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131.
Sayuki Iijima Kentaro Matsuura Tsunamasa Watanabe Koji Onomoto Takashi Fujita Kyoko Ito Etsuko Iio Tomokatsu Miyaki Kei Fujiwara Noboru Shinkai Atsunori Kusakabe Mio Endo Shunsuke Nojiri Takashi Joh Yasuhito Tanaka 《PloS one》2015,10(2)
The levels of expression of interferon-stimulated genes (ISGs) in liver are associated with response to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV). However, associations between the responses of ISGs to IFN-based therapy and treatment efficacy or interleukin-28B (IL28B) genotype have not yet been determined. Therefore, we investigated the early responses of ISGs and interferon-lambdas (IFN-λs) in peripheral blood mononuclear cells (PBMCs) during PEG-IFN/RBV plus NS3/4 protease inhibitor (PI) therapy. We prospectively enrolled 50 chronic hepatitis C patients with HCV genotype 1, and collected PBMCs at baseline, 8 and 24 h after the initial administration of PEG-IFN/RBV/PI. Levels of mRNAs for selected ISGs and IFN-λs were evaluated by real-time PCR. All 31 patients with a favorable IL28B genotype and 13 of 19 with an unfavorable genotype achieved sustained virological responses (SVR). Levels of mRNA for A20, SOCS1, and SOCS3, known to suppress antiviral activity by interfering with the IFN signaling pathway, as well as IRF1 were significantly higher at 8 h in patients with an unfavorable IL28B genotype than in those with a favorable one (P = 0.007, 0.026, 0.0004, 0.0006, respectively), especially in the non-SVR group. Particularly, the fold-change of IRF1 at 8 h relative to baseline was significantly higher in non-SVR than in SVR cases with an unfavorable IL28B genotype (P = 0.035). In conclusion, levels of several mRNAs of genes suppressing antiviral activity in PBMCs during PEG-IFN/RBV/PI differed according to IL28B genotypes, paralleling treatment efficacy. 相似文献
132.
Hiroshi Yamada Tadashi Abe Shun-Ai Li Shota Tago Peng Huang Masami Watanabe Satoru Ikeda Naohisa Ogo Akira Asai Kohji Takei 《Biochemical and biophysical research communications》2014
Dynasore, a specific dynamin GTPase inhibitor, suppresses lamellipodia formation and cancer cell invasion by destabilizing actin filaments. In search for novel dynamin inhibitors that suppress actin dynamics more efficiently, dynasore analogues were screened. N′-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide (DBHA) markedly reduced in vitro actin polymerization, and dose-dependently inhibited phosphatidylserine-stimulated dynamin GTPase activity. DBHA significantly suppressed both the recruitment of dynamin 2 to the leading edge in U2OS cells and ruffle formation in H1299 cells. Furthermore, DBHA suppressed both the migration and invasion of H1299 cells by approximately 70%. Furthermore, intratumoral DBHA delivery significantly repressed tumor growth. DBHA was much less cytotoxic than dynasore. These results strongly suggest that DBHA inhibits dynamin-dependent actin polymerization by altering the interactions between dynamin and lipid membranes. DBHA and its derivative may be potential candidates for potent anti-cancer drugs. 相似文献
133.
Nay Chi Htun Koichi Miyaki Chenxi Zhao Masaaki Muramatsu Noriko Sato 《Biochemical and biophysical research communications》2014
Higher cognitive performance, maintenance of mental health and psychological well-being require adequate prefrontal cortex (PFC) function. “Inverted U-shaped” dopamine model indicates optimal PFC dopamine level is important to attain its function while high or low levels have adverse effects. Catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) may be involved in this complex non-linear PFC dopamine regulation. We addressed whether genetic variation reflecting COMT and MTHFR activities can explain the inter-individual mental health differences in healthy Japanese men (n = 188). The mental health was measured by Mental Health Inventory (MHI)-5 score. The rs4633–rs4818–rs4680 haplotypes were used to represent the multilevel COMT activities, while for MTHFR, the functional single polymorphism, rs1801133 (C677T), was used. We examined the effectiveness of haplotype-based association analysis of COMT on mental health together with studying its interaction with MTHFR-C677T. As a result, the relation between activity-ranked COMT genotype and MHI-5 score showed a tendency to fit into an “inverted U-shaped” quadratic curve (P = 0.054). This curvilinear correlation was significant in the subjects with MTHFR-CC (P < 0.001), but not with MTHFR T-allele carriers (P = 0.793). Our pilot study implies a potential influence of COMT and MTHFR genotypic combination on normal variation of mental health. 相似文献
134.
