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Biomedical subjects

J M Brown

Publications and source records attributed to J M Brown.

At least 19 recordsLinked to original sources

Computerized histographic oxygen tension measurements of murine tumors.

As further work on tumor oxygenation results in the development of agents capable of modulating hypoxic cell radiosensitivity, and chemotherapeutic agents capable of targeting hypoxic cells, knowledge of relative tumor oxygenation takes on greater importance. The pO2 Histograph was used to characterize the oxygen tension of a murine sarcoma (RIF1) and a murine carcinoma (SCCVII), each with different hypoxic fractions. These tumors were studied sequentially to assess the suitability of the Histograph both as a research tool and, ultimately, as a clinical monitor of tumor hypoxia.

Animals

Differential expression of protein kinase C epsilon protein in lung cancer cell lines by ionising radiation.

The effect of ionising radiation on the regulation of gene and protein expression is complex. This study focuses on the translational regulational of the epsilon isoform of protein kinase C by ionising radiation. We found that protein kinase C epsilon is rapidly increased in the human lung adenocarcinoma cell line A549 following irradiation. Western blots showed increased accumulation of this protein at doses as low as 75 cGy after 15 min post irradiation. Maximal induction (11-fold over unirradiated cells) of PKC epsilon occurred at 150 cGy within 1 h after treatment by X-rays in A549 cells. The increased levels of PKC epsilon protein after X-rays does not require de novo protein or RNA synthesis, suggesting that this increase is post-translationally controlled. In contrast to A549 cells PKC epsilon levels in the large cell lung carcinoma cell line NCI H661 were not induced by radiation. In the small cell lung carcinoma cell line NCI N417, PKC epsilon was also not induced but a higher molecular weight PKC epsilon protein, suggestive of phosphorylation, appeared at 2 h after irradiation. The variation in induction or phosphorylation of PKC epsilon by ionising radiation in the cell lines tested in this study suggested that no clear correlation existed between intrinsic radiation sensitivity and PKC epsilon induction. To determine whether PKC epsilon does play a role in cell survival to irradiation, we used the protein kinase inhibitor staurosporin to decrease PKC activity and found that staurosporin sensitised cells to killing by ionising radiation. Pulsed field gel electrophoresis, however, indicated that DNA double-strand break repair was not decreased, suggesting that PKC epsilon is modifying the fidelity of rejoining and not the overall magnitude of repair. The regulation of PKC by ionising radiation will be discussed with respect to the biological consequences of gene induction by DNA damage agents.

Adenocarcinoma

Outbreak of pseudoinfection with Tsukamurella paurometabolum traced to laboratory contamination: efficacy of joint epidemiological and laboratory investigation.

From January 1988 to May 1989, one hospital in South Carolina reported 12 isolates of Tsukamurella paurometabolum from 10 patients. There were no common risk factors among the patients. Case-control studies revealed that the positive specimens were significantly more likely to have been processed in the TB/fungal room, to have been tissue samples, and to have been handled by one technician. Typing on the basis of biochemical, antimicrobial resistance, Southern blot, and ribotype profiles showed that the isolates from the outbreak were essentially identical and that they were distinguishable from each of two isolates obtained after the outbreak and from two type strains. These findings support the hypothesis of a common-source outbreak of pseudoinfection. There are reasons to believe that T. paurometabolum is present both in the environment and as a culture contaminant more often than has been recognized and that it is very rarely the true cause of infection in humans. Typing results show differences between one type strain and all of the other isolates studied in terms of colonial morphology, biochemistry, antimicrobial susceptibility, and ribotyping; these differences suggest that the nomenclature of T. paurometabolum may require further clarification.

Actinomycetales

A sensitive assay for the detection cytotoxic antibodies to mammalian cell surface antigens.

A microcytotoxicity assay for the detection of complement-dependent serum toxicity against adherent cells has been modified to include post-labeling of the target cells with [3H]leucine or [3H]thymidine. The adaptation represents a significant improvement over the visual counting of residual cells. The technique is more objective and less tedious than the original procedure, while retaining the features of economy of cells and sera, reproducibility, and sensitivity. Examples are given which demonstrate the suitability of the modified assay for the analysis of human and mouse tumor antigens using autologous, allogeneic, and syngeneic sera.

Animals