 (Arg3500-->Gln). A study of the assembly of recombinant apolipoprotein (a) with mutant low density lipoproteins.

In familial defective apolipoprotein B-100 (FDB), glutamine is substituted for arginine at position 3500 of the amino acid sequence. This mutation alters the structure of low density lipoproteins (LDL) and reduces their binding to LDL receptors. We studied the assembly in vitro of FDB-LDL with two recombinant apo(a) (r-apo(a)) isoforms containing 17 or 18 kringle IV-type repeats, respectively. R-apo(a) complexed to LDL in a concentration- and time-dependent manner. When we mixed normal LDL at protein concentrations from 1 to 10 mg/liter with 200 micrograms/liter r-apo(a) and incubated for 20 h, 15-44% of r-apo(a) were bound to LDL, forming an artificial Lp(a)-like particle. With LDL from a homozygous FDB patient, only 2-16% of r-apo(a) were complexed; heterozygous FDB-LDL bound 2-30% of r-apo(a). We also studied the effect of r-apo(a) on the interaction of the monoclonal antibody MB47 with normal and mutant apoB-100. FDB-LDL displayed enhanced binding of MB47. Adducts generated from normal LDL and r-apo(a) had an increased affinity for MB47, when compared to LDL alone. In contrast, r-apo(a) did not change MB47 reactivity when incubated with FDB-LDL. Altogether, our findings suggest that domains in apolipoprotein B which are important for the interaction with the LDL receptor play a role in the assembly of Lp(a) as well. They provide, in addition, an explanation for the observation that in Lp(a) of heterozygous FDB patients, the ratio of defective to normal apoB-100 is significantly smaller than in LDL from the same patients.

Adult↗
PubMed1994

Physical activity and lipoprotein lipid disorders.

Working muscle plays a central role in the control of lipid metabolism. Increased physical activity induces a number of positive changes in the metabolism of lipoproteins: serum triglycerides are lowered by the increased lipolytic activity and the production of native high density lipoprotein (HDL) particles is increased. The increased lecithin: cholesterol acyltransferase activity leads to an increased production of HDL2, which in addition is catabolised more slowly due to a decreased activity of hepatic lipase. The 3 effects explain the increased HDL levels of endurance trained individuals. These effects have been demonstrated in cross-sectional as well as longitudinal studies by different groups, and can be induced by training, independent of changes in bodyweight. The influence of endurance activity on the quality and quantity of low density lipoprotein (LDL) particles is a further reason for the antiatherogenic potential of increased physical activity. It has been shown by several groups that small dense LDL particles represent a particular risk factor for atherosclerosis. Recent studies presented strong evidence that LDL level and composition can be influenced favorably by physical activity. In addition to the direct influence of physical activity on lipids and lipoproteins, physical exercise may improve the disturbances of haemorheological factors, particularly those associated with hypertriglyceridaemia. In conclusion, there is increased evidence that physical activity is able to favourably influence all 3 components of the atherogenic lipoprotein phenotype: the HDL concentration increases, the concentration of small dense LDL decreases, and serum triglycerides are reduced.

Apolipoproteins↗
PubMed1993

Acute and delayed effects of prolonged exercise on serum lipoproteins. I. Composition and distribution of high density lipoprotein subfractions.

To investigate the effects of a single period of prolonged exercise on lipoprotein concentration and composition, the serum of 13 healthy, endurance-trained men was examined before and after (1 h, 20 h) a field test [running time, 130 (SD 7.4) min]. We found changes in composition of all of the lipoprotein fractions isolated. In detail, all very low density lipoprotein particle components were reduced after exercise; the most pronounced changes found were in the concentrations of phospholipids (PL) and triglycerides (TG) (PL, before vs 20 h after, P < 0.01; TG, before vs 20 h after, P < 0.01). The serum high density lipoprotein (HDL)-cholesterol mass was unchanged after exercise, but both HDL subfractions showed changes in composition. In HDL3 the relative amounts of cholesterol increased (unesterified free cholesterol; FC) before vs 20 h after, P < 0.05; cholesterylester (CE), before vs 20 h after, P < 0.01) and TG and PL decreased (TG and PL, before vs 20 h after, P < 0.05). The HDL2 particles became enriched in the relative amount of CE (before vs 20 h after, P < 0.01) and lost TG after exercise (before vs 20 h after, P < 0.01). The observation that all the changes in lipoprotein concentration and composition reached their maximal differences compared to the pre-exercise values 20 h afterwards would support the assumption that circulating lipoproteins play an important role in the regeneration period, refilling the intramuscular triglyceride stores.

