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Neural Regeneration Research 2020年第1期15卷 47-52页

作者： Sherif Rashad Kuniyasu Niizuma Teiji tominaga Department of Neurosurgery Tohoku University Graduate School of MedicineSendaiJapan Department of Neurosurgical Engineering and Translational Neuroscience Tohoku University Graduate School of MedicineSendaiJapan Department of Neurosurgical Engineering and Translational Neuroscience Graduate School of Biomedical EngineeringTohoku UniversitySendaiJapan

Over the past decades,tRNA was found to be a rich hub of RNA modifications such as 1-methyladenosine and 5-methycytosine modifications and others,holding more than half of all modifications occurring in RNA ***,tRNA was discovered to be a source of various small noncoding RNA species,such as the stress induced angiogenin cleaved tRNA halves(tiRNA)or the miRNA like tRNA derived *** cleavage under stress was fist discovered in bacteria and later was found to be conserved across different species,including *** cellular stress conditions,tRNA undergoes conformational changes and angiogenin cleaves it into 3′and 5′halves.5′tiRNA halves were shown to repress protein *** cleavage is thought of to be a cytoprotective mechanism by which cells evade apoptosis,however some data hints to the opposite;that tiRNA are cytotoxic or at least related to apoptosis *** cleavage also was shown to be affected by tRNA modifications via different enzymes in the cytosol and *** this review,we will highlight the biology of tRNA cleavage,show the evidence of it being cytoprotective or a marker of cell death and shed a light on its role in disease models and human diseases as well as possible future directions in this field of RNA research.

关键词： angiogenin apoptosis cell stress RNA modification stress granules stroke tiRNA translation repression tRNA tRNA cleavage

Ag7(MBISA)6 Nanoclusters Conjugated with Quinacrine for FRET-Enhanced Photodynamic Activity under Visible Light Irradiation

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物理化学学报 2018年第7期34卷 805-811页

作者： tominaga Chiaki HIKOSOU Dailo OSAKA Issey KAWASAK Hideya Department of Chemistry and Materials Engineering Faculty of Chemistry Materials and Bioengineering Kansai University Suita-shi Osaka 564-8680 Japan Center for Nano Materials and Technology Advanced Institute of Science and Technology 1-1 A

Singlet oxygen(1 O2) plays an important role in various applications, such as in the photodynamic therapy(PDT) of cancers,photodynamic inactivation of microorganisms, photo-degradation of toxic compounds, and photo-oxidation in synthetic chemistry. Recently,water-soluble metal nanoclusters(NCs) have been utilized as photosensitizers for the generation of highly reactive 1 O2 because of their high water solubility, low toxicity, and surface functionalizability for targeted substances. In the case of metal NC-based photosensitizers, the photo-physical properties depend on the core size of the NCs and the core/ligand interfacial structures. A wide range of atomically precise gold NCs have been reported; however, reports on the synthesis of atomically precise silver NCs are limited due to the high reactivity and low photostability(i.e., easy oxidation) of Ag NCs. In addition, there have been few reports on what kinds of metal NCs can generate large amounts of 1 O2. In this study, we developed a new one-pot synthesis method of water-soluble Ag7(MBISA)6(MBISA= 2-mercapto-5-benzimidazolesulfonic acid sodium salt) NCs with highly efficient 1 O2 generation ability under the irradiation of white light emitting diodes(LEDs). The molecular formula and purity were determined by electrospray ionization mass spectrometry and gel electrophoresis. To the best of our knowledge, this is the first report on atomically precise thiolate silver clusters(Agn(SR)m) for efficient 1 O2 generation under visible light irradiation. The 1 O2 generation efficiency of Ag7(MBISA)6 NCs was higher than those of the following known water-soluble metal NCs: bovine serum albumin(BSA)-Au25 NCs,BSA-Ag8 NCs, BSA-Ag14 NCs,Ag25(dihydrolipoic acid)14 NCs,Ag35(glutathione)18 NCs,and Ag75(glutathione)40 NCs. The metal NCs examined in this study showed the following order of 1 O2 generation efficiency under white light irradiation: Ag7(MBISA)6 > BSA-Ag14 > Ag75(SG)40 > Ag35(SG)18 >BSA-Au25 >>BSA-Ags(not detected)

