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121.
122.
Yano S Kazuno H Sato T Suzuki N Emura T Wierzba K Yamashita J Tada Y Yamada Y Fukushima M Asao T 《Bioorganic & medicinal chemistry》2004,12(13):3443-3450
A series of novel 6-methylene-bridged uracil derivatives have been optimized for clinical use as the inhibitors of human thymidine phosphorylase (TP). We describe their synthesis and evaluation. Introduction of a guanidino or an amidino group enhanced the in vitro inhibitory activity of TP comparing with formerly reported inhibitor 1. Their selectivity for TP based on uridine phosphorylase inhibitory activity was also evaluated. Compound 2 (TPI) has been selected for clinical evaluation based on its strong TP inhibition and excellent modulation of 2'-deoxy-5-(trifluoromethyl)uridine (F(3)dThd) pharmacokinetics. As a result, TAS-102 (a combination of F(3)dThd and TPI) is currently in phase 1 clinical studies. 相似文献
123.
Ohnishi M Sawada T Marumo K Harada K Hirose K Shimizu A Hayashimoto M Sato R Uchida N Kato H 《Letters in applied microbiology》2012,54(6):572-576
Aims: To evaluate the antimicrobial susceptibility and genetic relatedness of 11 Stenotrophomonas maltophilia isolates from an outbreak of bovine clinical mastitis in one herd and two isolates from two separate mastitis cases in two other herds. Methods and Results: Thirteen S. maltophilia isolates were obtained from milk samples from 11 cows from three dairy herds in Japan during 2008. We tested their susceptibility to 14 antimicrobials by broth microdilution and identified their genotypes by enterobacterial repetitive intergenic consensus 2 (ERIC2)‐PCR. Every cow had acute mild mastitis (slightly watery foremilk with flakes) without systemic symptoms and all resolved within 3–5 weeks of diagnosis. Eleven of the 13 isolates derived from nine cows in one herd over a 7‐month period exhibited a closely related ERIC2 type (A). The remaining two isolates derived from two cows from two other herds exhibited two distinct ERIC2 types (B and C). Most of the 13 isolates exhibited susceptibility to trimethoprim‐sulfamethoxazole, chloramphenicol, minocycline and levofloxacin; however, they were resistant to four β‐lactams, kanamycin, gentamicin and oxytetracycline. They were intermediate to enrofloxacin. Conclusions: Eleven closely related S. maltophilia isolates were involved in a herd outbreak of mastitis to some extent. Bovine S. maltophilia isolates exhibited resistance to many classes of antimicrobials. Significance and impact of study: This is a rare report of a herd outbreak of bovine mastitis involving closely related S. maltophilia isolates. 相似文献
124.
Sato C Manaka S Nakane D Nishiyama H Suga M Nishizaka T Miyata M Maruyama Y 《Biochemical and biophysical research communications》2012,417(4):1213-1218
Mycoplasma is a genus of bacterial pathogen that causes disease in vertebrates. In humans, the species Mycoplasma pneumoniae causes 15% or more of community-acquired pneumonia. Because this bacterium is tiny, corresponding in size to a large virus, diagnosis using optical microscopy is not easy. In current methods, chest X-rays are usually the first action, followed by serology, PCR amplification, and/or culture, but all of these are particularly difficult at an early stage of the disease. Using Mycoplasma mobile as a model species, we directly observed mycoplasma in buffer with the newly developed Atmospheric Scanning Electron Microscope (ASEM). This microscope features an open sample dish with a pressure-resistant thin film window in its base, through which the SEM beam scans samples in solution, from below. Because of its 2-3μm-deep scanning capability, it can observe the whole internal structure of mycoplasma cells stained with metal solutions. Characteristic protein localizations were visualized using immuno-labeling. Cells were observed at low concentrations, because suspended cells concentrate in the observable zone by attaching to sialic acid on the silicon nitride (SiN) film surface within minutes. These results suggest the applicability of the ASEM for the study of mycoplasmas as well as for early-stage mycoplasma infection diagnosis. 相似文献
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127.
Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction 总被引:2,自引:0,他引:2 下载免费PDF全文
Tanaka M Miyoshi J Ishizaki H Togawa A Ohnishi K Endo K Matsubara K Mizoguchi A Nagano T Sato M Sasaki T Takai Y 《Molecular biology of the cell》2001,12(5):1421-1430
The Rab3 small G protein family consists of four members, Rab3A, -3B, -3C, and -3D. Of these members, Rab3A regulates Ca(2+)-dependent neurotransmitter release. These small G proteins are activated by Rab3 GDP/GTP exchange protein (Rab3 GEP). To determine the function of Rab3 GEP during neurotransmitter release, we have knocked out Rab3 GEP in mice. Rab3 GEP-/- mice developed normally but died immediately after birth. Embryos at E18.5 showed no evoked action potentials of the diaphragm and gastrocnemius muscles in response to electrical stimulation of the phrenic and sciatic nerves, respectively. In contrast, axonal conduction of the spinal cord and the phrenic nerve was not impaired. Total numbers of synaptic vesicles, especially those docked at the presynaptic plasma membrane, were reduced at the neuromuscular junction approximately 10-fold compared with controls, whereas postsynaptic structures and functions appeared normal. Thus, Rab3 GEP is essential for neurotransmitter release and probably for formation and trafficking of the synaptic vesicles. 相似文献
128.
129.
Kazunori Sato 《Population Ecology》2009,51(3):411-418
In this paper, we investigate a spatially explicit metapopulation model with Allee effects. We refer to the patch occupancy
model introduced by Levins (Bull Entomol Soc Am 15:237–240, 1969) as a spatially implicit metapopulation model, i.e., each local patch is either occupied or vacant and a vacant patch can
be recolonized by a randomly chosen occupied patch from anywhere in the metapopulation. When we transform the model into a
spatially explicit one by using a lattice model, the obtained model becomes theoretically equivalent to a “lattice logistic
model” or a “basic contact process”. One of the most popular or standard metapopulation models with Allee effects, developed
by Amarasekare (Am Nat 152:298–302, 1998), supposes that those effects are introduced formally by means of a logistic equation. However, it is easier to understand
the ecological meaning of associating Allee effects with this model if we suppose that only the logistic colonization term
directly suffers from Allee effects. The resulting model is also well defined, and therefore we can naturally examine it by
Monte Carlo simulation and by doublet and triplet decoupling approximation. We then obtain the following specific features
of one-dimensional lattice space: (1) the metapopulation as a whole does not have an Allee threshold for initial population
size even when each local population follows the Allee effects; and (2) a metapopulation goes extinct when the extinction
rate of a local population is lower than that in the spatially implicit model. The real ecological metapopulation lies between
two extremes: completely mixing interactions between patches on the one hand and, on the other, nearest neighboring interactions
with only two nearest neighbors. Thus, it is important to identify the metapopulation structure when we consider the problems
of invasion species such as establishment or the speed of expansion. 相似文献
130.
C. Rossi A. Cuesta-Marcos I. Vales L. Gomez-Pando G. Orjeda R. Wise K. Sato K. Hori F. Capettini H. Vivar X. Chen P. Hayes 《Molecular breeding : new strategies in plant improvement》2006,18(4):355-366
We used a well-characterized barley mapping population (BCD 47 × Baronesse) to determine if barley stripe rust (BSR) resistance quantitative trait loci (QTL) mapped in Mexico and the USA were effective against a reported new race in Peru. Essentially the same resistance QTL were detected using data from each of the three environments, indicating that these resistance alleles are effective against the spectrum of naturally occurring races at these sites. In addition to the mapping population, we evaluated a germplasm array consisting of lines with different numbers of mapped BSR resistance alleles. A higher BSR disease severity on CI10587, which has a single qualitative resistance gene, in Peru versus Mexico suggests there are differences in pathogen virulence between the two locations. Confirmation of a new race in Peru will require characterization using a standard set of differentials, an experiment that is underway. The highest levels of resistance in Peru were observed when the qualitative resistance gene was pyramided with quantitative resistance alleles. We also used the mapping population to locate QTL conferring resistance to barley leaf rust and barley powdery mildew. For mildew, we identified resistance QTL under field conditions in Peru that are distinct from the Mla resistance that we mapped using specific isolates under controlled conditions. These results demonstrate the long-term utility of a reference mapping population and a well-characterized germplasm array for locating and validating genes conferring quantitative and qualitative resistance to multiple pathogens. 相似文献