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31.
The COMPACT approach for defining structural criteria for substrates and inducers of cytochrome P450 (CYP) enzymes which mediate the formation of reactive intermediates is discussed in the context of prediction of potential carcinogenicity. This is broadened to encompass structural studies on mammalian P450s, including those relevant to genetic polymorphism in man. The use of the COMPACT system, in parallel with the structure alert program HazardExpert (now incorporated into the Pallas system), for evaluating human carcinogenicity data is reported, as an example of the possible employment of a battery of short-term test procedures for safety evaluation. In particular, the importance of using the log P value (as a measure of compound lipophilicity) to assess the likelihood of a potentially toxic compound reaching the site of activation, is emphasized by the finding that most procarcinogens requiring metabolic activation by P450s are lipophilic in nature. 相似文献
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Tryptophan is a large neutral amino acid which is utilized in the biosynthesis of neuroactive substances such as serotonin and melatonin. However, it has been unclear where pools of tryptophan might be localized. Using a specific antiserum against tryptophan, we demonstrate that in the chicken retina tryptophan is present in radial glial cells and photoreceptors, but not in other neuronal elements. These data suggest that serotonergic neurones are probably dependent upon the transfer of tryptophan from the glial cells in order to manufacture serotonin and other tryptophan derivatives in the brain. If glia do supply tryptophan to neurones then this process will have significant practical implications for our basic understanding of and pharmacological manipulation of serotonergic systems. 相似文献
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RN White MA Cobb SE Brownlie CW Pattison DV Cumming DG Jones HA Williamson MH Yacoub 《Canadian Metallurgical Quarterly》1997,38(12):554-560
Skeletal muscle extra-aortic counterpulsation was performed in seven dogs with dilated cardiomyopathy. A left latissimus dorsi dynamic descending thoracic aortomyoplasty was used as the autologous counterpulsator. Pulse train stimulation in diastole was used to initiate contraction and fibre type transformation. Two of the dogs died within 48 hours of surgery. The device was successfully activated in the five remaining dogs, but in one individual it failed within 48 hours of activation. Serial echocardiographic examinations of dogs in which the device functioned successfully (n = 4) showed trends towards the decrease in the left ventricular systolic internal dimension, left ventricular diastolic internal dimension, E-point to septal separation and left atrial diameter in systole seven to 14 days following the procedure, although these changes failed to persist in the long-term. The results suggest that skeletal muscle for cardiac assistances such as extra-aortic muscle counterpulsation, might be a therapeutic option for dogs with cardiac failure due to dilated cardiomyopathy. 相似文献
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DV Leaming 《Canadian Metallurgical Quarterly》1997,23(4):527-535
A survey of the practice styles and preferences of members of the American Society of Cataract and Refractive Surgery with a United States ZIP code was performed in September 1996. Approximately 26% (1440) of the 5520 questionnaires mailed were returned by the November cutoff date. Three main profile questions were used to cross-tabulate data: age of the ophthalmologist, geographic location, and volume of cataract surgery per month. Current data were compared with data in previous annual surveys. 相似文献
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