[ATPase activity in the nervous system of fetuses, healthy piglets and piglets with splayleg syndrome].
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Biomedical subjects
Publications and source records attributed to E Kolb.
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In the development of a tumour a multistep process is existing, in which after activation of a cellular oncogen and after efficacy of a viral oncogenat first an avalanche-like increase of transforming, excluding the regulation of cell division proteins takes place. In many forms of tumours the transforming proteins possess the property of protein kinases and phosphorylize proteins situated in the area of the cell membrane. In some forms of tumours an enrichment in the area of the cell nucleus takes place. Secondarily, in the tumour cells frequently other oncogens are activated and an activation of further genes for the formation of growth factors or of proteins of the histocompatibility complex, respectively, occurs. Some transforming proteins themselves possess the properties of growth factors and of receptors, respectively, for the binding of such ones. Cocarcinogens activate the protein kinase C, e.g. the phorbol esters. Anticarcinogens influence the transcription, e.g. the vitamin A and the 1,25-dihydroxyvitamin D3. Vitamin A and analogous compounds increases the functional capacity of the immune defense.
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A survey is given of the biochemistry and importance of the prostaglandins, the thromboxanes, the prostacyclins and the leukotrienes. The formation of these compounds takes place from poly-unsaturated fatty acids and is regulated: here the phospholipase A2 plays a role. Among others the prostaglandins take part in the regulation of the blood supply of various tissues (heart, kidneys), in the regulation of the reproduction and in the evokation of labour. The thromboxanes and prostacyclins influence the aggregation and the desaggregation of the thrombocytes, respectively. The leukotrienes take part in the regulation of the permeability of the capillaries, in the migration of the leucocytes, the formation of inflammatory processes and in the evokation of asthma bronchiale. The insufficient intake leads to functional disturbances in various tissues, which partly are to be traced back to a decrease of the formation of the tissue hormones mentioned. An intake transgressing the demand has a favourable effect in various diseases: thus the inclination to aggregation of the thrombocytes is decreased and the development of arteriosclerotic changes is inhibited.
For pancreatic islet transplantation to become clinically applicable, chemical agents are needed which cause selective morphological alterations in the exocrine part of the organ within a few hours after application. DL-ethionine (Aet), cerulein (Cd), seleno-DL-methionine (SeMet) and seleno-DL-ethionine (SeAet) were given to rats during various time periods. At 4 h after i.p. injection, 40 mg/kg SeMet caused the greatest selective morphological alterations in the exocrine pancreas. Acinar structure disappeared, the exocrine cells were abnormal and their nuclei had various dimensions and forms. There were, however, no alterations in the islet cells. At this time, neither Aet, Cd, nor SeAet produced similar changes. SeMet was the most toxic substance and was taken up in the shortest time and in the greatest amount. This selective destructive SeMet effect allows better isolation of the islets from exocrine tissue thereby increasing islet yield and decreasing transplantation volume. Better islet purification may prevent an early rejection.
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Diffuse fibrinous-purulent peritonitis is an acute life threatening disease. Intensive care will at least for some time help to support vital functions even in patients with severe course, general intoxication, and multiple organ failure. A cure, however, can only be achieved if the cause for the intoxication syndrome can be eliminated by appropriate surgical procedures. The surgical procedures have to follow the general principles of septic surgery, including in certain cases air dressing, open treatment of wounds.
Therapeutic whole body hyperthermia (WBH) as an additional therapy in the treatment of cancer has been known for a long time and is beginning to attain acceptance. In a clinical study 28 patients were treated 70 times with WBH at a core temperature of 41.8 degrees C. Hyperthermia was induced and maintained with an extracorporal circuit (ECC). Patients were anaesthesized with nitrous oxygen, enflurane and fentanyl. Therefore artificial ventilation was mandatory. Invasive monitoring was used to control vital functions. The effect of WBH includes a rise in cardiac output and heart rate as well as a decrease in total vascular resistance and mean arterial pressure. Pulmonary function almost remains constant. A raised oxygen consumption is compensated by a rise of oxygen availability. In consequence of an augmented perspiratio insensibilis and the ECC, close observation of fluid and electrolyte balance is necessary. According to our experience the small number of complications and problems allows the treatment with WBH even of patients with a high risk of anaesthesia.
