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86 results on '"Yosuke, Nakagawa"'

1. Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease

Author

Yosuke Nakagawa and Hirotaka Komaba

Subjects
chronic kidney disease-mineral and bone disorder, fibroblast growth factor-23, glycerol-3-phosphate, parathyroid hormone, hyperparathyroidism, secondary, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.

Published
2024
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3. Impact of beta-tricalcium phosphate on preventing tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaw in rats

Author

Naoki Funayama, Takahiro Yagyuu, Mitsuhiko Imada, Yoshihiro Ueyama, Yosuke Nakagawa, and Tadaaki Kirita

Subjects
Medicine, Science
Abstract

Abstract Antiresorptive or antiangiogenic drugs can cause medication-related osteonecrosis of the jaw that is refractory. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) may be caused by procedures such as tooth extraction damage the alveolar bone, release bisphosphonates (BPs) and impede healing. This study investigated strategies for BRONJ prevention and molecular mechanisms of its onset. We assessed the effectiveness of filling extraction sockets with beta-tricalcium phosphate (β-TCP). Rats were administered zoledronic acid (ZA) 1.2 mg/kg once per week for 2 weeks, and a molar was extracted. They were randomly assigned to the β-TCP group (bone defects filled with 0.01 g of β-TCP) or control group. Tissue content measurements indicated 2.2 ng of ZA per socket in the β-TCP group and 4.9 ng in the control group, confirming BP distribution and BP adsorption by β-TCP in vivo. At 4 weeks after extraction, the β-TCP group had normal mucosal coverage without inflammation. Moreover, at 8 weeks after extraction, enhanced bone healing, socket coverage, and new bone formation were observed in the β-TCP group. Connective tissue in the extraction sockets suggested that local increases in BP concentrations may suppress the local autophagy mechanisms involved in BRONJ. Filling extraction sockets with β-TCP may prevent BRONJ.

Published
2023
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4. Case report: Unilateral masticatory atrophy caused by pure trigeminal motor neuropathy

Author

Kaoru Kinugawa, MD, Tomoo Mano, MD, PhD, Yosuke Nakagawa, DDS, PhD, Naoki Hotta, MD, and Kazuma Sugie, MD, PhD

Subjects
Unilateral masticatory muscle atrophy, Trigeminal nerve, Pure trigeminal motor neuropathy, Malocclusion, Magnetic resonance imaging, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Pure trigeminal motor neuropathy (PTMN) is characterized by trigeminal motor weakness without signs of trigeminal sensory dysfunction or involvement of other cranial nerves. We describe a rare case of an 83-year-old man with weakness and atrophy of the right masticatory muscle without any sensory disturbance. Brain computed tomography and magnetic resonance imaging revealed atrophy and fatty infiltration of the right masticatory muscle. Electromyography revealed abnormal spontaneous activity, chronic neurogenic motor unit potentials, and reduced interference patterns in the right temporalis and the masseter muscles. The patient was diagnosed with PTMN based on the clinical symptoms and examinations. Our case presents a rare clinical manifestation with unclear etiology.

Published
2022
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5. Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation

Author

Chiaki Kawabata, Hirotaka Komaba, Hiroaki Ishida, Yosuke Nakagawa, Naoto Hamano, Masahiro Koizumi, Genta Kanai, Takehiko Wada, Michio Nakamura, and Masafumi Fukagawa

Subjects
Diseases of the genitourinary system. Urology, RC870-923
Abstract

Rationale & Objective: Patients with chronic kidney failure have markedly elevated fibroblast growth factor 23 (FGF-23) levels and decreased soluble Klotho levels. However, no studies have examined the effects of hemodialysis initiation on the levels of these hormones and other parameters of mineral metabolism. Study Design: Prospective single-arm study. Setting & Participants: 20 individuals with incident kidney failure initiating hemodialysis. Exposure: Initiation of hemodialysis. Dose adjustments of phosphate binders and vitamin D receptor activators and use of calcimimetics, erythropoiesis-stimulating agents, and intravenous iron were prohibited. Outcomes: Changes in serum levels of FGF-23, soluble Klotho, and other biochemical parameters of mineral metabolism, measured before and after each hemodialysis session, for a total of 4 sessions over 5 days. Analytical Approach: Repeated-measures analysis of variance. Results: At baseline, participants had 18-fold higher median FGF-23 levels and 1.6-fold lower mean soluble Klotho levels compared with age- and sex-matched healthy individuals. Initiation of hemodialysis led to progressive reductions in serum phosphorus, intact parathyroid hormone, and FGF-23 levels, with dialysis-related fluctuations. No reductions were observed in levels of α1-microglobulin, which has molecular weight comparable to FGF-23. The magnitude of the FGF-23 level reductions was strongly associated with concomitant changes in serum phosphorus levels but not with the changes in intact parathyroid hormone levels. Soluble Klotho levels did not change after the initiation of hemodialysis. Limitations: Single-arm design, small sample size, short follow-up period. Conclusions: Initiation of hemodialysis in patients with chronic kidney failure led to progressive reductions in FGF-23 levels in association with reductions in serum phosphorus levels. These results suggest that phosphorus is a strong inducer of FGF-23 production and that regulation of FGF-23 production is a rapid process. Index Words: Chronic kidney failure, FGF23, hemodialysis, hyperphosphatemia, Klotho

Published
2020
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8. Examination of Suprahyoid Muscle Resection and Other Factors Affecting Swallowing Function in Patients With Advanced Oral Cancer After Surgical Resection and Reconstruction

Author

Yohei, Nakayama, Nobuhiro, Yamakawa, Yoshihiro, Ueyama, Takahiro, Yagyuu, Nobuhiro, Ueda, Yosuke, Nakagawa, Yuka, Takahashi, Sho, Arikawa, and Tadaaki, Kirita

Subjects
Otorhinolaryngology, Muscles, Quality of Life, Humans, Mouth Neoplasms, Surgery, General Medicine, Deglutition Disorders, Deglutition
Abstract

Dysphagia is one of the most common adverse effects associated with oral cancer therapy and could greatly impair postoperative quality of life. The objective of this study was to analyze postoperative swallowing outcomes and factors influencing postoperative swallowing function in patients with advanced oral cancer who underwent primary reconstruction after surgical resection to identify patients at risk of experiencing severe dysphagia after immediate reconstruction of surgical defects, and to determine an ideal approach to provide appropriate perioperative interventions. The swallowing status was evaluated at 4 week postoperatively using the Functional Oral Intake Scale. We also analyzed the effects of patient, tumor, surgical, and other factors on postoperative swallowing function. The study included 67 patients. At 4 weeks postoperatively, 11 patients showed reduced swallowing function, whereas 56 patients showed good swallowing function. The number of resected suprahyoid muscles (odds ratio, 1.55; 95% confidence interval, 1.03-2.32; P=0.035) was an independent factor influencing postoperative swallowing function. Thus, among patients who underwent radical resection of oral cancer with primary reconstruction, those with extensive resection of the suprahyoid muscles were at higher risk of developing postoperative dysphagia. These findings are expected to facilitate increased vigilance for dysphagia, better counseling, and appropriate rehabilitation interventions.

