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991.
992.
993.
A high-performance liquid chromatographic method was developed for the determination of a new proton pump inhibitor, YH1885 (I), in human plasma and urine, and rat blood and tissue homogenate using fenticonazole as an internal standard. The sample preparation was simple: a 2.5 volume of acetonitrile was added to the biological sample to deproteinize it. A 50-microliter aliquot of the supernatant was injected onto a C8 reversed-phase column. The mobile phase employed was methanol-0.005 M tetrabutylammonium dihydrogenphosphate (77:23, v/v), and it was run at a flow-rate of 1.0 ml/min. The column effluent was monitored using an ultraviolet detector at 270 nm. The retention times for I and the internal standard were 9.0 and 10.3 min, respectively. The detection limits for I in human plasma and urine, and in rat tissue homogenate (including blood) were 50, 100 and 100 ng/ml, respectively. The coefficients of variation of the assay (within- day and between-day) were generally low (below 8.84%) for human plasma and urine, and for rat tissue homogenate. No interferences from endogenous substances were found. 相似文献
994.
JK Ma BY Hikmat K Wycoff ND Vine D Chargelegue L Yu MB Hein T Lehner 《Canadian Metallurgical Quarterly》1998,4(5):601-606
The effect of a temperature increase to 52 degrees C or the addition of ethanol (6%) to an exponential Escherichia coli culture on putrescine and potassium transport was studied. The first stage of heat shock was accompanied by a decrease in the extent of DNA supercoiling, due to the dissociation of the putrescine-DNA complex. The loss of potassium ions at this phase produced a synergistic effect. The second phase of the heat shock was characterized by a reversal in the direction of putrescine and potassium transport, which was accompanied by restoration of the prestress extent of DNA supercoiling. An increase in the ATP pool and cell energy charge resulting from the uncoupling of the energy metabolism and synthetic processes also played an important role in the restoration of the DNA initial topology at the second phase of the heat shock via the activation of the energy-dependent gyrase or the heat shock protein DnaK. A mechanism is suggested that explains the involvement of putrescine in the regulation of DNA topology, which is a universal regulator of gene expression under stress, heat shock in particular. 相似文献
995.
We present the rare case of a girl surviving intrauterine listeria brain stem meningoencephalitis, who subsequently developed hydrocephalus, a trapped IV ventricle and an intramedullary cyst. Such cases have been reported only infrequently, and in earlier cases modern imaging studies were not available. Magnetic resonance imaging has been helpful in our patient to delineate the lesions and plan further treatment. 相似文献
996.
997.
GT Ko JC Chan VT Yeung CC Chow LW Tsang JK Li WY So HP Wai CS Cockram 《Canadian Metallurgical Quarterly》1998,21(8):1221-1225
OBJECTIVE: To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS: In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS: Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG > or = 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) > or = 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG > or = 5.6 mmol/l and an HbA1c > or = 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG > or = 5.4 mmol/l and a fructosamine > or = 235 mumol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG > or = 5.6 mmol/l and < 7.8 mmol/l and an HbA1c > or = 5.5% (n = 642) required an OGTT to confirm diabetes, thereby saving 77.7% [(2,877-642)/2,877] of the OGTTs performed. Similarly, only subjects who had an FPG > or = 5.4 mmol/l and < 7.8 mmol/l and a fructosamine > or = 235 mumol/l (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408-526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/l, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS: The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach approximately 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG. 相似文献
998.
