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Biomedical subjects
Publications and source records attributed to A Schmidt.
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Especially in their early phase of action carcinogens are strong inhibitors of cell proliferation. This is an apparent contradiction to the promoting activity of oncogens in the process of carcinogenesis. Because of obvious similarities between restorative and neoplastic growth processess on the tissue level we have studied the possibility, whether such similarities do exist also with regard to stimulatory activities in the serum. To overcome the non-specific inhibitory effect of a carcinogen, the serum of 2-acetylaminofluorene (AAF) treated male Sprague-Dawley rats was transferred to normal recipients. The results demonstrate that the proliferation of the same tissues (hepatocytes, adrenocortical cells, thymocytes) as in liver regenerating animals were stimulated by the serum of the carcinogen-treated rats. Whether the observed short-term effect corresponds to the so-called promoting activity of the carcinogen(s) is discussed. Nature and origin of the humoral stimulator(s) are still unknown.
Carcinogens of chemically unrelated structure and different organotropism cause a mitotic stimulation of adrenocortical epithelia in vivo. A similar response is observed in liver regenerating rats following partial hepatectomy or intoxication by carbon tetrachloride. It is very probable from these and other results that the short-term effect (48 hours p. applic.) is brought about by the emergence of humoral growth stimulators which are evidenced in restorative regeneration and, therefore, accounts for the promoting activity of carcinogens. Special problems resulting from false positive (indomethacin, sodium nitrite) and false negative (7,12-dimethylbenz(a)anthracene, ethionine) findings as well as such of the role of solvents are discussed. The proof of the "contradictory" test result by long-term treatment in the case of trinitroso-trimethylene-triamine, nitroso-ethyltert-butylamine or nitroso-diallylamine has shown the accuracy of this short-term test.
Large-scale purification of translational inhibitors present in interferon-treated mouse L cells, but not in untreated cells, led to the isolation of two interferon-induced activities. One is a protein kinase system that is activatable by double-stranded RNA and ATP and that phosphorylates a Mr 67,000 protein and the smallest subunit of eukaryotic initiation factor-2. The purified protein kinase is a strong translational inhibitor. The second activity is an enzyme that, with double-stranded RNA, slowly polymerizes ATP into oligoadenylate with a 2'-5' phosphodiester linkage. The oligo-isoadenylate in turn activates a potent inhibitor of mRNA translation.
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Congenital Hepatic fibrosis is an uncommon disease, which is autosomal recessive. Two forms of the disease are distinguished: a rare one becoming manifest in the neonatal period with signs of progressive renal failure secondary to polycystic kidneys, in such cases the liver fibrosis is usually asymptomatic, and the diagnosis is therefore often first established post mortem. In the other more usual form the patients present during infancy with bleeding from rupture of esophageal varices caused by portal hypertension. One case is reported, and the history of his two brothers are referred to. In our case a portacaval anastomosis was performed and the patient is asymptomatic with no signs of encephalopathy. His two brothers died, one of bleeding from esophageal varices, the other of hemolytic anemia. In both cases the diagnosis was first made post mortem.
The possible existence of circulating pancreatic type glucagon (immunoreactive glucagon as measured with a highly specific antibody) of extrapancreatic origin was investigated in 20-25 kg pigs after pancreatectomy. In intact conscious animals intravenous arginine infusions stimulated glucagon as well as insulin secretion, while blood glucose remained unaffected. Two weeks after pancreatectomy, and 48 hours after insulin withdrawal, basal glucagon and glucose concentrations were elevated (from 22 +/- 3.7 to 55 +/- 9.5 pmol/1 and 5.8 +/- 0.4 to 16.2 +/- 2.0 mmol/l, respectively), (mean +/- SEM), while insulin concentrations were either undetectable or very low. After pancreatectomy, however, glucagon concentrations no longer increased during arginine infusion. Gut type glucagon levels were not affected by pancreatectomy, and did not change during arginine infusion. When examined by gel filtration, plasma from unoperated pigs contained two components of pancreatic type glucagon, one coeluting with the glucagon marker, the other eluting earlier, probably reflecting larger molecular size. After pancreatectomy only this larger component was found in the plasma. The role of this component in the control of blood glucose is unknown.
