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Maeda, Shiro,Kobayashi, Masa-aki,Araki, Shin-ichi,Babazono, Tetsuya,Freedman, Barry I.,Bostrom, Meredith A.,Cooke, Jessica N.,Toyoda, Masao,Umezono, Tomoya,Tarnow, Lise,Hansen, Torben,Gaede, Peter,Jor Public Library of Science 2010 PLoS genetics Vol.6 No.2
<▼1><P>It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (<I>ACACB</I>) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of <I>ACACB</I> (rs2268388: intron 18 +4139 C > T, p = 1.4×10<SUP>−6</SUP>, odds ratio = 1.61, 95% confidence interval [CI]: 1.33–1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35×10<SUP>−8</SUP>, odds ratio = 1.61, 95% Cl: 1.35–1.91). Rs2268388 was also associated with type 2 diabetes–associated end-stage renal disease (ESRD) in European Americans (p = 6×10<SUP>−4</SUP>, odds ratio = 1.61, 95% Cl: 1.22–2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent <I>in vitro</I> functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that <I>ACACB</I> is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes.</P></▼1><▼2><P><B>Author Summary</B></P><P>Although cumulative epidemiological findings have suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy, no gene conferring susceptibility to diabetic nephropathy has been definitively identified. In a large-scale association study of 1,312 Japanese subjects with type 2 diabetes using SNPs from a Japanese SNP database, we show that the T-allele of <I>ACACB</I> rs2268388 is associated with diabetic nephropathy. We also show that the association is consistently observed in patients with type 2 diabetes and proteinuria across different ethnic groups, including populations of European descent. Because a DNA fragment corresponding to the disease susceptibility allele is shown to have higher enhancer activity, we hypothesize that the increase in the expression and/or activity of the encoded acetyl-coenzyme A carboxylase beta contributes to the development and progression of diabetic nephropathy. Our present analysis provides novel insight into the pathogenesis of diabetic nephropathy. This finding is important because diabetic nephropathy is a leading cause of end-stage renal disease and affects life expectancy in subjects with type 2 diabetes.</P></▼2>
( Takato Maeda ),( Hirotake Sakuraba ),( Hiroto Hiraga ),( Shukuko Yoshida ),( Yoichi Kakuta ),( Hidezumi Kikuchi ),( Shogo Kawaguchi ),( Keisuke Hasui ),( Tetsuya Tatsuta ),( Daisuke Chinda ),( Tatsu 대한장연구학회 2022 Intestinal Research Vol.20 No.1
Background/Aims: Thiopurines are key drugs for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Recently, NUDT15 polymorphism (R139C, c.415C>T) has been shown to be associated with thiopurine-induced adverse events in Asian populations. In patients with the C/T genotype, low-dose thiopurine treatment is recommended, but its long-term efficacy and tolerability remain unclear. This study aimed to uncover the long-term efficacy and appropriate dosage of thiopurine for IBD patients with the C/T genotype. Methods: A total of 210 patients with IBD (103 UC and 107 CD) determined to have NUDT15 R139C variants were enrolled. Clinical data were retrospectively reviewed from medical records. Results: Of 46 patients (21.9%) with the C/T genotype, 30 patients (65.2%) were treated with thiopurines. Three of whom (10.0%) discontinued thiopurine treatment due to adverse events and 27 of whom continued. The median maintenance dosage of 6-mercaptopurine was 0.25 mg/kg/day (range, 0.19-0.36 mg/kg/day), and 6-thioguanine nucleotides level was 230 (104-298) pmol/8×10<sup>8</sup> red blood cells. Cumulative thiopurine continuation rates for 120 months for patients with the C/C and C/T genotypes were not significantly different (P=0.895). Cumulative non-relapse rates in the patients with UC treated with thiopurine monotherapy and surgery-free rates in CD patients treated with combination therapy (thiopurines and anti-tumor necrosis factor-α agents) for maintenance remission were not significantly different at 60 months (C/C vs. C/T, P=0.339 and P=0.422, respectively). Conclusions: Low-dose thiopurine treatment is an effective and acceptable treatment for patients with C/T genotype. (Intest Res 2022;20:90-100)
Central Nervous System Drug Evaluation Using Positron Emission Tomography
Mizuho Sekine,Jun Maeda,Hitoshi Shimada,Tsuyoshi Nogami,Ryosuke Arakawa,Harumasa Takano,Makoto Higuchi,Hiroshi Ito,Yoshiro Okubo,Tetsuya Suhara 대한정신약물학회 2011 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.9 No.1
In conventional pharmacological research in the field of mental disorders, pharmacological effect and dose have been estimated by ethological approach and in vitro data of affinity to the site of action. In addition, the frequency of administration has been estimated from drug kinetics in blood. However, there is a problem regarding an objective index of drug effects in the living body. Furthermore, the possibility that the concentration of drug in blood does not necessarily reflect the drug kinetics in target organs has been pointed out. Positron emission tomography (PET) techniques have made progress for more than 20 years,and made it possible to measure the distribution and kinetics of small molecule components in living brain. In this article, we focused on rational drug dosing using receptor occupancy and proof-of-concept of drugs in the drug development process using PET.
