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Biomedical subjects

N T Bech-Hansen

Publications and source records attributed to N T Bech-Hansen.

47 records · Page 3Linked to original sources

Association of in vitro radiosensitivity and cancer in a family with acute myelogenous leukemia.

The gamma-ray sensitivity of skin fibroblasts from six members of a cancer family was investigated using a colony-forming assay. Fibroblasts from the three members with cancer (two sisters with acute myelogenous leukemia and the mother with cervical carcinoma) showed a significant (p less than 0.05) increase in radiosensitivity, while three members without cancer (the father and two sons) showed a normal radioresponse. The possibility that the increased gamma-ray sensitivity was due to defective DNA repair was investigated using assays for DNA repair replication, single-strand break rejoining, and removal of enzyme-sensitive sites in gamma-irradiated DNA. Results of these assays indicate that the kinetics of enzymatic repair of radiogenic DNA damage in general, and the rejoining of single-strand scissions and excision repair of base and sugar radioproducts in particular, were the same in the cell lines from the sensitive and clinically normal family members.

Adult↗

Rapid assays for evaluating the drug sensitivity of tumor cells.

Assays that assess the ability of cells to incorporate labeled precursors into acid-precipitable material in the presence of adriamycin, daunorubicin, puromycin, vinblastine, melphalan, or methotrexate were investigated as an approach to the detection of resistant cells in human tumor samples. Each assay was evaluated with suitable drug-resistant Chinese hamster ovary cell lines and normal human fibroblasts to determine whether the assays reflected the drug sensitivity of these lines. Moreover, the ability to detect the presence of drug-resistance cells in a mixed population was evaluated. Validated assays were then used to measure the drug sensitivity of cell samples from pleural and peritoneal effusions of patients, mainly with carcinoma of the breast or ovary. Though the responsiveness of the majority of the samples in these assays was similar to that of a human fetal lung fibroblast line, 37 of 142 samples displayed responses consistent with the presence of a significant proportion of drug-resistant cells. Of these 37 nonresponsive samples, 12 displayed nonresponsiveness to three drugs.

Antineoplastic Agents↗

Pleiotropic phenotype of colchicine-resistant CHO cells: cross-resistance and collateral sensitivity.

Colchicine resistant (CHR) mutants of CHO cells with reduced permeability to colchicine display extensive cross-resistance to a number of apparently unrelated compounds including puromycin, daunomycin, emetine, ethidium bromide and gramicidin D. A positive correlation was observed between the level of cross-resistance and the relative hydrophobicity of these compounds. The mutants also showed increased (collateral) sensitivity to local anaesthetics (procaine, tetracaine, xylocaine and propanolol), steroid hormones (1-dehydrotestosterone, corticosterone and 5beta-pregnan-3,20-dione) and some Triton X compounds. In general, the degree of the pleiotropic response (cross-resistance or collateral sensitivity) correlated with the degree of colchicine resistance in mutant lines. These results are consistent with the pleiotropic phenotype being the result of the same mutation(s) which confer colchicine resistance and support a model for resistance in which the reduced permeability is assumed to be the result of an alteration in the modulation of the fluidity of the surface membrane.

Anesthetics, Local↗

Saccharomyces cerevisiae petite mitochondrial DNA of suppressive and neutral haploids and of [rho-] diploids obtained from crossing [rho+] to a neutral petite.

An unusual property of GR25a [rho+] was the production of 20 to 30 percent [rho-] zygote colonies when crossed to a tester strain lacking mitochondrial DNA. Spontaneous [rho-] isolates of GR25a [rho+] were observed to be highly suppressive and to contain mitochondrial DNA of a parental buoyant density (1.685 g/cm3). Three ethidium bromide induced neutral petites of GR25 a [rho+] did not have detectable mitochondrial DNA and were neutral in crosses to [rho+] strains. Seven [rho-] zygote colony isolates obtained from crossing GR25a [rho+] to a neutral peptite were shown to contain abnormal mitochondrial DNA. Six zygote colony isolates had mitochondrial DNA of a buoyant density less than, or equal to, GR25a (1.682 - 1.685 g/cm3), whereas one isolate had a buoyant density greater than GR25a (1.688 g/cm3). It was suggested that abnormal mitochondrial DNA is generated during the mating reaction.

Crosses, Genetic↗

Somatic segretation, recombination, asymmetrical distribution and complementation tests of cytoplasmically-inherited antibiotic-resistance mitochondrial markers in S. cerevisiae.

Genetic analyses of 48-hr-old zygote-daughter-colony cells from crosses between chloramphenicol and erythromycin resistance markers located in mitochondrial DNA demonstrated homoplasmons of parental and recombinant genotypes, and heteroplasmons with recombinant and/or parental genotypes. Although the heteroplasmons were unstable and the homoplasmic components could be segregated by plating on selective media, the heteroplasmic state was often maintained beyond 19 cell divisions when grown on non-selective medium. Homoplasmons of recombinant genotype from repulsion crosses were observed with a frequency of 7.2, 9.0, 11.2 and 11.4 percent; two crosses with the resistance markers in coupling had 5.4 and 11.5 percent recombinants. Under non-selective conditions, the mitochondrial marker derived from the haploid parent of a mating type predominated in zygote-daughter-cells; this asymmetrical distribution could be reversed by selective pressure for the marker transmitted with low frequency. The challenge with chloramphenicol and erythromycin of zygotes from crosses of resistance-markers in repulsion revealed that inter-mitochondrial complementation was not occurring.

Chloramphenicol↗

Spondyloepiphyseal dysplasia tarda simulating juvenile arthritis: clinical and molecular genetic observations.

A sibship is reported in which two of three children developed a symmetrical polyarthropathy associated with a mild spondyloepiphyseal dysplasia. Although the physical findings resembled juvenile arthritis, laboratory investigations for inflammatory disease were entirely negative. Molecular studies in members of this family showed that none of them had any structural rearrangements or other major abnormality of the type II procollagen gene (COL2A1). The laboratory findings in this family with "pseudo-rheumatoid arthritis" do not exclude the possibility of a minor mutation of the type II procollagen gene or a defect in the processing of articular cartilage collagens.

Arthritis, Juvenile↗