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991.
Takeshi Yamazaki Megumi Yamamoto Yasuhiro Ishihara Shota Komatsu Eiji Munetsuna Masahiro Onizaki Atsuhiko Ishida Suguru Kawato Takao Mukuda 《PloS one》2013,8(2)
Background
Estrogen, a class of female sex steroids, is neuroprotective. Estrogen is synthesized in specific areas of the brain. There is a possibility that the de novo synthesized estrogen exerts protective effect in brain, although direct evidence for the neuroprotective function of brain-synthesized estrogen has not been clearly demonstrated. Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. The neurotoxicity of MeHg is region-specific, and the molecular mechanisms for the selective neurotoxicity are not well defined. In this study, the protective effect of de novo synthesized 17β-estradiol on MeHg-induced neurotoxicity in rat hippocampus was examined.Methodology/Principal Findings
Neurotoxic effect of MeHg on hippocampal organotypic slice culture was quantified by propidium iodide fluorescence imaging. Twenty-four-hour treatment of the slices with MeHg caused cell death in a dose-dependent manner. The toxicity of MeHg was attenuated by pre-treatment with exogenously added estradiol. The slices de novo synthesized estradiol. The estradiol synthesis was not affected by treatment with 1 µM MeHg. The toxicity of MeHg was enhanced by inhibition of de novo estradiol synthesis, and the enhancement of toxicity was recovered by the addition of exogenous estradiol. The neuroprotective effect of estradiol was inhibited by an estrogen receptor (ER) antagonist, and mimicked by pre-treatment of the slices with agonists for ERα and ERβ, indicating the neuroprotective effect was mediated by ERs.Conclusions/Significance
Hippocampus de novo synthesized estradiol protected hippocampal cells from MeHg-induced neurotoxicity via ERα- and ERβ-mediated pathways. The self-protective function of de novo synthesized estradiol might be one of the possible mechanisms for the selective sensitivity of the brain to MeHg toxicity. 相似文献992.
Toshiki Kuno Yohei Numasawa Hiroaki Miyata Toshiyuki Takahashi Koichiro Sueyoshi Takahiro Ohki Koji Negishi Akio Kawamura Shun Kohsaka Keiichi Fukuda 《PloS one》2013,8(8)
Objective
This study evaluated the manner in which coronary dominance affects in-hospital outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).Background
Previous studies have shown that left dominant coronary anatomies are associated with worse prognoses in patients with coronary artery disease.Methods
Data were analyzed from 4873 ACS patients undergoing PCI between September 2008 and April 2013 at 14 hospitals participating in the Japanese Cardiovascular Database Registry. The patients were grouped based on diagnostic coronary angiograms performed prior to PCI; those with right- or co-dominant anatomy (RD group) and those with left-dominant anatomy (LD group).Results
The average patient age was 67.6±11.8 years and both patient groups had similar ages, coronary risk factors, comorbidities, and prior histories. The numbers of patients presenting with symptoms of heart failure, cardiogenic shock, or cardiopulmonary arrest were significantly higher in the LD group than in the RD group (heart failure: 650 RD patients [14.7%] vs. 87 LD patients [18.8%], P = 0.025; cardiogenic shock: 322 RD patients [7.3%] vs. 48 LD patients [10.3%], P = 0.021; and cardiopulmonary arrest: 197 RD patients [4.5%] vs. 36 LD patients [7.8%], P = 0.003). In-hospital mortality was significantly higher among LD patients than among RD patients (182 RD patients [4.1%] vs. 36 LD patients [7.8%], P = 0.001). Multivariate logistic regression analysis revealed that LD anatomy was an independent predictor for in-hospital mortality (odds ratio, 1.75; 95% confidence interval, 1.06–2.89; P = 0.030).Conclusion
Among ACS patients who underwent PCI, LD patients had significantly worse in-hospital outcomes compared with RD patients, and LD anatomy was an independent predictor of in-hospital mortality. 相似文献993.
Masayuki Fujii Taro Hasegawa Shuji Takase Koichiro Goto 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1487-1488
Abstract It is found that application of oxime resin to an automated DNA synthesis and succeeding cleavage of DNA fragment bound to oxime resin by various nucleophiles, such as amines, alkoxides and protected peptides, give DNA conjugate molecules conventionally in moderate to good yields. 相似文献
994.
Mark J. Czaja Wen-Xing Ding Terrence M. Donohue Scott L. Friedman Jae-Sung Kim Masaaki Komatsu John J. Lemasters Antoinette Lemoine Jiandie D. Lin Jing-hsiung James Ou David H. Perlmutter Glenn Randall Ratna B. Ray Allan Tsung Xiao-Ming Yin 《Autophagy》2013,9(8):1131-1158
Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. 相似文献
995.