Published
2022
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12. Thermal Effects on Kerr Comb Generation in a CaF2 Whispering-Gallery Mode Microcavity

Author

Tomoya Kobatake, Takumi Kato, Hiroki Itobe, Yosuke Nakagawa, and Takasumi Tanabe

Subjects
Kerr optical frequency combs, solitons, whispering gallery modes, resonators, Applied optics. Photonics, TA1501-1820, Optics. Light, QC350-467
Abstract

We numerically investigate the dynamics of Kerr comb generation in a calcium fluoride whispering gallery mode (WGM) microcavity taking thermal effects into account. Soliton pulse generation is investigated in the presence of thermooptic (TO) and thermal expansion (TE) effects and particularly when the TO effect is negative. We found that, with optimized cavity parameters, self-induced cavity resonance shifts resulting from a negative TO effect allow the system to generate a soliton pulse with no wavelength scanning or dynamic power optimization, which are usually needed to achieve a soliton pulse with silica and other WGM microcavity systems. A negative TO effect automatically tunes the cavity resonance so that the cavity will achieve a soliton state. The competition between the TO and TE effects is also investigated in detail.

Published
2016
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13. Empagliflozin in Patients with Chronic Kidney Disease

Author

Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa McKinley, Alastair Woodman, Judi Graham, Niall Leonard, John Smyth, Vicki Adell, Samantha Hagan, Ben Caplin, Amin Oomatia, Eleanor Damian, Toluleyi Sobande, Tim Doulton, Michael Delaney, Mahmoud Montasser, Jenny Hansen, David Loader, Angela Moon, Frances Morris, Smeeta Sinha, Chukwuma Chukwu, Amy Hudson, Diane Campbell, Melanie Kershaw, Stephanie Whittaker, Ayesha Irtiza-Ali, Farid Ghalli, Heba Nosseir, Allison Leslie, Kate Trivedi, Donald Fraser, Mohammad Alhadj Ali, Sian Griffin, Farah Latif, Justyna Witczak, Alexa Wonnacott, Lynda Jeffers, Yvette Webley, Paul Phelan, Eve Miller-Hodges, Ailsa Geddes, Margaret Glenwright, Amy Hunter, Thomas Pickett, Jim Moriarty, Linda Hill, Amanda Tyler, Waqar Ayub, Gail Evans, Sue Hewins, Davina Hewitt, Kerry Read, Samira Bell, Leanne Cosgrove, Rachel Craik, Shona Murray, Nitin Bhandary, Holly Coles, Rashmi Easow, Maya Joseph, Arif Khwaja, Yvonne Jackson, Angeline Mbuyisa, Rachel Sellars, Nihil Chitalia, Cynthia Mohandas, Anca Gherman, Charlotte Kamundi, Olumide Olufuwa, Kieran McCafferty, Adedolapo Adeleke, Cara Healy, Damini Jeyarajah, Edward Kinsella-Perks, Richard Smith, Brian Camilleri, Carol Buckman, Jenny Finch, Vanessa Rivers, Andrew Connor, Sheila Carr, Lisa Shainberg, Andrew Lewington, Richard Baker, Suzannah Dorey, Kay Tobin, Rosalyn Wheatley, Debasish Banerjee, Richard Hull, Sharirose Abat, Riny Paul, Mahzuz Karim, Zay Htet, Saad Tufail, Ravi Varma, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Emily Tropman, Thahir Abdul-Samad, Anne Grace, Marie Phipps, Rebecca Suckling, Subash Somalanka, Bhrigu Sood, Pauline Swift, Sarah Acheampong, Kwame Ansu, Martia Augustin, Anna Sampson, Lynn Vinall, Kim Wren, Shamila Wanninayake, Nicholas Wooding, Heather Edwards, Lydia Owen, Stephanie Bolton, Marion Carson, Michael Matthews, Nigel Brunskill, Jorge Jesus-Silva, Alex Howson, Mary Quashie-Akponeware, Hilary Tindall, Chidambaram Nethaji, Helen Eldon, Rajan Patel, Patrick Mark, Alastair Rankin, Michael Sullivan, Kirsty Forsyth, Rowan McDougall, Tanaji Dasgupta, Louisa Davies, Maggie Ryder, Philip Grimmer, Clare Macdonald, Mary Webster, Newcastle Newcastle, Timothy Ellam, Edwin Wong, Christine Meshykhi, Andrea Webster, Peter Wilson, Enric Vilar, Jocelyn Berdeprado, Eunice Doctolero, Lily Wilkinson, Frank McCarroll, Hesham Ammar, Ying Kuan, Conor Moran, Girish Shivashankar, Ryan Campbell, Deborah Glowski, Paula McDermott, Amar Ali, Zuber Patel, Christine Bond, Gillian Whalley, Haitao Zhang, Liu Yang, Lihua Zhang, Tingting Kan, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Hong Cheng, Weijing Bian, Zhirui Zhao, Fengmin Shao, Huixia Cao, Xiaojing Jiao, Peiyuan Niu, Jianying Niu, Yu Chen, Lihong Zhang, Shenglang Zhu, Haiyan Lin, Shaopeng Yao, Jiehui Chen, Ying Jiang, Ying Hu, Huaying Xiao, Fuye Yang, Xinzhou Zhang, Baochun Guo, Qiu Jin, Lixia Liu, Xiangcheng Xiao, Yanyun Xie, Ting Meng, Chuanwen Xu, Jie Huang, Yanmei Xu, Weixin Kong, Xiaoliang Wang, Qianpan Liu, Xueying Wang, Ming Gao, Xiumei Hu, Ying 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Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative

