Biomedical subjects
Publications and source records attributed to G Fuchs.
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.
The treatment of three patients suffering from carbon tetrachloride intoxication with antithrombin III and plasma derivatives is reported. In these patients an acute liver failure had been proven, characterized by a disturbed protein synthesis and a severe haemostasis defect. The latter manifested itself by a consumption of platelets, clotting enzymes and the inhibitors antithrombin III and alpha 2-antiplasmin. It was due to an intravascular coagulation leading to disturbances in the microcirculation. This often letal circulus vitiosus could be stopped in these patients by treatment with antithrombin III concentrate combined with low dose heparin and fresh frozen plasma. Clinical improvements are discussed on the basis of the pathophysiology of the liver.
In connection with the function of a newly constructed absorption model the problem of interpretation of values obtained by models in regard of bioavailability is discussed. Wrong interpretations can be obtained if nonanalogous values are compared. An interpretation is proposed to calculate a value which is analogous to the relative bioavailability (calculated bioavailability). The efficiency of the absorption model and of the interpretation method is demonstrated by three examples of preparations of phenytoin, digoxin and chloramphenicol. We compared these results with the bioavailability of these preparations and we found a good correspondence.
Computer calculations are used to show the feasibility of a concept which explains the manifestation of a pathological cell function from a latent state by the phenomenon of extrachromosomal inheritance (through the mitochondrial genome) in mammalian cells. A hypothesis is submitted in which this principle is applied to the process of carcinogenesis. According to this concept, the manifestation of a tumor cell--after the initiation stage--entirely depends on stochastic events, i.e., random distribution of mitochondria during cell divisions, with an accumulation of the lesion in a few out of many cells. We feel that this concept comprises a better explanation of many characteristics and peculiarities of the phenomenon of carcinogenesis than do attempts which explain tumor formation as a phenomenon caused by mutation in a nuclear genome. A consideration of the principles presented automatically leads to a number of specific consequences with regard to carcinogenesis. Some of these consequences are discussed. They include: 1. the process of malignant transformation should not be irreversible for all the cells of a progeny; 2. the number of mitochondria in a cell type should be inversely correlated to tumor frequency; 3. the latent period should mainly be determined by the cell division rate and the "extent" of the initiating event; 4. susceptibility to carcinogenesis may be substantially higher if the number of mitochondria per cell line is increasing or decreasing, i.e., during the embryonic and fetal periods; 5. heterogeneous types of cells may arise from a single "initiated" cell, and 6. the process of malignant transformation should not necessarily be confined to one generation of the species. In addition, experimental approaches to support the submitted concept are suggested.
Cimetidine plasma concentration-response relationships were investigated in six healthy subjects using suppression of gastric acid secretion under continuous pentagastrin stimulation (1.5 micrograms/kg/hr) as a test model. With the Hill equation the sigmoid was preferable to the linear relationship between plasma concentration and effect, and there were significant correlations of 0.78 micrograms/ml (range 0.54 to 1.04 micrograms/ml) for 50% inhibition of gastric acid secretion was determined; mean concentration for 90% inhibition was calculated to be 3.9 micrograms/ml. The model described should allow determination of whether different patient populations (e.g., healthy subjects, patients with ulcers, male and female patients, patients with renal or liver disease) differ from one another in concentration-response relationships to histamine H2-receptor antagonists, so that appropriate drug plasma levels should be achieved for specific degrees of inhibition of gastric acid secretion.
Explore the source record for details and available documents.
Methanobacterium thermoautotrophicum growing on H2 plus CO2 as sole carbon and energy source was found to contain acetate thiokinase (Acetyl CoA synthetase; EC 6.2.1.1); Acetate + ATP + CoA leads to Acetyl CoA + AMP + PPi. The apparent Km value for acetate was 40 microM. Acetate kinase (EC 2.7.2.1) and phosphotransacetylase (EC 2.3.1.8) could not be detected. The specific activity of acetate thiokinase was high in cells grown with limited H2 and CO2 supply (approximately 100 nmol/min . mg protein), it was low in exponentially grown cells (2 nmol/min . mg protein). This corresponded with the finding that cells growing linearly in the presence of acetate assimilated the monocarboxylic acid in high amounts (greater than 10% of the cell carbon was derived from acetate), whereas exponentially growing cells did not (less than 1% of cell carbon was derived from acetate). These latter observations indicated that acetate thiokinase and free acetate are not involved in autotrophic CO2 fixation in M. thermoautotrophicum. The presence and some kinetic properties of succinate thiokinase (EC 6.2.1.5), adenylate kinase (EC 2.7.4.3), and inorganic pyrophosphatase (EC 3.6.1.1) are also described.
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.
Cultures of the autotrophic bacterium Methanobacterium thermoautotrophicum were shown to assimilate acetate when grown on CO2 and H2 in the presence of acetate. At 1 mM acetate 10% of the cell carbon came from acetate, the rest from CO2. At higher concentrations the percentage increased to reach a maximum of 65% at acetate concentrations higher than 20 mM. The data suggest that acetate may be an important carbon source under physiological conditions. The incorporation of acetate into alanine, aspartate and glutamate was studied in more detail. The cells were grown on CO2 and H2 in the presence of 1 mM U-14C-acetate. The three amino acids were isolated from the labelled cells by a simplified procedure. Alanine, aspartate and glutamate were found to have the same specific radioactivity. Degradation studies showed that C1 of alanine, C1 and C4 of aspartate, and C1 and C5 of glutamate were exclusively derived from CO2, whereas C2 and C3 of alanine and aspartate, and C3 and C4 of glutamate were partially derived from acetate. These findings and the presence of pyruvate synthase, phosphoenolpyruvate carboxylase and alpha-ketoglutarate synthase in M. thermoautotrophicum indicate that CO2 is assimilated into the three amino acids via acetyl CoA carboxylation to pyruvate, phosphoenolpyruvate carboxylation to oxaloacetate, and succinyl CoA carboxylation to alpha-ketoglutarate.
The involvement of reactions of the tricarboxylic acid cycle in autotrophic CO2 fixation in Methanobacterium thermoautotrophicum was investigated. The incorporation of succinate into glutamate (= alpha-ketoglutarate), aspartate (= oxaloacetate) and alanine (= pyruvate) was studied. The organism was grown on H2 plus CO2 at pH 6.5 in the presence of 1 mM [U-14C-]succinate. Significant amounts of the dicarboxylic acid were incorporated into cellular material under these conditions. Alanine, aspartate, and glutamate were isolated and their specific radioactivities were determined. Only glutamate was found to be labelled. Degradation of glutamate revealed that C-1 of glutamate was derived from CO2 and C-2--C-5 from succinate indicating that in M. thermoautotrophicum alpha-ketoglutarate is synthesized via reductive carboxylation of succinyl CoA. The finding that succinate was not incorporated into alanine and aspartate excludes that oxaloacetate and pyruvate are synthesized from alpha-ketoglutarate via isocitrate or citrate. This is taken as evidence that a complete reductive carboxylic acid cycle is not involved here in autotrophic CO2 fixation.
Explore the source record for details and available documents.
Fibrous dysplasia of the bone does not only occur in childhood as commonly believed, but may also be diagnosed during adult life as a stepwise progressing disease. Bone scans are useful to differentiate active from non-active disease. Suspicious accumulations of the radio-pharmaceutical which may be detected by total body scanning, should be confirmed by roentgen examination as a more specific method. Bone scan is helpful in early detection of focal disease and may visualize lesions in wide-spread disease for further radiological workup.
Explore the source record for details and available documents.