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Biomedical subjects

G Ott

Publications and source records attributed to G Ott.

At least 163 records · Page 9Linked to original sources

Inhibition of condensation in the late-replicating X chromosome induced by 5-azadeoxycytidine in human lymphocyte cultures.

The cytidine analogue 5-azadeoxycytidine (5-azadC) induces a very distinct inhibition of condensation in the genetically inactive, late-replicating X chromosome (XL) when applied to human lymphocyte cultures. One of the two X chromosomes in cytogenetically normal female cells becomes dramatically longer than its homologous partner. The highest rate of metaphases with an undercondensed XL chromosome is achieved when 5-aza-dC is added at a final concentration of 10(-5) M 2 h before cell harvesting. The interactions between 5-aza-dC and chromosomal DNA as well as the factors involved in X chromosome inactivation are discussed.

Azacitidine↗

Differential inhibition of sister chromatid condensation induced by 5-azadeoxycytidine in human chromosomes.

The deoxycytidine analogue 5-azadeoxycytidine (5-aza-dC) induces differential inhibition of sister chromatid condensation when cells are treated with this substance for two replication cycles, as the subsequent staining of metaphase chromosomes with Giemsa shows. The bifilarly substituted chromatid is dramatically longer than the unifilar one. A percentage of the metaphases treated with 5-aza-dC even show a complete undercondensation of the bifilarly substituted chromatid. The optimum conditions for inducing sister chromatid differentiation were determined. No method has been developed as yet to permit enhancement of the differential staining in 5-aza-dC-treated preparations. The interactions between 5-aza-dC and chromosomal DNA as well as the factors involved in the differential staining of sister chromatids are discussed.

Azacitidine↗

Heterochromatin in the chromosomes of the gorilla: characterization with distamycin A/DAPI, D287/170, chromomycin A3, quinacrine, and 5-azacytidine.

The chromosomes of the gorilla were extensively studied with various staining techniques labeling the different classes of heterochromatin. The chromosomal distribution of distamycin A/DAPI-, D287/170-, quinacrine-, and chromomycin A3-positive heterochromatic regions, as well as the nucleolus organizer regions, is described and compared with the karyotypes of other hominoid species. Lymphocyte cultures were treated with low doses of 5-azacytidine during the last hours of culture. This cytidine analog induces distinct undercondensation in 37 heterochromatic regions in the 24 gorilla chromosomes. The 5-azacytidine-induced undercondensations are localized not only in most of the distamycin A/DAPI-bright heterochromatic regions but also in many telomeric C-bands of the chromosomes. Furthermore, 5-azacytidine preserves the somatic pairing between heterochromatic regions from the interphase nuclei into the metaphase stage. The homeologies and differences in the chromosomal localization of the various classes of heterochromatin, 5-azacytidine-sensitive regions, 5-methylcytosine-rich DNA sequences, and satellite DNAs in the gorilla, chimpanzee, orangutan, and man are discussed.

5-Methylcytosine↗

Evolutionary conservation of fragile sites induced by 5-azacytidine and 5-azadeoxycytidine in man, gorilla, and chimpanzee.

Lymphocyte cultures from man, gorilla, and chimpanzee were treated with 5-azacytidine and 5-azadeoxycytidine. These cytidine analogues induce common fragile sites in the chromosome bands 1q42 and 19q13 of man. A rare fragile site is induced by 5-azadeoxycytidine in the band 1q24. The optimum conditions required for inducing these new fragile sites were determined by a series of experiments. The common fragile site in human chromosome 1q42 also exists in the gorilla and chimpanzee in the homologous band 1p32. The fragile site in human chromosome 19q13 was demonstrated in the gorilla in the homologous chromosome band 20q13. These are the first examples found of evolutionary highly conserved fragile sites in homologous chromosome bands in related primate species. The interaction between 5-azacytidine, 5-azadeoxycytidine, and chromosomal DNA; the evolutionary conservation of genes located within or closely adjacent to the fragile sites in the chromosome 1 of Hominoidea; and the phylogenetic origin of the two new common fragile sites are discussed.

Animals↗

Differential turnover of tRNAs of the queuosine family in Dictyostelium discoideum and its possible role in regulation.

In its natural environment the protist Dictyostelium discoideum grows on bacteria and queuosine-containing tRNAs of the bacteria serve as source of the nutrient factor queuine. This deazaguanine derivative is inserted into tRNAAsp, tRNAAsn, tRNAHis and tRNATyr of the amoebae. The axenic strain AX-2 of D. discoideum grows equally well in a defined medium with or without exogenous queuine. When queuine is omitted, changes occur in lactate levels, lactate dehydrogenase patterns and cytochromes and the amoebae cannot differentiate after a metabolic stress. In this report we show that growing cells contain two-fold higher levels of tRNAAsp and tRNATyr when sufficiently supplied with queuine, than those lacking queuine. In tRNAAsp a new, as yet unidentified, derivative of queuine has been discovered. When RNA synthesis is totally inhibited by actinomycin, tRNAAsp and tRNATyr remain stable in queuine-containing, but not in queuine-lacking cells. In contrast, tRNAAsn and tRNAHis become partially degraded in both conditions. We suggest that free queuine can be obtained from endogeneous tRNA and that differential salvage of queuine by tRNAs of the Q-family plays a role in the regulation of genes encoding components of redox chains.