Subjects
chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)

Published
2023

17. Clinical Phenotypes and the Clinical Course of Bullous Pemphigoid Receiving Dipeptidyl Pepitidase-4 Inhibitor Treatment: An Analysis of Cases in a Single Japanese Center

Author

Yosuke Nakagawa, Masao Toyoda, Nobumichi Saito, Noriko Kaneyama, Tomomichi Shimizu, Tomotaka Mabuchi, and Masafumi Fukagawa

Subjects
Internal Medicine, General Medicine
Abstract

Objective Several studies have shown an increased risk of bullous pemphigoid (BP) when receiving dipeptidyl pepitidase-4 inhibitor (DPP-4i) treatment. The present study explored the associations of DPP-4i treatment with the clinical phenotypes and clinical course of BP. Methods We analyzed data of 146 patients with BP at Tokai University School of Medicine from December 1, 2009, to December 31, 2021. We obtained data by a retrospective medical record review and compared the bullous pemphigoid disease area index (BPDAI) between diabetes patients receiving DPP-4i treatment and those not receiving DPP-4i treatment. We employed multivariable linear regression models to explore the association between the DPP-4i treatment and the BPDAI scores. Results Among 53 BP patients with diabetes, 33 had developed BP during treatment with DPP-4i agents, among which vildagliptin was the most frequently used. The urticaria/erythema scores of the BPDAI were significantly lower in patients who developed BP while receiving DPP-4i treatment than among others. Of note, 69.2% of the patients who stopped DPP-4i treatment experienced complete remission, and the clinical course was more favorable in patients with lower scores for urticaria/erythema than among others. Conclusion These findings suggest that, in patients who developed BP while receiving DPP-4i treatment, a noninflammatory phenotype may indicate a high likelihood that DPP-4i treatment contributes to the development of BP. The discontinuation of DPP-4i should be carefully considered in close consultation with dermatologists.

Published
2022

18. Interrelationships Between Sclerostin, Secondary Hyperparathyroidism, and Bone Metabolism in Patients on Hemodialysis

Author

Yosuke Nakagawa, Naoto Hamano, Miho Hida, Michio Nakamura, Yuichiro Takahashi, Hirotaka Komaba, Takatoshi Kakuta, Takehiko Wada, Hisae Tanaka, Takao Suga, Hiroo Takahashi, Hiroaki Ishida, Masafumi Fukagawa, and Toru Hyodo

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Parathyroid hormone, Context (language use), Biochemistry, Bone remodeling, chemistry.chemical_compound, Endocrinology, Bone Density, Renal Dialysis, Internal medicine, medicine, Humans, Prospective Studies, Dialysis, Adaptor Proteins, Signal Transducing, Aged, Bone mineral, business.industry, Biochemistry (medical), Middle Aged, Prognosis, medicine.disease, Cross-Sectional Studies, chemistry, Case-Control Studies, Sclerostin, Female, Hyperparathyroidism, Secondary, Secondary hyperparathyroidism, Bone Remodeling, Hemodialysis, business, Biomarkers, Follow-Up Studies
Abstract

Context Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure, but its role in the pathogenesis of renal bone disease remains unknown. Objective We aimed to explore the association of serum sclerostin with bone metabolism in patients undergoing hemodialysis, with a particular focus on parathyroid hormone (PTH)-dependent and PTH-independent pathways. Methods This cross-sectional and prospective cohort study included 654 patients undergoing hemodialysis at 10 facilities in Japan. We employed multivariable linear regression to explore whether sclerostin levels were associated with metacarpal bone mineral density (BMD), intact PTH, bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b). We employed mediation analyses to explore whether and to what extent the association of PTH with bone turnover markers is mediated by sclerostin. We also compared sclerostin levels between patients with and without previous or incident fractures. Results The median sclerostin level in hemodialysis patients was 3- to 4-fold higher than that in healthy individuals. Higher sclerostin levels were associated with higher metacarpal BMD and lower levels of intact PTH, BAP, and TRACP-5b. However, the relationships of sclerostin with bone turnover markers were substantially attenuated after adjustment for PTH. Mediation analysis suggested that the effects of PTH on bone turnover markers were mainly direct rather than mediated by sclerostin. Sclerostin levels were not associated with previous or incident fractures. Conclusion These findings suggest that in patients undergoing dialysis, sclerostin has only a limited role in bone metabolism and may not mediate the effect of PTH on bone turnover.

Published
2021
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20. Bi-material crystalline whispering gallery mode microcavity structure for thermo-opto-mechanical stabilization

Author

Hiroki Itobe, Yosuke Nakagawa, Yuta Mizumoto, Hiroi Kangawa, Yasuhiro Kakinuma, and Takasumi Tanabe

Subjects
Physics, QC1-999
Abstract

We fabricated a calcium fluoride (CaF2) whispering gallery mode (WGM) microcavity with a computer controlled ultra-precision cutting process. We observed a thermo-opto-mechanical (TOM) oscillation in the CaF2 WGM microcavity, which may influence the stability of the optical output when the cavity is employed for Kerr comb generation. We studied experimentally and numerically the mechanism of the TOM oscillation and showed that it is strongly dependent on cavity diameter. In addition, our numerical study suggests that a microcavity structure fabricated with a hybrid material (i.e. CaF2 and silicon), which is compatible with an ultra-high Q and high thermal conductivity, will allow us to reduce the TOM oscillation and stabilize the optical output.

