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排序方式: 共有116条查询结果,搜索用时 15 毫秒
81.
Lightning LK Jones JP Friedberg T Pritchard MP Shou M Rushmore TH Trager WF 《Biochemistry》2000,39(15):4276-4287
Mechanism-based inactivation of human liver P450 3A4 by L-754,394, a Merck compound synthesized as a potential HIV protease inhibitor, was investigated using recombinant P450 3A4. Enzyme inactivation was characterized by a small partition ratio (3.4 or 4.3 +/- 0.4), i.e., the total number of metabolic events undergone by the inhibitor divided by the number of enzyme inactivating events, lack of reversibility upon extensive dialysis, no decrease in the characteristic 450-nm species relative to control, and covalent modification of the apoprotein. The major and minor products formed during the inactivation of P450 3A4 were the monohydroxylated and the dihydrodiol metabolites of L-754,394, respectively. L-754,394 that had been adducted to P450 3A4 was hydrolyzed under the conditions used for SDS-PAGE, Ni(2+) affinity chromatography, and proteolytic digestion. In addition, the modification was not stable to the acidic conditions of HPLC separation and CNBr digestion. The labile nature of the peptide adduct and the nonstoichiometric binding of the inactivating species to P450 3A4 precluded the direct identification of a covalently modified amino acid residue or the peptide to which it was attached. However, Tricine SDS-PAGE in combination with MALDI-TOF-MS and homology modeling, allowed I257-M317 to be tentatively identified as an active site peptide, while prior knowledge of the stability of N-, O-, and S-linked conjugates of activated furans implicates Glu307 as the active site amino acid that is labeled by L-754, 394. 相似文献
82.
One possible treatment for cerebral aneurysms is a porous tubular structure, similar to a stent, called a flow diverter. A flow diverter can be placed across the neck of a cerebral aneurysm to induce the cessation of flow and initiate the formation of an intra-aneurysmal thrombus. This excludes the aneurysm from the parent artery and returns the flow of blood to normal. Previous flow diverting devices have been analyzed to determine optimal characteristics, such as braiding angle and wire diameter. From this information, a new optimized device was designed to achieve equivalent hemodynamic performance to the previous best device, but with better longitudinal flexibility to preserve physiological arterial configuration. The new device was tested in vitro in an elastomeric replica of the rabbit elastase induced aneurysm model and is now in the process of being tested in vivo. Particle image velocimetry was utilized to determine the velocity field in the plane of symmetry of the model under pulsatile flow conditions. Device hemodynamic performance indices such as the hydrodynamic circulation were evaluated from the velocity fields. Comparison of these indices with the previous best device and a control shows that the significant design changes of the device did not change its hemodynamic attributes (p?>?0.05). 相似文献
83.
Florian M. Steiner Birgit C. Schlick-Steiner James C. Trager Karl Moder Matthias Sanetra Erhard Christian Christian Stauffer 《Biological invasions》2006,8(2):117-123
Combining molecular and morphological evidence, an invasive ant in Missouri and Illinois, USA, is identified as Tetramorium tsushimae Emery, 1925, a polygynous-polycalic species native to East Asia. T. tsushimae is recorded as invasive for the first time. RFLP and worker morphometrics provide tools for reliable determination. Mitochondrial
DNA data reveal the probable geographic origin of the invasive populations to be Japan.
The first two authors contributed equally to this work. 相似文献
84.
Intranuclear structures in pyrimethamine-resistant isolates of the malaria parasite Plasmodium falciparum 总被引:2,自引:0,他引:2
The ultrastructure of the malaria parasite Plasmodium falciparum is well known, both from natural infections and from culture material ( Aikawa , 1977, Langreth et al., 1978). It is noteworthy that all of these studies were done with pyrimethamine-sensitive strains, e.g. FCR-3/Gambia. Except for spindle microtubules during schizogony, no intranuclear structures have been described in any of the asexual erythrocytic stages. In the course of isolating clones from the pyrimethamine-resistant strain Honduras I/CDC (V.K. Bhasin and W. Trager , in print) and checking by electron microscopy for the presence or absence of knobs, we noticed intranuclear structures that might be correlated with pyrimethamine resistance. For comparison, we then examined the multi-drug-resistant strain Indochina 1. We present here a first report on these structures as a basis for further studies. 相似文献
85.
86.
The respiratory requirements of Plasmodium falciparum were studied in vitro in continuous cultivation. The cultures were held in petri dishes containing the parasites incubated in different gas mixtures for periods of 72 to 144 hr with daily media changes. Atmospheres were combinations of 0.5 to 21% O2 mixed with 1 to 5% CO2 diluted with N2. Gas concentrations and the pH of media were measured with an analyzer. Best growth was realized in all cases at 3% O2 and 1 to 2% CO2. The culture appeared to be selfperpetuating in O2 concentrations as low as 0.5% providing the CO2 was not over 2%. Oxygen concentrations of 21% proved deleterious to growth. The parasite however, failed to grow in the highly reducing atmosphere of anaerobic “Brewer Jars,” suggesting that P. falciparum is an obligate microaerophile. 相似文献
87.
Christiane Gonalves Dall'Aglio-Holvorcem Woodruff W. Benson Lawrence E. Gilbert James C. Trager Jos Roberto Trigo 《Biochemical Systematics and Ecology》2009,37(4):442-451
Morphologically similar fire ants Solenopsis invicta and Solenopsis saevissima are broadly sympatric in southeastern Brazil. Chemistry from venom (2,6-dialkyl piperidine alkaloids) and cuticular hydrocarbons have been reported as potentially important tools for differentiating Solenopsis species. We have analysed two chemical classes in widely separated populations of S. invicta and S. saevissima and find that both piperidine alkaloids and cuticular hydrocarbons separate the two species. Piperidine alkaloids clustered S. invicta but not S. saevissima. Cuticular hydrocarbons strongly clustered both S. invicta and S. saevissima. One population morphologically identified as S. invicta presented piperidine alkaloids and cuticular hydrocarbons markedly different from either species. The distinctive piperidine alkaloid differences among populations of S. saevissima and the marked difference in piperidine alkaloid and hydrocarbon profiles of the anomalous population of S. invicta suggest undescribed species fire ant in southeastern Brazil. 相似文献
88.
89.
Abstract: Habitat fragmentation is considered a leading cause of plant extinction, and matrix models provide a powerful set of tools with which to identifying mechanisms that influence population declines. We surveyed the ecological literature to determine what components of plant demography have been studied in fragmented habitats, and determined the elasticity values of the vital rates influenced by these components. We found that there is a major disparity between the ecological processes and stages of life history with large demographic impacts and the focus of empirical research on plants in fragmented habitats. While the growth and survivorship of large, established individuals have the highest elasticity values, the focus of empirical research has been on components of reproduction and seedling dynamics. We argue that elucidating the demographic mechanisms underlying population declines in fragmented habitats, and developing strategies for mitigating these declines, will be challenging without a greater focus on understanding how fragmentation alters adult plant growth and survivorship. 相似文献
90.