[Modern and general practice-oriented lipid and lipoprotein diagnosis].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Luley.
Explore the source record for details and available documents.
In 13 healthy, male nonsmokers (mean age: 25.7 +/- 2.4 years) with normal fasting triglycerides we investigated postprandial changes of triglycerides in several lipoprotein fractions. After a 12-hour overnight fast they ingested a standardized lipid load (1,017 kcal) including 30,000 IU retinyl palmitate. Postprandially, total triglycerides increased significantly (p < 0.001) to a peak value of 221 +/- 81 mg/dl at 5 h. Two subjects had an exceptionally strong triglyceride response (peak values: 363 and 390 mg/dl). They had the highest levels of retinyl palmitate in the chylomicron and the nonchylomicron fraction, and one of them showed elevated intermediate-density lipoprotein values throughout the test period. In addition, they showed an altered early and an increased late postprandial insulin response. Thus, our data provide evidence that an exaggerated postprandial triglyceride response may point to an increased atherogenic risk even in healthy subjects with normal fasting triglycerides.
Two recent reports showed a lowering of elevated lipoprotein(a) levels upon treatment with fish oil. The aim of this paper was to confirm this finding and to establish a dose-effect relationship. A double blind, placebo controlled cross-over study was carried out in 48 subjects with apolipoprotein(a) ("Apo(a)") values between 34 and 1062 U/l (median 387 U/l). The subjects were divided into 3 groups receiving 3.5, 7.1 and 10.6 g omega-3 fatty acids/day during 28 days. Parameters measured were blood levels of eicosapentaenoic acid ("EPA"), Apo(a) and fasting blood lipids. EPA levels rose in the three dosage groups by factors 7, 9 and 14, respectively, if compared to values upon placebo. Triglycerides were significantly lowered in a dose depending manner. Apo(a), however, was not changed. This held true for different baseline Apo(a) values and different fish oil dosages. It is concluded that fish oil treatment during 4 weeks cannot lower elevated Apo(a) levels.
High-density lipoprotein (HDL) was fractionated by preparative isoelectric focussing into six distinct subpopulations. The major difference between the subfractions was in the molar ratio of apolipoprotein A-I to apolipoprotein A-II, ranging from 2.1 to 0.5. The least acidic particles had little apolipoprotein A-II, were larger and contained the most lipid. The efflux capacity of the HDL subfractions was tested with mouse peritoneal macrophages and a mouse macrophage cell line (P388D1), either fed with acetylated low-density lipoprotein or free cholesterol. All the HDL subfractions were equally able to efflux cholesterol. The efflux was concentration dependant and linear for the first 6 h. The HDL subfractions bound with high affinity (Kd = 6.7-7.9 micrograms/ml) at 4 degrees C to the cell surface of P388D1 cells (211,000-359,000 sites/cell). Ligand blotting showed that all the HDL subfractions bound to membrane polypeptides at 60, 100, and 210 kDa. These HDL binding proteins may represent HDL receptors. In summary HDL particles, which differed principally in ratio of apolipoprotein A-I to apolipoprotein A-II behaved in a similar manner for both cholesterol efflux and cell surface binding.
