455 results on '"Shimizu, M."'
Search Results
2. List of Contributors
- Author
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Adav, Sunil S., primary, Alapuranen, Marika, additional, Alcalde, Miguel, additional, Aro, N., additional, Atanasova, Lea, additional, Ballesteros, Antonio, additional, Bazafkan, Hoda, additional, Berg, Gabriele, additional, Berrin, Jean-Guy, additional, Bischof, Robert, additional, Blanquet, Senta, additional, Cardoza, Rosa Elena, additional, Casas-Flores, Sergio, additional, Chulalaksananukul, Warawut, additional, Contreras-Cornejo, Hexon Angel, additional, Cumagun, Christian Joseph R., additional, Dar, Manzoor H., additional, de Sousa, Marcelo V., additional, Derntl, Christian, additional, Do Vale, Luis H.F., additional, Dong, Zhiyang, additional, Dorcheh, Sedigheh Karimi, additional, Druzhinina, Irina, additional, El-Bondkly, Ahmed M.A., additional, Elsharkawy, M.M., additional, Felix, Carlos Roberto, additional, Ferreira, Nicolas Lopes, additional, Filho, Edivaldo X.F., additional, Geng, Anli, additional, González-Hernández, Roberto J., additional, Gruber, Sabine, additional, Gupta, Vijai K., additional, Gutiérrez, Santiago, additional, Hatvani, Lóránt, additional, Heiss-Blanquet, Senta, additional, Hermosa, Rosa, additional, Hernández-Cervantes, Arturo, additional, Hernández-Chávez, Marco J., additional, Herpoel-Gimbert, Isabelle, additional, Herrera-Estrella, Alfredo, additional, Hill, Robert, additional, Hyakumachi, M., additional, Ihrmark, Katarina, additional, Joensuu, J.J., additional, Karlsson, Magnus, additional, Körmöczi, Péter, additional, Kredics, László, additional, Kunamneni, Adinarayana, additional, Liu, Gang, additional, López-Bucio, Jesús Salvador, additional, López-Bucio, José, additional, Mach, Robert L., additional, Mach-Aigner, Astrid R., additional, Macías-Rodríguez, Lourdes, additional, Manczinger, László, additional, Margeot, Antoine, additional, Meenu, Katoch, additional, Miller, Robert N.G., additional, Monfil, Vianey Olmedo, additional, Monte, Enrique, additional, Monteiro, Valdirene Neves, additional, Mora-Montes, Héctor M., additional, Naeimi, Shahram, additional, Naznin, H.A., additional, Nevalainen, Helena, additional, Noronha, Eliane Ferreira, additional, O’Donovan, Anthonia, additional, Pakula, T., additional, Peterson, Robyn, additional, Plou, Francisco J., additional, Puranen, Terhi, additional, Qin, Lina, additional, Reithner, Barbara, additional, Ricart, Carlos A.O., additional, Rubio, María Belén, additional, Saldajeno, M.G.B., additional, Saloheimo, M., additional, Sarma, Birinchi K., additional, Schmoll, Monika, additional, Seiboth, Bernhard, additional, Seidl-Seiboth, Verena, additional, Sharma, Gauri Dutt, additional, Shimizu, M., additional, Shukla, Dhara, additional, Siddiquee, Shafiquzzaman, additional, Silva, Roberto Nascimento, additional, Singh, Akanksha, additional, Singh, Harikesh B., additional, Singh, Gurpreet, additional, Singh, Sudhanshu, additional, Singh, U.S., additional, Steindorff, Andrei Stecca, additional, Stewart, Alison, additional, Su, Xiaoyun, additional, Sze, Siu Kwan, additional, Tisch, Doris, additional, Trujillo-Esquivel, José E., additional, Tuohy, Maria G., additional, Upadhyay, R.S., additional, Vágvölgyi, Csaba, additional, Vahabi, Khabat, additional, Vankar, Padma S., additional, Vehmaanperä, Jari, additional, Vishwakarma, R.A., additional, Wang, Shaowen, additional, Zachow, Christin, additional, Zaidi, Najam W., additional, and Zeilinger, Susanne, additional
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- 2014
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3. Modeling of Driver's Collision Avoidance Behavior Based on Expression as Hybrid Dynamical System
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Kim, J.H., primary, Okuma, S., additional, Hayakawa, S., additional, Tsuchida, N., additional, Suzuki, T., additional, Hayashi, K., additional, Shimizu, M., additional, and Kido, S., additional
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- 2005
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4. Application of self-organizing silicone polymers for long-wearing lipsticks
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Shibata, M., primary, Shimizu, M., additional, Nojima, K., additional, Yoshino, K., additional, Hosokawa, H., additional, and Suzuki, T., additional
- Published
- 2001
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5. Contributors
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Adams, S.R., primary, Aikens, R., additional, Antić, S., additional, Bacskai, B.J., additional, Badminton, M.N., additional, Bakker Schut, T.C., additional, Bar-Am, I., additional, Blancaflor, E., additional, Bobanović, F., additional, Bodsworth, N., additional, Bolsover, S., additional, Bootman, M.D., additional, Bowser, D.N., additional, Bruining, H.A., additional, Buschman, H.P.J., additional, Campbell, A.K., additional, Caspers, P.J., additional, Chance, B., additional, Cody, S.H., additional, Cohen, L.B., additional, Coremans, J.M.C.C., additional, Cox, G.C., additional, Culbert, A.A., additional, DeBasio, R., additional, de Feijter, A.W., additional, Dempster, J., additional, Dubbin, P.N., additional, Dubinsky, Z., additional, Falk, C.X., additional, Florine-Casteel, K., additional, Foote, N., additional, Fricker, M.D., additional, Gadella, T.W.J., additional, Gilroy, S., additional, Gratton, E., additional, Gurney, A.M., additional, Haggart, R., additional, Hahn, K., additional, Haugland, R.P., additional, Herman, B., additional, Hoekstra, D., additional, Horton, M.A., additional, Hoyland, J., additional, Ichihara, A., additional, Ishida, H., additional, Johnson, I.D., additional, Jones, H.E., additional, Kain, S.R., additional, Kannan, M.S., additional, Kasten, F.H., additional, Katz, S., additional, Kendall, J.M., additional, Knight, H., additional, Knight, M.R., additional, Kok, J.W., additional, Kolega, J., additional, Kurtz, I., additional, Lemasters, J.J., additional, Lipp, P., additional, Llewellyn, D.H., additional, Loew, L., additional, Lyons, A., additional, Mackay, C., additional, Malik, Z., additional, Mason, W.T., additional, Masters, B.R., additional, McCann, T.J., additional, Mitchison, T.J., additional, Montibeller, J., additional, Myers, J., additional, O'Brien, W., additional, Plieth, C., additional, Ploem, J.S., additional, Post, P., additional, Prakash, Y.S., additional, Puppels, G.J., additional, Römer, T.J., additional, Rothmann, C., additional, Rutter, G.A., additional, Sala-Newby, G.B., additional, Sawin, K.E., additional, Shankar, G., additional, Sheppard, C.J.R., additional, Shimizu, M., additional, Shorte, S.L., additional, Sieck, G.C., additional, Simons, E.R., additional, Singer, V., additional, Skews, G., additional, So, P.T.C., additional, Somasundaram, B., additional, Tanaami, T., additional, Tavaré, J.M., additional, Taylor, S.S., additional, Taylor, K.M., additional, Taylor, D.L., additional, Theriot, J.A., additional, Tomkins, P., additional, Trosko, J.E., additional, Tsien, R.Y., additional, Wade, M.H., additional, White, N.S., additional, Williams, D.A., additional, Wolthuis, R., additional, Wu, J.-y., additional, Yip, K.-P., additional, Zečević, D., additional, and Zelenin, A.V., additional
- Published
- 1999
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6. Fracture mechanism of ferritic ductile cast iron in extremely low cycle fatigue
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Komotori, J., primary and Shimizu, M., additional
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- 1998
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7. Sustainable Ni/BaTiO3 catalysts for partial oxidation of methane to synthesis gas
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Shiozaki, R., primary, Andersen, A.G., additional, Hayakawa, T., additional, Hamakawa, S., additional, Suzuki, K., additional, Shimizu, M., additional, and Takehira, K., additional
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- 1997
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8. Electrochemical oxidation of propene using a membrane reactor with solid electrolyte
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Hamakawa, S., primary, Hayakawa, T., additional, Suzuki, K, additional, Shimizu, M., additional, and Takehira, K., additional
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- 1997