Yohei Hamada Takeshi Nishijima Hirokazu Komatsu Katsuji Teruya Hiroyuki Gatanaga Yoshimi Kikuchi Shinichi Oka 《PloS one》2013,8(7)
Objective
To compare the incidence of complicated cholelithiasis in patients receiving ritonavir-boosted atazanavir (ATV/r)- containing antiretroviral therapy with those on other protease inhibitors (PIs).Design
We conducted a single-center retrospective cohort study of patients who started either ritonavir-boosted ATV/r- or other PIs (ritonavir-boosted fosamprenavir, unboosted fosamprenavir, lopinavir/ritonavir, and ritonavir-boosted darunavir) -containing antiretroviral therapy.Methods
The incidence of complicated cholelithiasis was determined in each group. Complicated cholelithiasis was defined as follows: 1) cholelithiasis complicated by cholecystitis, cholangitis, or pancreatitis or 2) symptomatic cholelithiasis or choledocholithiasis which required invasive procedures such as cholecystomy and endoscopic retrograde cholangiopancreatography. The effects of ATV/r were estimated by univariate and multivariate Cox hazards models as the primary exposure.Results
Complicated cholelithiasis was diagnosed in 3 patients (2.23 per 1000 person-years) in the ATV/r group (n = 466), and 3 (1.64 per 1000 person-years) in the other PIs group (n = 776), respectively. The incidence was not statistically different in the two groups by log-rank test (P = 0.702). By univariate and multivariate analysis adjusted for age and body weight, ATV/r use was not associated with cholelithiasis. (HR = 1.365; 95% CI, 0.275–6.775; p = 0.704) (adjusted HR = 1.390; 95% CI, 0.276–7.017; p = 0.690). For the 3 patients who developed cholelithiasis in the ATV/r group, the time to the diagnosis of cholelithiasis was 18, 34, and 39 months, respectively.Conclusion
In this study, the incidence of complicated cholelithiasis was low and was not different between patients on ATV/r and those on other PIs. On the contrary to ATV/r-associated nephrolithiasis, the possible risk of cholelithiasis should not preclude the use of ATV/r. 相似文献996.
Chiori Yabuki Hidetoshi Komatsu Yoshiyuki Tsujihata Risa Maeda Ryo Ito Kae Matsuda-Nagasumi Kensuke Sakuma Kazumasa Miyawaki Naoya Kikuchi Koji Takeuchi Yugo Habata Masaaki Mori 《PloS one》2013,8(10)
Selective free fatty acid receptor 1 (FFAR1)/GPR40 agonist fasiglifam (TAK-875), an antidiabetic drug under phase 3 development, potentiates insulin secretion in a glucose-dependent manner by activating FFAR1 expressed in pancreatic β cells. Although fasiglifam significantly improved glycemic control in type 2 diabetes patients with a minimum risk of hypoglycemia in a phase 2 study, the precise mechanisms of its potent pharmacological effects are not fully understood. Here we demonstrate that fasiglifam acts as an ago-allosteric modulator with a partial agonistic activity for FFAR1. In both Ca2+ influx and insulin secretion assays using cell lines and mouse islets, fasiglifam showed positive cooperativity with the FFAR1 ligand γ-linolenic acid (γ-LA). Augmentation of glucose-induced insulin secretion by fasiglifam, γ-LA, or their combination was completely abolished in pancreatic islets of FFAR1-knockout mice. In diabetic rats, the insulinotropic effect of fasiglifam was suppressed by pharmacological reduction of plasma free fatty acid (FFA) levels using a lipolysis inhibitor, suggesting that fasiglifam potentiates insulin release in conjunction with plasma FFAs in vivo. Point mutations of FFAR1 differentially affected Ca2+ influx activities of fasiglifam and γ-LA, further indicating that these agonists may bind to distinct binding sites. Our results strongly suggest that fasiglifam is an ago-allosteric modulator of FFAR1 that exerts its effects by acting cooperatively with endogenous plasma FFAs in human patients as well as diabetic animals. These findings contribute to our understanding of fasiglifam as an attractive antidiabetic drug with a novel mechanism of action. 相似文献
997.
998.
Uta Konno Mariko Kouduka Daisuke D. Komatsu Kousuke Ishii Akari Fukuda Urumu Tsunogai Kazumasa Ito Yohey Suzuki 《Microbial ecology》2013,65(3):626-637
Freshwater aquifers in granitic rocks are widespread microbial habitats in the terrestrial subsurface. Microbial populations in deep granitic groundwater from two recently drilled (1 and 2 years) and two old boreholes (14 and 25 years) were compared. The 16S rRNA gene sequences related to “Candidatus Magnetobacterium bavaricum”, Thermodesulfovibrio spp. of Nitrospirae (90.5–93.1 % similarity) and a novel candidate division with <90 % similarity to known cultivated species were dominant in all boreholes. Most of the environmental clones closely related to the novel lineages in Nitrospirae, which have been detected exclusively in deep groundwater samples. In contrast, betaproteobacterial sequences related to the family Rhodocyclaceae were obtained only from the recently drilled boreholes, which had higher total cell numbers. Catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH) analysis supported the result from clone library analysis; betaproteobacterial cells were dominantly detected in recently drilled boreholes. These results suggest that while indigenous microbial populations represented by the novel phylotypes persisted in the boreholes for 25 years, betaproteobacterial species disappeared after 2 years owing to the change of substrate availability. 相似文献
999.
1000.
Abstract Intermolecular interaction is investigated for an isomeric pair of fluoro propane, CH3CF2CF3 (HFC–245cb, CB) and CH2FCF2CHF2 (HFC–245ca, CA). CB has a larger dipole moment than CA. This may suggest that CB has a larger intermolecular attractive interaction than CA; the reverse is, however, found from the experimental data: normal boiling point, critical temperature, and heat of vaporization. Systematic ab initio calculations have been done for both CB dimer and CA dimer, and confirmed that the former has a smaller attractive interaction than the latter. On the basis of these calculations, analytic functions have been constructed as the pair potential models for the two isomers. Each of these models has 11 Lennard-Jones and Coulomb interaction sites in the molecule. The present models can explain why CB dimer has a smaller attractive interaction than CA dimer, and they will easily be extended to a series of fluoro propanes, and make it possible to perform the systematic molecular simulation studies. 相似文献