PubMed Health⌕ Search

Biomedical subjects

G M Kostner

Publications and source records attributed to G M Kostner.

At least 145 records · Page 8Linked to original sources
PubMed1991

Lipoprotein (a) concentrations as risk indicators for atherosclerosis.

The plasma concentration of different lipoproteins were measured in 102 control children, in 42 children with a parent suffering from coronary heart disease (CHD), and in 50 children with a parent with cerebrovascular disease (CVD). Significant differences between controls and children in the other two groups were found for apolipoprotein A I, apolipoprotein B, and high density lipoprotein-cholesterol. Children of parents with CHD differed from controls in total cholesterol and apolipoprotein A II concentrations. A highly significant difference furthermore was found in lipoprotein (a) concentrations from children of parents with CHD in comparison with controls, but not between children of parents with CVD and controls. The difference in lipoprotein (a) concentrations (children of parents with CHD compared with controls) were only noticed in children above the age of 10 years. This could be explained by the observed rise of lipoprotein (a) between age 2 and 13 years, which was much more pronounced in the group with parents who had CHD. Plasma glycosaminoglycan concentrations were also measured in the three groups. They were significantly higher in children of parents with CHD and CVD compared with controls; they also varied with age.

Adolescent↗
PubMed1991

Lipoprotein metabolism and atherogenesis: implications for therapy.

The causes of atherosclerosis are numerous, but disturbances in lipid and lipoprotein (LP) metabolism undoubtedly play a key role. Although there exist multiple forms of genetic and secondary hyperlipoproteinemias linked with premature vascular diseases there are only a few LP that need to be considered: low-density LP, beta-very-low-density LP, chylomicron remnants and LP(a). In addition, low HDL levels have been found to represent an independent risk factor. Prolonged residence times of these LP lead to chemical modification and interaction with platelets, smooth muscle cells, endothelial cells and macrophages. Atherogenesis is thus a concerted action. Knowledge of the metabolic pathways of most of these LP is necessary in order to be able to specifically influence hyperlipoproteinemia with dietary measures or, ultimately, with lipid-lowering drugs.

Arteriosclerosis↗
PubMed1990

Activation of soluble guanylate cyclase by nitrovasodilators is inhibited by oxidized low-density lipoprotein.

In the presence of oxidized low-density lipoprotein the stimulatory effects of nitric oxide, sodium nitroprusside and S-nitrosoglutathione on soluble guanylate cyclase partially purified from bovine platelets were diminished in a concentration-dependent manner with IC50 values around 100 micrograms total cholesterol/ml. This inhibitory effect was potentiated about 10-fold when the enzyme was pre-incubated with the lipoprotein for 10 minutes at 37 degrees C which indicates a direct interaction of the lipoprotein with the guanylate cyclase. As oxidized low-density lipoprotein is present in the wall of atherosclerotic arteries, we suggest that the impaired response of atherosclerotic blood vessels to vasodilators may be due to a diminished activation of smooth muscle guanylate cyclase.

Animals↗
PubMed1990

A comparative study of the localization of plasminogen and apolipoprotein(a) in human carcinomas.

Recently, it was reported that there is a significant elevation of total plasma apolipoprotein(a) level in cancer patients. Because of their structural homology and immunological cross-reactivity, localization of the plasminogen and the apolipoprotein(a) was comparatively studied in cancerous tissues of breast (N = 4) and colon (N = 3) by immunofluorescence. The following results were obtained: 1) Tumor cells isolated or in nodules were strongly stained in all cancerous samples using antiserum against Pg, absorbed or not with Lp(a). 2) Tumor cells were lightly stained in two breast carcinomas, using anti-Lp(a) serum. All other carcinomas were negative. The staining was abolished when anti-Lp(a) serum was absorbed with Pg. 3) Blood vessels were strongly stained using antiserum against Lp(a) even when it was absorbed with Pg. Anti-Pg serum decorated only a few capillaries. These results show that the two proteins have different localizations: Lp(a) is seen exclusively in the vascular system. The component present at the surface of tumor cells is plasminogen (or plasmin) but not Lp(a).

Adenocarcinoma↗
PubMed1990

Immunochemical determination of lipoprotein Lp(a): comparison of Laurell electrophoresis and ELISA.