关键词： Silver nanoclusters Singlet oxygen Photodynamic therapy Organic dyes FRET Hybrid photosensitizers

Quality of ulcer healing in gastrointestinal tract:Its pathophysiology and clinical relevance

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World Journal of Gastroenterology 2012年第35期18卷 4811-4822页

作者： Tetsuo Arakawa Toshio Watanabe Tetsuya Tanigawa Kazunari tominaga Yasuhiro Fujiwara Kenichi Morimoto Department of Gastroenterology Osaka City University Graduate School of Medicine

In this paper, we review the concept of quality of ulcer healing （QOUH） in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease （PUD） has been a chronic disease with a cycle of repeated healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori （H. pylorl~, which is also the cause of ulcer recur- rence. However, H. pylori-negative ulcers are pres- ent in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated. Within the scars of healed ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence. Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macro- phages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in ulcer re- currence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a defi- ciency and/or an imbalance of endogenous growth fac- tors. Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn＇s disease and ulcer- ative colitis.

关键词： Quality of ulcer healing Peptic ulcer dis-ease Recurrence Prostaglandin Cytokines Growthfactors

Efficacy of the revised Vienna Classification for diagnosing colorectal epithelial neoplasias

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World Journal of Gastroenterology 2009年第19期15卷 2351-2356页

作者： Kenji tominaga Sumio Fujinuma Takuro Endo Yoshihisa Saida Kei Takahashi Iruru Maetani Division of Gastroenterology Department of Internal MedicineToho University Ohashi Medical Center2-17-6 OhashiMeguro-kuTokyo 153-8515Japan Third Department of Surgery Toho University Ohashi Medical Center2-17-6 OhashiMeguro-kuTokyo 153-8515Japan Department of Surgical Pathology Toho University Ohashi Medical Center2-17-6 OhashiMeguro-kuTokyo 153-8515Japan

AIM： To prospectively investigate the efficacy of the revised Vienna Classification for diagnosing colorectal epithelial neoplastic lesions in cold biopsy ***： Patients were selected for inclusion if they had colorectal epithelial lesions that were not considered suitable for direct endoscopic resection,These included colorectal polyps ≥ 10 mm and lesions suspected of being carcinomas capable of invading the colorectal submucosa or beyond, including strictures, based on the cold biopsies obtained from each lesion prior to resection. We investigated the relationship between diagnoses based on cold biopsy samples using the revised Vienna Classification and resected specimens of the same lesions, and the therapeutic implications of diagnoses made using the revised Vienna Classification. The same cold biopsy specimens were also examined using the Japanese Group Classification guidelines, and compared with the resected specimens of the same lesions for ***： A total of 179 lesions were identified. The sensitivity, specificity, positive and negativepredictive values of the revised Vienna Classification for distinguishing between intramucosal lesions and submucosal invasive carcinomas in cold biopsy specimens was 22.2%, 100%, 100%, and 71.4%,respectively, and for distinguishing between intramucosal lesions and those invading the submucosa or beyond was 59.7%, 100%, 100%, and 37.6%,respectively. The sensitivity, specificity, positive and negative predictive values of the Japanese Group Classification for distinguishing between intramucosal lesions and submucosal invasive carcinomas in cold biopsy specimens was 83.3%, 91.4%, 83.3%. and 91.4%, respectively, and for distinguishing between intramucosal lesions and those invading the submucosa or beyond was 95.1%, 91.4%, 97.9%, and 82.1%, respectively. A total of 137 of 144 carcinomas that had invaded the submucosa or beyond and three high-grade intraepithelial neoplasias were diagnosed as ＂carcinoma＂

