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排序方式: 共有605条查询结果,搜索用时 792 毫秒
81.
Mitsunori Kono Tsuneo Oda Michiko Tawada Takashi Imada Yoshihiro Banno Naohiro Taya Tetsuji Kawamoto Hidekazu Tokuhara Yoshihide Tomata Naoki Ishii Atsuko Ochida Yoshiyuki Fukase Tomoya Yukawa Shoji Fukumoto Hiroyuki Watanabe Keiko Uga Akira Shibata Hideyuki Nakagawa Satoshi Yamamoto 《Bioorganic & medicinal chemistry》2018,26(2):470-482
A series of tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their potential as novel orally efficacious retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of Th17-driven autoimmune diseases. We carried out cyclization of the phenylglycinamide core by structure-based drug design and successfully identified a tetrahydroisoquinoline carboxylic acid derivative 14 with good biochemical binding and cellular reporter activity. Interestingly, the combination of a carboxylic acid tether and a central fused bicyclic ring was crucial for optimizing PK properties, and the compound 14 showed significantly improved PK profile. Successive optimization of the carboxylate tether led to the discovery of compound 15 with increased inverse agonistic activity and an excellent PK profile. Oral treatment of mice with compound 15 robustly and dose-dependently inhibited IL-17A production in an IL23-induced gene expression assay. 相似文献
82.
Hidekazu Tanaka Takahiro Yamaguchi Kae Hachiya Kazuhiro Miwa Jun Shinoda Masahide Hayashi Shinichi Ogawa Hironori Nishibori Satoshi Goshima Masayuki Matsuo 《Reports of Practical Oncology and Radiotherapy》2018,23(3):215-219
Aim
To define the optimal margin on MRI scans in the re-radiation planning of recurrent glioblastoma using methionine positron emission tomography (MET-PET).Background
It would be very useful if the optimal margin on MRI to cover the uptake area on MET-PET is known.Materials and Methods
CT, MRI, and MET-PET were performed separately over the course of 2 weeks. Among the MRI scans, we used the contrast-enhanced T1-weighted images (Gd-MRI) and T2-weighted images (T2-MRI). The Gd-MRI-based clinical target volume (CTV) (CTV-Gd) and the T2-MRI-based CTV (CTV-T2) were defined as the contrast-enhanced area on Gd-MRI and the high intensity area on T2-MRI, respectively. We defined CTV x mm (x = 5, 10, 15, 20) as x mm outside the CTV. MET-PET-based CTV (CTV-MPET) was defined as the area of accumulation of MET-PET. We calculated the sensitivity and specificity of CTV-Gd and CTV-T2 following comparison with CTV-MPET, which served as the gold standard in this study.Results
The sensitivity of CTV-T2 5 mm (98%) was significantly higher than CTV-T2 (87%), and there was no significant difference in the sensitivity between CTV-T2 5 mm and CTV T2 10, 15, or 20 mm. The sensitivity of CTV-Gd 20 mm (97%) was lower than that of CTV-T2 5 mm (98%).Conclusions
A margin of at least 5 mm around the high intensity area on T2-MRI is necessary in the target volume delineation of recurrent glioblastoma for the coverage of MET-PET findings in re-radiation therapy planning. 相似文献83.
Hidekazu Tanaka Takahiro Yamaguchi Kae Hachiya Shingo Kamei Satoshi Ishihara Masahide Hayashi Shinichi Ogawa Hironori Nishibori Satoshi Goshima Masayuki Matsuo 《Reports of Practical Oncology and Radiotherapy》2018,23(1):28-33
Aim
This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer.Background
A total of 1091 patients with localized prostate cancer were recruited between March 2006 and July 2014. The patients were stratified into low- (n = 205 [18.8%]), intermediate- (n = 450 [41.2%]), high- (n = 345 [31.6%]), and very high-risk (n = 91 [8.3%]) groups according to the National Comprehensive Cancer Network classification. All patients were irradiated via IMRT at a dose of 74–78 Gy with or without androgen-deprivation therapy. The mean follow-up period was 50 months (range, 2–120 months).Results
The biochemical failure-free rate (BFFR), the clinical failure-free rate, and the overall survival rate at the 5-year follow-up for all patients was 91.3%, 96.2%, and 99.1%, respectively. In univariate analysis, the prostate-specific antigen (PSA) levels (≤20 vs. >20 ng/ml) were significantly correlated with BFFR. A trend toward higher BFFR was noted in patients with a Gleason score (GS) of ≤7 than in patients with GS ≥8. In multivariate analysis, only PSA (≤20 vs. >20 ng/ml) was significantly correlated with BFFR. The cumulative incidence rate of gastrointestinal and genitourinary toxicity (≥grade 2) at the 5-year follow-up was 11.4% and 4.3%, respectively.Conclusions
The findings of this study indicate that IMRT is well tolerated and is associated with both good long-term tumor control and excellent outcomes in patients with localized prostate cancer. 相似文献84.
