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101.
Masato Hayakawa Tatsuya Ohyama Yoko Yamaguchi Shingo Iwabuchi Tomohiko Nakagawa Tamie Nakajima 《Molecular simulation》2013,39(9):644-656
To elucidate the specific interactions between the peroxisome proliferator-activated receptor (PPARα) and ligand GW409544 (GW), we obtained the solvated structures of the PPARα+GW complexes for human, mouse and rat by classical molecular mechanics calculations, and investigated their electronic properties by ab initio fragment molecular orbital calculations. The results indicate that the positively charged amino acids (Lys and Arg) of PPARα make a major contribution to the binding between PPARα and GW. In addition, it was clarified that Ser280 and Tyr314 of human and rat PPARα have a large attractive interaction with GW, while Ser280, Tyr314 and His440 of mouse PPARα have large interaction. These results on the difference in specific interactions between human and mouse/rat PPARα will be useful for predicting the effects of new chemicals on the human body based on the biomedical studies for the experimental animals such as mouse and rat. 相似文献
102.
Naoko Aizawa Hiroshi Kunikata Fumihiko Nitta Yukihiro Shiga Kazuko Omodaka Satoru Tsuda Toru Nakazawa 《PloS one》2016,11(2)
Purpose
To investigate the relationship between various characteristics of a normal population and laser speckle flowgraphy (LSFG) measurements of mean blur rate (MBR) in the optic nerve head (ONH).Methods
A total of 189 eyes of 189 normal subjects (93 male, 96 female, mean age 45 ± 14 years old, age range: 20–72) without any history of hypertension, hyperlipidemia or diabetes were enrolled. ONH microcirculation was measured with LSFG and overall MBR (MA), vessel-area MBR (MV), and tissue-area MBR (MT) were derived from these measurements. The statistical association of these measurements with characteristics such as sex, age, intraocular pressure (IOP) and systolic blood pressure (SBP) was then determined.Results
There was a trend towards decreased IOP and MV and increased SBP with age (P = 0.002, P = 0.035, and P = 0.006, respectively). Furthermore, IOP, MV and SBP were correlated with age (r = -0.23, P = 0.011; r = -0.24, P < 0.001; and r = 0.30, P < 0.001, respectively). Separate multiple regression analyses of independent contributing factors revealed that sex and IOP contributed to MA (P < 0.001 and P = 0.002, respectively), sex, IOP, and age contributed to MV (P < 0.001, P = 0.003, and P = 0.024, respectively), while only IOP contributed to MT (P = 0.003).Conclusion
In a normal population, MBR was affected by IOP in both the large vessel and capillary areas of the ONH, but not by SBP. MV was also affected by age and sex, while MT was stable independent of age or sex. 相似文献103.
Stable isotope and radiocarbon compositions of methane emitted from tropical rice paddies and swamps in Southern Thailand 总被引:1,自引:0,他引:1
Fumiko Nakagawa Naohiro Yoshida Atsuko Sugimoto Eitaro Wada Takahito Yoshioka Shingo Ueda Pisoot Vijarnsorn 《Biogeochemistry》2002,61(1):1-19
Stable isotopes (13C, D) and radiocarbon weremeasured in methane bubbles emitted from rice paddies and swamps in southernThailand. Methane emitted from the Thai rice paddies was enriched in13C (mean 13C; –51.5 ±7.1 and–56.5 ± 4.6 for mineral soil and peat soil paddies,respectively)relative to the reported mean value of methane from temperate rice paddies(– 63 ± 5). Large seasonal variation was observed in13C(32) in the rice paddies, whereas variationinD was much more smaller (20), indicating that variation in13C is due mainly to changes in methane production pathways.Values of 13C were lower in swamps (–66.1 ±5.1)than in rice paddies. The calculated contribution of acetate fermentation from13C value was greater in rice paddies (mineral soils:62–81%, peat soils: 57–73%) than in swamps (27–42%). Din methane from Thai rice paddies (–324± 7 (n=46)) isrelativelyhigher than those from 14 stations in Japanese rice paddies ranging from–362 ± 5 (Mito: n=2) to –322 ± 8(Okinawa: n=3), due tohigher D in floodwaters. 14C content in methane produced fromThai rice paddies (127±1 pMC) show higher 14Cactivity compared with previous work in paddy fields and those from Thai swamps(110±2 pMC). 相似文献
104.
