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41.
Shimamura T Shibata J Kurihara H Mita T Otsuki S Sagara T Hirai H Iwasawa Y 《Bioorganic & medicinal chemistry letters》2006,16(14):3751-3754
5-Pyrimidinyl-2-aminothiazole 1 was identified as an inhibitor of cyclin-dependent kinases (CDKs) by a screening of the Merck sample repository. The introduction of a methyl group at the C-5 or C-6 position on the pyrimidine ring, directed toward the gate keeper residue of CDK4 (Phe93), led to significant enhancement of selectivity for CDK4 over other CDKs. Compound 3 exhibited more than 300-fold selectivity for CDK4 over CDK1, 2, 5, 7, and 9. Subsequent improvements in aqueous solubility afforded compound 4, which is available for further in vivo studies and this compound inhibited pRb phosphorylation and BrdU incorporation in tumor models. 相似文献
42.
Matsunaga H Hokari R Ueda T Kurihara C Hozumi H Higashiyama M Okada Y Watanabe C Komoto S Nakamura M Kawaguchi A Nagao S Sekiyama A Miura S 《American journal of physiology. Gastrointestinal and liver physiology》2011,301(3):G555-G564
Psychological stress is an environmental factor considered to be a precipitating factor of inflammatory bowel disease. Interleukin (IL)-18 plays a role in stress-induced aggravation in some diseases. The aim of this study was to establish a model of murine colitis exacerbated by psychological stress and to clarify the role of IL-18 in this model. Male C57Bl/6 mice and IL-18(-/-) mice were used for this study. The mice received dextran sulfate sodium (DSS) for induction of colitis. Some mice were exposed to psychological stress using a communication box. Body weight, colonic length, and histological inflammation were measured for assessment of colitis. Tumor necrosis factor (TNF)-α and IL-18 expression in the colon and IL-18 expression in the adrenal gland were analyzed using real-time PCR. The effect of anti-IL-18 antibody was also investigated. Effects of TNF-α and IL-18 on cytokine expressions were studied using the colonic epithelial cell line LS174T. Induction of psychological stress in DSS-treated wild-type mice significantly exacerbated colitis with enhanced expression of proinflammatory cytokines and IL-18. However, induction of psychological stress in DSS-treated IL-18(-/-) mice did not aggravate colitis compared with that in the IL-18(-/-) group given only DSS treatment. Stress-induced aggravation of colitis was ameliorated significantly by anti-IL-18 antibody treatment. IL-18 did not enhance TNF-α-induced expression of intercellular adhesion molecule-1 or IL-8 in LS174T. We established a model of colitis exacerbated by psychological stress. Psychological stress enhanced IL-18 expression and plays a proinflammatory role in stress-induced aggravation of colitis. 相似文献
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Yuichi Tsuda Kaori Iwasawa Makoto Yamaguchi 《Bioscience, biotechnology, and biochemistry》2018,82(5):856-861
We investigated the respective effects of the acute supplementation of valine, leucine, and isoleucine on metabolism-related markers by administering a swimming exercise test to rats. As a behavioral analysis, we evaluated the effect of valine and that of leucine on spontaneous activity after exercise. Acute supplementation of valine before exercise significantly suppressed the depression of the liver glycogen and the blood glucose after exercise, whereas leucine decreased the blood glucose and isoleucine had no effect. Valine or leucine supplementation significantly decreased the plasma corticosterone level after exercise, while isoleucine had no effect. In the behavioral analysis, valine significantly increased the spontaneous activity after exercise, whereas leucine had no effect. These results indicate that in rats, the acute supplementation of valine, not leucine or isoleucine, is effective for maintaining liver glycogen and blood glucose and increasing spontaneous activity after exercise, which could contribute to the reduction of fatigue during exercise. 相似文献
45.