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9. Effect of Nitric Acid on the Isotopic Exchange Reaction between H2 and HDO(v) over a Hydrophobic Platinum Catalyst
- Author
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Wei, Y-Z., primary, Takeshita, K., additional, Shimizu, M., additional, Kumagai, M., additional, and Takashima, Y., additional
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- 1994
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10. OPERATION EXPERIENCES WITH JT-60U PLASMA FACING COMPONENTS AND EVALUATION TESTS OF B4C-OVERLAID CFC/GRAPHITES
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ANDO, T., primary, YAMAMOTO, M., additional, ARAI, T., additional, KAMINAGA, A., additional, SASAJIMA, T., additional, SAIDOH, M., additional, JIMBOU, R., additional, KODAMA, K., additional, SHIMIZU, M., additional, AKIBA, M., additional, NAKAMURA, K., additional, ARAKI, M., additional, SUZUKI, S., additional, DAIRAKU, M., additional, YOKOYAMA, K., additional, FUKAYA, K., additional, BOLT, H., additional, and LINKE, J., additional
- Published
- 1993
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11. Affinity Separation of Protein by Gel-Matrix Membrane
- Author
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KURAHASHI, H., primary, IMAI, M., additional, and SHIMIZU, M., additional
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- 1992
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12. MATERIAL BEHAVIOR OF GRAPHITE AND C/C COMPOSITE DIVERTOR PLATES IN JT-60
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Takatsu, H., primary, Eto, M., additional, Ando, T., additional, Yamamoto, M., additional, Kodama, K., additional, Arai, T., additional, Kaminaga, A., additional, Horiike, H., additional, Shimizu, M., additional, Fukaya, K., additional, and Oku, T., additional
- Published
- 1991
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13. Novel Oxidation of Phenols by a Copper(II) Complex Catalyst/O2 System
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Takehira, K., primary, Shimizu, M., additional, Watanabe, Y., additional, Hayakawa, T., additional, and Orita, H., additional
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- 1991
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14. Syrbactin class proteasome inhibitor-induced apoptosis and autophagy occurs in association with p53 accumulation and Akt/PKB activation in neuroblastoma
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Archer, C R, Koomoa, D L T, Mitsunaga, E M, Clerc, J, Shimizu, M, Kaiser, M, Schellenberg, B, Dudler, R, Bachmann, A S, University of Zurich, and Bachmann, A S
- Subjects
1303 Biochemistry ,3004 Pharmacology ,10126 Department of Plant and Microbial Biology ,580 Plants (Botany) - Published
- 2010
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15. Grain Size Effect in Low Cycle Fatigue of Steel Under Mean Strain
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KOMOTORI, J., primary and SHIMIZU, M., additional
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- 1989
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16. Interleukin 6 and its Receptor: Pathological Role in Autoimmunity and Lymphoid Malignancy
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HIRANO, T., primary, TAGA, T., additional, YAMASAKI, K., additional, MATSUDA, T., additional, TANG, B., additional, SUEMATSU, S., additional, HORII, Y., additional, HIRATA, Y., additional, YAWATA, H., additional, MURAGUCHI, A., additional, KISHIMOTO, T., additional, KAWANO, M., additional, MIYASAKA, N., additional, and SHIMIZU, M., additional
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- 1989
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17. JT-60 DIVERTOR PUMPING SYSTEM AND ITS INITIAL OPERATION IN OHMICALLY HEATED DIVERTOR DISCHARGES
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ANDO, T., primary, NAKAMURA, H., additional, YOSHIDA, H., additional, SUNAOSHI, H., additional, ARAI, T., additional, AKINO, N., additional, HIROKI, S., additional, YAMAMOTO, M., additional, OHKUBO, M., additional, SHIMIZU, M., additional, and KONDO, I., additional
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- 1986
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18. SUPERCONDUCTING GAP AND EXCITONIC MECHANISM OF HIGH-Tc SUPERCONDUCTORS
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TANAKA, J., primary, KAMIYA, K., additional, SHIMADA, M., additional, SHIMIZU, M., additional, TANAKA, M., additional, and TANAKA, Y., additional
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- 1987
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19. EVALUATION OF FATIGUE STRENGTH OF THE JT-60 VACUUM VESSEL BASED ON THE DYNAMIC RESPONSE ANALYSIS UNDER THE ELECTROMAGNETIC FORCE
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Takatsu, H., primary, Shimizu, M., additional, Ohta, M., additional, Nakamura, Y., additional, Sakai, K., additional, and Uchino, K., additional
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- 1983
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20. TESTS OF A COOLING AND HEATING SYSTEM MODEL FOR JT-60 VACUUM VESSEL
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KAJIURA, S., primary, OWADA, K., additional, SATO, H., additional, FURUYAMA, M., additional, SHIMIZU, M., additional, and SHIMIZU, T., additional
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- 1983
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21. EFFECT OF FIBER ORIENTATION ON STABLE CRACK GROWTH IN FRP
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Kunio, T., primary, Shimizu, M., additional, and Sohmiya, S., additional
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- 1984
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22. FATIGUE CRACK FORMATION ASSOCIATED WITH CYCLIC SLIP DEFORMATION ALONG PRIOR AUSTENITE GRAIN BOUNDARIES
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Kunio, T., primary, Shimizu, M., additional, Yamada, K., additional, and Enomoto, M., additional
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- 1978
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23. ROLE OF OXIDATION IN MICRO-FRACTURE PROCESS OF AISI 316 STAINLESS STEEL IN HIGH TEMPERATURE LOW CYCLE FATIGUE
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Kunio, T., primary, Shimizu, M., additional, Yamada, K., additional, Fukumoto, M., additional, and Ito, M., additional
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- 1984
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24. THE EFFECT OF SIZE OF NON-METALLIC INCLUSION ON THE DUCTILE FRACTURE BEHAVIOUR OF PURE IRON
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Kunio, T., primary, Shimizu, M., additional, and Kobayashi, Y., additional
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- 1978
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25. FIRST WALL DESIGN AND LOW-Z MATERIAL DEVELOPMENT IN JT-60
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Nakamura, H., primary, Masuda, M., additional, Miyauchi, Y., additional, Shimizu, M., additional, Ogiwara, N., additional, Yamamoto, M., additional, Ohta, M., additional, and Owada, K., additional
- Published
- 1981
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26. CHEMICAL STRUCTURE AND PHARMACOLOGICAL ACTIVITIES OF DIPHENYLETHYLPIPERAZINE DERIVATIVES
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Nakamura, H., primary, Natsuka, K., additional, Motoyoshi, S., additional, Yokoyama, Y., additional, Ishii, K., additional, and Shimizu, M., additional
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- 1981
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27. FATIGUE CRACK PROPAGATION IN STAINLESS STEEL SUBJECTED TO REPEATED THERMAL SHOCK
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Shimizu, M., primary, Brown, M.W., additional, and Miller, K.J., additional
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- 1984
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28. THE FLUIDIC SEQUENCE AND DIGITAL CONTROL SYSTEM FOR THE CYLINDRICAL GRINDING PROCESS
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TOGINO, K., primary, SHIMIZU, M., additional, and NAGASHIMA, M., additional
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- 1968
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29. Remarkable shifts in the megabenthic community structure over four decades in Tokyo Bay, Japan, in relation to environmental variations.