关键词： Biopsy Cancer Colonoscopy Colorectalepithelial neoplasia Revised Vienna Classification

Vibrational dynamics of the CN stretching mode of [Ru(CN)_6]^(4-) in D_2O studied by nonlinear infrared spectroscopy

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Science China(Physics,Mechanics & Astronomy) 2010年第6期53卷 1013-1019页

作者： Jumpei TAYAMA Motohiro BANNO Kaoru OHTA Keisuke tominaga Graduate School of Science Kobe University Molecular Photoscience Research Center Kobe University PRESTO JST4-1-8 Honcho KawaguchiSaitamaJapan 332-0012Japan

We have studied vibrational dynamics of the T1u mode of the CN stretching mode of [Ru(CN)6 ]4- in D2O by infrared(IR) nonlinear spectroscopy such as an IR three-pulse photon echo experiment and polarization-sensitive IR pump-probe spectroscopy. The isotropic component of the pump-probe signal shows a bi-exponential decay with time constants of 0.8 ps and 20.8 ps. The fast and slow components correspond to the rapid equilibration between the T1u mode and the Raman active modes of the CN stretching mode and the vibrational population relaxation from the v=1 state of the T1u mode,respectively. Anisotropy of the pump-probe signal decays with a time constant of 3.1 ps,which is due to the time evolution of the superposition states of the triply degenerate T1u modes. Three pulse photon echo measurements showed that the time correlation function of the frequency fluctuation decays bi-exponentially with time constants of 80 fs and 1.4 ps. These time constants depend only on the solute and are independent of the solvent,whereas the amplitudes depend on both the solute and solvent.

关键词： nonlinear IR spectroscopy metal complex aqueous solution

Diversion colitis and pouchitis: A mini-review

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World Journal of Gastroenterology 2018年第16期24卷 1734-1747页

作者： Kentaro tominaga Kenya Kamimura Kazuya Takahashi Junji Yokoyama Satoshi Yamagiwa Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

Diversion colitis is characterized by inflammation of the mucosa in the defunctioned segment of the colon after colostomy or ileostomy. Similar to diversion colitis, diversion pouchitis is an inflammatory disorder occurring in the ileal pouch, resulting from the exclusion of the fecal stream and a subsequent lack of nutrients from luminal bacteria. Although the vast majority of patients with surgically-diverted gastrointestinal tracts remain asymptomatic, it has been reported that diversion colitis and pouchitis might occur in almost all patients with diversion. Surgical closure of the stoma, with reestablishment of gut continuity, is the only curative intervention available for patients with diversion disease. Pharmacologic treatments using short-chain fatty acids, mesalamine, or corticosteroids are reportedly effective for those who are not candidates for surgical reestablishment; however, there are no established assessment criteria for determining the severity of diversion colitis, and no management strategies to date. Therefore, in this mini-review, we summarize and review various recently-reported treatments for diversion disease. We are hopeful that the information summarized here will assist physicians who treat patients with diversion colitis and pouchitis, leading to better case management.

关键词： Diversion colitis Diversion pouchitis Ileitis Inflammatory bowel disease

Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells

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Cellular & Molecular Immunology 2012年第5期9卷 399-409页

作者： Akihisa Nagata Naoki Takezako Hiroyuki Tamemoto Hiromi Ohto-Ozaki SatoshiOhta Shin-ichi tominaga Ken Yanagisawa Department of Biochemistry School of Medicine Jichi Medical University Shimotsuke-shi Tochigi Japan Hematology Division National Hospital Organization Disaster Medical Center of Japan Tachikawa-shi Tokyo Japan