Published
2016
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21. Inhibition of the ATR kinase enhances 5-FU sensitivity independently of nonhomologous end-joining and homologous recombination repair pathways

Author

Takeshi K. Matsui, Eiichiro Mori, Genro Kashino, Atsuhisa Kajihara, Yoshihiko M. Sakaguchi, Tadaaki Kirita, Sotaro Kikuchi, Soichiro S. Ito, Masatoshi Hasegawa, Shinko Kobashigawa, Fumika Kitayoshi, Hitoki Nanaura, Kazuma Sugie, Mari Nakanishi, Masaya Matsubayashi, Shigehiro Tamaki, Akihisa Takahashi, and Yosuke Nakagawa

Subjects
0301 basic medicine, DNA End-Joining Repair, Ultraviolet Rays, DNA repair, DNA damage, Ataxia Telangiectasia Mutated Proteins, Biochemistry, 03 medical and health sciences, Cell Line, Tumor, Neoplasms, Humans, Protein Kinase Inhibitors, Molecular Biology, 030102 biochemistry & molecular biology, Chemistry, Kinase, Autophosphorylation, DNA replication, Recombinational DNA Repair, Cell Biology, Cell cycle, Neoplasm Proteins, Cell biology, Non-homologous end joining, 030104 developmental biology, Drug Resistance, Neoplasm, Fluorouracil, Homologous recombination
Abstract

The anticancer agent 5-fluorouracil (5-FU) is cytotoxic and often used to treat various cancers. 5-FU is thought to inhibit the enzyme thymidylate synthase, which plays a role in nucleotide synthesis and has been found to induce single- and double-strand DNA breaks. ATR Ser/Thr kinase (ATR) is a principal kinase in the DNA damage response and is activated in response to UV– and chemotherapeutic drug–induced DNA replication stress, but its role in cellular responses to 5-FU is unclear. In this study, we examined the effect of ATR inhibition on 5-FU sensitivity of mammalian cells. Using immunoblotting, we found that 5-FU treatment dose-dependently induced the phosphorylation of ATR at the autophosphorylation site Thr-1989 and thereby activated its kinase. Administration of 5-FU with a specific ATR inhibitor remarkably decreased cell survival, compared with 5-FU treatment combined with other major DNA repair kinase inhibitors. Of note, the ATR inhibition enhanced induction of DNA double-strand breaks and apoptosis in 5-FU–treated cells. Using gene expression analysis, we found that 5-FU induced the activation of the intra-S cell-cycle checkpoint. Cells lacking BRCA2 were sensitive to 5-FU in the presence of ATR inhibitor. Moreover, ATR inhibition enhanced the efficacy of the 5-FU treatment, independently of the nonhomologous end-joining and homologous recombination repair pathways. These findings suggest that ATR could be a potential therapeutic target in 5-FU–based chemotherapy.

Published
2020
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22. Serum sclerostin levels and mortality in hemodialysis patients: An 8-year prospective study

Author

Yosuke Nakagawa, Hirotaka Komaba, Takehiko Wada, Hiroo Takahashi, Yuichiro Takahashi, Toru Hyodo, Miho Hida, Takao Suga, Takatoshi Kakuta, and Masafumi Fukagawa

Subjects
Nephrology
Abstract

Introduction: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure. Sclerostin might be involved in the pathogenesis of vascular calcification, but few studies have examined the association between sclerostin and mortality in hemodialysis patients. Methods: We analyzed a prospective cohort of 654 patients undergoing maintenance hemodialysis. The primary exposure variable was the baseline serum sclerostin level measured at study enrollment. The primary outcome was 8-year all-cause mortality. Mortality risk was assessed using Cox regression models adjusted for potential confounders. Results: During a median follow-up of 7.6 years (interquartile range, 4.1–8.0 years), 229 of the 654 participants died. In a univariate analysis, serum sclerostin levels were not associated with mortality (HR per doubling, 0.94; 95% CI, 0.76–1.17). This result was unchanged after adjustment for age, sex, dialysis vintage, diabetes, prior cardiovascular disease, and body mass index (HR per doubling, 0.92; 95% CI, 0.72–1.17). Similar results were obtained for cardiovascular mortality. Conclusion: Serum sclerostin levels were not associated with mortality in maintenance hemodialysis patients. Further research is required to determine the role of sclerostin in vascular calcification and cardiovascular disease in kidney failure.

Published
2022

25. Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation

Author

Hiroaki Ishida, Masahiro Koizumi, Naoto Hamano, Hirotaka Komaba, Chiaki Kawabata, Michio Nakamura, Masafumi Fukagawa, Takehiko Wada, Yosuke Nakagawa, and Genta Kanai

Subjects
Fibroblast growth factor 23, Kidney, medicine.medical_specialty, business.industry, medicine.medical_treatment, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, Calcitriol receptor, Hyperphosphatemia, medicine.anatomical_structure, Endocrinology, Nephrology, Internal medicine, Internal Medicine, medicine, Analysis of variance, Hemodialysis, business, Klotho, Hormone
Abstract

Rationale & Objective: Patients with chronic kidney failure have markedly elevated fibroblast growth factor 23 (FGF-23) levels and decreased soluble Klotho levels. However, no studies have examined the effects of hemodialysis initiation on the levels of these hormones and other parameters of mineral metabolism. Study Design: Prospective single-arm study. Setting & Participants: 20 individuals with incident kidney failure initiating hemodialysis. Exposure: Initiation of hemodialysis. Dose adjustments of phosphate binders and vitamin D receptor activators and use of calcimimetics, erythropoiesis-stimulating agents, and intravenous iron were prohibited. Outcomes: Changes in serum levels of FGF-23, soluble Klotho, and other biochemical parameters of mineral metabolism, measured before and after each hemodialysis session, for a total of 4 sessions over 5 days. Analytical Approach: Repeated-measures analysis of variance. Results: At baseline, participants had 18-fold higher median FGF-23 levels and 1.6-fold lower mean soluble Klotho levels compared with age- and sex-matched healthy individuals. Initiation of hemodialysis led to progressive reductions in serum phosphorus, intact parathyroid hormone, and FGF-23 levels, with dialysis-related fluctuations. No reductions were observed in levels of α1-microglobulin, which has molecular weight comparable to FGF-23. The magnitude of the FGF-23 level reductions was strongly associated with concomitant changes in serum phosphorus levels but not with the changes in intact parathyroid hormone levels. Soluble Klotho levels did not change after the initiation of hemodialysis. Limitations: Single-arm design, small sample size, short follow-up period. Conclusions: Initiation of hemodialysis in patients with chronic kidney failure led to progressive reductions in FGF-23 levels in association with reductions in serum phosphorus levels. These results suggest that phosphorus is a strong inducer of FGF-23 production and that regulation of FGF-23 production is a rapid process. Index Words: Chronic kidney failure, FGF23, hemodialysis, hyperphosphatemia, Klotho

Published
2020

27. Nonlinear dynamic analysis of traveling wave-type ultrasonic motors

Author

Yosuke Nakagawa, Akiro Saito, and Takashi Maeno

Subjects
Ultrasonic equipment -- Analysis, Piezoelectric ceramics -- Mechanical properties, Piezoelectric ceramics -- Electric properties, Chaos theory -- Analysis, Business, Electronics, Electronics and electrical industries
Abstract

A study is presented where the nonlinear dynamic response of the traveling-type ultrasonic motor (USM) is analyzed by measurements and numeric calculations. It is concluded that the model proposed can be applied to the other traveling wave-type USMs such as ring-type and disc-type USMs as this model is capable of representing the characteristics of the traveling wave-type USM.