Kiyoshi Kano Ayami Kitamura Takashi Matsuwaki Masami Morimatsu Kunihiko Naito 《Molecular reproduction and development》2010,77(1):29-37
Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase (RTK). We recently identified homozygous smallie mutant mice (BKS.HRS. Ddr2slie/slie/J, Ddr2slie/slie mutants), which lack a functional DDR2. Ddr2slie/slie mutant mice are dwarfed and infertile due to peripheral dysregulation of the endocrine system. To understand the role of DDR2 signaling in spermatogenesis, we studied the expression of several receptors, enzymes, and proteins related to spermatogenesis in wild‐type and Ddr2slie/slie mutant mice at 10 weeks and 5 months of age. DDR2 were expressed in adult wild‐type male mice in Leydig cells. The number of differentiated spermatozoa in the seminal fluid was significantly lower in the Ddr2slie/slie mutant mice than in the wild‐type mice. The number of TUNEL‐positive cells was significantly greater in 5‐month‐old Ddr2slie/slie mutants. Testosterone was significantly reduced at 5 months of age, but LH was similar in both types of mice at both 10 weeks and 5 months of age. The expression levels of LH receptors (Lhcgr), StAR, P450scc, and Hsd3β6 were not significantly different between the two types of mice at 10 weeks of age, but they were significantly reduced in 5‐month‐old Ddr2slie/slie mutants compared to wild‐type mice of the same age. DDR2 was expressed in the Leydig cells of adult wild‐type male mice. In conclusion, our results indicated that DDR2 signaling plays a critical role in the maintenance of male spermatogenesis. Mol. Reprod. Dev. 77: 29–37, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
135.
Nobuhiro Hayashi Masami Takeuchi Teruyuki Nakanishi Keiichiro Hashimoto Johannes Martinus Dijkstra 《Fish & shellfish immunology》2010,28(1):72-76
The cytoplasmic tail of mammalian CD8α binds the kinase LCK in a zinc-dependent manner. In analogy with a previous study for humans (Kim et al., 2003) peptides were synthesized from rainbow trout CD8α and LCK. Surface plasmon resonance (SPR) analysis indicated that also in fish these molecules bind to each other in a zinc-dependent manner. 相似文献
136.
Miyako Kusano Atsushi Fukushima Henning Redestig Makoto Kobayashi Hitomi Otsuki Hitoshi Onouchi Satoshi Naito Masami Yokota Hirai Kazuki Saito 《Amino acids》2010,39(4):1013-1021
Methionine (Met) is an essential amino acid for all organisms. In plants, Met also functions as a precursor of plant hormones,
polyamines, and defense metabolites. The regulatory mechanism of Met biosynthesis is highly complex and, despite its great
importance, remains unclear. To investigate how accumulation of Met influences metabolism as a whole in Arabidopsis, three methionine over-accumulation (mto) mutants were examined using a gas chromatography–mass spectrometry-based metabolomics approach. Multivariate statistical
analyses of the three mto mutants (mto1, mto2, and mto3) revealed distinct metabolomic phenotypes. Orthogonal projection to latent structures–discriminant analysis highlighted discriminative
metabolites contributing to the separation of each mutant and the corresponding control samples. Though Met accumulation in
mto1 had no dramatic effect on other metabolic pathways except for the aspartate family, metabolite profiles of mto2 and mto3 indicated that several extensive pathways were affected in addition to over-accumulation of Met. The pronounced changes
in metabolic pathways in both mto2 and mto3 were associated with polyamines. The findings suggest that our metabolomics approach not only can reveal the impact of Met
over-accumulation on metabolism, but also may provide clues to identify crucial pathways for regulation of metabolism in plants. 相似文献
137.