Yoshinori Hiyama Tsuyoshi Asai Osamu Wada Hideto Maruno Shingo Nitta Kiyonori Mizuno Yasunobu Iwasaki Shuichi Okada 《PloS one》2015,10(1)
This study aimed to determine gait ability at hospital discharge in patients undergoing total knee arthroplasty (TKA) as an indicator of the risk of falling. Fifty-seven patients undergoing primary TKA for knee osteoarthritis participated in this study. Gait variability measured with accelerometers and physical function including knee range of motion (ROM), quadriceps strength, walking speed, and the Timed Up and Go (TUG) test were evaluated preoperatively and at discharge from the hospital (1 month before and 5 days after surgery). All patients were discharged directly home at 5 days after surgery. Knee flexion of ROM, quadriceps strength, walking speed, and the TUG test results were significantly worse at hospital discharge than preoperatively (p < 0.001). However, gait variability was not significantly different before and after TKA. This result indicated that patients following TKA surgery could walk at hospital discharge as stably as preoperatively regardless of the decrease in physical function, including knee ROM, quadriceps strength, and gait speed after surgery. 相似文献
105.
Po-sung Chu Hirotoshi Ebinuma Nobuhiro Nakamoto Kazuo Sugiyama Shingo Usui Yuko Wakayama Nobuhito Taniki Akihiro Yamaguchi Shunsuke Shiba Yoshiyuki Yamagishi Takaji Wakita Toshifumi Hibi Hidetsugu Saito Takanori Kanai 《PloS one》2015,10(5)
Hepatitis C virus (HCV) genotype 1 infections are significantly more difficult to eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes and CD56+CD3− NK cells from cases of chronic hepatitis C were analyzed and assessed by treatment effect. Two strains of HCV were used to co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+ lymphocytes, but not NK cells, was significantly impaired in genotype 1 infection, compared to genotype 2. When peripheral blood mononuclear cells from healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+ lymphocytes, but not NK cells, was observed. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression-correlated IFN-γ production. In conclusion, Decreased NKG2D expression on CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior treatment response to PEG-IFN/ribavirin therapy compared to genotype 2. 相似文献
106.
Shingo Noguchi Hiroshi Mukae Toshinori Kawanami Kei Yamasaki Kazumasa Fukuda Kentarou Akata Hiroshi Ishimoto Hatsumi Taniguchi Kazuhiro Yatera 《PloS one》2015,10(4)
Background
The causative pathogens of healthcare-associated pneumonia (HCAP) remain controversial, and the use of conventional cultivation of sputum samples is occasionally inappropriate due to the potential for oral bacterial contamination. It is also sometimes difficult to determine whether methicillin-resistant Staphylococcus aureus (MRSA) is a true causative pathogen of HCAP.Methods
We evaluated the bacterial diversity in bronchoalveolar lavage fluid (BALF) using molecular and cultivation methods in 82 HCAP patients. BALF specimens were obtained from the lesions of pneumonia using bronchoscopy. The bacterial flora was analyzed according to the clone library method using amplified fragments of the 16S ribosomal RNA gene with universal primers. In addition, sputum cultures and the above specimens were assessed.Results
Eighty (97.6%) of the 82 BALF samples obtained from the patients with HCAP showed positive polymerase chain reaction results. The predominant phylotypes detected in the BALF in this study included bacteria common in cases of community- and hospital-acquired pneumonia. In addition, the phylotypes of streptococci and anaerobes were detected in 19 (23.2%) and 8 (9.8%) cases, respectively. In particular, phylotypes of streptococci were highly detected among the patients 75 of age or older. Staphylococcus aureus was cultured in 23 (28.0%) cases using conventional cultivation methods and detected in only 6 (7.3%) cases as predominant phylotypes according to the clone library method.Conclusions
The clone library analysis of BALF in the HCAP patients detected heterogeneous bacteria and a high incidence of streptococci compared with that observed using cultivation methods. In addition, the results of our study may indicate a lower incidence of MRSA than previously expected in HCAP patients. 相似文献107.
Xia Jiang Tatsuo Kanda Shingo Nakamoto Tatsuo Miyamura Shuang Wu Osamu Yokosuka 《Experimental cell research》2014
Previous studies demonstrated that androgen receptor (AR) is expressed in human hepatocellular carcinoma (HCC), one of the male-dominant diseases. Glucose-regulated protein 78 kDa (GRP78/Bip), which has a role in cancer development, is one of the androgen response genes in prostate cell lines. The aim of this study was to investigate the impact of AR on endoplasmic reticulum (ER)-stress signaling in human hepatoma. AR and GRP78 expressions were examined in human liver tissue panels. Human hepatoma cells stably expressing short hairpin RNA targeting AR and cells over-expressing AR were generated. The expressions of ER-stress molecules and AR were measured by real-time RT-PCR and Western blotting. The effect of AR on ER-stress responsive gene expression was examined by reporter assay. Strong positive correlation between AR mRNA and GRP78 mRNA was observed in stage I/II-HCCs. AR enhanced ER-stress responsive element activities and GRP78 expression, and regulated ER-stress response in hepatocytes. Sorafenib strongly induced significant apoptosis in HepG2 cells by the inhibition of AR and inhibition of the downstream GRP78. AR seems a co-regulator of GRP78 especially in earlier-stage HCC. AR plays a critical role in controlling ER-stress, providing new therapeutic options against HCC. 相似文献
108.