Published
2008

28. ATR inhibition enhances 5-fluorouracil sensitivity independent of non-homologous end-joining and homologous recombination repair pathway

Author

Fumika Kitayoshi, Takeshi K. Matsui, Mari Nakanishi, Masaya Matsubayashi, Akihisa Takahashi, Shinko Kobashigawa, Atsuhisa Kajihara, Yoshihiko M. Sakaguchi, Masatoshi Hasegawa, Tadaaki Kirita, Yosuke Nakagawa, Eiichiro Mori, Genro Kashino, Sotaro Kikuchi, Kazuma Sugie, Shigehiro Tamaki, Hitoki Nanaura, and Soichiro S. Ito

Subjects
Blot, Non-homologous end joining, chemistry.chemical_compound, biology, Chemistry, DNA repair, Kinase, biology.protein, Phosphorylation, Homologous recombination, Thymidylate synthase, DNA, Cell biology
Abstract

The anticancer agent, 5-fluorouracil (5-FU), is typically applied in the treatment of various types of cancers because of its properties. Thought to be an inhibitor of the enzyme thymidylate synthase which plays a role in nucleotide synthesis, 5-FU has been found to induce single- and double-strand DNA breaks. The activation of ATR occurs as a reaction to UV- and chemotherapeutic drug-induced replication stress. In this study, we examined the effect of ATR inhibition on 5-FU sensitivity. Using western blotting, we found that 5-FU treatment led to the phosphorylation of ATR. Surviving fractions were remarkably decreased in 5-FU with ATR inhibitor (ATRi) compared to 5-FU with other major DNA repair kinases inhibitors. ATR inhibition enhanced induction of DNA double-strand breaks and apoptosis in 5-FU-treated cells. Using gene expression analysis, we found that 5-FU could induce the activation of intra-S checkpoint. Surprisingly,BRCA2-deficient cells were sensitive to 5-FU in the presence of ATRi. In addition, ATR inhibition enhanced the efficacy of 5-FU treatment, independent of non-homologous end-joining and homologous recombination repair pathways. Findings from the present study suggest ATR as a potential therapeutic target for 5-FU chemotherapy.

Published
2020
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29. Bite injuries caused by transcranial electrical stimulation motor-evoked potentials’ monitoring: incidence, associated factors, and clinical course

Author

Sachiko Yata, Tsunenori Takatani, Nobuhiro Ueda, Hiroyuki Nakase, Tadaaki Kirita, Yosuke Nakagawa, Hiroko Shimotsuji, Hideki Shigematsu, Masahiko Kawaguchi, Yasushi Motoyama, and Mitsuru Ida

Subjects
Adult, Male, medicine.medical_specialty, Oral Surgeon, Transcranial Direct Current Stimulation, 03 medical and health sciences, Bites, Human, 0302 clinical medicine, Hematoma, Japan, 030202 anesthesiology, Tongue, Monitoring, Intraoperative, Anesthesiology, medicine, Humans, Elective surgery, Aged, Monitoring, Physiologic, Aged, 80 and over, Univariate analysis, business.industry, Incidence, Perioperative, Middle Aged, Evoked Potentials, Motor, medicine.disease, Electric Stimulation, Dysgeusia, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Anesthesia, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

The incidence of bite injuries associated with transcranial electrical stimulation motor-evoked potentials monitoring reportedly ranges from 0.13 to 0.19%. However, in clinical practice, bite injuries appear to occur more frequently than previously reported. Our aim was to identify the incidence of and perioperative risk factors associated with bite injuries caused by transcranial electrical stimulation motor-evoked potential monitoring. Patients who underwent elective surgery with transcranial electrical stimulation motor-evoked potential monitoring at a single tertiary hospital in Japan between June 2017 and December 2017 were included in this study. All patients were assessed by oral surgeons preoperatively and postoperatively. The associated factors with bite injuries were explored by the univariate analysis. 12 of 186 patients experienced 13 bite injuries, including three lip, six oral mucosa, and four tongue injuries. No patient required suture repair. 11 of 12 patients had uneventful postoperative courses and were cured within 12 postoperative days. One patient with a tongue ulcer and a hematoma had difficulty in oral intake and persistent dysgeusia. Patient severe movement during transcranial electrical stimulation motor-evoked potential monitoring was associated with bite injuries (p = 0.03). The incidence of bite injuries assessed by oral surgeons was 6.5% in patients with transcranial electrical stimulation motor-evoked potential monitoring, and the patients with severe movement during the monitoring tended to incur bite injuries. In rare cases, transcranial electrical stimulation motor-evoked potential monitoring may cause difficulty in oral intake and dysgeusia.

Published
2018
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30. Heat Meets DNA: DNA Damage and Repair

Author

Yosuke Nakagawa, Eiichiro Mori, Atsuhisa Kajihara, and Tadaaki Kirita

Subjects
0301 basic medicine, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Chemistry, DNA damage, DNA, Cell biology
Published
2018
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31. BRCA2 protects mammalian cells from heat shock

Author

Ichiro Ota, Takahiko Nakagawa, Atsuhisa Kajihara, Tadaaki Kirita, Takeo Ohnishi, Akihisa Takahashi, Masatoshi Hasegawa, Masaya Matsubayashi, Akiho S. Murata, Yosuke Nakagawa, Eiichiro Mori, and Soichiro S. Ito

