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Biomedical subjects

W Scheid

Publications and source records attributed to W Scheid.

At least 19 recordsLinked to original sources

Time-saving in biological dosimetry by using the automatic metaphase finder Metafer2.

The amount of time-saving by using the Metafer2 metaphase finder for routine analysis of radiation-induced chromosome aberrations (biological dosimetry) was determined. Metaphases were prepared by standard methods from cultures of human peripheral blood lymphocytes and stained either with Giemsa or with the FPG method. The metaphase finder was used for detecting metaphases on the microscope slides and for automatically processing the evaluation data. In our laboratory, standardized analysis of 1000 metaphases requires at least 3 working days for cell culturing and slide preparation and 51.5 working hours for cytogenetic analysis. When using the metaphase finder the time required for cytogenetic analysis is reduced to 17.3 working hours (time-saving factor: 51.5/17.3 h = 3.0). In our prolonged method, including more than one scoring of each slide and karyotyping of metaphases with chromosome aberrations, the analysis times for 1000 cells are 132 and 70 working hours, respectively (time saving factor: 132/70 h = 1.9).

Automation

Significance testing in mutagen screening: the dependence of statistical power on the control sample size.

The continuous accumulation of control data in multicellular mutagen screening systems prompted us to study the dependence of the statistical power on the size of the control sample (for fixed control values). Two widely used screening systems were chosen: dicentric chromosomes in human lymphocytes and recessive sex-linked lethals in Drosophila melanogaster. The power increases rapidly at first as the control sample size increases, then levels off at a few tens of thousands of control units tested and thereafter remains almost constant up to the historical control. The practical implications from our study are discussed.

Animals

A model for testing the mutagenicity of excimer laser radiation in ophthalmology.

Because excimer laser radiation is applied more and more in therapeutic and refractive corneal surgery, the possibility of mutagenic side effects of this treatment should be considered. A mutagenicity model is presented approximating closely the ophthalmological conditions when mutagenic effects are studied: Heparinized human blood is filled into the anterior chamber of an enucleated cow eye. After irradiation of the cornea with the excimer laser, the blood is removed and whole blood cultures are set up. Lymphocytes are stimulated, fixed during metaphase, and scored for chromatid and chromosome aberrations. First results obtained with this model after 248 nm laser irradiation (500 J, 277 mJ/cm2, 10 or 20 Hz) revealed no mutagenic effects. However, when the blood was exposed under the same physical conditions in a quartz chamber (positive control), statistically highly significant increases of the yields of chromatid aberrations were observed.

Adult

[Induction of chromosome aberrations in human lymphocytes as a model for evaluating the mutagenic effect of excimer laser irradiation in ophthalmology].

A model for testing the mutagenicity of excimer laser radiation in ophthalmology is presented. In contrast to other studies using cell monolayers, in our study with this model human peripheral lymphocytes (heparinized whole blood) are exposed to laser irradiation at different conditions. The possible mutagenicity of secondary radiation after exposure of the cornea is also considered. The heparinized blood is either injected into the anterior chamber of an enucleated bovine eye or filled into a quartz chamber (positive control). After irradiation the lymphocytes are stimulated and fixed during metaphase, after which the metaphases are scored for chromatid and chromosome aberrations. In the positive control group, exposure to 248 nm excimer laser radiation (500 J, 277 mJ/cm2, 10 and 20 Hz) was followed by a highly significant increase in the yield of chromatid aberrations (chromatid breaks and achromatic lesions).

Animals

Enhancement of the mutagenicity of anticancer drugs by the calcium antagonists verapamil and fendiline.

The enhancement of the mutagenicity of anticancer drugs by the calcium antagonists verapamil (CAS 52-53-9) and fendiline (CAS 13042-18-7) is reviewed. Both calcium antagonists enhance synergistically the induction of chromosome aberrations (dicentric and ring chromosomes) in cultured human lymphocytes by the antitumor agent bleomycin. Since two other calcium antagonists, nifedipine and diltiazem, when tested with the same system, did not show this effect, the comutagenicity of verapamil and fendiline does not seem to be related with calcium antagonism per se. Verapamil furthermore potentiates the induction of various chromosome and chromatid aberrations in Chinese hamster ovary (CHO) cells in vitro by the antitumor agent mitomycin C. In bacteria (Salmonella typhimurium) verapamil enhances synergistically the induction of gene mutations (frameshifts) by several anticancer drugs, including various anilinoacridine derivatives. When applied alone, neither verapamil which was tested in each of the three studies (human lymphocytes, CHO-cells, and bacteria) nor fendiline, which was tested only in human lymphocytes, proved to be mutagenic. To explain the comutagenicity of verapamil and fendiline, it is assumed that they prevent the mutagen (e.g., bleomycin) to be extruded from the cell. Consequently, the mutagen would be accumulated intracellularly and this would enhance its efficiency.