ST2 protein is a soluble splicing variant of ST2L protein, which is the receptor for interleukin-33 （IL-33）. Previously, we reported that soluble ST2 suppressed the signal transduction of lipopolysaccharide （LPS） and cytokine production in monocytic cells. To investigate whether or not this inhibitory effect occurs in dendritic cells, which are the key players in innate and adaptive immunity, human monocyte-derived dendritic cells were pre-treated with soluble ST2 protein before LPS stimulation. Although soluble ST2 did not attenuate the LPS-induced maturation of dendritic cells, pre-treatment with soluble ST2 suppressed cytokine production and inhibited LPS signaling. Moreover, the proliferation of naive T cells was inhibited significantly by soluble ST2 pre-treatment. IL-33 had little effect on the cytokine production of immature monocyte-derived dendritic cells. Furthermore, soluble ST2 protein was internalized into dendritic cells, suggesting that soluble ST2 protein acts by a noncanonical mechanism other than the sequestration of IL-33.

关键词： dendritic cells LPS signal transduction ST2 TLR4

Safety and efficacy of transpapillary bridged bilateral side-by-side stenting for unresectable malignant hilar biliary obstruction

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Hepatobiliary & Pancreatic Diseases International 2017年第6期16卷 659-661页

作者： Hirotsugu Maruyama Kazunari tominaga Kunihiro Kato Satoshi Sugimori Masatsugu Shiba Toshio Watanabe Yasuhiro Fujiwara Department of Gastroenterology Osaka City University Graduate School of Medicine 1-4-3 Asahimachi Abeno-ku Osaka 545-8585 Japan

To the Editor:Biliary drainage is most frequently performed among endoscopic procedures using pancreatobiliary endoscopy.A large-diameter metallic stent can significantly extend the patency period rather than a plastic stent for extrahepatic biliary stricture.;However,the optimal drainage for the hilar biliary obstruction is still controversial.

关键词： Safety and efficacy of transpapillary bridged bilateral side-by-side stenting for unresectable malignant hilar biliary obstruction

Gastroduodenal ulcer bleeding in elderly patients on low dose aspirin therapy

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World Journal of Gastroenterology 2018年第34期24卷 3908-3918页

作者： Koh Fukushi Keiichi tominaga Kazunori Nagashima Akira Kanamori Naoya Izawa Mimari Kanazawa Takako Sasai Hideyuki Hiraishi Department of Gastroenterology Dokkyo Medical University Department of General Internal Medicine 2 Kawasaki Medical School General Medical Center

AIM To determine the clinical characteristics of elderly patients of hemorrhagic gastroduodenal ulcer on low-dose aspirin(LDA)*** A total of 1105 patients with hemorrhagic gastroduodenal ulcer treated in our hospital between January 2000 and March 2016 were grouped by age and drugs used,and these groups were compared in several *** groups were compared in terms of length of hospital stay,presence/absence of hemoglobin(Hb)decrease,presence/absence of blood transfusion,Forrest Ⅰ,percentage of Helicobacter pylori infection,presence/absence of underlying disease,and percentage of severe *** The percentage of blood transfusion(62.6%vs 47.7%,P<0.001),Hb decrease(53.8% vs 40.8%,P<0.001),and the length of hospital stay(23.5 d vs 16.7 d,P<0.001)were significantly greater in those on drug *** percentage of blood transfusion(65.3%vs 47.8%,P<0.001),Hb decrease(54.2%vs 42.1%,P<0.001),and length of hospital stay(23.3 d vs 17.5 d,P<0.001)were significantly greater in the *** comparison with the LDA monotherapy group,the percentage of severe cases was significantly higher in the LDA combination therapy group when elderly patients were concerned(16.1%vs34.0%,P=0.030).Meanwhile,among those on LDA monotherapy,there was no significant difference between elderly and non-elderly(16.1%vs 16.0%,P=0.985).CONCLUSION A combination of LDA with antithrombotic drugs or nonsteroidal anti-inflammatory drugs(NSAIDs)contributes to *** advanced age is not an aggravating factor when LDA monotherapy is used.

关键词： Hemorrhagic gastroduodenal ulcer Low-dose aspirin Antithrombotic drugs Elderly patients Proton pump inhibitor