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Kodama K, Kuroki M, Yamakawa T, Shimizu M, Kintsu H, and Horiguchi T
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- Animals, Japan, Fishes physiology, Aquatic Organisms physiology, Ecosystem, Biomass, Mollusca physiology, Crustacea physiology, Crustacea growth & development, Bays, Environmental Monitoring, Biodiversity
- Abstract
We investigated long-term changes in the megabenthic community in Tokyo Bay, Japan, using data from fisheries-independent trawl surveys conducted from 1977 to 2023. In addition, we examined the potential relationship between changes in biotic communities and environmental conditions. The total abundance and biomass exhibited an increasing trend until 1987, followed by a substantial decline from the late 1980s to the 1990s due to a decrease in small to medium-sized fish and crustacean species. Meanwhile, a marked increase in the number of large fish (including elasmobranchs), mollusks, and echinoids, was observed in the 2000s. These shifts in the megabenthic community structure were correlated with an increase in water temperature and a decrease in nutrient concentrations and copepod densities. Cumulative evidence suggests that a remarkable shift in the megabenthic community structure occurred between the 1970s and the 2020s, which was possibly associated with variations in the environmental conditions in Tokyo Bay., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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30. Periostin in Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression by Enhancing Cancer and Stromal Cell Migration.
- Author
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Miyako S, Koma YI, Nakanishi T, Tsukamoto S, Yamanaka K, Ishihara N, Azumi Y, Urakami S, Shimizu M, Kodama T, Nishio M, Shigeoka M, Kakeji Y, and Yokozaki H
- Subjects
- Humans, Cell Line, Tumor, Cell Movement, Extracellular Signal-Regulated MAP Kinases metabolism, Periostin, Proto-Oncogene Proteins c-akt metabolism, Tumor Microenvironment, Cancer-Associated Fibroblasts metabolism, Esophageal Neoplasms genetics, Esophageal Neoplasms pathology, Esophageal Squamous Cell Carcinoma metabolism
- Abstract
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are involved in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). CAF-like cells were generated through direct co-culture of human bone marrow-derived mesenchymal stem cells, one of CAF origins, with ESCC cells. Periostin (POSTN) was found to be highly expressed in CAF-like cells. After direct co-culture, ESCC cells showed increased malignant phenotypes, such as survival, growth, and migration, as well as increased phosphorylation of Akt and extracellular signal-regulated kinase (Erk). Recombinant human POSTN activated Akt and Erk signaling pathways in ESCC cells, enhancing survival and migration. The suppression of POSTN in CAF-like cells by siRNA during direct co-culture also suppressed enhanced survival and migration in ESCC cells. In ESCC cells, knockdown of POSTN receptor integrin β4 inhibited Akt and Erk phosphorylation, and survival and migration increased by POSTN. POSTN also enhanced mesenchymal stem cell and macrophage migration and endowed macrophages with tumor-associated macrophage-like properties. Immunohistochemistry showed that high POSTN expression in the cancer stroma was significantly associated with tumor invasion depth, lymphatic and blood vessel invasion, higher pathologic stage, CAF marker expression, and infiltrating tumor-associated macrophage numbers. Moreover, patients with ESCC with high POSTN expression exhibited poor postoperative outcomes. Thus, CAF-secreted POSTN contributed to tumor microenvironment development. These results indicate that POSTN may be a novel therapeutic target for ESCC., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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31. Rare but impaired flavin-containing monooxygenase 3 (FMO3) variants reported in a recently updated Japanese mega-databank of genome resources.
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Shimizu M, Makiguchi M, Hishinuma E, Saito S, Hiratsuka M, and Yamazaki H
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- Humans, Codon, Terminator, Japan, Oxygenases genetics, Oxygenases metabolism, Methylamines
- Abstract
Genetic variants of human flavin-containing monooxygenase 3 (FMO3) were investigated using an updated Japanese population panel containing 54,000 subjects (the previous panel contained 38,000 subjects). One stop codon mutation and six amino acid-substituted FMO3 variants were newly identified in the updated databank. Of these, two substituted variants (p.Thr329Ala and p.Arg492Trp) were previously identified in compound haplotypes with p.[(Glu158Lys; Glu308Gly)] and were associated with the metabolic disorder trimethylaminuria. Three recombinant FMO3 protein variants (p.Ser137Leu, p.Ala334Val, and p.Ile426Val) expressed in bacterial membranes had similar activities toward trimethylamine N-oxygenation (∼75-125 %) as wild-type FMO3 (117 min
-1 ); however, the recombinant novel FMO3 variant Phe313Ile showed moderately decreased FMO3 catalytic activity (∼20 % of wild-type). Because of the known deleterious effects of FMO3 C-terminal stop codons, the novel truncated FMO3 Gly184Ter variant was suspected to be inactive. To easily identify the four impaired FMO3 variants (one stop codon mutation and three amino-acid substitutions) in the clinical setting, simple confirmation methods for these FMO3 variants are proposed using polymerase chain reaction/restriction fragment length polymorphism or allele-specific PCR methods. The updated whole-genome sequence data and kinetic analyses revealed that four of the seven single-nucleotide nonsense or missense FMO3 variants had moderately or severely impaired activity toward trimethylamine N-oxygenation., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (© 2023 Published by Elsevier Ltd on behalf of The Japanese Society for the Study of Xenobiotics.)- Published
- 2024
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32. Neutrophil-lymphocyte ratio being associated with mortality risk in patients receiving antifibrotic therapy.
