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161.
162.
SE Barrie BP Haynes GA Potter FC Chan PM Goddard M Dowsett M Jarman 《Canadian Metallurgical Quarterly》1997,60(5-6):347-351
Two potent non-steroidal inhibitors (CB7645 and CB7661) of human cytochrome P450(17alpha) were tested for in vivo activity in WHT mice. There were no signs of toxicity, but there was no effect on the androgen-dependent organs. The pharmacokinetics and biochemistry of the compounds in mice were investigated. Following i.p. administration of 0.5 mmol/kg of CB7645 and CB7661, peak plasma levels of 13.4 and 3.4 microM, respectively, occurred after 2-4 h, both compounds were cleared rapidly (terminal half-lives 2.7 and 3.3 h, respectively) and neither was detectable at 24 h. CB7645 produced some decrease in plasma testosterone at 4 h, but this was not sustained. When tested in vitro against the WHT testicular enzyme, the CB7645 and CB7661 were competitive inhibitors with K(i) values of 10 and 13 nM, respectively. However, the K(m) for the substrate progesterone was lower at 4.3 nM. These data indicate that, for effective and continuous inhibition of the murine cytochrome P450(17alpha) enzyme, higher peak levels of the compounds would be required, and these levels would need to be maintained throughout the treatment period. 相似文献
163.
164.
Most theoretical approaches to perception of heading rely on the directions of image velocity vectors as the primary source of heading information. The research described in this article examined an additional source of information for determining heading: distributions of image velocity magnitudes. Displays simulated observer motion relative to rigid three-dimensional environments. Depth was distributed nonuniformly such that image velocity magnitudes provided, for some display conditions, conflicting heading information relative to the radial directions of the flow field. Results indicated that image velocity magnitudes influenced heading performance, suggesting that the perception of heading is not based solely on the radial structure of the directions of image flow. 相似文献
165.
RN Roberts BP Norman CG Harrison NR Heaton JK Law V Wadehra HM Younger CP West 《Canadian Metallurgical Quarterly》1996,41(2):44-46
The aim of the study was to carry out an audit of 283 hysterectomies performed for menstrual disorders over a one year period, and to determine the satisfaction of the women concerned towards their treatment. The medical records of these patients were examined, and they were each sent a questionnaire, 69% of which were completed and returned. The most common presenting symptoms were menorrhagia and dysmenorrhoea. In 53% of cases no clinical abnormality was postulated and in 31% of cases no pathological abnormality was found. The preoperative clinical and pathological diagnoses were in agreement for 59% of patients. Over 90% of women were satisfied with the management of their case by their GP and the gynaecology outpatient clinic. The use of patient-controlled analgesia systems was associated with better post-operative pain relief than intramuscular injections. Thirteen percent of patients required blood transfusion; 21% suffered some form of postoperative complication, most of which were minor. Ninety-four percent of the women were pleased that they had undergone hysterectomy, and 76% wished that they had had the operation sooner. It was concluded that hysterectomy is perceived positively by patients and should not necessarily be considered as a last resort treatment for menstrual disorders. 相似文献
166.
167.
BP Engelward G Weeda MD Wyatt JL Broekhof J de Wit I Donker JM Allan B Gold JH Hoeijmakers LD Samson 《Canadian Metallurgical Quarterly》1997,94(24):13087-13092
3-methyladenine (3MeA) DNA glycosylases remove 3MeAs from alkylated DNA to initiate the base excision repair pathway. Here we report the generation of mice deficient in the 3MeA DNA glycosylase encoded by the Aag (Mpg) gene. Alkyladenine DNA glycosylase turns out to be the major DNA glycosylase not only for the cytotoxic 3MeA DNA lesion, but also for the mutagenic 1,N6-ethenoadenine (epsilonA) and hypoxanthine lesions. Aag appears to be the only 3MeA and hypoxanthine DNA glycosylase in liver, testes, kidney, and lung, and the only epsilonA DNA glycosylase in liver, testes, and kidney; another epsilonA DNA glycosylase may be expressed in lung. Although alkyladenine DNA glycosylase has the capacity to remove 8-oxoguanine DNA lesions, it does not appear to be the major glycosylase for 8-oxoguanine repair. Fibroblasts derived from Aag -/- mice are alkylation sensitive, indicating that Aag -/- mice may be similarly sensitive. 相似文献
168.
UDP-galactose 4-epimerase from yeast Kluyveromyces fragilis is a dimeric molecule of 75 kDa per subunit with one molecule of cofactor NAD per dimer. It undergoes unfolding and complete dissociation in presence of 8 M urea at pH 7.0 by 10 min. It can be functionally reconstituted almost quantitatively in 2 h by dilution with 20 mM sodium phosphate buffer, pH 7 containing 1 mM extraneous NAD under a second order kinetics [Bhattacharyya, D. (1993) Biochemistry 32, 9726-9734]. Denaturation between 10-60 min inversely affects both the rate and maximum recovery of activity upon refolding. Aggregation of this protein has not been observed under these conditions. The time dependent reaction at the unfolded state is independent of pH between 5.4-10.4 but strongly dependent on temperature of denaturation between 0-20 degrees C. Unfolding at 0 degrees C divides the protein largely into two populations-34% of fast folding species following an apparent first order kinetics and 59% of slow folding species following a second order kinetics of reactivation. A very fast folding species of low abundance 3.5-7.5% depending on temperature of denaturation has been identified, which gets active status within the dead time of mixing. Interaction with the active site directed fluorescence probe 1-anilino 8-naphthalene sulfonic acid (1-ANS) and estimation of bound NAD suggest that the catalytic region of this enzyme is not formed in the long term denatured samples. The whole process of reactivation is catalysed by peptidyl prolyl cis-trans isomerase and thus suggests that one or more proline residues stereochemically control the rate limiting step of reactivation. 相似文献
169.
170.
KM Harris DJ Malenka MF Haney JE Jayne B Hettleman JF Plehn BP Griffin 《Canadian Metallurgical Quarterly》1997,80(6):741-745
This study sought to determine whether there is a quantitative improvement in mitral regurgitation (MR) after aortic valve replacement (AVR) for aortic stenosis (AS) and, if so, the mechanisms for this change. MR frequently accompanies AS. The addition of mitral valve replacement to AVR significantly increases the risk of surgery. Although previous studies have suggested a qualitative improvement in MR severity after AVR, semiquantitative analysis of this improvement has not been documented nor have the underlying mechanisms been examined. We evaluated 28 patients who had undergone 2-dimensional echo and color flow Doppler imaging an average of 1.5 +/- 2.5 months before and 2.5 +/- 4.2 months after AVR. Maximum MR area, MR percentage (MR area/left atrial area), mitral annular area, left atrial area, aortic gradient, and parameters of left ventricular geometry were measured to evaluate MR severity and to assess functional mechanisms for improvement in MR. There was a significant decrease in MR area (5.5 +/- 2.8 cm2 vs 2.5 +/- 1.9 cm2, p < or =0.0001) and MR percentage (25 +/- 11% vs 12 +/- 10% after operation, p < or =0.0001) between preoperative and postoperative studies. There was a significant reduction in aortic gradient, mitral annular area, left atrial area, and left ventricular length postoperatively. In univariate analysis, MR improvement was related to the lower preoperative left ventricular fractional area change (p = 0.027) and to the changes in fractional area change (p = 0.001) and left ventricular systolic area (p = 0.001). Thus, improvement in MR after AVR is related to changes in left ventricular function postoperatively. These data suggest that reduction in MR is due not only to decreased intraventricular pressure, but also to changes in ventricular morphology. 相似文献