In a series of animal studies we have clearly demonstrated since 1970 that calcium overload of the arterial wall is crucially involved in the pathogenesis of arteriosclerotic lesions. Following excessive calcium uptake, vascular stretch compliance and distensibility were lost together with structural integrity. Conversely, calcium antagonists that counteract abundant calcium uptake were found to prevent pathogenic mural calcium accumulation and damage. These effects were realized with light and electron microscopy as well as with measurements of calcium accumulation using atomic absorption spectrometry and radiocalcium. The experiments were carried out on rats exposed to various well-known risk factors such as nicotine, alloxan diabetes, high doses of vitamin D3, or dihydrotachysterol. Another particularly vasotoxic factor appeared to be hypertension, which develops in spontaneously hypertensive Okamoto rats (SHRs), in hypertensive NaCl-loaded salt-sensitive Dahl-S rats, and in rats with nephrogenic Goldblatt hypertension. Interestingly, aging arteries in animals and humans also exhibit, as a characteristic phenomenon, a steady increase in arterial calcium content. This natural age-dependent calcium accumulation is further enhanced in severe diabetics, heavy smokers, and hypertensive patients. However, the most excessive degree of toxic calcium overload, correlated with dramatic structural damage, occurred in human coronary artery plaques. Here, in "fatty streaks" (type I plaques according to World Health Organization classification), the mural calcium content exhibited a rise by 13 times above normal; in type II lesions (fibrous plaques), the increase in calcium was 24-fold; and in type III plaques, i.e., in "complicated lesions of stenosing character," calcium overload amounted to a value greater than 80 times above that found in healthy coronary segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Conventional determination of apolipoprotein E isomorphs comprises ultracentrifugation of 1-5 ml serum, delipidation of very low density lipoproteins (VLDL), and isoelectric focusing (IEF) in polyacrylamide gels. In order to reduce the sample volume and to avoid nonspecific protein bands, immunoblotting was proposed. Now we describe a methodological variant that uses 25 microliters serum, replaces ultracentrifugation by precipitation of apoE-containing lipoproteins with polyethylene glycol, and delipidation by dissolution in detergent. IEF is carried out in agarose. This allows specific immunofixation of apoE-containing bands with 10 microliters antiserum per sample. This method yields apoE patterns that are specific and well resolved. Also, it offers considerable savings of time and equipment involved.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To evaluate digestion, absorption and postprandial lipemia of diverse fats before and after fish oil capsule therapy (with ethylester) 20 healthy volunteers were recruited. A significant increase (p less than 0.001) in fecal fat excretion after fish oil capsule therapy, as well as serious diarrhoea after fat loads with 100 g of fish oil was noted. It was found, that under fish oil fat loads the total triglyceride content of the mucosa was significantly (p less than 0.001) lower compared to butter fat loads. Decrease digestion and absorption of omega-3 fatty acids was postulated.
Three clonal subpopulations (A, B, C) isolated from the same rhabdomyosarcoma of the rat were tested and compared for their susceptibility to differentiation induction using retinoic acid (RA), dimethylformamide (DMF), and N-monomethylformamide (NMF). These subpopulations differ in that a block to spontaneous differentiation is imposed at different stages which are characteristic for each subpopulation. Whereas tumor cell proliferation was significantly inhibited (P less than 0.001) in all three subpopulations, the effects of RA, DMF, and NMF on tumor cell differentiation were strikingly heterogeneous. The response was most marked in subpopulation C, as evidenced by a significant increase in the number of terminally differentiated myotube-like giant cells (P less than 0.001) and in biochemical differentiation, as indicated by the creatine kinase activity (P less than 0.05). Between 5% (DMF and NMF) and 30% (RA) of the mononuclear cells in subpopulation C exhibited thick and thin myofilaments, which were never observed in the mononuclear cells of the control. In contrast, subpopulation A and B responded to RA, DMF, and NMF quite heterogeneously with an increase in biochemical differentiation, whereas terminally differentiated myotube-like giant cells were never observed. These results demonstrate that the therapeutic potential of differentiation induction in malignant tumors may be impaired by tumor heterogeneity.
Fish oil capsules are increasingly used by self-medicating patients. We studied 22 commercial fish oil and menhaden oil preparations in respect to accompanying substances that could be harmful. The substances measured were: cholesterol as determined by gas liquid chromatography, heavy metals measured by atomic absorption, and vitamin A as determined by high-performance liquid chromatography (HPLC). The contents of cholesterol and heavy metals were in ranges which can be regarded as negligible; the content of vitamin A in menhaden oils, however, was found in amounts which warrant that pregnant women do not exceed the dosage as recommended by the manufacturers.
We report on the establishment of a model for differentiation induction in sarcomas, using the clonal rhabdomyosarcoma cell line BA-HAN-1C. This rhabdomyosarcoma cell line is composed of morphologically undifferentiated mononuclear stem cells, some of which spontaneously fuse to form terminally differentiated multinuclear myotube-like giant cells. The deprivation of fetal calf serum (FCS) or the exposure to retinoic acid, respectively, resulted in a significant inhibition of proliferation (P less than 0.001) and a marked increase in cellular differentiation as shown by a significant increase in the number of myotube-like giant cells (P less than 0.001) and in the creatine kinase activity (P less than 0.05) used as a biochemical marker of differentiation. Furthermore, after exposure to retinoic acid about 30% of the mononuclear tumour cells exhibited morphological features of rhabdomyogenic differentiation, such as bundles of thick and thin myofilaments, which had never been observed in the mononuclear cells of untreated cultures. These results confirm that the inverse linkage between proliferation and differentiation known from embryonic myogenesis is preserved in our rhabdomyosarcoma cell line. The failure to induce terminal differentiation by exposure to retinoic acid in all the cells of our clonal cell line indicates that some tumour cells might epigenetically be blocked from responding to retinoic acid. The temporary growth retardation observed after FCS-deprivation suggests that autocrine stimulation of proliferation may be operating in our cell line, too.