Subjects
0301 basic medicine, Cancer Research, Physiology, DNA damage, RAD51, Biology, Chinese hamster, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cricetinae, Physiology (medical), medicine, Animals, Humans, DNA Breaks, Double-Stranded, Fibroblast, BRCA2 Protein, Phosphorylated Histone H2AX, Hyperthermia, Induced, biology.organism_classification, Molecular biology, enzymes and coenzymes (carbohydrates), 030104 developmental biology, medicine.anatomical_structure, chemistry, Cell culture, 030220 oncology & carcinogenesis, biological phenomena, cell phenomena, and immunity, Homologous recombination, Heat-Shock Response, DNA
Abstract

Heat shock induces DNA double-strand breaks (DSBs) in mammalian cells. Mammalian cells are capable of repairing DSBs by utilising the homologous recombination (HR) pathway. Breast cancer susceptibility gene 2 (BRCA2) is known to regulate the HR pathway. Here, we investigate the role of BRCA2 in repairing DNA damage induced by heat shock.Chinese hamster lung fibroblast cell lines and human tongue squamous cell carcinoma SAS cells were used. RAD51 foci formation assay was used as an HR indicator. Heat sensitivity was analysed with colony forming assays. Phosphorylated histone H2AX (γH2AX) intensity, which correlates with the number of DSBs, was analysed with flow cytometry.RAD51 foci appeared with heat shock, and the number of cells with RAD51 foci was maximal at about 4 h after heat shock. Heat-induced RAD51 foci co-localised with γH2AX foci. BRCA2-deficient cells were sensitive to heat when compared to their parental wild-type cells. Heat-induced γH2AX was higher in BRCA2-deficient cells compared to parental cells. In SAS cells, cells transfected with BRCA2-siRNA were more sensitive to heat than cells transfected with negative control siRNA. Apoptotic bodies increased in number more rapidly in BRCA2-siRNA transfected cells than in cells transfected with negative control siRNA when cells were observed at 48 h after a heat treatment. In addition, cells deficient in BRCA2 were incapable of activating heat-induced GBRCA2 has a protecting role against heat-induced cell death. BRCA2 might be a potential molecular target for hyperthermic cancer therapy.

Published
2017
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32. Metacarpal bone mineral density by radiographic absorptiometry predicts fracture risk in patients undergoing maintenance hemodialysis

Author

Takehiko Wada, Yosuke Nakagawa, Miho Hida, Hirotaka Komaba, Takao Suga, Takatoshi Kakuta, Naoto Hamano, and Masafumi Fukagawa

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Radiography, 030232 urology & nephrology, Asymptomatic, 03 medical and health sciences, Fractures, Bone, 0302 clinical medicine, Absorptiometry, Photon, Interquartile range, Bone Density, Renal Dialysis, medicine, Humans, Dialysis, Bone mineral, business.industry, Hazard ratio, Metacarpal Bones, medicine.disease, 030104 developmental biology, Nephrology, Hemodialysis, Radiology, medicine.symptom, business, Kidney disease
Abstract

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guideline update suggests bone mineral density testing to assess fracture risk in patients with chronic kidney disease, but dual-energy X-ray absorptiometry is not available in most dialysis facilities. Radiographic absorptiometry is an inexpensive and quick method for evaluating bone mineral density. Therefore, we analyzed a historical cohort of 456 maintenance hemodialysis patients to determine whether metacarpal bone mineral density measured by digital image processing, a computer-assisted radiographic absorptiometry technique, predicts fracture risk. At baseline, the median metacarpal bone mineral density T-score was -2.05 (interquartile range, -3.35 to -0.99). During a mean follow-up of 5.3 years, there were 16 clinical fractures and 11 asymptomatic vertebral fractures as estimated by height loss. Metacarpal bone mineral density T-score was significantly lower in patients who sustained a clinical fracture than in those remaining event-free. Decreasing metacarpal bone mineral density T-score was significantly associated with increased risk of clinical fracture (hazard ratio, 1.41 per 1 standard deviation decrease in bone mineral density T-score [95% confidence interval, 1.09 to 1.83]; the hazard ratio for lowest versus highest tertile was 4.86 [1.03 to 22.92]. Similar associations were observed between metacarpal bone mineral density T-score and vertebral fracture or any fracture. The results were robust to different analysis strategies and were consistent across different subgroups. Thus, radiographic absorptiometry could be a useful tool for primary screening of hemodialysis patients at high risk for fracture. Additional studies are required to determine the predictive ability of radiographic absorptiometry techniques compared to dual-energy X-ray absorptiometry or other established methods.

Published
2019

33. Magnesium as a Janus-faced inhibitor of calcification

Author

Hirotaka Komaba, Yosuke Nakagawa, and Masafumi Fukagawa

Subjects
0301 basic medicine, medicine.medical_specialty, 030232 urology & nephrology, chemistry.chemical_element, 03 medical and health sciences, Mice, 0302 clinical medicine, Calcification, Physiologic, Internal medicine, medicine, Animals, Humans, Magnesium, Renal Insufficiency, Chronic, Vascular Calcification, Vascular calcification, Klotho, Osteomalacia, Minerals, business.industry, medicine.disease, 030104 developmental biology, Endocrinology, chemistry, Nephrology, Knockout mouse, Complication, business, Calcification, Kidney disease
Abstract

Vascular calcification is a life-threatening complication in patients with chronic kidney disease. Magnesium is a potent inhibitor of calcification and attracting attention as a new therapeutic candidate. ter Braake and colleagues demonstrate that magnesium supplementation strikingly prevents vascular calcification in Klotho knockout mice. However, these mice also show osteomalacia, indicating that magnesium has a Janus face. Maximizing the beneficial effects of magnesium without causing bone mineralization defects is an important next challenge.

Published
2019

34. FP295Acute kidney injury promotes osteoid formation in rats

Author

Kaichiro Sawada, Naoto Hamano, Hideyuki Yamato, Yosuke Nakagawa, Hiroaki Ishida, Masafumi Fukagawa, Michio Nakamura, Hirotaka Komaba, and Takehiko Wada

Subjects
Transplantation, Pathology, medicine.medical_specialty, Osteoid Formation, Nephrology, business.industry, Osteoid, Kidney injury, Medicine, business
Published
2019
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35. Interrelationships Between Sclerostin, Secondary Hyperparathyroidism, and Bone Metabolism in Patients on Hemodialysis.