In 9 of 450 patients with Hodgkin's disease the fibrosis of retroperitoneal lymphnodes has been diagnosed by lymphangiographys. 5 cases with fibrosis were assigned to the clinical stage III B, and 4 cases to the stage IV B. According to the microscopic subclassification nodular sclerosis was diagnosed 7 times, the mixed type and lymphocytic depletion were found in 1 case. Lymphnode fibrosis developed spontaneously in 1 case, in three other patients following cytostatic treatment and in 5 patients after combination of radiation and chemotherapy. It has been concluded from these results that lymphnode fibrosis is induced mostly by therapy. Spontaneous fibrosis is a rare event in Hodgkin's disease.
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0,0-Dimethyl(1-hydroxy-2,2,2-trichlorethyl)phosphonate (Trichlorfon; TCP) was tested for carcinogenic activity in male and female Syrian hamsters (Mesocricetus auratus Waterhouse) by intraperitoneal administration. The period of administration was 90 weeks, when maximum total doses of 204 mg (male) and 206 mg (female) TCP per animal had been injected. The study was terminated at 100 weeks. There was no statistically significant difference, when compared the total tumour incidence, or the incidence of malignant and benign tumours separated, of the groups of treated and control animals. These findings were independent from whether the groups of TCP-injected animals and controls were combined or divided by sex.
Extracts of 14 species of phototrophic bacteria, partly grown with different sulfur compounds, were tested for their ability to form volatile sulfur compounds from adenylylsulfate (APS) and 3'-phosphoadenylylsulfate (PAPS). The Rhodospirillum species showed marked activities with both APS and PAPS while the Rhodopseudomonas species seem to prefer PAPS. The Chromatiaceae exhibited the strongest activities with APS, whereas Chlorobium limicola had equally high activity with PAPS.
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Serum lysozyme (muramidase) concentrations were determined in five patients with Morbus Crohn before and after resection of inflammated bowel areas. The serum lysozyme activity which was elevated before surgical treatment in all patients fell to normal values after bowel resection within a few hours. Our findings suggest, that the elevated serum lysozyme reflects an increased lysozyme production in the inflammated bowel tissue.
Crude extracts of Rhodospirillum rubrum catalyzed the formation of acid-volatile radioactivity from (35S) sulfate, (35S) adenosine-5'-phosphosulfate, and (35S) 3'-phosphoadenosine-5'-phosphosulfate. An enzyme fraction similar to APS-sulfotransferases from plant sources was purified 228-fold from Rhodospirillum rubrum. It is suggested here that this enzyme is specific for adenosine-5'-phosphosulfate, because the purified enzyme fraction metabolized adenosine-5'-phosphosulfate; 3'-phosphoadenosine-5'-phosphosulfate, however, only at a rate of 1/10 of that with adenosine-5'-phosphosulfate. Further, the reaction with 3'-phosphoadenosine-5'-phosphosulfate was inhibited with 3'-phosphoadenosine-5'-phosphate whereas this nucleotide had no effect on the reaction with adenosine-5'-phosphosulfate. For this activity with adenosine-5'-phosphosulfate the name APS-sulfotransferase is suggested. This APS-sulfotransferase needs thiols for activity; good rates were obtained with either dithioerythritol or reduced glutathione; other thiols like cysteine, 2'-3'-dimercaptopropanol or mercaptoethanol are less effective. The electron donor methylviologen did not catalyze this reaction. The pH-optimum was about 9.0; the apparent Km for adenosine-5'phosphosulfate was determined to be 0.05 mM with this so far purified enzyme fraction. Enzyme activity was increased with K2SO4 and Na2SO4 and was inhibited by 5'-AMP. These properties are similar to assimilatory APS-sulfotransferases from spinach and Chlorella.
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The effect of peripheral and intraportal infusions on 0.86 pmol/kg-min-1 of glucagon on plasma glucose, plasma insulin, and glucose tolerance was examined in four normal subjects. Peripheral glucagon concentrations increased by 60--90 pmol/1 during intraportal and 70--180 pmol/1 during peripheral infusions. The infusions caused increases in plasma glucose levels of approximately 1 mmol/1, and in plasma insulin levels of 75--100%, regardless of route of administration. Intravenous glucose tolerance tests carried out during the glucagon infusions showed that glucose tolerance remained within the normal range and was uninfluenced by the route of administration.