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991.
MJ Tilby H McCartney KA Gould CC O'Hare JA Hartley AG Hall BT Golding PD Lawley 《Canadian Metallurgical Quarterly》1998,11(10):1162-1168
Bifunctional alkylating agents, such as those based on nitrogen mustard, form important parts of many anti-cancer chemotherapy protocols and are responsible for increased incidences of secondary tumors in successfully treated patients. These drugs generally form a majority of monofunctional DNA adducts, although the bifunctional adducts appear to be necessary for their powerful cytotoxic and antitumor effects. The relative importance of bifunctional as opposed to monofunctional adducts in the varied biological consequences of drug exposure has not been studied in detail, particularly in relation to the role and specificity of biochemical responses to therapy-related DNA damage. A simple method is described for the preparation of useful quantities of a pure monofunctional derivative of the nitrogen mustard-based drug melphalan. Monohydroxymelphalan was prepared by partial hydrolysis, purified by reversed phase chromatography, and characterized by MS, NMR, and HPLC. Contamination with melphalan was =0.2%. The heat labile DNA base adducts formed by monohydroxymelphalan were shown to contain undetectable levels of cross-linked species. The ratio of adenine to guanine adducts was 0.62, similar to the equivalent ratio for melphalan. The sequence-dependent pattern of alkylation of purified DNA was indistinguishable from that of melphalan, but required a higher dose to achieve comparable extents of reaction. The specificities of two monoclonal antibodies that recognize melphalan-DNA adducts were investigated using DNA alkylated with [3H]monohydroxymelphalan. Adducts on this DNA showed similar immunoreactivities to adducts formed by melphalan. This shows clearly that neither antibody was specific for cross-linked adducts and that it is therefore possible to quantify adducts formed by both monohydroxymelphalan and melphalan with high sensitivities. The availability of monohydroxymelphalan in addition to melphalan, together with sensitive immunoassays for adducts on extracted DNA and in individual cells, constitutes a useful system for investigating cellular responses to the DNA modifications formed by a clinically relevant drug. 相似文献
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This paper examines the development of an expert system shell to present the Mental Health Act 1983 to social workers In Dyfed. It considers the nature of the Mental Health Act and why it was deemed appropriate for such a project. The relevance of such a system to the training of social workers is then considered. The paper then describes the system itself and its potential use. In conclusion the lessons gained by the experiences of those developing the system are outlined. 相似文献
994.
P. Hartley Ph.D. I. Pillinger Ph.D. C. E. N. Sturgess Ph.D. 《JOM Journal of the Minerals, Metals and Materials Society》1991,43(10):12-14
The development of nonlinear finite-element methods has enabled the analysis of many complex problems. This article overviews current applications and developments in three-dimensional finite-element plasticity techniques for modeling metal-forming processes. The overview covers the period 1986–1991 and concentrates predominantly on nonproprietary work in Europe, although some reference to work in the Far East is included. 相似文献
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Pulmonary emboli from renal cell carcinoma may be more common than previously suspected. A case is reported of renal cell carcinoma presenting with a massive pulmonary embolus. Pulmonary embolectomy followed by radical nephrectomy with venocavotomy and tumor thrombectomy was successfully performed. 相似文献