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Biomedical subjects

U Graf

Publications and source records attributed to U Graf.

At least 73 records · Page 4Linked to original sources

[Renal side effects of treatment with cyclosporin A in rheumatoid arthritis and after bone marrow transplantation].

Renal function was studied prospectively in 6 patients with rheumatoid arthritis and non-prospectively in 5 patients after bone marrow transplantation. Both groups were treated with cyclosporin A. Functionally and histologically the results suggest tubulotoxicity of cyclosporin A which seems to be dose-related and reversible. Also found in the urine of these patients were yellow, as yet undescribed crystalline bodies often included in casts.

Aged↗

Mutation induction in repair-deficient strains of Drosophila.

Experimental evidence indicates a polygenic control of mutagenesis in Drosophila melanogaster. In oocytes chromosome aberrations detected as half-translocations or dominant lethals depend on a repair system which in a number of genetically nonrelated strains shows different repair capacities. Sister chromatic exchanges (SCE) are easily studied as ring chromosome losses. They develop through a genotype controlled mechanism from, premutational lesions. Stocks with particular pairs of third chromosomes were discovered in which increased sensitivity of larvae to the toxic effects of a monofunctional alkylating agent (MMS) correlates with high frequencies of x-ray induced SCE's. Sex-linked mutagen-sensitive mutants could be shown to control mutation fixation: Pronounced maternal effects were found when sperm carrying particular types of premutational lesions were introduced into different types of mutant oocytes. The mutant mus(1)101D1 was found to be unable to process lesions induced by the crosslinking agent nitrogen mustard (HN2) into point mutations (measured as sex-linked recessive lethals). Alkylation damage leads to increased point mutation frequencies in the excision repair deficient mutant mei-9L1, but to reduced frequencies in the post-replication repair deficient mutant mei-41D5. It became clear that the study of maternal effects on mutagenized sperm represents an efficient tool to analyze the genetic control of mutagenesis in the eukaryotic genome of Drosophila melanogaster.

Alkylating Agents↗

[Psychological aspects relating to artificial donor insemination (ADI) (author's transl)].

Discussed in this paper is the psychic situation of sterile couples who resort to artificial insemination, using donor semen (ADI). --Careful psychodiagnostic checking prior to ADI seems to be essential to forestalling psychic problems. ADI treatment should be applied solely to really sterile couples of stable psychic status and with good communication between the two partners. A method of psychological preparation for ADI is described. Psychodiagnostic examinations should be followed by specific gynaecological checks. Such approach will yield at least two advantages: 1. Gynaecological examination will not be necessary, if contra-indications are concluded from psychological checking 2. Early psychological assessment of sterile couples will become possible. Favourable psychic development of both couples and children born as a result of ADI will be an additional advantage of high probability.

Attitude↗

Lack of correlation between MMS-toxicity in larvae and in adults of mutagen-sensitive mutants of Drosophila melanogaster.

Adult males of 20 different stocks of Drosophila melanogaster, including 16 with various X-linked mutagen-sensitive mutations, were tested for sensitivity to the lethal action of methyl methane sulfonate (MMS) in a continuous feeding experiment. It was impossible to establish a correlation between MMS-toxicity in adults and MMS-toxicity in larvae. In addition, experiments to examine the fertility of MMS-treated flies of four mutagen-sensitive strains and one wild-type strain were performed. These experiments demonstrated that the spermatogonia of mei-9L1 and mei-41D5 in larvae and in adults are more sensitive to MMS than the spermatogonia of the wild-type strain or the other two mutagen-sensitive strains.

Administration, Oral↗

Mutagen-sensitive mutants in Drosophila melanogaster: effects on premutational damage.