Adult↗
PubMed1993

Acute and delayed effects of prolonged exercise on serum lipoproteins. II. Concentration and composition of low-density lipoprotein subfractions and very low-density lipoproteins.

To investigate the effects of a single period of prolonged exercise on lipoprotein concentration and composition, 13 healthy endurance-trained men were examined before and after (1 h, 20 h) a cross-country run [30 km, time: 130 (SD 7.4) min]. The data show that following acute exercise, serum triglyceride (TG) concentration were reduced (36%) as a consequence of a reduced number (31%) of very low density lipoprotein (VLDL) particles. Changes in composition of VLDL were present but less evident. In contrast to this, acute exercise did not induce significant changes in the average concentration of individual low-density lipoprotein (LDL) subfractions. However, changes in dense LDL [density (d) > 1.044 g.ml-1] concentration were significantly correlated to changes in serum TG: a reduction of dense LDL occurred in subjects with large reductions in serum TG. In addition, LDL composition changed significantly. Immediately (1 h) after exercise the TG content of all LDL subfractions was reduced. These reductions were significant in large (d = 1.006-1.037 g.ml-1) and small LDL (1.044-1.063 g.ml-1). It can be concluded therefore from our study that acute exercise primarily altered the composition of LDL subfractions while their concentration remained stable.

Adult↗
PubMed1993

Prevention of endotoxin-induced monokine release by human low- and high-density lipoproteins and by apolipoprotein A-I.

Interaction of endotoxin (lipopolysaccharide [LPS]) with human lipoproteins is known to prevent the LPS-induced activation of human monocytes and release of cytokines (monokines). LPS was exposed to lipoprotein classes separated by ultracentrifugation and to apolipoprotein A-I. Then monocytes were added, and the LPS activation of monocytes was determined by measuring the induced monokines. Failure of LPS to induce monokine release was called LPS inactivation caused by lipoproteins or apolipoproteins. The LPS inactivation is shown to be a function of low-density lipoproteins. High-density lipoproteins inactivate LPS to a much lesser extent. The very-low-density lipoproteins cannot inactivate LPS. Lipid components seemed not absolutely required for LPS inactivation, because purified human apolipoprotein A-I without its physiological lipid complement also inhibits LPS-induced monokine release.

Adult↗
PubMed1993

Accumulation of "small dense" low density lipoproteins (LDL) in a homozygous patients with familial defective apolipoprotein B-100 results from heterogenous interaction of LDL subfractions with the LDL receptor.

The interaction of LDL and LDL subfractions from a patient homozygous for familial defective apoB-100 (FDB) has been studied. His LDL cholesterol ranged from 2.65 to 3.34 g/liter. In cultured fibroblasts, binding, internalization, and degradation of the patient's LDL was diminished, but not completely abolished. The patient's apolipoprotein E concentration was low, and the amount of apolipoprotein E associated with LDL was not elevated over normal. LDL were separated into six subfractions: LDL-1 (1.019-1.031 kg/liter), LDL-2 (1.031-1.034 kg/liter), LDL-3 (1.034-1.037 kg/liter), LDL-4 (1.037-1.040 kg/liter), LDL-5 (1.040-1.044 kg/liter), and LDL-6 (> 1.044 kg/liter). LDL-5 and LDL-6 selectively accumulated in the patient's plasma. Concentrations of LDL-1 to 3 were normal. The LDL receptor-mediated uptake of LDL-1 and LDL-2 could not be distinguished from normal LDL. LDL-3 and LDL-4 displayed reduced uptake; LDL-5 and LDL-6 were completely defective in binding. When apolipoprotein E-containing particles were removed by immunoabsorption before preparing subfractions, LDL-3 and LDL-4, but not LDL-1 and LDL-2, retained some receptor binding activity. We conclude that in FDB, LDL-1 and LDL-2 contain sufficient apolipoprotein E to warrant normal cellular uptake. In LDL-3 and LDL-4, the defective apoB-100 itself displays some receptor binding; LDL-5 and LDL-6 are inable to interact with LDL receptors and accumulate in plasma.

Adolescent↗
PubMed1992

Distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and HDL subfractions of untrained and trained normolipemic men.

The distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and within HDL subfractions (HDL2b, HDL2a, HDL3) was examined in 26 sedentary and 19 endurance trained normolipemic male individuals. The concentrations of lipids and apolipoproteins in serum and HDL subfractions and the concentrations of LpA-I and LpA-I:A-II were determined. Significant differences (Mann-Whitney-U-test) were found in serum concentrations of apoB (P < 0.05), apoA-II (P < 0.01) and LpA-I:A-II (P < 0.001). In HDL3 apoA-II concentration was significantly lower in the trained group (P < 0.05) but in HDL2 subclasses the concentrations of apoA-I and apoA-II did not differ between the groups. Despite similar concentrations of the two apolipoproteins, there were difference in the distribution of lipoprotein species within HDL2 subfractions. The concentrations of LpA-I did not differ, but the concentrations of LpA-I:A-II particles were higher in the trained group. Untrained and trained had similar concentrations of apoA-II (in HDL2b) but obviously more apoA-II containing particles and this leads to the assumption that within HDL2 of endurance trained individuals LpA-I:A-II particles have a lower apoA-II content compared with particles of untrained individuals. The data emphasize, that normolipemic individuals of different maximum oxygen uptake have a different distribution and composition of lipoprotein species (LpA-I, LpA-I:A-II).

Adult↗
PubMed1992

Probucol, incorporated into LDL particles in vivo, inhibits generation of lipid peroxides more effectively than endogenous antioxidants alone.

One of the first steps in lipid autoxidation leads to the generation of lipid peroxides (LPO). The time course of LPO generation during Cu++ catalyzed oxidation of LDL before and after treatment with probucol was determined in this study. Before analysis the samples had been stored for about 3 years at -20 degrees C. The results show that in LDL samples without probucol the total antioxidative potential had been depleted during the long-term storage. In contrast, LDL containing probucol showed almost no signs of lipid autoxidation. In addition, the ratio of vitamin E to cholesterol was significantly higher in serum samples containing probucol. We conclude that, in vivo, probucol is incorporated into LDL particles in concentrations high enough to inhibit even early steps of lipid autoxidation.

Antioxidants↗
PubMed1992

Low density lipoproteins inhibit endotoxin activation of monocytes.

Human serum and low density lipoproteins (LDLs) were shown to inactivate endotoxin (lipopolysaccharide [LPS]) by testing the effect of LPS interactions with serum or LDL on the activation of human monocytes. Sera and LDL preparations from four patients with familial hypercholesterolemia were used to demonstrate the inhibition of LPS from inducing interleukin-1 release. Before LDL removal by immunoapheresis, the patients' sera were able to inactive approximately fivefold more LPS than after LDL removal. The LPS-inactivating capacity lost during apheresis could essentially be retrieved in the LDL-rich eluate from the immunoadsorption columns. Because patients were treated frequently with immunoapheresis, their LDL levels before LDL removal were not markedly elevated. These patients' sera before LDL removal were shown to inactivate amounts of LPS comparable to those inactivated by the sera from three healthy volunteers. LDL prepared by ultracentrifugation showed similar LPS inactivation as LDL prepared by immunoapheresis. We conclude that the inhibition of LPS-induced monocyte activation by human serum is dependent to a large extent on the LDL fraction. LDLs were demonstrated to inhibit LPS from inducing interleukin-1 release by human monocytes.

Adult↗
PubMed1991

Influence of acute maximal exercise on lecithin:cholesterol acyltransferase activity in healthy adults of differing aerobic performance.

To document the possible influence of a single episode of maximal aerobic stress on the serum lecithin:cholesterol acyltransferase (LCAT) activity in subjects with differing histories of training, two groups of healthy male adults [controls (C), n = 18, 28.6 years, SD 5.2, 50.1 ml.kg-1.min-1 maximal O2 uptake (VO2max), SD 5.3; endurance trained athletes (T), n = 18, 31.4 years, SD 8.8, 65.0 ml.kg-1.min-1 VO2max, SD 2.8] were examined in a maximal aerobic stress test. In addition to the routine assessment of lipid status, LCAT activity was measured immediately before and after exercise. At rest nearly identical LCAT activity values were found in both groups: C 64.4 nmol.ml-1.h-1, SD 16.7 vs T 65.0 nmol.ml-1.h-1, SD 20.9. The post-exercise LCAT values induced by the maximal stress test increased significantly to (C) 95.7 nmol.ml-1.h-1, SD 23.5, +48.6%, P less than 0.001; (T) 83.5 nmol.ml-1.h-1, SD 24.3, +29.1%, P less than 0.01. Neither the pre nor the postexercise individual LCAT activity values showed any significant correlation to the corresponding data on physical performance.

Adolescent↗