Author

Yosuke Nakagawa, Hirotaka Komaba, Naoto Hamano, Hisae Tanaka, Takehiko Wada, Hiroaki Ishida, Michio Nakamura, Hiroo Takahashi, Yuichiro Takahashi, Toru Hyodo, Miho Hida, Takao Suga, Takatoshi Kakuta, and Masafumi Fukagawa

Subjects
BONE metabolism, SCLEROSTIN, HEMODIALYSIS patients, BONE density, BONE remodeling
Abstract

Context: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure, but its role in the pathogenesis of renal bone disease remains unknown. Objective: We aimed to explore the association of serum sclerostin with bone metabolism in patients undergoing hemodialysis, with a particular focus on parathyroid hormone (PTH)-dependent and PTH-independent pathways. Methods: This cross-sectional and prospective cohort study included 654 patients undergoing hemodialysis at 10 facilities in Japan. We employed multivariable linear regression to explore whether sclerostin levels were associated with metacarpal bone mineral density (BMD), intact PTH, bone alkaline phosphatase (BAP), and tartrateresistant acid phosphatase-5b (TRACP-5b). We employed mediation analyses to explore whether and to what extent the association of PTH with bone turnover markers is mediated by sclerostin. We also compared sclerostin levels between patients with and without previous or incident fractures. Results: The median sclerostin level in hemodialysis patients was 3- to 4-fold higher than that in healthy individuals. Higher sclerostin levels were associated with higher metacarpal BMD and lower levels of intact PTH, BAP, and TRACP-5b. However, the relationships of sclerostin with bone turnover markers were substantially attenuated after adjustment for PTH. Mediation analysis suggested that the effects of PTH on bone turnover markers were mainly direct rather than mediated by sclerostin. Sclerostin levels were not associated with previous or incident fractures. Conclusion: These findings suggest that in patients undergoing dialysis, sclerostin has only a limited role in bone metabolism and may not mediate the effect of PTH on bone turnover. [ABSTRACT FROM AUTHOR]

Published
2022
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36. Homologous recombination preferentially repairs heat-induced DNA double-strand breaks in mammalian cells

Author

Takeo Ohnishi, Masatoshi Hasegawa, Tadaaki Kirita, Yosuke Nakagawa, Eiichiro Mori, Akihisa Takahashi, Douglas L. Pittman, and Atsuhisa Kajihara

Subjects
0301 basic medicine, Cancer Research, Phosphorylated Histone H2AX, Physiology, DNA repair, fungi, RAD51, LIG4, Biology, Molecular biology, Non-homologous end joining, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, chemistry, Cell culture, Physiology (medical), Homologous recombination, DNA
Abstract

Heat shock induces DNA double-strand breaks (DSBs), but the precise mechanism of repairing heat-induced damage is unclear. Here, we investigated the DNA repair pathways involved in cell death induced by heat shock.B02, a specific inhibitor of human RAD51 (homologous recombination; HR), and NU7026, a specific inhibitor of DNA-PK (non-homologous end-joining; NHEJ), were used for survival assays of human cancer cell lines with different p53-gene status. Mouse embryonic fibroblasts (MEFs) lacking Lig4 (NHEJ) and/or Rad54 (HR) were used for survival assays and a phosphorylated histone H2AX at Ser139 (γH2AX) assay. MEFs lacking Rad51d (HR) were used for survival assays. SPD8 cells were used to measure HR frequency after heat shock.Human cancer cells were more sensitive to heat shock in the presence of B02 despite their p53-gene status, and the effect of B02 on heat sensitivity was specific to the GThe HR pathway plays an important role in the survival of mammalian cells against death induced by heat shock via the repair of heat-induced DNA DSBs.

Published
2016
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38. [Secondary osteoporosis. Disordered bone metabolism in chronic kidney disease.]

Author

Yosuke, Nakagawa and Hirotaka, Komaba

Subjects
Chronic Kidney Disease-Mineral and Bone Disorder, Bone Density, Humans, Osteoporosis, Hyperparathyroidism, Secondary, Renal Insufficiency, Chronic
Abstract

In patients with chronic kidney disease(CKD), mineral metabolism abnormalities such as hyperphosphatemia, decreased 1,25-dihydroxyvitamin D, and elevated parathyroid hormone develop as kidney function declines, which lead to vascular calcification and a variety of skeletal abnormalities, collectively termed renal osteodystrophy. Because CKD patients have increased risk of bone fractures, it is important to assess fracture risk by measuring bone mineral density and bone metabolism markers. In addition to management of secondary hyperparathyroidism, medications for osteoporosis could be a reasonable option for preventing fracture.

Published
2018

39. Impressions and Congruency of Pictures and Voices of Characters in 'The Idolmaster'

Author

Ryo Takaoka, Yosuke Nakagawa, Masashi Yamada, and Naoto Hayash

Subjects
Space (commercial competition), Psychology, Semantic differential method, Character design, Starlight, Cognitive psychology
Abstract

The impressions of pictures and voices of the characters in “The Idolmaster” were investigated. In Experiment 1, pictures of 61 characters who appear in the mobile game, “The Idolmaster, Cinderella Girls Starlight Stage” were used as stimuli. Moreover, voice recordings of the title calls spoken by voice actress were used as stimuli in Experiment 1. The participants were requested to rate their impressions of the stimuli. The results of factor analysis showed that the impression space was constructed by three factors: “activity”, “coolness” and “evaluation”. In Experiment 2, the congruency between the pictures and the voices was investigated. The results showed that coincidence in both the activity and the coolness factors was important for the congruency between the pictures and voices.

