Adult onset cardiac dilatation in a transgenic mouse line with Galβ1,3GalNAc α2,3-sialyltransferase II (ST3Gal-II) transgenes: a new model for dilated cardiomyopathy

Sugar chain abnormalities in glycolipids and glycoproteins are associated with various diseases. Here, we report an adult onset cardiac dilatation in a transgenic mouse line with Galβ1,3GalNAc α2,3-sialyltransferase II (ST3Gal-II) transgenes. The transgenic hearts at the end-stage, at around 7 months old, were enlarged, with enlarged cavities and thin, low-tensile walls, typical of dilated cardiomyopathy. Although no apparent change was found in heart gangliosides, glycosylation of heart proteins was altered. Interestingly, sugar moieties not directly related to the ST3Gal-II catalytic reaction were also changed. Significant increases in calreticulin and calnexin were observed in hearts of the transgenic mice. These results suggest that expression of ST3Gal-II transgenes induces abnormal protein glycosylation, which disorganizes the endoplasmic/sarcoplasmic reticulum quality control system and elevates the calreticulin/calnexin level, resulting in suppression of cardiac function. The transgenic mice showed 100% incidence of adult onset cardiac dilatation, suggesting great potential as a new model for dilated cardiomyopathy

Sex differences in the safety of S‐1 plus oxaliplatin and S‐1 plus cisplatin for patients with metastatic gastric cancer

Previous studies have shown sex‐related differences in the incidence of adverse events following treatment with fluoropyrimidines, however the mechanism of this difference is unknown. We examined sex‐related differences in the safety of S‐1 plus oxaliplatin (SOX) and S‐1 plus cisplatin (CS) in 663 metastatic gastric cancer patients taking part in a phase III study. The incidences of leukopenia (odds ratio [OR] 1.9; P = .015), neutropenia (OR 2.2; P = .002), nausea (OR 2.0; P = .009), and vomiting (OR 2.8; P < .001) were increased in women versus men treated with SOX, while vomiting (OR 2.9; P < .001) and stomatitis (OR 1.8; P = .043) were increased in women versus men treated with CS. In contrast, male patients treated with CS experienced thrombocytopenia more often (OR 0.51; P = .009). The mean relative dose intensity of S‐1 in SOX was 75.4% in women and 81.4% in men (P = .032). No difference in efficacy was observed between women and men undergoing either regimen. Sex‐related differences in adverse reactions during SOX and CS treatment were confirmed in this phase III study. Further translational research studies are warranted to pursue the cause of this difference

Gene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1

金沢大学医薬保健研究域薬学系Purpose: Solute carrier OCTN1 (SLC22A4) is an orphan transporter, the physiologically important substrate of which is still unidentified. The aim of the present study was to examine physiological roles of OCTN1. Methods: We first constructed octn1 gene knockout (octn1-/-) mice. Metabolome analysis was then performed to identify substrates in vivo. The possible association of the substrate identified with diseased conditions was further examined. Results: The metabolome analysis of blood and several organs indicated complete deficiency of a naturally occurring potent antioxidant ergothioneine in octn1-/- mice among 112 metabolites examined. Pharmacokinetic analyses after oral administration revealed the highest distribution to small intestines and extensive renal reabsorption of [3H]ergothioneine, both of which were much reduced in octn1-/- mice. The octn1-/- mice exhibited greater susceptibility to intestinal inflammation under the ischemia and reperfusion model. The blood ergothioneine concentration was also much reduced in Japanese patients with Crohn\u27s disease, compared with healthy volunteers and patients with another inflammatory bowel disease, ulcerative colitis. Conclusions: These results indicate that OCTN1 plays a pivotal role for maintenance of systemic and intestinal exposure of ergothioneine, which could be important for protective effects against intestinal tissue injuries, providing a possible diagnostic tool to distinguish the inflammatory bowel diseases. © 2010 Springer Science+Business Media, LLC

Benzene substituted with bipyridine and terpyridine as electron-transporting materials for organic light-emitting devices