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Takuma S, Suzuki Y, Kono M, Hasegawa H, Hashimoto D, Yokomura K, Mori K, Shimizu M, Inoue Y, Yasui H, Hozumi H, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, and Suda T
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- Humans, Neutrophils, Retrospective Studies, Lymphocytes, Steroids, Lung Diseases, Interstitial drug therapy, Idiopathic Pulmonary Fibrosis
- Abstract
Background: Antifibrotic therapy is widely used for patients with progressive fibrotic interstitial lung disease (ILD), regardless of etiology. There is an urgent need for a simple, inexpensive, and repeatable biomarker to evaluate disease severity and mortality risk., Methods: This retrospective multicohort study assessed the neutrophil-lymphocyte ratios (NLRs) of 416 patients with ILD who received antifibrotic therapy (Hamamatsu cohort, n = 217; Seirei cohort, n = 199). The mortality risk vs. NLR relationship was evaluated at therapy initiation and 1 year. The optimal NLR cutoff of 2.7 was selected according to the mortality risk., Results: Survival was shorter in patients with high NLR than with low NLR (median: 2.63 vs. 4.01 years). The NLR classification results (cutoff: 2.7) were longitudinally preserved in >70 % of the patients, and patients with consistently high NLR had a higher risk of mortality than others (median, 2.97 vs. 4.42 years). In multivariate analysis, high NLR was significantly associated with mortality independent of age, sex, forced vital capacity, lung diffusing capacity for carbon monoxide (D
LCO ), or the gender-age-physiology (GAP) index. A combined GAP index-NLR assessment classified mortality risk into four groups. Subset analyses revealed that NLR assessment was more applicable to patients without advanced disease, not taking steroids, and with idiopathic pulmonary fibrosis (IPF) than to patients with advanced disease, taking steroids, and patients with Non-IPF., Conclusion: High NLR was associated with an increased mortality risk in patients with ILDs receiving antifibrotic therapy. Assessment of NLR may help predict disease severity and mortality risk in antifibrotic therapy., Competing Interests: Declaration of competing interest The authors declare that no competing interests exist., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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33. Early mobilization for acute heart failure: A scoping and a systematic review.
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Okamura M, Kataoka Y, Taito S, Fujiwara T, Ide A, Oritsu H, Shimizu M, Shimizu Y, Someya R, and Konishi M
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- Humans, Hospitalization, Early Ambulation, Heart Failure therapy
- Abstract
Early mobilization of hospitalized patients is beneficial under certain circumstances. This has been applied in clinical practice for patients with acute heart failure (HF). However, its current definition, effectiveness, and safety are not well established. This review aimed to clarify the current definition of "early mobilization," and summarize its effectiveness and safety in acute HF. We conducted a scoping review to define early mobilization (Part 1) and a systematic review and meta-analysis (Part 2) to evaluate its effectiveness and safety. For Part 1, we searched MEDLINE (Ovid), and for Part 2, we searched the Cochrane Central Register of Controlled Trials, MEDLINE (Ovid), Embase (ProQuest Dialog), CINAHL, and PEDro. We included 12 studies in Part 1 and defined early mobilization as protocol-based interventions or walking within 3 days of admission. Based on this definition, two observational studies were included in Part 2, with no randomized controlled trials. Early mobilization may result in a large reduction in the readmission rate compared with that of the control (two studies, 283 participants: odds ratio 0.25, 95 % confidence interval 0.14 to 0.42; I
2 = 0 %; low certainty evidence). We could not define frequency, intensity, or quantity because many of the included studies did not describe them. In conclusions, our review suggests that early mobilization, defined as protocol-based interventions or walking within 3 days of admission, may be associated with a low readmission rate in patients with acute HF. Future studies are essential, to investigate the causal relationship between early mobilization and possible outcomes., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2024
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34. Prevention of vincristine-induced peripheral neuropathy by protecting the endothelial glycocalyx shedding.
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Ohmura K, Kinoshita T, Tomita H, Okada H, Shimizu M, Mori K, Taniguchi T, Suzuki A, Iwama T, and Hara A
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- Humans, Mice, Animals, Vincristine adverse effects, Quality of Life, Glycocalyx, Peripheral Nervous System Diseases chemically induced, Peripheral Nervous System Diseases prevention & control
- Abstract
Vincristine-induced peripheral neuropathy (VIPN) adversely affects the quality of life and treatment continuity of patients. The endothelial glycocalyx (eGCX) protects nerves from harmful substances released from the capillary vessels, but its role in peripheral neuropathy remains unclear. We investigated the impact of eGCX protection on VIPN. Using a murine model of VIPN, we administered nafamostat mesylate to protect the eGCX shedding, and analyzed the eGCX integrity and manifestation of peripheral neuropathy. Nafamostat treatment suppressed allodynia associated with neuropathy. Additionally, nafamostat administration resulted in the suppression of increased vascular permeability in capillaries of peripheral nerves, further indicating its positive influence on eGCX in VIPN model mice. This study provided the importance of eGCX in VIPN. With the potential for rapid clinical translation through drug repositioning, nafamostat may be a new promising treatment for the prevention of VIPN., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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35. Long-term monitoring of indoor, outdoor, and personal exposure to gaseous chemical compounds.
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Uchiyama S, Noguchi M, Hishiki M, Shimizu M, Kunugita N, Isobe T, and Nakayama SF
- Abstract
Seasonal variations of chemical compounds in indoor air and outdoor air and personal exposure to these chemicals were continuously monitored for 6 years using four types of passive sampling devices: PSD-BPE/DNPH packed with 2,4-dinitrophenylhydrazine and trans-1,2-bis(2-pyridyl)ethylene coated silica for ozone and carbonyls; PSD-VOC packed with Carboxen 572 or Active Carbon Beads particles for volatile organic compounds; PSD-TEA packed with triethanolamine impregnated silica for acid gases; and PSD-TEA packed with phosphoric acid impregnated silica for basic gases. Many chemical compounds except for nitrogen dioxide, formic acid, and benzene showed seasonal variations with high concentrations in summer and low concentrations in winter. In particular, formaldehyde, nonanal, 2-ethyl-1-hexanol, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, and ammonia concentrations showed remarkable seasonal variation. For example, the concentration of formaldehyde in February and August was 5.9 and 40 μg/m
3 , respectively, a difference of about 7 times. Although there were large differences in the concentrations in each house, the fluctuation pattern was almost the same every year in each house. By contrast, nitrogen dioxide, formic acid, and benzene concentrations were low in summer and high in winter. These compounds were generated by kerosine and gas stoves in winter. Long-term continuous monitoring revealed that annual mean concentrations could be estimated using data from February and August. Personal exposure concentrations could be classified into four patterns: chemicals affected by the indoor environment such as formaldehyde, chemicals affected by the outdoor environment such as ozone, chemicals affected by the occupational environment such as hexane, and background level chemicals such as benzene (without kerosine and gas stoves). Indoor and outdoor measurements are means to investigate the "health" of each environment. Personal exposure measurement using PSD-samplers is suitable for assessing the health risk of chemical compounds to humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2024
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36. Cancer Pain Management in Patients Receiving Inpatient Specialized Palliative Care Services.
