Biomedical subjects
Publications and source records attributed to H Wohlert.
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The antibiotic, streptozotocin, has carcinostatic, carcinogenic, and diabetogenic properties. Moreover, it is capable of inducing the enzyme tyrosine aminotransferase in a permanent line of rat liver cells. In the present publication, the effects of streptozotocin upon the induction of tyrosine aminotransferase, NAD synthesis, and methylation of DNA in different organs were analyzed in vivo. If administered alone, streptozotocin slightly induced tyrosine aminotransferase. The induction of tyrosine aminotransferase caused by tryptophan or nicotinamide was inhibited by streptozotocin. Streptozotocin reduced the NAD content of the liver. NAD synthesis induced by tryptophan was reduced by streptozotocin, while that induced by nicotinamide was enhanced. DNA methylation in the form of 5-methyl cytosine was not influenced by streptozotocin.
1. The content of 5-methylcytosine of the DNA of 11-day old mice embryos was compared with that of the DNA of different plasmocytoms. 2. Furthermore the DNA content was determined in different transplantable tumors and normal organs of the rat and the mouse. 3. By the aid of liquid chromatography significant differences could be demonstrated in the content of 5-methylcytosine of the DNA of BALB/c-mice or NMRI-mice and the DNA of the plasmocytom MOPC 104 E and MOPC 141, but not in the case of MOPC 321. 4. Clear differences could be observed with restriction enzymes: the DNA of all the plasmocytoms studied is more digested with Hpa II and Hha I than the DNA of the embryos. This is not the case however with MSP I. 5. The DNA of three transplantable tumors tested contains less 5-methylcytosine than the one of the liver kidney of the mouse and the rat. This was confirmed with restriction enzymes too.
Erythroleucemic cells of rats were induced by DMSO for the terminal erythroid differentiation. The base composition and the 5 MC content of the DNA were analyzed by HPLC and a significant difference between non-induced and induced cells was not found. The analysis of labelled DNA by the restriction enzymes Hha I, Hpa II, and Msp I did not result in a different pattern before and after the induction. These results suggest that the 5 MC content of the DNA does not change during the induced terminal erythroid differentiation.
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Embryos of the sea urchin Psammechinus miliaris have been labelled after fertilization with [6(-3)H]uridine and cultured in filtered sea water. 32-cell, blastula, gastrula and pluteus stages were harvested. The DNA from these embryos was purified and hydrolyzed and the nuclear bases were analyzed by means of high performance liquid chromatography. The ratios of 5-methylcytosine and cytosine demonstrate that the concentrations of 5-methylcytosine are essentially the same in the developmental stages examined (gamma = 95%), which contradicts the hypothesis that methylation of DNA plays a role in cell differentiation.
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NAD acts not only as a coenzyme in oxidation-reduction processes but also as substrate for adenoribosylation of different proteins. Patients suffering from rheumatoid arthritis show a disturbance in their tryptophan metabolism. Since tryptophan represents a precursor of NAD we turned our attention to the activity of the ADPR transferase, being the enzyme of adenoribosylation, as well as to the synthesis of NAD derived from nicotinamide in human lymphocytes. Lymphocytes of patients with rheumatoid arthritis did not show any differences in their activities as compared with those of control persons, regardless of different measures applied to the patients.
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OBJECTIVE: The anti-arthritic reactivity of the IL-1 receptor antagonist IL-1ra was tested in male DBA/1xB10A(4R) mice suffering from potassium peroxochromate-induced arthritis. METHODS: Inflammatory arthritis was induced in male DBA/1xB10A(4R) mice by the intraplantar application of potassium peroxochromate and was quantified by the determination of the arthritis index, whole blood chemiluminescence, serum sulfhydryls and nitric oxides. Culture supernatants of the fibroblasts were assayed spectrophotometrically for collagenase release. RESULTS: Overt arthritic symptoms, as measured by the arthritis index, were significantly inhibited after two intraperitoneal injections of 2 mg/kg IL-1ra. The phorbol-ester-stimulated chemiluminescent response of monocytes and polymorphonuclear leukocytes in whole murine blood, which increased 5-fold during the development of arthritis, was normalized to the level of healthy controls. The oxidation of serum sulfhydryls was inhibited by 25%, and the serum levels of nitric oxides was depressed by 40%. In vitro the IL-1-dependent induction of collagenase of rabbit synovial fibroblasts was completely suppressed in the presence of 0.4 mg/ml IL-1ra. CONCLUSION: IL-1ra may prove useful to control the consequences of enhanced free radical production in inflammatory rheumatic diseases.