New electron-transporting materials for organic light-emitting devices (OLEDs) based on trisubstituted benzene with both bipyridine and terpyridine, 1,3-bisbipyridyl-5-terpyridylbenzene (BBTB) and 1-bipyridyl-3,5-bisterpyridylbenzene (BTBB), were developed. Glass transition temperatures of BBTB and BTBB were 93 degrees C and 108 degrees C, respectively, and BTBB was completely amorphous with no melting point. Electron mobilities of BTBB exceeded the order of 10(-4) cm(2) V-1 s(-1), while those of BBTB were very high and reached 10(-3) cm(2) V-1 s(-1) at an electric field of approximately 500 kV cm(-2). These high mobilities contributed to a low voltage operation. For example, in the case of the conventional aluminum trisquinolinol (Alq)-based fluorescent OLED with BTBB, current densities of 3.5 mA cm(-2) and 100 mA cm(-2) were reached at voltages of 3.0 V and 4.5 V, respectively. In addition, ionization potentials of BBTB (6.33 eV) and BTBB (6.50 eV) were sufficiently large to confine holes in common emissive layers.ArticleJOURNAL OF MATERIALS CHEMISTRY. 22(14):6765-6773 (2012)journal articl

Bipyridyl-substituted benzo[1,2,3]triazoles as a thermally stable electron transporting material for organic light-emitting devices

We developed new electron-transporting materials (ETMs) for organic light-emitting devices (OLEDs) based on benzo[1,2,3] triazole and two bipyridines. Four derivatives based on the same skeleton were synthesized with four different substituents: phenyl (BpyBTAZ-Ph), biphenyl (-BP), m-terphenyl (-mTP), and o-terphenyl (-oTP). These BpyBTAZ compounds have good thermal stabilities, and their decomposition temperatures were greater than 410 degrees C, which is significantly higher than that of tris(8-quinolinolato) aluminium (Alq), the conventional OLED material. BpyBTAZ compounds show preferable amorphous nature, and moreover, the glass transition temperatures (T(g)s) of both BpyBTAZ-TP compounds exceed 100 degrees C. Furthermore, BpyBTAZ-BP exhibits no melting point and is fully amorphous. The electron affinities of the materials are as large as 3.3 eV and their electron mobility is sufficiently high. These characteristics accounted for a reduction in the operational voltage of OLEDs with BpyBTAZ compounds compared with the reference device with Alq as an ETM. Specifically, the electron mobility of all the BpyBTAZ compounds exceeds 1 x 10(-4) cm(2) V(-1) s(-1) at an electric field of 1 MV cm(-1). In addition, it was revealed that both BpyBTAZ-TP-based devices showed longer luminous lifetimes and smaller voltage increases during continuous operation at 50 mA cm(-2), compared with the Alq reference device.ArticleJOURNAL OF MATERIALS CHEMISTRY. 21(32):11791-11799 (2011)journal articl

北陸地区におけるスクリーニング上部消化管内視鏡検査での咽頭観察の現状

[背景・目的] 現在, スクリーニング上部消化管内視鏡検査における咽頭領域の観察が十分に浸透しているとはいい難い状況である. 北陸地区における上部消化管内視鏡での咽頭観察の現状について調査した. [方法] 日本消化器内視鏡学会専門医114名にアンケートを送付し, 回答のあった73名を対象とし調査した. [結果] 咽頭観察を全例に行っている医師は79.5%, スクリーニングに画像強調観察(image-enhanced endoscopy:IEE)を用いた(I群)のは61.6%であった. 観察時間はI群が白色光(W群)と比べ有意に長く(p<0.001), 1年以内の癌の発見率はI群がW群と比べ有意に高かった(p=0.007). 問題点として, 観察の困難さ, 苦痛増強の可能性などの意見が多かった. [結論] スクリーニングにおける咽頭観察において, 癌の発見にはIEEにて時間をかけて観察することが重要である可能性が示唆された. 今後, さらなる咽頭観察の啓蒙活動が重要と考えられる.出版者照会後に全文公