It is reported on recent recognitions in the activation of cellular oncogens by carcinogens, by exchange (translocation) of genes within various chromosomes as well as by infection by the proviruses DNA of retroviruses. Cellular oncogens can be activated by a mutation already by the exchange of a base in a desoxyribonucleotide. Mutations develop under the influence of carcinogens. The protein changed in a amino acid portion accepts transforming properties. The Epstein-Barr virus furthers the increase of the number of B-lymphocytes. In this case may take place a translocation of the oncogen c-myc of the chromosome 8 into the region of the gen-recombination for the formation of the polypeptide chains of the immunoglobulins in the chromosomes 2, 14, and 22, respectively: in this area is an acceleration factor for the transcription. Cellular oncogens may be activated by retroviruses also by the long terminal repetitive parts of the proviruses. Papilloma viruses relatively frequently appear in the carcinomas of the cervix.
By investigations on domestic and laboratory animals great progress was achieved in the clarification of the mechanism of action and of the metabolism of mycotoxins. The aflatoxins which inhibit the synthesis of RNA in the liver and which lead to a liver necrosis are all over the world of great importance as harmful substances for man and animals. The chronic intake in subtoxic doses has a tumour-evoking effect. The amatoxins of the green Amanita phalloides are also hepatotoxic: they inhibit the synthesis of messenger RNA in the hepatocytes. The ergot alcaloids unite with alpha-adrenoceptors and evoke an inhibition of the effectiveness of beta-adrenoreceptors: they effect a vasoconstriction, a contraction of the uterus and an inhibition of the prolactin secretion. The ochratoxins have an influence on the transcription and have a nephrotoxic and teratogenic effect. The trichothezene toxins inhibit the protein synthesis and already in a low dose decrease the formation of coagulation factors and of immunoglobulins. The zearalenon has an estrogen effect: it is bound to estrogen receptors and influences the transcription in the cell nuclei. Patulin has a tumour-evoking effect. Nutrients infested by fungi are to be excluded from the consumption by man.
Great progress was achieved in the clarification of the molecular structure and the mechanism of action of the toxins of pathogenic forms of bacteria. Proportions of toxins of Corynebacterium diphtheriae and of Pseudomonas aeruginosa transfer from the NAD and ADP-ribose protein to an amino acid of the elongation factor 2. Thus the protein synthesis is much inhibited. The cholera toxin and the L-toxin from Escherichia coli have a similar structure. They transfer an ADP-ribose portion from NAD to the GTP-protein of the adenylate cyclase complex, by which means the GTPase activity is reduced. The increase of the cAMP content leads to an increase of the permeability of the cells of the intestinal epithelium. The tetanospasmin decreases the production of the inhibitingly acting neurotransmitters ( glycin ) from intermediate neurons and thus evokes spasms. The botulinum toxin inhibits the release of acetylcholine from the motor end-plates and leads to paralyses. Staphylococcus aureus and Clostridium perfringens form among others cytolysins which are injurious to membranes.
The ascorbic acid plays an important part by activation of hydroxylation reactions in various biosyntheses, such as in that of tropocollagen, bile acids and carnitine. It also considerably participates in the detoxication of compounds by hydroxylation and in the maintenance of the cytochrome P 450 contents in the liver. A sufficient supply is of importance for the absorption and accumulation of iron as well as for the efficiency of the immune system. After application of 14C-labelled ascorbic acid the compound is retained mainly in the brain, the salivary glands, the adrenal glands, the testes and in the eye lens. The largest contents of ascorbic acid lies in the pituitary gland, in the adrenal glands and in the eye lens. The need of ascorbic acid varies in man in dependence upon the state of development and the loads between 30 and 60 mg/die. In great smokers, after operations and traumas as well as when infections are present the intake of 100 to 200 mg a day are recommended. When more 1 g a day are taken the utilization decreases, the decomposition and the excretion, respectively, increase. A dose of more than 2 g a day inhibits the phagocytosis activity of leucocytes.