Biomedical subjects
Publications and source records attributed to M Müller.
Half-maximal rate of the ATP- and ubiquitin-dependent proteolysis of rabbit reticulocytes, determined in a cell-free system, require 0.5 mg/ml of mitochondria-containing stroma (MCS) protein at a fixed ATP concentration or 100 microM ATP at a fixed protein concentration. 20 microM hemin caused 50% inhibition of degradation of MCS.
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Biochemical analyses from endomyocardial biopsies indicate that cardiac energy metabolism is altered in patients with end-stage cardiac failure. Myocardial energy production is predominantly based on fatty acid oxidation. Carnitine, a naturally occurring compound, plays an essential role in fatty acid oxidation by carrying long-chain fatty acids into the mitochondrial matrix where they undergo beta-oxidation. In experimental animals, myocardial carnitine deficiency may cause cardiomyopathies which are reversible with carnitine substitution. Rare human diseases, as systemic carnitine deficiency, are associated with impaired cardiac function. We therefore investigated carnitine metabolism in patients with cardiac failure. Plasma and myocardial carnitine levels were measured in 55 patients undergoing cardiac transplantation because of end-stage cardiac failure based on dilated cardiomyopathy (DC, n = 30) or coronary artery disease (CAD, n = 22). Elevated plasma carnitine levels (controls: 49 +/- 12 microM; DC: 82 +/- 38 microM; p less than 0.001, CAD: 86.9 +/- 21.6 microM; p less than 0.05) were found in both patient groups (Fig. 1). Plasma carnitine did not correlate with creatinine (Fig. 2). Compared to controls, myocardial carnitine levels were significantly reduced: DC: 5.9 +/- 1.45 nmol/mg NCP; CAD: 5.84 +/- 1.84 nmol/mg NCP; controls: 15.6 +/- 5.4 nmol/mg NCP (Fig. 3). No correlation between myocardial and plasma levels was found (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)
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The suitability of a biosynthetically produced [15N] yeast-protein-thermitasehydrolysate ([15N] YPTH), [15N] yeast protein and [15N] glycine for use as 15N-tracers was tested in three groups of four infants each. The [15N] YPTH was obtained by hydrolysing 15N-labelled yeast protein with thermitase, a proteinase from Thermoactinomyces vulgaris. Following oral single-pulse labelling in a dosage of 10 mg 15N/kg body weight the 15N-excretion in stools and urine as well as the 15N-abundance in plasma proteins and in the TCA-soluble plasma fraction were determined. The [15N] YPTH differs from [15N] glycine in terms of the complete distribution of 15N among all 20 amino acids. This could be demonstrated by a distinctly lower [15N]ammonia (0.5 per cent) and a higher [15N2] urea excretion (5.0 per cent) compared with [15N] glycine (1.2 and 3.4 per cent respectively). The faecal loss of 15N from the [15N] YPTH was 3.7 per cent of the tracer dose, while the corresponding value after administration of [15N] yeast protein was found to be 7.4 per cent on average. There were no differences between the tracer substances in terms of the measured 15N-abundance in the plasma proteins (mean: 0.07 atom per cent excess) and in the TCA-soluble fraction (mean: 0.21 atom per cent excess).
A report is given on a newborn calf showing mucosal hemorrhage and melena. All blood clotting tests, except for prothrombin time (which proved to be initially prolonged), had normal results. The striking recurrent thrombocytopenia was successfully treated with prednisolone. Autoimmune idiopathic thrombocytopenia is suspected as a possible cause.
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The advantage of a standardized oligopeptide formula (Peptisorb päd) for dietary management of diarrhea was proved in 10 infants aged 1 to 10 months with body weights between 4000 and 8860 g. The nitrogen balance turned to normal already at day 3 to 4 of the treatment due to the rapid increase of food supply. Whole body protein parameters estimated by 15N yeast protein thermitase hydrolyzate as a tracer substance were already normalized at that time. Protein synthesis amounted to 5.0 +/- 1.5 g/kg/day, protein breakdown to 3.7 +/- 1.5 g/kg/day and net protein gain to 1.3 +/- 0.6 g/kg/day, resp. Reutilisation rate of endogenous nitrogen was found to be 83%. This correlates with the relatively high nitrogen supply of the oligopeptide diet in comparison to mother's milk feeding. Approximately 15% of the administered amount of total nitrogen were excreted in the feces in contrast to only 5.8% of the 15N tracer dose, indicating the higher losses of endogenous nitrogen due to enteritis. The absorption of the medium chain triglycerides from the diet was 97.5% at an average and thus extremely high.
Activated species of oxygen produced in the hypoxic rat liver leave the cells and attack the membrane of circulating erythrocytes. Therefore the metabolic and structural changes of red blood cells may be appropriate indicators of an oxidative loading in tissues. The circulating erythrocytes exert a profound protective, "radical scavenger effect" on the liver tissue.
The efficacy and tolerability of a conventional vitamin K1 preparation containing polyoxyethylated castor oil as solubilizer were compared with those of a new compound containing mixed micelles as solubilizer in 30 patients. A statistically significant increase in the thrombotest was detected after treatment in both groups. No hematological or chemical toxicity was observed during the observation period. One patient had an anaphylactoid reaction after intravenous injection of the mixed micelles preparation. Intradermal testing yielded positive results. The authors conclude that intravenous administration of vitamin K preparations should be reserved for acute emergencies.
Human mononuclear blood cells (MBC) express procoagulant activity PCA) upon stimulation in vitro. This thromboplastin activity is generated in monocytes under the influence of T-helper cell-derived signals. The own experiments described here served to establish the methodological basis for human MBC PCA generation in vitro and its measurement. Using Con A as stimulant it was shown that maximum PCA could be detected after 6-8 h of incubation. Incubation of the cells at 37 degrees C resulted in much higher PCA as compared to 40 degrees C. But in most experiments the specific differences between unstimulated controls and the Con A treated cells were more marked at 40 degrees C, because the "spontaneous" activation of controls occurred more slowly. The "spontaneous" activation of controls has been the most troublesome problem throughout the experiments, and was most likely due to traces of endotoxin in the media used. Choosing an incubation temperature of 40 degrees C it was shown that neither glass-adherent (AC) nor non-adherent cells (NAC) responded sufficiently to Con A when incubated separately. Addition of NAC to AC restored the capability to respond to Con A. NAC pulse-stimulated with Con A were able to activate AC. The same has been true for 20 h incubation supernatants of Con A-pulsed NAC. Finally, some two-way MBC mixed culture experiments are described which have been conducted under apparently endotoxin-free conditions. These results clearly show cellular PCA generation to be a sensitive indicator of allogenic recognition.
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Recent developments in preparatory procedures for electron microscopy and immunocytochemistry are presented as a background for the morphological diagnosis of bone dysplasia. With the new low temperature embedding techniques and the availability of monoclonal antibodies raised against the main matrix macromolecules, biopsies have proved to be an important complement to clinical and radiological workup and they may sometimes provide the final clue to the diagnosis.