Drosophila melanogaster males from a Basc stock were mutagenized with either X-rays, ethyl methanesulfonate (EMS), or nitrogen mustard (HN2). Groups of identically treated males were crossed to different types of female. Sex-linked recessive lethals were scored as a genetic end point. The females used were homozygous for X-chromosomal mutations (mus(1)101D1, mus(1)104D1, mei-9 or mei-41D5) which lead to defective DNA repair and which increase the mutagen sensitivity of larvae. Females from a white stock with normal DNA repair capacities served as controls. The premutational lesions induced in mature sperm are only processed after insemination by the maternal enzyme systems present in the oocytes. Differences in the efficiency of the processing of lesions can lead to maternal effects on the frequency of mutations recovered from mutagenized sperm. It was found that, with the exception of mus(1)104D1, all mutants analysed significantly modify the mutation fixation of one or more types of premutational lesions. The most drastic effect is found with the mus(1)101D1 stock in which HN2-induced DNA cross-links do not lead to sex-linked recessive lethals. It is assumed that mus(1)101D1 is defective in an early step of DNA cross-link repair. Our first set of data clearly demonstrates that the study of maternal effects in Drosophila is an efficient tool to analyse the in vivo function of repair mutations on chemically induced mutagenesis.

Animals↗

[The effect of treatment on circulating immune complexes in rheumatoid arthritis (author's transl)].

Immune complexes were demonstrated by leucocyte phagocytosis assay in 37 of 55 patients with rheumatoid arthritis. After treatment with gold salts, penicillamine, alpha-mercaptopropionylglycine, immunosuppressive agents or levamisole a substantial fall or elimination of demonstrable circulating immune complexes occurred. In-vitro studies revealed that gold salts in therapeutic concentrations inhibited the phagocytosis of immune complexes, while other drugs - penicillamine, levamisole and all anti-inflammatory agents including corticosteroids - lack this effect. The reduction in circulating immune complexes under basic therapy may be due to a beneficial effect of these agents on the disease process itself. This test may, therefore, be of value in assessing the efficacy of drug treatment.

Antigen-Antibody Complex↗

A protective effect of caffeine on drosophila larvae treated with methyl methanesulfonate.

Lethality induced in larval populations of Drosophila melanogaster was recorded after treatment with (1) caffeine, (2) MMS or (3) caffeine plus MMS. The mixture of caffeine plus MMS was less toxic than expected from the effects observed after treatment with either substance individually. It is postulated that in the combined treatment the caffeine, by inhibiting semiconservative DNA replication, allows for some additional time for repair of alkylated DNA by a repair pathway which is not sensitive to caffeine, possibly excision repair.

Animals↗

Caffeine toxicity in drosophila strains having different MMS sensitivities.

Larvae of Drosophila melanogaster were fed with caffeine, and the induced lethality was recorded using two different methods. With a wild-type strain a whole dose-response curve was obtained. The two sexes were equally sensitive. Four genetically different strains, showing different MMS sensitivities, were tested with two caffeine doses. The strains differed significantly in their caffeine sensitivity, but there existed no correlation between MMS and caffeine sensitivity.

Animals↗

[Demonstration and analysis of immune complexes in rheumatic diseases].

By means of an immunofluorescence technique, immune complexes have been demonstrated in circulating blood leukocytes, in serum and in joint effusions of patients with various rheumatic diseases. Such complexes are present within cell inclusions in about 30% of patients with rheumatoid arthritis (RA). RA patients has immune complexes in serum in 75% of cases and in joint effusions in over 80% of cases. Soluble immune complexes were demonstrated in the serum of about 30% of age-matched patients with degenerative joint disease, while such complexes are present in the serum of only 1.5% of a younger, normal control group. The immune complexes chiefly contain IgG, frequently IgM and only rarely IgA. CO complement component can frequently be demonstrated within such complexes. In RA patients a statistically significant correlation (p less than 0.001) could be established between the presence of soluble immune complexes and erythrocyte sedimentation rate, but no correlation was observed between the presence of such complexes and the Lansbury joint index. The possible pathogenetic role of immune complex clearance by circulating leukocytes in rheumatoid arthritis is discussed.

Antigen-Antibody Complex↗