Hiroyuki Kimura Saki Yamauchi Hidekazu Kawashima Kenji Arimitsu Yusuke Yagi Yuji Nakamoto Kaori Togashi Masahiro Ono Hideo Saji 《Bioorganic & medicinal chemistry letters》2018,28(17):2949-2952
The tripeptide formyl–Met–Leu–Phe (fMLF) is a prototype of N-formylated chemotactic peptides for neutrophils owing to its ability to bind and activate the G protein-coupled formyl peptide receptor (FPR). Here, we developed an 18F-labeled fMLF derivative targeting FPR as a positron emission tomography (PET) imaging probe for bacterial infections. The study demonstrates that the fMLF derivative fMLFXYk(FB)k (X?=?Nle) has a high affinity for FPR (Ki?=?0.62?±?0.13?nM). The radiochemical yield and purity of [18F]fMLFXYk(FB)k were 16% and >96%, respectively. The in vivo biodistribution study showed that [18F]fMLFXYk(FB)k uptake was higher in the bacterial infected region than in the non-infected region. We observed considerably higher infection-to-muscle ratio of 4.6 at 60?min after [18F]fMLFXYk(FB)k injection. Furthermore, small-animal PET imaging studies suggested that [18F]fMLFXYk(FB)k uptake in the bacterial infected region was clearly visualized 60?min after injection. 相似文献
85.
Comprehending life history of migratory fish, onset of migration in particular, is a key biological and ecological research topic that still has not been clarified. In this paper, we propose a simple mathematical model for the onset of fish migration in the context of a stochastic optimal stopping theory, which is a new attempt to our knowledge. Finding the criteria of the onset of migration reduces to solving a variational inequality of a degenerate elliptic type. As a first step of the new mathematical modeling, mathematical and numerical analyses with particular emphasis on whether the model is consistent with the past observation results of fish migration are examined, demonstrating reasonable agreement between the theory and observation results. The present mathematical model thus potentially serves as a simple basis for analyzing onset of fish migration. 相似文献
86.
Yuichi Kunori Masahiro Koizumi Tsukio Masegi Hidenori Kasai Hiroshi Kawabata Yuzo Yamazaki Akiyoshi Fukamizu 《European journal of biochemistry》2002,269(23):5921-5930
Although the alpha-chymases of primates and dogs are known as chymotrypsin-like proteases, the enzymatic properties of rodent alpha-chymases (rat mast cell protease 5/rMCP-5 and mouse mast cell protease 5/mMCP-5) have not been fully understood. We report that recombinant rMCP-5 and mMCP-5 are elastase-like proteases, not chymotrypsin-like proteases. An enzyme assay using chromogenic peptidyl substrates showed that mast cell protease-5s (MCP-5s) have a clear preference for small aliphatic amino acids (e.g. alanine, isoleucine, valine) in the P1 site of substrates. We used site-directed mutagenesis and computer modeling approaches to define the determinant residue for the substrate specificity of mMCP-5, and found that the mutant possessing a Gly substitution of the Val at position 216 (V216G) lost elastase-like activity but acquired chymase activity, suggesting that the Val216 dominantly restricts the substrate specificity of mMCP-5. Structural models of mMCP-5 and the V216G mutant based on the crystal structures of serine proteases (rMCP-2, human cathepsin G, and human chymase) revealed the active site differences that can account for the marked differences in substrate specificity of the two enzymes between elastase and chymase. These findings suggest that rodent alpha-chymases have unique biological activity different from the chymases of other species. 相似文献
87.