The lipoprotein Lp(a) concentrations in serum from 520 persons (317 men and 203 women) were measured by two different Laurell electrophoresis assays (one in house and one commercial) and by an ELISA technique, using polyclonal antibodies from two different animal species. The following results were obtained. 1. The two Laurell techniques gave similar results. The mean values of all three methods were comparable, whereas median values obtained by ELISA were markedly lower (0.85, 0.97 and 0.057 g/l for the two Laurell assays and the ELISA, respectively). 2. All three methods correlated very well with a correlation coefficient of greater than 0.95. 3. Women had significantly higher values than men (p less than 0.01). It was concluded that Lp(a) serum concentrations in the 'pathological range' could be measured with high enough precision by Laurell electrophoresis and by ELISA using polyclonal antibodies from different animal species.

Electrophoresis↗
PubMed1990

Is the atherogenicity of Lp(a) caused by its reactivity with proteoglycans?

Apo B-containing lipoproteins from human plasma were studied for their ability to form complexes with glycosaminoglycans (GAG) and proteoglycans (PG) in the presence of Ca++ and Mg++ ions. We studied low density lipoproteins (LDL), Lp(a) as well as Lpa-, a particle generated from Lp(a) by removing the specific antigen (apo-a). The strongest reactivity with all apo B-containing lipoproteins was found with PG, followed by GAG isolated from human aorta, and by chondroitin-6-sulphate. Lp(a), on the other hand, formed complexes with the highest glycan:lipoprotein ratio using all three complexing agents. Treatment of Lp(a) with neuraminidase did not change the reactivity. The reactivity of Lpa-, on the other hand, was between that of Lp(a) and LDL. Lipoprotein glycan complexes were incubated with mouse peritoneal macrophages. This caused cholesterol ester accumulation and foam cell formation. The amount of cholesterol ester formed correlated highly significantly with the reactivity of a given lipoprotein with different glycans. Sera obtained from patients suffering from myocardial infarction (MI) were incubated with LDL and Lp(a) and the reisolated lipoproteins were also incubated with macrophages. Lipoproteins reisolated from MI plasma caused foam cell formation with MPM to a greater extent than reisolated material incubated with normal plasma. The highest cholesteryl ester accumulation was found when Lp(a) reisolated from MI plasma was incubated with MPM. These results may at least partly explain the higher atherogenicity of Lp(a) in comparison with LDL.

Animals↗
PubMed1990

Postprandial hyperlipemia and platelet eicosanoid metabolism.

Platelet aggregations stimulated with different concentrations of collagen or ADP were reduced during postprandial hyperlipemia in normolipemic subjects. The concomitant formation of platelet AA metabolites (TXB2, 12-HHT, 12-HETE), however, was not significantly altered.

Adult↗
PubMed1990

Interaction of lipoprotein Lp[a] with the B/E-receptor: a study using isolated bovine adrenal cortex and human fibroblast receptors.

The ability of different lipoprotein Lp[a] preparations to compete with LDL-binding to the B/E-receptor was investigated by ligand blot and filter assays. Lp[a] was purified from donors with various genetic polymorphic forms by affinity chromatography using lysine-Sepharose or specific immunoadsorbers. These preparations were free of "LDL-like" material. Part of Lp[a] was reduced and freed from specific apo[a] antigen yielding "Lpa-." 125I-labeled low density lipoproteins (LDL) were incubated with B/E-receptor preparations from bovine adrenal cortex or from human skin fibroblasts, and the competition with unlabeled LDL, Lp[a], Lpa-, apo[a], and apoE-free HDL was studied by a ligand blot or filter assay technique. The following results were obtained. 1) LDL and Lpa- were equally potent in displacing 125I-labeled from B/E-receptor in the ligand blot and the filter assay. Lpa + ( = Lp[a]) also displaced LDL but to a much lesser degree: 50% displacement was observed with LDL and Lpa- at a 1-fold excess, whereas a 7.5-fold excess was required of Lpa +. 2) Apo[a], as well as apoE-free HDL, did not compete with LDL binding. 3) Competition experiments using B/E-receptors from bovine adrenal cortex or from human skin fibroblasts were comparable. 4) There was no difference in the behavior of Lp[a] isolated from the two affinity chromatography methods. 5) Lp[a] of different genetic variants behaved virtually identically. The results are discussed from the point of view of the in vivo metabolism of Lp[a].

Adrenal Cortex↗
PubMed1990

Physiological and clinical importance of lipoprotein(a).