M Sorensen M Sehested IJ Christensen JK Larsen PB Jensen 《Canadian Metallurgical Quarterly》1998,77(12):2152-2161
To study the evolution of camptothecin (CPT) resistance, we have established two small-cell lung cancer cell lines with low (3.2-fold, NYH/CAM15) and high (18-fold, NYH/CAM50) resistance to CPT by stepwise drug exposure. NYH/CAM50 cells had reduced topoisomerase I (topo I) content and activity, and consequently CPT-induced DNA single strand breaks (SSBs) were reduced, as measured by alkaline elution. In contrast, NYH/CAM15 cells had identical topo I content and activity as compared with wild-type (wt) cells. CPT-mediated SSBs and the rate of their reversal after drug removal were also equal in wt and NYH/CAM15 cells, as were doubling time, the fraction of cells in S-phase and DNA synthesis rate in response to CPT. As the conversion of DNA SSBs to DNA double strand breaks (DSBs) is thought to represent a critical event leading to cell death, we measured DNA DSBs by neutral elution. In contrast to DNA SSBs, CPT induced fewer DNA DSBs in NYH/CAM15 than in wt cells. DNA flow cytometry showed that, in CPT-treated cells, the G1 phase was emptied as cells accumulated in late S- and G2M phase. A Spearman rank correlation showed that depletion of G1 and accumulation in late S and G2M correlated to CPT sensitivity in these three cell lines. In conclusion, acquired resistance to CPT can occur without a reduction in either topo I enzyme or CPT-induced cleavable complex formation, while a decrease in the level of CPT-induced DNA DSBs may be of major importance in the early stages of CPT resistance. 相似文献
999.
RS Clark PM Kochanek DW Marion JK Schiding M White AM Palmer ST DeKosky 《Canadian Metallurgical Quarterly》1996,16(2):253-261
The effect of posttraumatic hypothermia (brain temperature controlled at 32 degrees C for 4 h) on mortality after severe controlled cortical impact (CCI) was studied in rats. Four posttraumatic brain temperatures were compared: 37 degrees C (n = 10), 36 degrees C (n = 4), 32 degrees C (n = 10), and uncontrolled (UC; n = 6). Rats were anesthetized and subjected to severe CCI (4.0-m/s velocity, 3.0-mm depth) to the exposed left parietal cortex. At 10 min posttrauma the rats were cooled or maintained at their target brain temperature, using external cooling or warming. Brain temperature in the UC group was recorded but not regulated, and rectal temperature was maintained at 37 +/- 0.5 degrees C. After 4 h, rats were rewarmed over a 1-h period to 37 degrees C, extubated, and observed for 24 h. In the 37 and 36 degree C groups, 24-h mortality was 50% (37 degrees C = 5/10, 36 degrees C = 2/4). In the 32 degree C group, 24-h mortality was 10% (1/10). In the UC group, brain temperature was 35.4 +/- 0.6 degrees C during the 4-h treatment period and 24-h mortality was 0% (0/6). Mortality was higher in groups with brain temperatures > or = 36 degrees C versus those with brain temperatures < 36 degrees C (50 vs. 6%, respectively; p < 0.05). Additionally, electroencephalograms (EEG) were recorded in subsets of each temperature group and the percentage of time that the EEG was suppressed (isoelectric) was determined. Percentage of EEG suppression was greater in the hypothermic (32 degrees C, n = 6; UC, n = 4) groups than in the normothermic (36 degrees C, n = 3; 37 degrees C, n = 6) groups (23.3 +/- 14.3 vs. 1.2 +/- 3.1%, respectively; p < 0.05). Posttraumatic hypothermia suppressed EEG during treatment and reduced mortality after severe CCI. The threshold for this protective effect appears to be a brain temperature < 36 degrees C. Thus, even mild hypothermia may be beneficial after severe brain trauma. 相似文献
1000.
DL Boger J Goldberg W Jiang W Chai P Ducray JK Lee RS Ozer CM Andersson 《Canadian Metallurgical Quarterly》1998,6(8):1347-1378
Full details of the preparation of iminodiacetic acid diamide dimer (2040 compounds), trimer (560 compounds), and tetramer (1596 compounds) libraries by multistep convergent solution-phase synthesis for studying protein-protein interactions are provided. The libraries were assembled in a format providing small 8-10 compound mixtures and the deconvolution of many of the small mixtures to identify screening leads by resynthesis of the individual components have been conducted for 320 of the individual compounds to date. A representative example of the subsequent exploration of the structure-activity relationships for an identified receptor binding antagonist (200 additional individual compounds) and steps taken for potential elaboration to a receptor dimerization agonist are defined with preparation of representative linked dimers (70 compounds). 相似文献