Hwang, Chul-Min,Ishida, Masayoshi,Ito, Hiroshi,Maeda, Tetsuhiko,Nakano, Akihiro,Kato, Atsushi,Yoshida, Tetsuya The Korean Institute of Electrical Engineers 2012 The Journal of International Council on Electrical Vol.2 No.2
Polymer electrolyte-based unitized reversible fuel cells (URFCs) combine the functionality of a fuel cell and an electrolyzer in a single device. In this study, the influence of hydrophobic agent in the gas diffusion layer (GDL) of URFC was investigated. The titanium (Ti)-felt GDL which treated with different percent of PTFE emulsion was intensively tested with various humidification temperature conditions in the single cell of URFC. I-V performance curves and divided three overpotentials were compared and analyzed in the fuel cell mode. The electrolyzer performances were also evaluated with the I-V curves. Experimental results showed that the GDLs with high PTFE contents have better performance in the dry conditions. On the other hand, the increased PTFE contents accelerate flooding problem in the wet condition and it is related with rising concentration overpotential. The electrolyzer performances are almost same with different PTFE contents of GDL.
Degradation Mechanisms of a Li-S Cell using Commercial Activated Carbon
Norihiro Togasaki,Aiko Nakao,Akari Nakai,Fujio Maeda,Seiichi Kobayashi,Tetsuya Osaka The Korean Electrochemical Society 2023 Journal of electrochemical science and technology Vol.14 No.4
In lithium-sulfur (Li-S) batteries, encapsulation of sulfur in activated carbon (AC) materials is a promising strategy for preventing the dissolution of lithium polysulfide into electrolytes and enhancing cycle life, because instead of solid-liquid-solid reactions, quasi-solid-state (QSS) reactions occur in the AC micropores. While a high weight fraction of sulfur in S/AC composites is essential for achieving a high energy density of Li-S cells, the deterioration mechanisms under such conditions are still unclear. In this study, we report the deterioration mechanisms during charge-discharge cycling when the discharge products overflow from the AC. Analysis using scanning electron microscopy and energy-dispersive X-ray spectrometry confirms that the sulfur in the S/AC composites migrates outside the AC as cycling progresses, and it is barely present in the AC after 20 cycles, which corresponds to the capacity decay of the cell. Impedance analysis clearly shows that the electrical resistance of the S/AC composite and the charge-transfer resistance of QSS reactions significantly increase as a result of sulfur migration. On the other hand, the charge-discharge cycling performance under limited-capacity conditions, where the discharge products are encapsulated inside the AC, is extremely stable. These results reveal the degradation mechanism of a Li-S cell with micro-porous carbon and provide crucial insights into the design of a S/AC composite cathode and its operating conditions needed to achieve stable cycling performance.
( Mayumi Toyama ),( Yasuyuki Okuma ),( Mitsutoshi Yamamoto ),( Kenichi Kashihara ),( Kazuto Yoshda ),( Hidemoto Saiki ),( Tetsuya Maeda ),( Yoshio Tsuboi ),( Takeo Nakayama ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1
Background: Parkinson`s disease (PD) is increasingly recognized as multidimensional disorder. In addition to classic motor symptoms, patients have a variety of non-motor symptoms (NMS) that substantially affect quality of life (QoL). However, the prevalence of NMS and the relative impact of non-motor symptoms on QoL in PD have not been well documented in Japanese PD patients. In this study, we have the following objectives: 1) To determine the prevalence of NMS in Japanese PD patients. 2) To study the impact of NMS on the QoL in Japanese PD patients. Methods: This was a multi-center cross-sectional epidemiologic study. We recruited outpatients from seven Neurology departments at general hospitals across Japan between October 2010 and September 2011. A total of 824 Japanese PD patients was included in this study. NMS of patients was evaluated by Non-Motor Symptoms Scale (NMSS). Parkinson`s Disease Questionnaire-39 (PDQ-39) was used to evaluate the QoL of PD patients. Multivariate analyses were used to evaluate the direct impact of NMSs on QoL using PDQ-39, after adjusting for age, sex, disease duration, and the Unifi ed Parkinson`s Disease Rating Scale (UPDRS) Part I, Part II, Part III and Part IV. Results: The mean of total NMSS score was 37.4±35.4. The highly prevalent NMSS domains were sleep/fatigue (87.6%) and urinary (86.1%). The highly prevalent NMSS items were nocturia (72.0%) and constipation (71.6%). In multivariate analyses after adjustment for age, sex, disease duration, UPDRS Part I, Part II, Part III, and Part IV, total score of NMSS has statistical signifi cance with PDQ-39 (p=0.00, ß=0.16, Adj-R squared=0.65). Conclusions: NMS were highly prevalent in Japanese PD patients. NMS have a direct negative impact on QoL in Japanese PD patients.