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排序方式: 共有1203条查询结果,搜索用时 15 毫秒
41.
Ueda S Mizuki M Ikeda H Tsujimura T Matsumura I Nakano K Daino H Honda Zi Z Sonoyama J Shibayama H Sugahara H Machii T Kanakura Y 《Blood》2002,99(9):3342-3349
Stem cell factor (SCF) has crucial roles in proliferation, survival, and differentiation of hematopoietic stem cells and mast cells through binding to c-Kit receptor (KIT). Chemotaxis is another unique function of SCF. However, little is known about the intracellular signaling pathway of SCF/KIT-mediated cell migration. To investigate the signaling cascade, we made a series of 22 KIT mutants, in which tyrosine (Y) residue was substituted for phenylalanine (F) in the cytoplasmic domain, and introduced into BAF3 cells or 293T cells. On stimulation with SCF, BAF3 expressing KIT(WT)(WT) showed cell migration and Ca(2+) mobilization. Among 22 YF mutants, Y567F, Y569F, and Y719F showed significantly reduced cell migration and Ca(2+) mobilization compared to WT. In Y567F, Lyn activation on SCF stimulation decreased and C-terminal Src kinase (Csk) suppressed KIT-mediated Ca(2+) influx and cell migration, suggesting that Y567-mediated Src family kinase (SFK) activation leads to Ca(2+) influx and migration. Furthermore, we found that p38 mitogen-activated protein kinase (p38 MAPK) and Erk1/2 were also regulated by Y567/SFK and involved in cell migration, and that p38 MAPK induced Ca(2+) influx, thereby leading to Erk1/2 activation. In Y719F, the binding of phosphatidylinositol 3'-kinase (PI3K) to KIT was lost and KIT-mediated cell migration and Ca(2+) mobilization were suppressed by PI3K chemical inhibitors or dominant-negative PI3K, suggesting the involvement of Y719-mediated PI3K pathway in cell migration. Combination of Csk and the PI3K inhibitor synergistically reduced cell migration, suggesting the cooperation of SFK and PI3K. Taken together, these results indicate that 2 major KIT signaling pathways lead to cell migration, one is Y567-SFK-p38 MAPK-Ca(2+) influx-Erk and the other is Y719-PI3K-Ca(2+) influx. 相似文献
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Mizuki Hachiya Shin Murata Hiroshi Otao Takehiko Ihara Katsuhiko Mizota Toyoko Asami 《Journal of Physical Therapy Science》2015,27(12):3663-3666
[Purpose] This study aimed to verify the usefulness of a 50-m round walking test
developed as an assessment method for walking ability in the elderly. [Subjects] The
subjects were 166 elderly requiring long-term care individuals (mean age, 80.5 years).
[Methods] In order to evaluate the factors that had affected falls in the subjects in the
previous year, we performed the 50-m round walking test, functional reach test, one-leg
standing test, and 5-m walking test and measured grip strength and quadriceps strength.
[Results] The 50-m round walking test was selected as a variable indicating fall risk
based on the results of multiple logistic regression analysis. The cutoff value of the
50-m round walking test for determining fall risk was 0.66 m/sec. The area under the
receiver operating characteristic curve was 0.64. The sensitivity of the cutoff value was
65.7%, the specificity was 63.6%, the positive predictive value was 55.0%, the negative
predictive value was 73.3%, and the accuracy was 64.5%. [Conclusion] These results suggest
that the 50-m round walking test is a potentially useful parameter for the determination
of fall risk in the elderly requiring long-term care.Key words: 50-meter round walk test, Local elderly individuals, Falls 相似文献
44.
Air-stable, storable, and highly efficient chiral zirconium catalysts for enantioselective Mannich-type, aza Diels-Alder, aldol, and hetero Diels-Alder reactions
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Kobayashi S Ueno M Saito S Mizuki Y Ishitani H Yamashita Y 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(15):5476-5481
For the synthesis of optically active compounds, chiral catalysts have attracted much attention because large quantities of optically active molecules can be prepared from a small amount of a chiral source. However, many chiral catalysts are often unstable in air (oxygen) and/or in the presence of water. This is especially the case in chiral Lewis acid catalysis, because most Lewis acids are air- and moisture-sensitive. Therefore, many catalysts are prepared in situ in an appropriate solvent just before use, and they cannot be stored for extended periods. We have developed air-stable, storable, and highly efficient chiral zirconium Lewis acids. The catalysts promoted asymmetric Mannich-type, aza Diels-Alder, aldol, and hetero Diels-Alder reactions efficiently with high enantioselectivities. A key to stabilizing the catalysts is an appropriate combination of chiral zirconium Lewis acids with molecular sieves, and the zirconium-molecular sieves-combined catalysts can be stored for extended periods in air at room temperature without loss of activity. Moreover, it has been demonstrated that the catalysts can be recovered and reused. 相似文献
45.
