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Biomedical subjects

T E Evans

Publications and source records attributed to T E Evans.

At least 19 recordsLinked to original sources

Mitigation of tokamak disruptions using high-pressure gas injection.

High-pressure gas-jet injection of neon and argon is shown to be a simple and robust method to mitigate the deleterious effects of disruptions on the DIII-D tokamak. The gas jet penetrates to the central plasma at its sonic velocity. The deposited species dissipates >95% of the plasma by radiation and substantially reduces mechanical stresses on the vessel caused by poloidal halo currents. The gas-jet species-charge distribution can include >50% fraction neutral species which inhibits runaway electrons. The favorable scaling of this technique to burning fusion plasmas is discussed.

Journal Article↗

Antimutagenicity of WR-1065 in L5178Y cells exposed to accelerated (56)Fe ions.

The ability of the aminothiol WR-1065 [N-(2-mercaptoethyl)-1,3-diaminopropane] to protect L5178Y (LY) cells against the cytotoxic and mutagenic effects of exposure to accelerated (56)Fe ions (1.08 GeV/nucleon) was determined. It was found that while WR-1065 reduced the mutagenicity in both cell lines when it was present during the irradiation, the addition of WR-1065 after the exposure had no effect on the mutagenicity of the radiation in either cell line. No marked protection against the cytotoxic effects of exposure to (56)Fe ions was provided by WR-1065 when added either during or after irradiation in either cell line. We reported previously that WR-1065 protected the LY-S1 and LY-SR1 cell lines against both the cytotoxicity and mutagenicity of X radiation when present during exposure, but that its protection when administered after exposure was limited to the mutagenic effects in the radiation-hypersensitive cell line, LY-S1. The results indicate that the mechanisms involved differ in the protection against cytotoxic compared to mutagenic effects and in the protection against damage caused by accelerated (56)Fe ions compared to X radiation.

Animals↗

Genotoxic effects of high-energy iron particles in human lymphoblasts differing in radiation sensitivity.

The effects of (56)Fe particles and (137)Cs gamma radiation were compared in TK6 and WTK1 human lymphoblasts, two related cell lines which differ in TP53 status and in the ability to rejoin DNA double-strand breaks. Both cell lines were more sensitive to the cytotoxic and clastogenic effects of (56)Fe particles than to those of gamma rays. However, the mutagenicity of (56)Fe particles and gamma rays at the TK locus was the same per unit dose and was higher for gamma rays than for (56)Fe particles at isotoxic doses. The respective RBEs for TK6 and WTK1 cells were 1.5 and 1.9 for cytotoxicity and 2.5 and 1.9 for clastogenicity, but only 1 for mutagenicity. The results indicate that complex lesions induced by (56)Fe particles are repaired less efficiently than gamma-ray-induced lesions, leading to fewer colony-forming cells, a slightly higher proportion of aberrant cells at the first division, and a lower frequency of viable mutants at isotoxic doses. WTK1 cells (mutant TP53) were more resistant to the cytotoxic effects of both gamma rays and (56)Fe particles, but showed greater cytogenetic and mutagenic damage than TK6 cells (TP53(+)). A deficiency in the number of damaged TK6 cells (a) reaching the first mitosis after exposure and (b) forming viable mutants can explain these results.

Cell Line↗

UK guidelines for the use of inhaled nitric oxide therapy in adult ICUs. American-European Consensus Conference on ALI/ARDS.