- Author
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Tagami K, Chiu SW, Kosugi K, Ishiki H, Hiratsuka Y, Shimizu M, Mori M, Kubo E, Ikari T, Arakawa S, Eto T, Shimoda M, Hirayama H, Nishijima K, Ouchi K, Shimoi T, Shigeno T, Yamaguchi T, Miyashita M, Morita T, Inoue A, and Satomi E
- Subjects
- Humans, Pain Management, Palliative Care methods, Inpatients, Longitudinal Studies, Prospective Studies, Pain complications, Cancer Pain therapy, Cancer Pain complications, Neoplasms complications, Neoplasms therapy
- Abstract
Context: Cancer pain is a common complication that is frequently undertreated in patients with cancer., Objectives: This study is aimed at assessing the time needed to achieve cancer pain management goals through specialized palliative care (SPC)., Methods: This was a multicenter, prospective, longitudinal study of inpatients with cancer pain who received SPC. Patients were continuously followed up until they considered cancer pain management successful, and we estimated this duration using the Kaplan-Meier method. We investigated the effectiveness of pain management using multiple patient-reported outcomes (PROs) and quantitative measures, including pain intensity change in the Brief Pain Inventory. A paired-sample t-test was used to compare the pain intensity at the beginning and end of the observation period., Results: Cancer pain management based on the PROs was achieved in 87.9% (385/438) of all cases. In 94.5% (364/385) of these cases, cancer pain management was achieved within 1 week, and the median time to pain management was 3 days (95% confidence interval [CI], 2-3). The mean worst pain intensity in the last 24 h at the start and end of observation were 6.9 ± 2.2 and 4.0 ± 2.3, respectively, with a difference of -2.9 (95% CI, -3.2 to -2.6; p < 0.01). Overall, 81.6% of the patients reported satisfaction with cancer pain management, and 62 adverse events occurred., Conclusion: SPC achieved cancer pain management over a short period with a high level of patient satisfaction resulting in significant pain reduction and few documented adverse events., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
37. Simple confirmation methods for rare but impaired variants of human flavin-containing monooxygenase 3 (FMO3) found in an updated genome resource databank.
- Author
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Shimizu M, Makiguchi M, Yokota Y, Shimamura E, Matsuta M, Nakamura Y, Harano M, and Yamazaki H
- Subjects
- Humans, Alleles, Oxygenases genetics
- Abstract
Forty-seven new nonsense or missense human flavin-containing monooxygenase 3 (FMO3) variants were recently identified in an updated Japanese population reference panel. Of these, 20 rare single-nucleotide substitutions resulted in moderately or severely impaired FMO3 activity. To easily identify these 20 FMO3 variants (2 stop codon mutations, 2 frameshifts, and 16 amino-acid substitutions) in the clinical setting, simple confirmation methods for impaired FMO3 variants are proposed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) or allele-specific PCR methods. Using PCR-RFLP, FMO3 variants p.Arg51Gly, p.Met66Lys, p.Asn80Lys, p.Val151Glu, p.Val187fsTer25, p.Gly193Arg, p.Val283Ala, p.Asp286His, p.Val382Ala, and p.Phe451Leu were digested by the designated restriction enzymes and confirmed using reference cDNAs. In contrast, the FMO3 variants p.Gly39Val, p.Arg238Ter, p.Arg387Cys, p.Arg387His, p.Leu457Trp, and p.Met497Arg were not digested, whereas the wild type was digested. FMO3 variants p.Gly11Asp, p.Lys416fsTer72, p.Gln427Ter, and p.Thr453Pro were confirmed using allele-specific PCR systems. The previously identified FMO3 p.Arg500Ter variant has a relatively high frequency and was differentiated from p.Arg500Gln in two steps, i.e., enzyme restriction followed by allele-specific PCR, similar to the method for p.Arg387Cys and p.Arg387His. These systems should facilitate easy detection in the clinical setting of FMO3 variants in Japanese subjects susceptible to low drug clearance possibly caused by impaired FMO3 function., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (© 2023 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
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38. Trajectory of GFR Decline and Fluctuation in Albuminuria Leading to End-Stage Kidney Disease in Patients With Biopsy-Confirmed Diabetic Kidney Disease.
- Author
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Yamanouchi M, Sawa N, Toyama T, Shimizu M, Oshima M, Yoshimura Y, Sugimoto H, Kurihara S, Oba Y, Ikuma D, Mizuno H, Sekine A, Suwabe T, Hoshino J, Ubara Y, Hara S, Furuichi K, and Wada T
- Abstract
Introduction: Data on longitudinal trajectory of kidney function decline and fluctuation in albuminuria leading to end-stage kidney disease (ESKD) is sparse in patients with type 2 diabetes., Methods: Using data from an observational study of patients with type 2 diabetes and biopsy-confirmed diabetic kidney disease (DKD), generalized additive mixed models (GAMMs) were performed to quantify patterns of longitudinal trajectory of estimated glomerular filtration rate (eGFR) decline to ESKD associated with repeated measures of urine albumin-to-creatinine ratio (ACR)., Results: Over a median follow-up period of 3.3 years, 155 of 319 patients progressed to ESKD. Among these patients, 91.6% exhibited a curvilinear pattern in their eGFR trajectory. The median coefficient of variation for ACR, representing the variability in ACR measurements, was 48.9 (interquartile range: 36.9, 68.2). The median compound annual growth rate (CAGR) for ACR, reflecting the variation in ACR progression over time, was 43.6% (interquartile range: 0.0, 102.5); and 84.5% of patients developed nephrotic-range albuminuria, with a majority remaining nephrotic and subsequently progressing to ESKD. There was a positive association between the instantaneous speed of eGFR decline and ACR., Conclusion: The observed curvilinear pattern in eGFR trajectory, high variability in ACR progression over time, and positive correlation between the speed of eGFR decline and ACR highlight the complex dynamics of disease progression and emphasize close monitoring of ACR fluctuation over time in patients with DKD., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)
- Published
- 2023
- Full Text
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39. A decreasing plasma concentration of a toxicologically active metabolite 9-carboxymethoxymethylguanine after dialysis - A potential new clinical biomarker for improving encephalopathy in patients treated with acyclovir.