Amino Acids↗

[Hard metal pulmonary fibrosis].

A 20-year-old labourer, employed in the metal powder industry, developed increasing shortness of breath and serious urge to cough after 2 1/4 years of exposition to cobalt and tungsten carbide powder. On admission 9 months later pulmonary changes were demonstrated radiographically indicating hard-metal-dust lung. Detailed clinical assessment including transpleural biopsy and lingula resection as well as histochemical investigations and follow-up observations permitted access to the pathogenesis and morphology of the disease. By introduction of steroid treatment, before conclusion of diagnostic steps, limitation of the inflammatory primary reaction was possible inasmuch as loss of pulmonary function could be arrested despite massive, histologically verified, tendency for fibrosis.

Adult↗

[Risk and severity of alpine ski accidents and their social significance].

The alpine ski accidents have been studied for the last ten years in the Region of Davos-Klosters, Switzerland. Possibilities of prevention were analyzed. The accident risk has drastically decreased for immobilizing injuries of the lower extremities. Simultaneously, however, the pattern of injuries moved to the upper extremities. The accidents became, according to several criteria, less severe. Future preventive measures should be aimed primarily at reducing fall frequency and intensity.

Athletic Injuries↗

Immunoradiometric assay for human thyroglobulin and variations in thyroid pathology.

A specific and sensitive double antibody radioimmunoassay for measuring human serum thyroglobulin (Tg) has been developed. Serum Tg levels are reported for patients with differentiated and undifferentiated thyroid carcinomas, post-treated and untreated hyperthyroidism, thyroiditis, and cold nodular goiters. We have studied results of serum Tg levels in the follow-up and care of patients who have undergone total thyroidectomy for differentiated thyroid carcinomas. Tg has no diagnostic value in the detection of thyroid cancer, but is a reliable index of metastatic growth in the follow-up of patients with differentiated carcinomas. In addition, serum Tg determination might be helpful in the aetiological diagnosis of bone or lung metastases of unknown origin.

Carcinoma↗

[An expanded basic documentation of treatment and follow-up for operated cancer patients (author's transl)].

Presented is a program of recording all facts in the fate of a cancer patient relevant for therapy and prognosis in a manner suitable for EDP. Beside optimal medical treatment it is the substance of the documentation system to produce the complete pathogram of all registered cancer patients. From the day of establishment of the diagnosis and the begin of clinical treatment in the Evgl. Krankenhaus up to the following 5 years the cancer patient runs through a strongly termed and tumor specific follow-up. All informations and facts are registered in a codable medical record, a basic documentation for tumor patients, a follow-up and a final questionaire. In the so coded pathogram of the cancer patient we only use international binding classifications and coding systems. The pathogram is the result of a longer development and testing time in the surgical department of a smaller hospital. The presented principles of documentation include all basis necessary for the establishment of a clinical cancer registry and documentation follow-up.

Documentation↗

Size analysis of heterogeneous nuclear RNA in an aqueous gel system.

We have analyzed the size distribution of heterogeneous nuclear RNA (hnRNA) from cultured murine cells in an aqueous gel system consisting of 1.8% polyacrylamide and 0.5% agarose. hnRNA, labeled in vivo with 32P at a low specific activity, was labeled in vitro at its 3'-end with NaB3H4, and fractionated by gel electrophoresis. The ratio of log 32P/3H cpm was determined for each gel fraction and shown to be linearly related to distance migrated. The ratio of 32P/3H cpm was used to predict the molecular weight of 28-S and 18-S RNAs and shown to be within approx. 10% of the known molecular weight. Denaturation of hnRNA with heat or dimethyl sulfoxide gave similar number and weight average molecular weight when analyzed by gel electrophoresis. The same hnRNA analyzed by sucrose gradient velocity sedimentation had a similar number average molecular weight but much higher weight average molecular weight.

Cell Line↗

[Bone sarcoma (author's transl)].

Sarcogenesis essentially follows two laws: The frequency of sarcoma is distributed according to the mesenchymal cell content in the different sections of the body. The sites of predilection are found within the same tissue systems in zones of increased growth activity and cell division. Clinical oncogenic statistics show that other factors apart from quantity of sarcogenic noxae and latent period are important in producing the malignancy. The synopsis of histology, X-ray findings and clinical examination is significant for diagnosis and for prognosis the degree of spread (TNM classification), localization and therapy. Early operation is still the most successful and most decisive therapeutic measure. The necessity for a supervised cancer follow-up is also shown in these tumors.

Adolescent↗