Osami Shoji Takashi Fujishiro Shingo Nagano Shota Tanaka Takuya Hirose Yoshitsugu Shiro Yoshihito Watanabe 《Journal of biological inorganic chemistry》2010,15(8):1331-1339
Cytochrome P450BSβ, a H2O2-dependent cytochrome P450 catalyzing the hydroxylation of long-alkyl-chain fatty acids, lacks the general acid–base residue
around the heme, which is indispensable for the efficient generation of the active species using H2O2. On the basis of the crystal structure of the palmitic acid bound form of cytochrome P450BSβ, it was suggested that the role of the general acid–base function was provided by the carboxylate group of fatty acids. The
participation of the carboxylate group of the substrate was supported by the fact that cytochrome P450BSβ can catalyze oxidations of nonnatural substrates such as styrene and ethylbenzene in the presence of a series of short-alkyl-chain
carboxylic acids as a dummy molecule of fatty acid. We refer to a series of short-alkyl-chain carboxylic acids as a “decoy
molecule”. As shown here, we have clarified the crystal structure of the decoy-molecule-bound form and elucidated that the
location of its carboxylate group is virtually the same as that of palmitic acid in the heme cavity, indicating that the carboxylate
group of the decoy molecule serves as the general acid–base catalyst. This result further confirms that the role of the acid–base
function is satisfied by the carboxylate group of the substrates. In addition, the structure analysis of the substrate-free
form has clarified that no remarkable structural change is induced by the binding of the decoy molecule as well as fatty acid.
Consequently, whether the carboxylate group is positioned in the active site provides the switching mechanism of the catalytic
cycle of cytochrome P450BSβ. 相似文献
109.
Ad N Cheng DC Martin J Berglin EE Chang BC Doukas G Gammie JS Nitta T Wolf RK Puskas JD 《Innovations (Philadelphia, Pa.)》2010,5(2):74-83
OBJECTIVE:: This purpose of this consensus conference was to determine whether surgical atrial fibrillation (AF) ablation during cardiac surgery improves clinical and resource outcomes compared with cardiac surgery alone in adults undergoing cardiac surgery for valve or coronary artery bypass grafting. METHODS:: Before the consensus conference, the consensus panel reviewed the best available evidence, whereby systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of validity and importance. Evidence-based statements were created, and consensus processes were used to determine the ensuing recommendations. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of recommendation. RESULTS:: The consensus panel agreed on the following statements in patients with AF undergoing cardiac surgery concomitant surgical ablation: CONCLUSIONS:: Given these evidence-based statements, the consensus panel stated that, in patients with persistent and permanent AF undergoing cardiac surgery, concomitant surgical ablation is recommended to increase incidence of sinus rhythm at short- and long-term follow-up (class 1, level A); to reduce the risk of stroke and thromboembolic events (class 2a, level B); to improve EF (class 2a, level A); and to exercise tolerance (class 2a, level A) and long-term survival (class 2a, level B). 相似文献
110.
Shingo Nakajima Tohru Hira Yuzuru Eto Kozo Asano Hiroshi Hara 《Regulatory peptides》2010,159(1-3):148-155
We previously demonstrated that intraduodenal administration of an arginine-rich β51–63 peptide in soybean β-conglycinin suppresses food intake via cholecystokinin (CCK) secretion in rats. However, the cellular mechanisms by which the β51–63 peptide induces CCK secretion remain to be clarified. In the present study, we examined whether the extracellular calcium-sensing receptor (CaR) mediates β51–63-induced CCK secretion in murine CCK-producing enteroendocrine cell line STC-1. CCK secretion and changes in intracellular Ca2+ concentration in response to β51–63 peptide were measured in STC-1 cells under various extracellular Ca2+ concentrations and after treatment with a CaR antagonist. Intracellular Ca2+ concentrations in response to β51–63 peptide and extracellular Ca2+ were also measured in CaR-expressing human embryonic kidney (HEK-293) cells. The β51-63 peptide induced CCK secretion and intracellular Ca2+ mobilization in STC-1 cells under normal (1.2 mM) extracellular Ca2+ conditions in a dose-dependent manner. These responses to β51–63 peptide were reduced by the removal of intra- or extracellular Ca2+ but enhanced by increasing extracellular Ca2+ concentrations. Intracellular Ca2+ mobilization induced by extracellular Ca2+ was also increased by the pretreatment with β51–63 peptide. Treatment with a specific CaR antagonist (NPS2143) inhibited β51–63-induced CCK secretion and intracellular Ca2+ mobilization. In addition, HEK-293 cells transfected with CaR acquired sensitivity to the β51–63 peptide. From these results, we conclude that CaR is the β51–63 peptide sensor responsible for the stimulation of CCK secretion in enteroendocrine STC-1 cells. 相似文献