- Author
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Unita R, Adachi K, Inada A, Shimizu M, Beppu S, and Yamazaki H
- Subjects
- Humans, Antiviral Agents adverse effects, Consciousness Disorders chemically induced, Consciousness Disorders drug therapy, Renal Dialysis, Acyclovir adverse effects, Brain Diseases drug therapy
- Abstract
Although acyclovir is a key drug for the treatment of herpes infections, a consciousness disorder known as "acyclovir encephalopathy" is among its side effects. We encountered a patient with encephalopathy and measured the plasma and cerebrospinal fluid concentrations of acyclovir and its toxicologically active metabolite 9-carboxymethoxymethylguanine (CMMG). Before dialysis, cerebrospinal fluid concentrations of acyclovir and CMMG in this patient with a consciousness disorder were approximately 10% and 1%, respectively, of their plasma concentrations. After 3 days of dialysis, plasma CMMG levels decreased to detectable but below quantitative levels (<0.1 μg/mL), resulting in normal consciousness. These results suggest that decreasing plasma CMMG concentration could be one of clinical biomarkers for improving consciousness in patients with encephalopathy associated with acyclovir., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
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40. The innate immune receptor RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function.
- Author
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Kani K, Kasai K, Tada Y, Ishibashi R, Takano S, Igarashi N, Ichimura-Shimizu M, Tsuneyama K, Furusawa Y, and Nagai Y
- Subjects
- Animals, Mice, Obesity metabolism, RNA, Ribosomal, 16S genetics, Diet, High-Fat adverse effects, Weight Gain, Immunity, Innate, Mice, Inbred C57BL, Metabolic Syndrome, Gastrointestinal Microbiome physiology
- Abstract
Radioprotective 105 (RP105) plays a key role in the development of high-fat diet (HFD)-induced metabolic disorders; however, the underlying mechanisms remain to be understood. Here, we aimed to uncover whether RP105 affects metabolic syndrome through the modification of gut microbiota. We confirmed that body weight gain and fat accumulation by HFD feeding were suppressed in Rp105
-/- mice. Fecal microbiome transplantation from HFD-fed donor Rp105-/- mice into HFD-fed recipient wild-type mice significantly improved various abnormalities associated with metabolic syndrome, including body weight gain, insulin resistance, hepatic steatosis, macrophage infiltration and inflammation in the adipose tissue. In addition, HFD-induced intestinal barrier dysfunction was attenuated by fecal microbiome transplantation from HFD-fed donor Rp105-/- mice. A 16S rRNA sequence analysis indicated that RP105 modified gut microbiota composition and was involved in the maintenance of its diversity. Thus, RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
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41. Utility of a Systematic Approach to Selecting Candidate Prodrugs: A Case Study Using Candesartan Ester Analogues.
- Author
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Shimizu M, Fukami T, Okura K, Taniguchi T, Nomura Y, and Nakajima M
- Subjects
- Animals, Humans, Esters, Caco-2 Cells, Intestines, Prodrugs pharmacokinetics
- Abstract
Development of prodrugs is a useful strategy to overcome some disadvantages of candidate drugs. Recently, we established a systematic approach to selecting appropriate prodrugs, and validated the utility of this approach using oseltamivir analogues. In this study, the utility of the approach was further examined using candesartan cilexetil and 20 kinds of its analogues having various types of side chain as model compounds. Log D values of analogues (2.5 to 4.7) were higher than that of candesartan (1.0), their active metabolite, and the results were reasonable for the purpose of improving permeability of candesartan. The analogues tended to be more soluble in artificial intestinal fluids than in artificial gastric fluid, owing to their acidic physicochemical characteristics. Their membrane permeabilities were not correlated with log D values, which can be attributed to the metabolism in Caco-2 cells used in this system. In human hepatocytes and enterocytes, 11 out of the 20 analogues were immediately hydrolyzed to candesartan, and species differences were observed in the hydrolysis efficiency. This study confirmed the utility of the systematic approach for selection of appropriate prodrugs that could be proceeded to in vivo pharmacokinetics study, with selection of suitable experimental animals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
42. Roles of human cytochrome P450 3A4/5 in dexamethasone 6β-hydroxylation mediated by liver microsomes and humanized liver in chimeric mice metabolically suppressed with azamulin.
- Author
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Uehara S, Shimizu M, Suemizu H, and Yamazaki H
- Subjects
- Humans, Mice, Animals, Hydroxylation, Cytochrome P-450 CYP3A metabolism, Liver metabolism, Dexamethasone pharmacology, Dexamethasone metabolism, Microsomes, Liver metabolism, Cytochrome P-450 Enzyme System metabolism
- Abstract
The urinary metabolic ratio of 6β-hydroxydexamethasone to dexamethasone reportedly acts as a noninvasive marker for human cytochrome P450 (P450) 3A4/5, which is induced by rifampicin in humanized-liver mice. In the current study, the pharmacokinetics of dexamethasone in humanized-liver mice after intravenous administration (10 mg/kg) were investigated using azamulin (a time-dependent P450 3A4/5 inhibitor). After intravenous dexamethasone administration, significant differences were observed in the time-dependent plasma and 24-h urinary concentrations of 6β-hydroxydexamethasone between untreated humanized-liver mice and humanized-liver mice treated with azamulin (daily oral doses of 15 mg/kg for 3 days). The mean ratios of 6β-hydroxydexamethasone to dexamethasone for the maximum concentrations, the areas under the plasma concentration-versus-time curves, and urinary concentrations were significantly lower in the azamulin-treated group (59%, 58%, and 41% of the untreated values, respectively). 6β-Hydroxydexamethasone formation was suppressed by 93% by replacing control human liver microsomes with P450 3A4/5-inactivated liver microsomes. These results suggest that the oxidation of dexamethasone in humans is mediated mainly by P450 3A4/5 (which is suppressed by azamulin), and that humanized-liver mice orally treated with azamulin may constitute an in vivo model for metabolically inactivated P450 3A4/5 in human hepatocytes transplanted into chimeric mice., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest., (Copyright © 2023 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
43. A family study of compound variants of flavin-containing monooxygenase 3 (FMO3) in Japanese subjects found by urinary phenotyping for trimethylaminuria.