Mizuki Sone Takeshi Toyoda Young‐Man Cho Jun‐ichi Akagi Kohei Matsushita Yasuko Mizuta Tomomi Morikawa Akiyoshi Nishikawa Kumiko Ogawa 《Journal of applied toxicology : JAT》2019,39(6):868-876
Phosphorylated histone H2AX (γ‐H2AX) has been demonstrated as a DNA damage marker both in vitro and in vivo. We previously reported the effects of genotoxic carcinogens in the urinary bladder of rats by immunohistochemical analysis of γ‐H2AX using samples from 28‐day repeated‐dose tests. To evaluate the application of γ‐H2AX as a biomarker of carcinogenicity in the bladder, we examined species differences in γ‐H2AX formation in the urinary bladder of mice. Six‐week‐old male B6C3F1 mice were treated orally with 12 chemicals for 4 weeks. Immunohistochemical analysis demonstrated that N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine, p‐cresidine and 2‐acetylaminofluorene (2‐AAF), classified as genotoxic bladder carcinogens, induced significant increases in γ‐H2AX levels in the bladder urothelium. In contrast, genotoxic (2‐nitroanisole, glycidol, N‐nitrosodiethylamine and acrylamide) and non‐genotoxic (dimethylarsinic acid and melamine) non‐bladder carcinogens did not upregulate γ‐H2AX. Importantly, 2‐nitroanisole, a potent genotoxic bladder carcinogen in rats, significantly increased the proportion of γ‐H2AX‐positive cells in rats only, reflecting differences in carcinogenicity in the urinary bladder between rats and mice. Significant upregulation of γ‐H2AX was also induced by uracil, a non‐genotoxic bladder carcinogen that may be associated with cell proliferation, as demonstrated by increased Ki67 expression. 2‐AAF caused γ‐H2AX formation mainly in the superficial layer, together with reduced and disorganized expression of uroplakin III, unlike in rats, suggesting the mouse‐specific cytotoxicity of 2‐AAF in umbrella cells. These results suggest γ‐H2AX is a useful biomarker reflecting species differences in carcinogenicity in the urinary bladder. 相似文献
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Sachiko Hojo Atsushi Mizukoshi Kenichi Azuma Jiro Okumura Satoshi Ishikawa Mikio Miyata Masami Mizuki Hideo Ogura Kou Sakabe 《International journal of hygiene and environmental health》2018,221(8):1085-1096
Background
Recently, with rapid changes in the Japanese lifestyle, the clinical condition of patients with multiple chemical sensitivity (MCS) may also have undergone change. Thus, we conducted a new survey for subjective symptoms, ongoing chemical exposures, the prevalence of allergic diseases, and presumed onset/trigger factors in patients with MCS and compared results with those of an old survey from ten years ago.Methods
The new survey was conducted from 2012 to 2015 and the old survey was independently conducted from 1999 to 2003, meaning it was not a follow-up study. Patients were initially diagnosed by physicians at five medical institutions with MCS specialty outpatient services, with 111 and 103 patients participating in the new and old surveys, respectively. The controls were a general population living in Japan, with 1313 and 2382 participants in the new and old surveys, respectively. Subjective symptoms and ongoing chemical exposure were evaluated using a quick environmental exposure sensitivity inventory. Additionally, from clinical findings recorded by an attending physician, the prevalence of allergic diseases and presumed onset/trigger factors were evaluated. Differences between new and old surveys were analyzed using logistic regression analyses and significance tests.Results
Compared with ten years ago: (1) Regarding factors affecting patients with ongoing chemical exposures, the proportion of patients affected decreased significantly for two items only (insecticides and second-hand smoke). The proportion of controls showing ongoing exposure to 8 out of 10 items changed significantly. (2) In patients, scores for chemical intolerances, other intolerances, and life impacts increased significantly. (3) In terms of the prevalence of allergic diseases among patients with MCS, bronchial asthma (adjusted odds ratio [AOR]: 5.19), atopic dermatitis (AOR: 3.77), allergic rhinitis (AOR: 5.34), and food allergies (AOR: 2.63) increased significantly, while hay fever (AOR: 0.38) and drug allergies (AOR: 0.40) decreased significantly. (4) With regard to construction and renovation, which was the presumed predominant onset/trigger factor for MCS 10 years ago, this decreased from 68.9% to 35.1%; in contrast, electromagnetic fields (0.0%–26.1%), perfume (0.0%–20.7%), and medical treatment (1.9%–7.2%) increased significantly, confirming the diversification of onset/trigger factors.Conclusion
Compared to ten years ago, for patients with MCS, an increase in avoidance behavior toward chemical substance exposures, which were presumed to be aggravating factors for symptoms, was confirmed. It has been suggested that the ongoing chemical exposure of the general population in Japan has largely changed. In addition, for patients with MCS, chemical intolerances and life impacts have become severe, the prevalence of the main allergic diseases has increased, and onset/trigger factors have become diversified. 相似文献49.
50.
Hiroshi Hasegawa Tetsuharu Kaneko Manabu Endo Chihiro Kanno Morio Yamazaki Sadanoshin Yaginuma Hiroki Igarashi Hideaki Honma Seiichiro Masui Mizuki Suto Yukihiko Sakisaka Hiroshi Ishihata 《Materials》2021,14(12)
Acute-type lateral ridge defects (25 mm × 6 mm × 5 mm) were bilaterally created in the mandibles of four dogs (two defects per animal). The defects were reconstructed with particulate autologous bone and covered with a microperforated titanium membrane (Ti-honeycomb membrane, TiHM) or an existing conventional titanium mesh as control. The samples were dissected after 16 weeks postoperatively and processed for radiographic, histologic, and histomorphometric analyses. Regenerated tissue and bone volume were significantly larger in the TiHM group than in the control group (p = 0.05; p = 0.049). In contrast, bone mineral density was similar between the two groups. Histomorphometric analysis revealed that the regenerated bone area and calcific osseous area were larger in the TiHM group than in the control group; however, the differences were not significant. The efficacy of TiHM was generally satisfactory with the potential to become a standard tool for the GBR procedure; however, early membrane exposure will be a major problem to overcome. 相似文献