The clonal rat rhabdomyosarcoma cell line BA-HAN-1C was tested for its susceptibility to differentiation induction with different polar compounds. This cell line is composed of proliferating mononuclear tumour cells, some of which spontaneously fuse to form terminally differentiated postmitotic myotube-like giant cells. Exposure of BA-HAN-1C cells to dimethylsulphoxide (DMSO), hexamethylene bisacetamide (HMBA), sodium butyrate (NaBut) and N-monomethylformamide (NMF) resulted in a significant inhibition of proliferation (P less than 0.001) and in a simultaneous increase in differentiation. The response was most pronounced after exposure to NMF as evidenced by a marked increase in the creatine kinase activity used as a biochemical marker of differentiation (P less than 0.05) and the number of terminally differentiated myotube-like giant cells (P less than 0.001). Furthermore, about 5% of the mononuclear cells exhibited thick and thin myofilaments which were never observed in the mononuclear cells of the control. In contrast, the effects of DMSO, HMBA and NaBut were exclusively confined to a significant increase in biochemical differentiation (P less than 0.05), whereas no increase in morphological differentiation was observed and the number of myotube-like giant cells even significantly (P less than 0.001) decreased. This heterogeneous response to differentiation induction with different polar compounds probably indicates different mechanisms of action and suggests that the induction of biochemical differentiation might be independently regulated from events leading to cell fusion and terminal differentiation.
A fully mechanized immunonephelometric method is described for the rapid and specific determination of apolipoprotein A-II in serum. The method utilizes commercially available sheep antiserum against human apolipoprotein A-II. Nephelometry was performed with the Behring Nephelometer Analyzer (BNA). A single determination can be performed in 12 minutes, requiring 10 microliters sample volume. The measuring range is about 0.08 to 1.25 g/l apolipoprotein A-II. Precision is characterized by intra-assay coefficients of variation of 3.37%, 3.93% and 4.49% for apolipoprotein A-II concentrations of 1.22 g/l, 0.376 g/l and 0.185 g/l, and inter-assay coefficients of variation of 4.27% for an apolipoprotein A-II concentration of 0.404 g/l, respectively. Accuracy of the method is shown by the close correlation of results with those from radial immunodiffusion (r = 0.913, y = 1.091 x -0.033, n = 75).
BA-HAN-1C is a clonal rat rhabdomyosarcoma cell line composed of proliferating mononuclear cells, which partly fuse to terminally differentiated postmitotic myotube-like giant cells. The exposure to retinoic acid in vitro resulted in time- and dose-dependent changes of both cell differentiation and cell growth. The mononuclear cells revealed bundles of newly formed thick and thin myofilaments, never observed in untreated cultures, and exhibited signs of contact inhibition. In addition, there was a statistically significant increase (P less than 0.001) in the number of terminally differentiated postmitotic myotube-like giant cells and in the creatine kinase activity (P less than 0.05) which was used as a biochemical differentiation marker. At the same time cell growth was significantly inhibited (P less than 0.001) in vitro and a decrease in plating efficiency, as well as in saturation density, was observed. These data demonstrate that retinoic acid can suppress cell growth and simultaneously initiate differentiation in a malignant mesenchymal tumor cell line. However, despite the clonal nature of BA-HAN-1C, the complete status of terminal differentiation was not achieved by all tumor cells. The reason why not all tumor cells responded to retinoic acid is unknown at the present time and will have to be the subject of further studies.
Explore the source record for details and available documents.
Omega-3-fatty acids are increasingly used by the selfmedicating patient. Since fish oils in capsules are regarded as dietary food, there are neither official regulations in the Federal Republic of Germany concerning a minimum content of omega-3-fatty acids nor detailed rules for the limitation of autoxidation of these highly reactive substances. Both fatty acid composition and the degree of lipid peroxidation were measured in this study in 23 OTC fish oil preparations. The proportion of omega-3-fatty acids was in most fish oils about 30%; exceptions were the only ethyl ester among the preparations with 59% and the cod liver oils (13% to 22%). Regarding the peroxide value considerable differences were found: the lowest was 2 and the highest was 44.7. Since lipid peroxides and their degradation products are basically toxic, a limitation of the allowed degree of lipid peroxidation in fish oils is strongly recommended.