- Author
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Shimizu M, Yamamoto A, Makiguchi M, Shimamura E, Yokota Y, Harano M, and Yamazaki H
- Subjects
- Child, Female, Humans, Infant, East Asian People genetics, Metabolism, Inborn Errors genetics, Oxygenases genetics, Oxygenases metabolism
- Abstract
Phenotype-gene analyses and the increasing availability of mega-databases have revealed the impaired human flavin-containing monooxygenase 3 (FMO3) variants associated with the metabolic disorder trimethylaminuria. In this study, a novel compound variant of FMO3, p.[(Val58Ile; Tyr229His)], was identified in a 1-year-old Japanese girl who had impaired FMO3 metabolic capacity (70%) in terms of urinary trimethylamine N-oxide excretion levels divided by total levels of trimethylamine and its N-oxide. One cousin in the family had the same p.[(Val58Ile); (Tyr229His)]; [(Glu158Lys; Glu308Gly)] FMO3 haplotype and had a similar FMO3 metabolic capacity (69%). In a family study, the novel p.[(Val58Ile); (Tyr229His)] compound FMO3 variant was also detected in the proband 1's mother and aunt. Another novel compound FMO3 variant p.[(Glu158Lys; Met260Lys; Glu308Gly; Ile426Thr)] was identified in a 7-year-old girl, proband 2. This novel compound FMO3 variant was inherited from her mother. Recombinant FMO3 Val58Ile; Tyr229His variant and Glu158Lys; Met260Lys; Glu308Gly; Ile426Thr variant showed moderately decreased capacities for trimethylamine N-oxygenation compared to wild-type FMO3. Analysis of trimethylaminuria phenotypes in family studies has revealed compound missense FMO3 variants that impair FMO3-mediated N-oxygenation in Japanese subjects; moreover, these variants could result in modified drug clearances., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
44. High hepatic and plasma exposures of atorvastatin in subjects harboring impaired cytochrome P450 3A4∗16 modeled after virtual administrations and possibly associated with statin intolerance found in the Japanese adverse drug event report database.
- Author
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Adachi K, Ohyama K, Tanaka Y, Sato T, Murayama N, Shimizu M, Saito Y, and Yamazaki H
- Subjects
- Humans, Drug Interactions, East Asian People, Adverse Drug Reaction Reporting Systems, Atorvastatin adverse effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Cytochrome P-450 CYP3A Inhibitors adverse effects
- Abstract
Drug interactions between atorvastatin and cytochrome P450 (P450) 3A substrates/inhibitors lead to an increased incidence of skeletal muscle or hepatic toxicity. However, in this survey, among 483 Japanese subjects administered atorvastatin alone, more than half (258) experienced statin intolerance and were unable to continue using the drug. Although many factors underly atorvastatin toxicity, the intrinsic clearance rate might be a contributing causal factor. The impaired P450 3A4 p.Thr185Ser variant, CYP3A4∗16 (rs12721627), has been identified in East Asians with an allele frequency of 2.2%. Pharmacokinetically modeled plasma concentrations of atorvastatin increased after a virtual oral dose of 40 mg in CYP3A4∗16 homozygotes; the maximum concentration and area under the concentration curve, respectively, were 3.3-fold and 4.2-fold those in subjects homozygous for CYP3A4∗1. In subjects with CYP3A4∗16/∗16, the virtual hepatic concentrations of atorvastatin after daily doses of 10 mg for a week were similar to or higher than the plasma concentrations. These results suggest that the estimated high virtual plasma and hepatic exposures obtained by pharmacokinetic modeling in subjects harboring impaired allele CYP3A4∗16 may be one of the causal factors for statin intolerance in a manner similar to the well-known drug interactions caused by co-administrations of CYP3A inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
45. Long-term outcome and risk factors associated with events in patients with atrial fibrillation treated with oral anticoagulants: The ASSAF-K registry.
- Author
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Hatori Y, Sakai H, Hatori N, Kunishima T, Namiki A, Shimizu M, Toyosaki N, Kuwajima M, and Sato N
- Subjects
- Male, Humans, Middle Aged, Aged, Aged, 80 and over, Warfarin therapeutic use, Prospective Studies, Anticoagulants therapeutic use, Hemorrhage chemically induced, Hemorrhage epidemiology, Hemorrhage complications, Risk Factors, Registries, Administration, Oral, Atrial Fibrillation complications, Atrial Fibrillation drug therapy, Atrial Fibrillation chemically induced, Stroke epidemiology, Stroke etiology, Stroke prevention & control
- Abstract
Background: Oral anticoagulant therapy for atrial fibrillation (AF) has changed dramatically. Direct oral anticoagulant (DOAC) therapy is administered by general practitioners and specialists. However, the beneficial long-term effects and safety of DOACs have not been well investigated in real-world clinical practice., Methods: The ASSAF-K (a study of the safety and efficacy of OAC therapy in the treatment of AF in Kanagawa), a prospective, multi-center, observational study, was conducted to clarify patient characteristics, status of OAC treatment, long-term outcomes, and adverse events, including cerebrovascular disease, bleeding, and death., Results: A total of 4014 patients were enrolled (hospital: 2500 cases; clinic: 1514 cases). The number of patients in the final dataset was 3367 (mean age, 72.6 ± 10.0 years; males, 66.3 %). CHA
2 DS2 -VASc and HAS-BLED scores were 3.0 ± 1.6 and 2.2 ± 1.0, respectively. The risk factors of the primary composite outcome (all-cause death, serious bleeding events, cerebral hemorrhage, and stroke) were higher age, lower body mass index, lower diastolic blood pressure, lower creatine clearance, history of heart failure, history of stroke, and medication of anti-platelet agents. The event-free rates of the primary composite outcome with DOACs, warfarin, and without OACs were 92.7 %, 88.0 %, and 87.4 %, respectively. The event rate of DOACs was significantly lower than that of warfarin [HR 0.63 (95 % CI 0.48-0.81)], and similar results were observed after adjustment for AF stroke risk score [HR 0.70 (95 % CI 0.54-0.90)]. Serious bleeding events tended to occur less frequently with DOACs compared with warfarin [unadjusted HR 0.53 (95 % CI 0.31-0.91), adjusted HR 0.61 (95 % CI 0.33-1.11)]., Conclusions: This multi-center registry demonstrated the long-term outcome in patients with AF treated with and without OACs and suggests that DOAC therapy is safe and beneficial in hospitals and clinics., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests regarding the present study., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
46. Administration of spermidine attenuates concanavalin A-induced liver injury.
- Author
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Ando T, Ito D, Shiogama K, Sakai Y, Abe M, Ideta T, Kanbe A, Shimizu M, and Ito H
- Subjects
- Animals, Mice, Concanavalin A pharmacology, Spermidine pharmacology, Spermidine therapeutic use, Spermidine metabolism, Liver metabolism, Anticoagulants pharmacology, RNA, Messenger metabolism, Chemical and Drug Induced Liver Injury, Chronic metabolism, Chemical and Drug Induced Liver Injury drug therapy, Chemical and Drug Induced Liver Injury prevention & control, Chemical and Drug Induced Liver Injury metabolism
- Abstract
A previous study revealed that treatment with the anticoagulant heparin attenuated concanavalin A (ConA)-induced liver injury. The administration of spermidine (SPD) increased urokinase-type plasminogen activator (uPA) levels in the serum. uPA is clinically used for the treatment of some thrombotic diseases such as cerebral infarction. Therefore, SPD may attenuate ConA-induced liver injury that is exacerbated by blood coagulation. The present study investigated the effect of SPD on liver injury in mice with autoimmune hepatopathy induced by ConA. A model of liver injury was created by intravenous injection of ConA into mice. SPD was administered in free drinking water and was biochemically and pathologically examined over time. The administration of SPD to ConA-treated mice significantly reduced liver injury. However, SPD treatment upregulated the mRNA expression of TNF-α and IFN-ϒ in the livers of ConA-treated mice. In contrast, the mRNA expression of tissue factor in the livers of SPD-treated mice was decreased after ConA injection. The frequency of lymphocytes and lymphocyte activation were not affected by SPD administration in ConA-treated mice. SPD treatment increased uPA levels in the serum and decreased the level of D-dimer in ConA-treated mice. Moreover, SPD decreased fibrin in the livers of ConA-treated mice. These results indicated that SPD treatment increased anticoagulant ability by increasing of uPA and attenuated ConA-induced liver injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
