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Biomedical subjects

T R Lee

Publications and source records attributed to T R Lee.

28 records · Page 2Linked to original sources

Oxygen transfer from the nitro group of a nitroaromatic radiosensitizer to a DNA sugar damage product.

Mechanisms based on one-electron oxidation appear incomplete in explaining cellular radiosensitization by nitroaromatic compounds such as misonidazole. Evidence is presented for a novel mechanism that may be involved in enhancing DNA strand breakage due to a variety of agents, including ionizing radiation, that generate carbon-centered radicals on DNA deoxyribose. Under anaerobic conditions the carbon-centered radical generated selectively at C-5' of deoxyribose of thymidylate residues in DNA by the antitumor antibiotic neocarzinostatin reacts with misonidazole to produce a DNA damage product in the form of 3'-(formyl phosphate)-ended DNA. In an 18O-transfer experiment we find that the carbonyl oxygen of the activated formyl moiety (trapped as formyl-Tris) is derived from the nitro group oxygen of misonidazole. This result strongly supports a mechanism in which a nitroxide radical adduct, formed by the addition of misonidazole to the radical at C-5' of deoxyribose, cleaves between the N and O so as to form an oxy radical precursor of the formyl moiety and a two-electron reduction species of misonidazole.

Antibiotics, Antineoplastic↗

Public attitudes towards chemical hazards.

Public concern over chemical hazards is increasing in a context where overall life expectancy has rapidly improved. However, people's expectations of safety continue to exceed the presently attained levels and a mistrust of technological expertise is pervasive. Paradoxically this may arise because the ordinary person has assimilated scientific notions of causality that partially replace religious or magical explanations for accidents and catastrophes. The public's perceptions of risk frequently diverge considerably (in either direction) from the probabilistic risk assessments made by engineers and scientists. Both assessments are usually wrong: reconciliation rather than confrontations should be sought. The public is not 'irrational', it has different reasons and values. A brief view is given of the methodology and main findings of research on perceived risk, both comparative approaches and those where perceptions of a single hazard are explored in detail. Illustrative studies of community attitudes to pesticides, chemical food additives and of people's beliefs about nuclear power are outlined.

Accidents↗

Effective communication of information about chemical hazards.

Given that the best available means have been used to assess the risks arising from a chemical process or product, it is a crucial aspect of management to inform the employees and the public. This task of communicating may fall to industry, government, regulating authority, professional association or an environmental protection group. It requires some understanding of the public's perceptions of the risks involved and an ethical duty to try to modify attitudes judged to be either over-anxious or complacent. There is as yet no structured knowledge on communication about chemical hazards as such. Also, circumstances vary enormously. Hence, this paper deploys the general analytic framework constructed within social psychology and reviews the extensive experimental research (and some field studies) with the aim of providing understanding and some guidance. It considers the basic modelling of attitude change as induced by printed or verbal communications. The variables influencing the effectiveness of communications are divided into: the source (e.g. his/her credibility, power or attractiveness); the message (e.g. emotional versus logical; one-sided versus both-sided arguments); and modality or media effects (e.g. spoken versus written; the mass media; campaigns).

Accidents, Occupational↗

Enzyme cytochemistry of blood and marrow cells.

Diseases of the blood and bone marrow are commonly associated with abnormalities of oxido-reductase and lysosomal enzymes within individual erythrocytes and leucocytes. There are considerable technical difficulties, however, in adapting enzyme histochemical techniques to the study of haemopoietic tissue since individual cells are readily disrupted during processing, show variable enzyme activity according to the stage of maturation, and possess a lipoprotein cytoplasmic membrane which hinders reagent penetration. Cytochemical techniques for the study of oxido-reductase systems are of importance in the study of the neutrophil in infected patients, the erythrocyte in glucose-6-phosphate dehydrogenase deficiency, and the primitive blast cell in acute leukaemia. Lysosomal enzymes are of importance in the study of the neutrophil in infected patients and in the differential diagnosis of acute leukaemia. Some examples of recent studies of these enzyme systems are given to illustrate technical procedures involving cytocentrifugation of cells on to glass slides, adjustment of the osmolality of the reaction mixture, and the study of smeared cells as opposed to cells incubated in suspension.

Acid Phosphatase↗

The cytocentrifuge NBT test.

The NBT test is a non-specific test of neutrophil membrane stimulation which has application to the study of neutrophil function, particularly in the septicaemic patient. An improved cytochemical test which eliminates potential sources of laboratory error has been developed. Venous or capillary blood samples may be studied and the technique can be applied to the neutropenic patient since available neutrophils are concentrated by cytocentrifugation. Clinical evaluation in 443 patients is described.

Adolescent↗