Kenichiro Inoue Shinichi Ueda Hidekazu Nayeshiro Nobuharu Moritome Hiroyuki Inouye 《Phytochemistry》1984,23(2):312-318
Administration of p13C- and p2H-labelled precursors to Streptocarpus dunnii cell cultures demonstrated that the naphthoquinones formed through aunique prenylation mode are biosynthesized via 4-(2'-carboxyphenyl)-4-oxobutanoic acid, 1,4-dihydroxy-2-naphthoic acid, lawsone and lawsone 2-prenyl ether, and that the anthraquinones are biosynthesized through prenylation of 2-carboxy-4-oxo-1-tetralone at the carboxy-bearing carbon atom to form 2-carboxy-2-prenyl-4-oxo-1-tetralone,or through ipso attack of the prenyl group on the corresponding carbon atom of 1,4-dihydroxy-2-naphthoic acid. 相似文献
88.
Yoshiaki Fujimiya Youichi Suzuki Ko-ichi Oshiman Hidekazu Kobori Koichi Moriguchi Hisako Nakashima Yonezo Matumoto Shogo Takahara Takusaburo Ebina Ryuichi Katakura 《Cancer immunology, immunotherapy : CII》1998,46(3):147-159
We have isolated a novel type of natural tumoricidal product from the basidiomycete strain, Agaricus blazei Murill. Using the double-grafted tumor system in Balb/c mice, treatment of the primary tumor with an acid-treated fraction
(ATF) obtained from the fruit bodies resulted in infiltration of the distant tumor by natural killer (NK) cells with marked
tumoricidal activity. As shown by electrophoresis and DNA fragmentation assay, the ATF also directly inhibited tumor cell
growth in vitro by inducing apoptotic processing; this apoptotic effect was also demonstrated by increased expression of the
Apo2.7 antigen on the mitochondrial membranes of tumor cells, as shown by flow-cytometric analysis. The ATF had no effect
on normal mouse splenic or interleukin-2-treated splenic mononuclear cells, indicating that it is selectively cytotoxic for
the tumor cells. Cell-cycle analysis demonstrated that ATF induced the loss of S phase in MethA tumor cells, but did not affect
normal splenic mononuclear cells, which were mainly in the G0G1 phase. Various chromatofocussing purification steps and NMR
analysis showed the tumoricidal activity to be chiefly present in fractions containing (1→4)-α-D-glucan and (1→6)-β-D-glucan, present in a ratio of approximately 1:2 in the ATF (molecular mass 170 kDa), while the final purified fraction, HM3-G
(molecular mass 380 kDa), with the highest tumoricidal activity, consisted of more than 90% glucose, the main component being
(1→4)-α-D-glucan with (1→6)-β branching, in the ratio of approximately 4:1.
Received: 27 August 1997 / Accepted 22 December 1997 相似文献
89.
Efficient isolation of human parainfluenza viruses 1 and 3 using MNT‐1, a human malignant melanoma cell line system that exhibits an apparent cytopathic effect 下载免费PDF全文
Ko Sato Oshi Watanabe Suguru Ohmiya Fumiko Chiba Masahiro Hayashi Tamio Suzuki Kazuyoshi Kawakami Hidekazu Nishimura 《Microbiology and immunology》2016,60(11):801-805
Isolation of human parainfluenza virus (HPIV) serotypes 1 and 3 from clinical specimens is not very efficient because of the lack of a cell culture system capable of inducing CPE. In this study, the utility of a melanoma cell line, MNT‐1, that allows HPIV growth and displays CPE was demonstrated. In particularly, the efficiency of isolating HPIV1 and HPIV3 using MNT‐1 was greater than for cell lines conventionally used for HPIV isolation. Our demonstrated efficacy of HPIV1 and HPIV3 isolation with apparent CPE using the MNT‐1 cell culture system has the potential to improve virus isolation from clinical specimens. 相似文献
90.
R Mochizuki Y Ishizuka K Yanai Y Koga A Fukamizu K Murakami 《Biochimica et biophysica acta》1999,1446(3):397-402
Human neurochondrins have been cloned from a brain cDNA library. The human neurochondrin-1 and -2 predict leucine-rich (15.8 and 15.9%) proteins of 729 and 712 amino acid residues, with molecular weights of 78.9 and 77.2 kDa, respectively. The deduced amino acid sequence indicates 98% identity among human, mouse and rat species. Northern analysis indicates that about 4 kb human neurochondrin mRNAs are abundant in the fetal and the adult brain. 相似文献