47. Inhibitory effect of non-alcoholic steatohepatitis on colon cancer liver metastasis.
- Author
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Yamada S, Morine Y, Ikemoto T, Saito Y, Miyazaki K, Shimizu M, Tsuneyama K, and Shimada M
- Subjects
- Male, Mice, Animals, Mice, Inbred C57BL, Liver pathology, Disease Models, Animal, RNA, Messenger metabolism, Non-alcoholic Fatty Liver Disease, Liver Neoplasms pathology, Colonic Neoplasms pathology
- Abstract
Background: The incidence of non-alcoholic steatohepatitis (NASH) is dramatically increasing, but the effect of NASH on colon cancer liver metastasis (CLM) is controversial. The aim of this study was to investigate the impact and mechanism of action of NASH on CLM using a western diet (WD)-fed mouse model., Methods: Six-week-old male C57BL/6 J mice were used. They were divided into the WD group and control group with normal diet. MC38 colon cancer cells were injected into the spleen at 2, 6, 8 and 16 weeks, and mice were killed at 2 weeks after injection to evaluate hepatic steatosis, fibrosis, metastasis and mRNA/protein expression in the liver., Results: Only mice fed a WD for 16 weeks showed hepatic fibrosis. These mice showed significantly higher alanine aminotransferase and total cholesterol levels compared with the control group (p < 0.05). The WD group showed significantly lower tumor number and smaller tumor diameter (p < 0.05). In the WD group, expression of SAA1, IL6, STAT3 and MMP9 mRNA in the liver was significantly lower than in the control group (p < 0.05). Serum amyloid A1 protein expression was also lower in the WD group., Conclusions: The WD-fed NASH mouse model showed an inhibitory effect on CLM. Suppressed interleukin-6/signal transducer and activator of transcription 3 signaling and serum amyloid A/matrix metalloproteinase 9 expression may affect this phenomenon., Competing Interests: Declaration of competing interest The authors have no conflict of interest related to this study., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
48. Pneumatosis cystoides coli associated with intestinal spirochetosis.
- Author
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Yamazaki K, Kushima R, Ozawa N, and Shimizu M
- Subjects
- Humans, Intestines, Pneumatosis Cystoides Intestinalis diagnostic imaging, Pneumatosis Cystoides Intestinalis complications
- Abstract
Competing Interests: Conflict of interest All authors declare no conflicts of interest.
- Published
- 2023
- Full Text
- View/download PDF
49. Short-chain fatty acids profiling in biological samples from a mouse model of Sjögren's syndrome based on derivatized LC-MS/MS assay.
- Author
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Nagatomo R, Kaneko H, Kamatsuki S, Ichimura-Shimizu M, Ishimaru N, Tsuneyama K, and Inoue K
- Subjects
- Animals, Chromatography, Liquid methods, Disease Models, Animal, Fatty Acids, Volatile analysis, Feces chemistry, Hemiterpenes, Isobutyrates analysis, Mice, Pentanoic Acids, Propionates analysis, Sjogren's Syndrome, Tandem Mass Spectrometry methods
- Abstract
An analytical platform is required to characterize the short-chain fatty acids (SCFAs) in a mouse model of pathological immune conditions. Therefore, liquid chromatography tandem mass spectrometry combined with 2-picolylamine derivatization and a comprehensive study of SCFAs distribution based on serum, saliva, feces, liver, and brain from a mouse model of Sjögren's syndrome (SS) is performed. The design of experiments is used to achieve efficient 2-picolylamine derivatization, and optimize the reaction conditions. Twelve SCFAs are derivatized, and separated on a reversed-phase C
18 column. All SCFAs show high linearity (r2 > 0.995) and intra/inter-day accuracy values from 71.6% to 115.6% (precision < 13.7%). This method was used to determine SCFAs concentrations in the serum, saliva, feces, liver, and brain of an SS model mice, and isobutyric acid, valeric acid, isovaleric acid, and 2-methylbutyric acid in liver from SS were significantly different compared with control group. Moreover, the preliminary evaluation of propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid in saliva is conducted based on the respective SS stages and are correlated with these histological scores. This analytical platform for the widely SCFAs profiling in several tissues can be a clue for studying unclear immune pathophysiology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
50. Further survey of genetic variants of flavin-containing monooxygenase 3 (FMO3) in Japanese subjects found in an updated database of genome resources and identified by phenotyping for trimethylaminuria.
- Author
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Shimizu M, Hirose N, Kato M, Sango H, Uenuma Y, Makiguchi M, Hishinuma E, Saito S, Hiratsuka M, and Yamazaki H
- Subjects
- Humans, Japan, Recombinant Proteins, Nucleotides, Benzydamine
- Abstract
The number of single-nucleotide substitutions of human flavin-containing monooxygenase 3 (FMO3) recorded in mega-databases is increasing. Moreover, phenotype-gene analyses have revealed impaired FMO3 variants associated with the metabolic disorder trimethylaminuria. In this study, four novel amino-acid substituted FMO3 variants, namely p.(Gly191Asp), p.(Glu414Gln), p.(Phe510Ser), and p.(Val530CysfsTer1), were identified in the whole-genome sequences in the Japanese population reference panel (8.3K JPN) of the Tohoku Medical Megabank Organization. Additionally, four variants, namely p.(Ile369Thr), p.(Phe463Val), p.(Arg500Gln), and p.(Ala526Thr) FMO3, were found in the 8.3K JPN database but were already recorded in the National Center for Biotechnology Information database. Novel FMO3 variants p.[(Met1Leu)] and p.[(Trp231Ter)] were also identified in phenotype-gene analyses of 290 unrelated subjects with self-reported malodor. Among the eight recombinant FMO3 variants tested (except for p.[(Met1Leu)] and p.[(Trp231Ter)]), Arg500Gln and Gly191Asp FMO3, respectively, had lower and much lower capacities for trimethylamine and/or benzydamine N-oxygenation activities than wild-type FMO3. Because another FMO3 mutation p.[(Gly191Cys)] with diminished recombinant protein activity was previously detected in two independent probands, Gly191 would appear to be important for FMO3 catalytic function. Analysis of whole-genome sequence data and trimethylaminuria phenotypes revealed missense FMO3 variants that severely impaired FMO3-mediated N-oxygenations in Japanese subjects that could be susceptible to low drug clearances., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
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