OBJECTIVE: Although unlicensed, inhaled nitric oxide (NO) therapy is now widely used in the United Kingdom. Our aim was to produce guidelines for the clinical application of inhaled NO in adult intensive care practice, based upon the current level of published information. METHODS: The published data regarding the use of inhaled NO in the acute respiratory distress syndrome and right-sided cardiac failure was presented, analysed and discussed. Recommendations based on these data as well as on current experience in the United Kingdom were formulated. DESIGN: An expert group comprising intensive care specialists from within the United Kingdom, representatives from the European Society of Intensive Care Medicine and the Society of Critical Care Medicine and individuals from the Departments of Health and Industry related to the field was assembled. RESULTS: United Kingdom guidelines for the indications, contraindications, dose, delivery, monitoring and scavenging of inhaled NO therapy were produced. CONCLUSIONS: The need for additional quality research to establish evidence of efficacy and safety was emphasized. The guidelines are designed to act within the context of current practice and knowledge and should be revised as further data emerge.

Acute Disease↗

Chelatable iron and copper can be released from extracorporeally circulated blood during cardiopulmonary bypass.

During cardiopulmonary bypass surgery blood is extracorporeally oxygenated and circulated before returning to the systemic arterial circulation. Blood undergoing extracorporeal dilution and circulation is exposed to non-physiological surfaces, which cause the activation of several regulatory cascades. Cells are also subjected to damaging shear stresses. Under such conditions neutrophils can be 'activated' to release reactive oxygen intermediates such as O2- and H2O2, and other cells can release proteolytic enzymes and metalloproteins. Collectively, these events can result in the release of micromolar quantities of redox active iron and copper. Bleomycin-detectable iron and phenanthroline-detectable copper were found in two out of four mock bypass experiments. However, there was no correlation between the presence of chelatable iron and copper and the activation of neutrophils measured as elastase.

Bleomycin↗

Mutagenesis and transformation of C3H 10T 1/2 cells treated with ethyl methanesulfonate.

Survival, mutagenesis and transformation were measured in mouse embryo C3H 10T 1/2 cells following treatment with ethyl methanesulfonate (EMS). Ouabain-resistant cells and transformed cells were isolated, and reconstruction experiments were carried out to determine the optimum conditions for the measurement of mutation and transformation frequencies. Survival was measured by plating efficiency; mutagenesis was measured in terms of the induction of cells able to form colonies in the presence of ouabain; and transformation was measured by the induction of cells forming either morphologically altered colonies on a monolayer of contact-inhibited cells or of cells capable of forming colonies in semi-solid media. When confluent monolayers were incubated for 4 h after treatment with EMS, to allow excision repair before the resumption of DNA synthesis, survival as well as the frequencies of both mutation and transformation increased. When this repair (or holding) period was extended to 24 h, the frequencies of mutation and transformation both decreased as compared to the 4-h holding period. Thus, the holding periods affect the frequencies of EMS-induced mutagenesis and transformation similarly.

Animals↗

Cycloheximide resistance of Physarum polycephalum.

In the presence of cycloheximide, wild-type plasmodia of Physarum polycephalum exhibit an immediate decrease in deoxyribonucleic acid synthesis, a reduction in the incorporation of [3H]thymidine into thymidine triphosphate, and an increase in the level of thymidine triphosphate, as well as a decrease in protein synthesis. In this study, we have utilized a cycloheximide-resistant (Cycr) amoebic strain selected from a population of cells mutagenized with nitrosoguanidine. Segregation data indicate that the resistance is due to a single mutation. We have used this Cycr mutant to construct Cycr plasmodial strains. Ribosomes isolated from such Cycr plasmodia showed resistance to cycloheximide in vitro, in contrast to ribosomes isolated from wild-type plasmodia. The Cycr plasmodia showed none of the cycloheximide-induced biochemical effects. Plasmodia heterozygous for the resistance marker were sensitive to cycloheximide with regard to growth but showed an intermediate response in the biochemical parameters. Heterokaryons formed by fusion of various proportions of the sensitive and resistant plasmodia showed a resistance with regard to both growth and biochemical parameters which was directly related to the fraction of Cycr plasmodia present in the heterokaryons. The data are consistent with the hypothesis that the effects of cycloheximide on deoxyribonucleic acid synthesis and nucleoside metabolism are secondary to the effect of the drug on protein synthesis in this organism.

Cycloheximide↗