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21.
The NADPH-dependent metabolism of ifosphamide catalyzed by rat liver microsomes was investigated in order to identify individual P450 enzymes that activate this anti-cancer drug and to ascertain their relationship to the P450 enzymes that activate the isomeric drug cyclophosphamide. Pretreatment of rats with phenobarbital or clofibrate increased by up to 8-fold the activation of both ifosphamide and cyclophosphamide catalyzed by isolated liver microsomes. Studies using P450 form-selective inhibitory antibodies demonstrated that constitutively expressed P450s belonging to subfamily 2C (forms 2C11/2C6) make significant contributions to the activation of both oxazaphosphorines in uninduced male rat liver microsomes, while the phenobarbital-inducible P450 2B1 was shown to be a major catalyst of these activations in phenobarbital-induced microsomes. Pretreatment of rats with dexamethasone increased liver microsomal activation of ifosphamide approximately 6-fold without a corresponding effect on cyclophosphamide activation rates. Ifosphamide activation catalyzed by dexamethasone-induced liver microsomes was minimally inhibited by anti-P450 2B or anti-P450 2C antibodies, but was selectively inhibited by anti-P450 3A antibodies. Selective inhibition of liver microsomal ifosphamide activation was also effected by the macrolide antibiotic triacetyloleandomycin, an inhibitor of several dexamethasone-inducible 3A P450s. These studies establish that a dexamethasone-inducible family 3A P450 can make an important contribution to rat liver microsomal ifosphamide activation, and suggest that dexamethasone pretreatment might provide a useful approach for modulation of ifosphamide metabolism in order to improve its therapeutic efficacy in cancer patients. 相似文献
22.
G Stoll S Müller B Schmidt P van der Meide S Jung KV Toyka HP Hartung 《Canadian Metallurgical Quarterly》1993,142(6):1866-1875
This study reports the cellular localization of interferon-gamma (IFN-gamma) and MHC class II antigen (Ia) in the spinal cord of rats with experimental autoimmune encephalomyelitis induced by adoptive transfer of myelin basic protein-specific T cells. Numerous IFN-gamma-positive cells, stained with two different monoclonal antibodies against IFN-gamma, were present from days 3 to 7 after cell transfer. Their number was greatly reduced on day 10. A subpopulation of T cells was IFN-gamma positive. Moreover, a large number of ED1-positive macrophages contained IFN-gamma immunoreactivity. The transient presence of immune cells containing IFN-gamma immunoreactivity in experimental autoimmune encephalomyelitis suggests a pathogenic role of this cytokine in immune-mediated demyelination of the central nervous system. 相似文献
23.
24.
Torshin Ivan Y.; Weber Irene T.; Harrison Robert W. 《Protein engineering, design & selection : PEDS》2002,15(5):359-363
Empirical criteria for identification of hydrogen bonds wereanalyzed to produce a set of geometrically consistent criteria.For a data set of 30 structures, application of a set of purelygeometrical criteria, along with exclusion of abnormal backboneconformations, also excluded a common interaction of Ser/Thrside chains with Asp/Glu side chains ([ST]/[DE] pairs). Theseinteractions were termed `bifurcated hydrogen bonds/', whichimplies delocalization of a positively charged hydrogen of hydroxylbetween the two acceptor atoms of the carboxylic group. These`bifurcated/' interactions are among the most common packingpatterns for [ST]/[DE] pairs of side chains. Therefore, theidentification of hydrogen bonds cannot be based on geometricalcriteria only and requires introduction of some physico-chemicalcriteria. 相似文献
25.
The multipurpose mask set described, which consists of three stepper reticles, contains 95% of all test structures required for CMOS process development and random defect detection, thereby dramatically reducing the stepper reticle inventory and the frequency of reticle changes. Realizing the mask set by two dozen standard unit processes minimizes the feedback loop for defect density data, parametric data and unit process data 相似文献
26.
Daniel Röhnert Fritz Phillipp Helfried Reuther Till Weber Egbert Wessel Michael Schütze 《Oxidation of Metals》2007,68(5-6):271-293
The initial stages of the metal-dusting process on Alloy 800 at 620 °C were investigated by light optical microscopy, RAMAN
spectroscopy, atomic-force microscopy, Auger electron spectroscopy, transmission-electron microscopy and electron back-scatter
diffraction. As it turned out the incubation period for metal-dusting is characterized by simultaneous formation of a heterogeneously
growing oxide scale and deposition of carbon. The material surface shows different tarnish colors depending on the substrate-grain
orientation with different susceptibility to the beginning of metal-dusting attack. “Low-index” grains were not attacked within
the times investigated while the other grain orientations showed pitting. Carbon is evidently incorporated into the oxide
scale from the very beginning of exposure with different intensities depending on the underlying substrate-grain orientation
leading to differences in the tarnish colors. As a consequence carbides are formed even underneath “dense” oxide layers. Evidently
metal-dusting attack starts at positions of the oxide scale where “higher carbon concentrations” are present. 相似文献
27.
C Wilken W Baltes I Mehlitz R Tiebach R Weber 《Zeitschrift für Lebensmittel-Untersuchung und -Forschung》1985,180(6):496-497
A rapid procedure for the isolation and clean-up on a silica gel column is described for the determination of Ochratoxin A from pork kidneys. The detection limit is 0.3 microgram/kg. 相似文献
28.
29.
F Würschmidt H Bünemann C Bünemann HP Beck-Bornholdt HP Heilmann 《Canadian Metallurgical Quarterly》1994,170(5):302-304
BACKGROUND: The influence of tumor and patient characteristics on survival as well as acute normal tissue toxicity was retrospectively analyzed. PATIENTS AND METHODS: 427 patients with inoperable non-small cell lung cancer were retrospectively analyzed. Two thirds received a total dose of at least 70 Gy, and one third was irradiated with 60 to 66 Gy (2.0 to 2.5 Gy per fraction; split-course technique). 92% had a Karnofsky performance index of > or = 80%. Kaplan-Meier survival curves were generated and comparisons were made by the log-rank test. Prognostic factors were adjusted for by a proportional hazards analysis. RESULTS: Five-year survival rates (+/- SE) and the median survival times (95% confidence interval) were 2 +/- 2% and 11.1 months (9.1 ... 14.5) after 60 to 66 Gy; 8 +/- 2% and 14.9 months (13.3 ... 16.5) after 70+ Gy. The difference was significant in univariate (p = 0.0013) and multivariate analysis (p = 0.0006). Tumor stage (p = 0.0029: I + II > III; IIIA > IIIB) and gender (p = 0.0387: female > male patients) reached significance in multivariate analysis. Acute pneumonitis and esophagitis were observed in 11% and 9% of cases. CONCLUSIONS: Inoperable non-small cell lung cancer stage I to IIIA should be treated in a curative intention with total doses of about 70 Gy. This is feasible with acceptable normal tissue toxicity. Stage IIIB patients have a particular bad prognosis and should only be treated palliatively. 相似文献
30.
HP Raghuveer 《Canadian Metallurgical Quarterly》1994,8(3):107-109
A case of Solitary Central Neurofibroma in a 53 years old female is reported. This is an apparently single primary lesion, in which physical and Radiological examination failed to reveal other bony lesions or the stigmata of multiple neurofribomatosis. 相似文献