Masaki Asada Tetsuo Obitsu Atsushi Kinoshita Yoshihiko Nakai Toshihiko Nagase Isamu Sugimoto Motoyuki Tanaka Hiroya Takizawa Ken Yoshikawa Kazutoyo Sato Masami Narita Shuichi Ohuchida Hisao Nakai Masaaki Toda 《Bioorganic & medicinal chemistry letters》2010,20(8):2639-2643
A series of novel N-acylsulfonamide analogs were synthesized and evaluated for their binding affinity and antagonist activity for the EP3 receptor subtype. Representative compounds were also evaluated for their inhibitory effect on PGE2-induced uterine contraction in pregnant rats. Among those tested, a series of N-acylbenzenesulfonamide analogs were found to be more potent than the corresponding carboxylic acid analogs in both the in vitro and in vivo evaluations. The structure activity relationships (SAR) are also discussed. 相似文献
138.
Shunsuke Ohashi Tatsuya Iemura Naoki Okada Shingo Itoh Hayato Furukawa Masaaki Okuda Mayumi Ohnishi-Kameyama Takuro Ogawa Hideaki Miyashita Tadashi Watanabe Shigeru Itoh Hirozo Oh-oka Kazuhito Inoue Masami Kobayashi 《Photosynthesis research》2010,104(2-3):305-319
Minor but key chlorophylls (Chls) and quinones in photosystem (PS) I-type reaction centers (RCs) are overviewed in regard to their molecular structures. In the PS I-type RCs, the prime-type chlorophylls, namely, bacteriochlorophyll (BChl) a′ in green sulfur bacteria, BChl g′ in heliobacteria, Chl a′ in Chl a-type PS I, and Chl d′ in Chl d-type PS I, function as the special pairs, either as homodimers, (BChl a′)2 and (BChl g′)2 in anoxygenic organisms, or heterodimers, Chl a/a′ and Chl d/d′ in oxygenic photosynthesis. Conversions of BChl g to Chl a and Chl a to Chl d take place spontaneously under mild condition in vitro. The primary electron acceptors, A 0, are Chl a-derivatives even in anoxygenic PS I-type RCs. The secondary electron acceptors are naphthoquinones, whereas the side chains may have been modified after the birth of cyanobacteria, leading to succession from menaquinone to phylloquinone in oxygenic PS I. 相似文献
139.
Hiroki Obata Noritaka Kawashima Masami Akai Kimitaka Nakazawa Tatsuyuki Ohtsuki 《Journal of electromyography and kinesiology》2010,20(1):55-60
The purpose of this study was to characterize the effects of aging on the stretch reflex in the ankle muscles, and in particular to compare the effects on the ankle dorsi-flexor (tibialis anterior: TA) and the plantar-flexor (soleus: SOL). Stretch reflex responses were elicited in the TA and SOL at rest and during weak voluntary contractions in 20 elderly and 23 young volunteers. The results indicated that, in the TA muscle, the elderly group had a remarkably larger long-latency reflex (LLR), whereas no aging effect was found in the short latency reflex (SLR). These results were very different from those in the SOL muscle, which showed significant aging effects in the SLR and medium latency reflex (MLR), but not in the LLR. Given the fact that the LLR of the TA stretch reflex includes the cortical pathway, it is probable that the effects of aging on the TA stretch reflex involve alterations not only at the spinal level but also at the cortical level. The present results indicate that the stretch reflexes of each of the ankle antagonistic muscles are affected differently by aging, which might have relevance to the neural properties of each muscle. 相似文献
140.
Katayama T Tanaka M Moriizumi J Nakamura T Brouchkov A Douglas TA Fukuda M Tomita F Asano K 《Applied and environmental microbiology》2007,73(7):2360-2363
Phylogenetic analysis of bacteria preserved within an ice wedge from the Fox permafrost tunnel was undertaken by cultivation and molecular techniques. The radiocarbon age of the ice wedge was determined. Our results suggest that the bacteria in the ice wedge adapted to the frozen conditions have survived for 25,000 years. 相似文献