Lipoprotein(a) is a genetically regulated trait, and its concentration in serum seems to be independent from that of other lipoprotein classes. It can be detected by ultracentrifugation in the d = 1.05-1.12 g/ml density range. Based on epidemiological observations Lp(a) is an independent risk factor for coronary heart disease. Its structure resembles LDL, but contains, in addition to apolipoprotein B 100, the disulphide-linked apoprotein(a). Apoprotein(a) shares a striking homology with plasminogen, consisting multiple repeating domains similar to kringle IV, a single kringle V and an inactive protease segment. The heterogeneity of Lp(a) complex is determined by the apoprotein(a) moiety. It seems so, that atherogenic properties of Lp(a) can be explained by its binding to glycosaminoglycans and inhibition of fibrinolysis. This latter effect is carried out by the kringle domains, which can interact with the plasminogen activators and plasmin binding sites on endothelial surface. The atherogenic properties of Lp(a) are expressed over 30 mg/dL serum concentration. Well-known antilipidemic drugs do not affect its serum level and genetically determined phenotype. Diseases leading to secondary hyperlipoproteinemia may influence the lipoprotein(a) level, too.

Arteriosclerosis↗
PubMed1990

[The role of apolipoproteins in lipid metabolism].

There is little doubt today that apolipoproteins play a key role in lipid metabolism and thus in atherogenesis. There are five major classes of apo Lp known: Apo AI, the main component of HDL not only mediates the action of LCAT, a key enzyme in cholesterol metabolism, but also through specific cell receptors is responsible for the reverse cholesterol transport, which is discussed as the main atherogenic process. Apo B is necessary for the secretion of neutral lipids out of the liver and the intestine. In addition, apo B containing lipoproteins are recognized by specific cell surface receptors leading to the fast removal of cholesterol rich fractions from circulation. Apo C proteins regulate the activity of lipoprotein lipase, the key enzyme of triglyceride metabolism. Apo E containing lipoproteins are recognized by the B/E-receptor with a 10 to 100 fold affinity. There exists, however, another specific receptor for Apo E, which is responsible for the fast removal of the atherogenic remnants from circulation. Apo E in addition serves to secrete deposited cholesterol out of macrophages and foam cells. Apolipoprotein(a) is a peculiar fraction of apo B containing lipoproteins whose biological function is completely unknown. Cloning of the cDNA revealed striking similarities of apo(a) with the structure of plasminogen. The cross connection of Lp(a) with hemostasis and thrombogenesis is currently focus of intensive research. The knowledge of the specific function of apolipoproteins in lipid metabolism arose to a great extent from the characterization of apo-Lp isoforms and their impact of atherogenesis. In addition, intensive research by molecular biology techniques helped to unravel the pathophysiology in a wide array.

Apolipoproteins↗
PubMed1989

Characterization of isoelectric subspecies of asialo-beta 2-glycoprotein I.

Isoelectric focusing of purified beta 2-glycoprotein I (beta 2-G-I) revealed five major bands with isoelectric points (pI) between 5.1 and 6.1. Neuraminidase treatment decreased the number of bands to two (pI 8.0 and 8.2). The two asialo subfractions of beta 2-G-I were purified by cation-exchange column chromatography. The more basic isoform II was found to have a higher content of lysine. Western-blot analysis of different plasma samples confirmed the heterogeneity of beta 2-G-I in plasma. Plasma treated with neuraminidase showed two bands irrespective of the number of isoforms as well as of the concentration in native plasma. This led us to the conclusion that human plasma beta 2-G-I consists of two isoproteins that are sialylated to different extents.

Apolipoproteins↗
PubMed1989

Effects of low- and high-density lipoproteins on the proliferation of human breast cancer cells in vitro: differences between hormone-dependent and hormone-independent cell lines.

The influence of low- and high-density lipoproteins on the proliferation of human breast cancer cells in culture was studied. We compared total cell number after incubation for 48 hr in culture medium containing or lacking plasma lipoproteins. Marked differences were found between hormone-dependent (MCF-7, T-47-D, ZR-75) and hormone-independent (MDA-MB-231, HBL-100) mammary tumor cell lines. The cells also reacted differently on the different lipoproteins offered in the medium. Human low-density lipoproteins (LDL) exhibited a marked stimulation of the growth of hormone-independent cell lines but no or only toxic effects upon the hormone-sensitive lines. Human high-density lipoproteins (HDL) stimulated the proliferation of all cell lines in a dose-dependent manner but hormone-independent cells showed a higher response. These findings point towards different utilizations of nutrients in hormone-dependent and hormone-independent cells.

Breast Neoplasms↗
PubMed1989

Isotope dilution gas chromatography-mass spectrometry for the study of eicosanoid metabolism in human blood platelets.