添加氧载体提高泰乐菌素发酵的得率 总被引:9,自引:0,他引:9
通过添加氧载体(如正十二烷、全氟化碳等),提高了发酵系统中的氧传递速度,从而促进了泰乐菌素的生物合成。当加入5%的正十二烷或全氟化碳,泰乐菌素的生成量分别提高14%和8%;在加入正十二烷和全氟化碳的同时,再加入载体Aid—PlusML—50D,可使泰乐菌素的生成量分别提高19%和20%。 相似文献
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Takahiro K. Fujiwara Kokoro Iwasawa Ziya Kalay Taka A. Tsunoyama Yusuke Watanabe Yasuhiro M. Umemura Hideji Murakoshi Kenichi G. N. Suzuki Yuri L. Nemoto Nobuhiro Morone Akihiro Kusumi 《Molecular biology of the cell》2016,27(7):1101-1119
The mechanisms by which the diffusion rate in the plasma membrane (PM) is regulated remain unresolved, despite their importance in spatially regulating the reaction rates in the PM. Proposed models include entrapment in nanoscale noncontiguous domains found in PtK2 cells, slow diffusion due to crowding, and actin-induced compartmentalization. Here, by applying single-particle tracking at high time resolutions, mainly to the PtK2-cell PM, we found confined diffusion plus hop movements (termed “hop diffusion”) for both a nonraft phospholipid and a transmembrane protein, transferrin receptor, and equal compartment sizes for these two molecules in all five of the cell lines used here (actual sizes were cell dependent), even after treatment with actin-modulating drugs. The cross-section size and the cytoplasmic domain size both affected the hop frequency. Electron tomography identified the actin-based membrane skeleton (MSK) located within 8.8 nm from the PM cytoplasmic surface of PtK2 cells and demonstrated that the MSK mesh size was the same as the compartment size for PM molecular diffusion. The extracellular matrix and extracellular domains of membrane proteins were not involved in hop diffusion. These results support a model of anchored TM-protein pickets lining actin-based MSK as a major mechanism for regulating diffusion. 相似文献
48.
T Sugawara K Irie H Iwasawa T Yoshikawa S Okuno H K Watanabe T Kato M Shibukawa Y Ito 《Carbohydrate research》1992,230(1):117-149
omega-(Methoxycarbonyl)alkyl glycopyranosides of D-mannose having C4, C7, C9, C12, and C15 carbon chains, L-fucose and 2-acetamido-2-deoxy-D-mannose having C7 and C9 carbon chains, D-xylose and 2-acetamido-2-deoxy-L-fucose having a C9 carbon chain, and 9-(methoxycarbonyl)-3,6-dioxanonyl glycopyranosides of D-mannose, 2-acetamido-2-deoxy-D-mannose, and L-fucose were synthesized as intermediates for coupling to human serum albumin in order to examine the effect of chain length and hydrophobicity of the spacer arm on the binding specificity of lectins. 8-(Methoxycarbonyl)octyl glycosides of beta-D-Man-(1----2)-alpha-D-Man, alpha-D-Man-(1----2)-alpha-D-Man, alpha-D-ManNAc-(1----2)-alpha-D-Man, beta-D-GlcNAc-(1----2)-alpha-D-Man, and their 6-O-positional isomers, beta-D-Man-(1----6)-alpha-D-Man, alpha-D-Man-(1----6)-alpha-D-Man, alpha-D-ManNAc-(1----6)-alpha-D-Man, and beta-D-GlcNAc-(1----6)-alpha-D-Man, were also synthesized. 相似文献
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50.
Soluble IL-2 receptor in AIDS. Correlation of its serum level with the classification of HIV-induced diseases and its characterization 总被引:10,自引:0,他引:10
M Honda K Kitamura K Matsuda Y Yokota N Yamamoto R Mitsuyasu J C Chermann T Tokunaga 《Journal of immunology (Baltimore, Md. : 1950)》1989,142(12):4248-4255
By using a fluorescence sandwich ELISA, elevated IL-2R levels were detected in the sera from both HIV-infected hemophiliacs and other HIV-infected patients. The serum IL-2R levels were reflective of the classification of HIV-induced diseases by the Centers for Disease Control. Moreover, the IL-2R levels were negatively correlated most prominently with CD4 cell counts, with lymphocyte counts, and with a decrease in the CD4-CD8 ratio but not with either WBC counts or B cell counts. As striking elevations of serum IL-2R were noted in AIDS patients with group IVD infection, the serum IL-2R was purified sequentially by using size-exclusion HPLC, high-pressure chromatofocusing, and H48 affinity HPLC. The isoelectric point values of IL-2R were separated into 4.2 and 3.8, whereas the Mr was determined to be only 45 kDa by immunoprecipitation with H48 antibody followed by SDS-PAGE. However, production of cellular and supernatant IL-2R was not elevated in PBMC of patients with AIDS or in any of the 19 HIV-I- or HIV-II-infected cell line cells. In contrast, PBMC from patients with adult T cell leukemia and cell line cells that expressed human T cell lymphotropic virus -I or -II produced soluble IL-2R, constitutively. The mechanisms by which serum levels of IL-2R might be elevated in HIV-infected patients are discussed in comparison with that in adult T cell leukemia patients. 相似文献