Animals

Enhancement of bleomycin-induced DNA damage by exposing isolated DNA to high concentrations of the calcium antagonist verapamil.

The calcium antagonist verapamil was found to enhance synergistically the DNA (desoxyribonucleic acid) strand breakage activity of the radiomimetic antitumor agent bleomycin in vitro. The induction of single and double strand breaks in isolated DNA was investigated by agarose gel electrophoresis. Three types of DNA (two plasmids and one native eukaryotic DNA) were used as target molecules. The effect of verapamil was concentration dependent (concentration range tested: 0.75-3.0 mmol/l). However, at those low concentrations, as they were used in cytotoxicity assays and cytogenetic experiments, no potentiating effect of verapamil on bleomycin action could be observed. The significance of these findings is discussed with respect to various hypothesis concerning the potentiation of tumor drug efficiency by verapamil and other calcium antagonists.

Animals

Chromosome aberrations induced in human lymphocytes by an X-radiation accident: results of a 4-year postirradiation analysis.

After occupational and medical radiation exposures structural chromosome aberrations may be induced in the lymphocytes of the irradiated persons. Many authors have estimated the radiation dose from the yields of dicentric aberrations. We analysed the influence on the dicentric yield of increasing time intervals between irradiation and blood sampling from a person involved in an X-radiation accident (radiography). During a 4-year follow-up we observed an approximately 7-fold decline of the dicentric yield up to the 25th month and thereafter an almost constant value. Since the decline did not commence until around the 10th month after the exposure, an exponential decrease of dicentric yield with time should be considered with reservation in this study, although it cannot be entirely ruled out. We conclude that in 'biological dosimetry' blood should be sampled as early as possible after the exposure. Furthermore, computation of 'half-times' of lymphocytes to allow for a delay in blood sampling seems uncertain after partial body exposures to high doses. Therefore in such cases dose estimates obtained 1 or more years after irradiation should be considered as minimum values.

Accidents

[Neuropsychiatry today (author's transl)].

Neurology and psychiatry are combined in the easily misunderstandable term "Neuropsychiatry" as equal ranking sister disciplines. Neurology with its rectilinear development and the gain in important auxiliary methods enjoys general high respect. It is quite different with psychiatry. It is tainted with the events of the National Socialist domination. Its logical therapeutic methods are associated with inhumanity. Etiology and pathogenesis of the "endogenous" psychoses are still veiled in darkness. This gap in knowledge, detrimental to the prestige of psychiatry, is filled with theories, hypotheses and speculations. An extensively popularized psychology questions some concepts of a classical psychiatry wrongly described as conservative. Such uncertainty is alive even in the ranks of psychiatrists, to the detriment of their responsibility. Psychiatry must serve the care of the individual patient, renouncing all possible temptations. Some success can be expected from the "out-patient services" but this demands professional knowledge and critical ability besides activity.

Electroconvulsive Therapy

Influence of cysteamine on differential staining of BUdR-substituted human chromosomes.

In 5-bromodeoxyuridine (BUdR)-substituted human chromsomes stained with 4'-6-diamidino-2-phenylindole (DAPI) differential staining is suppressed totally by the H+-donor cysteamine (concentration 0.08 M). We propose that differential staining appears because the double BUdR-substituted chromatid will be disintegrated via a photosensitive dye-visible light system. It is suggested that cysteamine prevents the production of strand breaks in DNA and, consequently, differential staining in BUdR-substituted chromosomes. Furthermore it is shown that differential staining with DAPI causes irreversible changes in the double BUdR-substituted chromatid. This finding can be explained with the above mentioned mechanism.

Bromodeoxyuridine