Stable isotope dilution gas chromatography-mass spectrometry provides one of the most important techniques for the quantitative measurement of eicosanoids. This technique was applied to the quantitation of hydroxyeicosatetraenoic acids, hydroxyheptadecatrienoic acid, thromboxane B2 and prostaglandin F2 alpha formed during platelet aggregation after stimulation of gel-filtered platelets with thrombin (0.25 U/ml) or collagen (2 micrograms/ml). Similar amounts of hydroxyheptadecatrienoic acid and thromboxane B2 were found after platelet activation. The ratio of formation of 12-hydroxyeicosatetraenoic acid to thromboxane B2 varied from donor to donor. Only small amounts of prostaglandin F2 alpha (up to 200 pg per 2.0.10(8) platelets) and basic values of 15-hydroxyeicosatetraenoic acid (up to 100 pg per 2.0.10(8) platelets) were measured using gas chromatography with negative ion chemical ionization mass spectrometry. In addition, different stable isotope dilutions were prepared and are discussed in detail.

Arachidonic Acids↗
PubMed1989

Is there any correlation between platelet aggregation, plasma lipoproteins, apoproteins and membrane fluidity of human blood platelets?

Fluorescence anisotropy (which is inversely related to membrane fluidity) of gel filtered platelets of 18 normolipemic subjects (20-26 years) was measured after incubation with three different fluorescent probes (DPH, TMA-DPH, and 6-As). These values were correlated to both platelet aggregation parameters after stimulation with ADP (4 microM), epinephrine (10 microM) or collagen (2 micrograms/ml PRP) and to plasma lipids, lipoproteins and apoproteins. Fluorescence anisotropy values after DPH-labeling of platelets were only negatively correlated to TG (p less than 0.05). No correlation was found between fluorescence anisotropy values of DPH, TMA-DPH and 6-As to LDL-C, Lp(a), HDL-C and HDL3-C (p less than 0.01). However, fluorescence anisotropy values of DPH and TMA-DPH were negatively correlated to apoproteins A2 and B (p less than 0.05). No correlations were found between fluorescence anisotropy after DPH labeling and different aggregation parameters. TMA-DPH and 6-As fluorescence anisotropy values are correlated to epinephrine induced stimulation (p less than 0.01).

Adult↗
PubMed1989

Influence of morphology and malignancy of three new human melanoma cell lines on the cyclooxygenase pathway.

Three newly established human melanoma cell lines (WU-BI, PN-JC, MJ-ZJ) of different morphology and different stage of malignancy were incubated with ionophore A23187 (2.5 to 40 microM) or arachidonic acid (AA, 6.25 to 100 microM). PGF2 alpha, 6-keto-PGF1 alpha, PGE2, TXB2 and 2,3-dinor-TXB2 from isolated cells and supernatants were measured by negative ion chemical ionization gas chromatography/mass spectrometry (GC/MS). PGE2 decreased in the fibroblastoid MJ-ZJ cells from 36.7 ng/mg cell protein about 70% (A23187) and about 20% (AA), respectively. However, in the cell supernatant PGE2 increased up to 295.4 +/- 66.5 ng/mg cell protein. Production of PGF2 alpha and PGE2 increased up to 5.7 +/- 1.2 ng/mg cell protein for polydendritic WU-BI cells and spindle shaped PN-JC cells. Up to 9.3 +/- 4.3 ng PGF2 alpha and 13.4 +/- 4.7 ng PGE2 was measured for WU-BI and PN-JC in the cell supernatants. All three melanoma cell lines completely lacked formation of 6-keto-PGF1 alpha, TXB2, and 2,3-dinor-TXB2.

Arachidonic Acids↗
PubMed1989

Postprandial hyperlipemia inhibits platelet aggregation without affecting prostanoid metabolism.

The objective of this work was to characterize changes in platelet aggregability during postprandial hypertriglyceridemia with special emphasis on arachidonic acid metabolism. Ten healthy young men consumed 100 g fat after a fasting period of 12 hr. In-vitro platelet aggregation induced by ADP and collagen was measured at 0, 3, 5, and 9 hours after the fat intake. The major arachidonic acid metabolites, 12-hydroxyeicosatetraenoic acid (12-HETE), thromboxane A2 (TXA2), prostaglandin F2 alpha (PGF2a), and prostaglandin E2 (PGE2) produced during collagen-induced platelet activation were quantified by gas chromatography/mass spectrometry. A significant decrease in platelet aggregability induced by both ADP and collagen was detected during the postprandial hyperlipemia. No significant changes could be found in the prostanoid pattern of collagen activated platelets. There was no correlation between the degree of the inhibition of platelet aggregation and the relative or absolute increase of triglyceride-levels in the plasma during the postprandial hyperlipemia.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