Published
2018
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40. Detection of γH2AX foci in mouse normal brain and brain tumor after boron neutron capture therapy

Author

Shin-ichiro Masunaga, Hiroki Tanaka, Tsubasa Watanabe, Hiroyuki Michiue, Yosuke Nakagawa, Masaru Narabayashi, Yoshinori Sakurai, Minoru Suzuki, Koji Ono, Natsuko Kondo, and Yuko Kinashi

Subjects
0301 basic medicine, Chemistry, DNA damage, business.industry, Brain tumor, Linear energy transfer, Neutron radiation, medicine.disease, Neutron temperature, Ionizing radiation, 03 medical and health sciences, Neutron capture, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Cancer research, Radiology, Nuclear Medicine and imaging, Original Research Article, Irradiation, Nuclear medicine, business
Abstract

Aim In this study, we investigated γH2AX foci as markers of DSBs in normal brain and brain tumor tissue in mouse after BNCT. Background Boron neutron capture therapy (BNCT) is a particle radiation therapy in combination of thermal neutron irradiation and boron compound that specifically accumulates in the tumor. 10 B captures neutrons and produces an alpha ( 4 He) particle and a recoiled lithium nucleus ( 7 Li). These particles have the characteristics of extremely high linear energy transfer (LET) radiation and therefore have marked biological effects. High LET radiation causes severe DNA damage, DNA DSBs. As the high LET radiation induces complex DNA double strand breaks (DSBs), large proportions of DSBs are considered to remain unrepaired in comparison with exposure to sparsely ionizing radiation. Materials and methods We analyzed the number of γH2AX foci by immunohistochemistry 30 min or 24 h after neutron irradiation. Results In both normal brain and brain tumor, γH2AX foci induced by 10 B(n,α) 7 Li reaction remained 24 h after neutron beam irradiation. In contrast, γH2AX foci produced by γ-ray irradiation at contaminated dose in BNCT disappeared 24 h after irradiation in these tissues. Conclusion DSBs produced by 10 B(n,α) 7 Li reaction are supposed to be too complex to repair for cells in normal brain and brain tumor tissue within 24 h. These DSBs would be more difficult to repair than those by γ-ray. Excellent anti-tumor effect of BNCT may result from these unrepaired DSBs induced by 10 B(n,α) 7 Li reaction.

Published
2016
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41. Thermal Effects on Kerr Comb Generation in a CaF2 Whispering-Gallery Mode Microcavity

Author

Hiroki Itobe, Tomoya Kobatake, Yosuke Nakagawa, Takumi Kato, and Takasumi Tanabe

Subjects
Cavity resonance, lcsh:Applied optics. Photonics, Physics::Optics, Kerr optical frequency combs, 01 natural sciences, Thermal expansion, 010309 optics, Resonator, Optics, 0103 physical sciences, Thermal, solitons, lcsh:QC350-467, Electrical and Electronic Engineering, whispering gallery modes, 010306 general physics, Physics, Soliton pulse, business.industry, lcsh:TA1501-1820, resonators, Atomic and Molecular Physics, and Optics, Wavelength, Optoelectronics, Soliton, Whispering-gallery wave, business, lcsh:Optics. Light
Abstract

We numerically investigate the dynamics of Kerr comb generation in a calcium fluoride whispering gallery mode (WGM) microcavity taking thermal effects into account. Soliton pulse generation is investigated in the presence of thermooptic (TO) and thermal expansion (TE) effects and particularly when the TO effect is negative. We found that, with optimized cavity parameters, self-induced cavity resonance shifts resulting from a negative TO effect allow the system to generate a soliton pulse with no wavelength scanning or dynamic power optimization, which are usually needed to achieve a soliton pulse with silica and other WGM microcavity systems. A negative TO effect automatically tunes the cavity resonance so that the cavity will achieve a soliton state. The competition between the TO and TE effects is also investigated in detail.

Published
2016

42. Influence of Nose Radius on Surface Integrity in Ultra-precision Cylindrical Turning of Single-crystal Calcium Fluoride

Author

Hiroi Kangawa, Yosuke Nakagawa, Takasumi Tanabe, Yasuhiro Kakinuma, Yuta Mizumoto, and Hiroki Itobe

Subjects
Imagination, Engineering drawing, Materials science, Fabrication, Chemical substance, media_common.quotation_subject, 02 engineering and technology, 01 natural sciences, Optical micro-resonator, 010309 optics, Optics, 0103 physical sciences, Surface roughness, General Environmental Science, media_common, business.industry, Single crystal, Radius, 021001 nanoscience & nanotechnology, Surface integrity, General Earth and Planetary Sciences, 0210 nano-technology, business, Science, technology and society
Abstract

Optical micro-resonators attract interests as essential components to develop optical signal processing circuits which can reduce energy loss. Single-crystal calcium fluoride (CaF2) could be the most suitable material from a viewpoint of optical property. To satisfy high form accuracy and surface roughness, ultra-precision cylindrical turning (UPCT) is a feasible fabrication process. In previous research, it was indicated that the tool with sharper nose radius could make UPCT more stable and reduce subsurface damage. In this study, the tool with much smaller nose radius 0.01mm was applied, then, the influence on surface integrity was investigated by TEM observation.

Published
2016
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43. DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV

Author

Shin-Ichi Miyatake, Yoshinori Sakurai, Hasegawa Masatoshi, Minoru Suzuki, Natsuko Kondo, Yuki Hirota, Hiroki Tanaka, Yosuke Nakagawa, Tsubasa Watanabe, Koji Ono, Yuko Kinashi, Masaru Narabayashi, Shin-ichiro Masunaga, and Takeo Ohnishi

Subjects
0301 basic medicine, Time Factors, DNA Repair, DNA damage, Biophysics, Linear energy transfer, Boron Neutron Capture Therapy, Cell Line, DNA Ligase ATP, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Animals, Neutron, Irradiation, General Environmental Science, chemistry.chemical_classification, DNA ligase, Radiation, Chemistry, fungi, Radiochemistry, Dose-Response Relationship, Radiation, Neutron temperature, Neutron capture, 030104 developmental biology, 030220 oncology & carcinogenesis, DNA, DNA Damage
Abstract

Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

Published
2015
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44. Advances in boron neutron capture therapy (BNCT) at kyoto university - From reactor-based BNCT to accelerator-based BNCT

Author

Takushi Takata, Minoru Suzuki, Shin-ichiro Masunaga, Masaru Narabayashi, Hiroki Tanaka, Yosuke Nakagawa, Nozomi Fujimoto, Yuko Kinashi, Tsubasa Watanabe, Akira Maruhashi, Yoshinori Sakurai, Natsuko Kondo, and Koji Ono

Subjects
Particle therapy, medicine.medical_treatment, Nuclear engineering, Accelerator-based system, General Physics and Astronomy, Nuclear reactor, law.invention, Clinical study, Neutron capture, Boron neutron capture therapy, law, medicine, BNCT, Research reactor, Reactor-based system, Neutron irradiation
Abstract

At the Kyoto University Research Reactor Institute (KURRI), a clinical study of boron neutron capture therapy (BNCT) using a neutron irradiation facility installed at the research nuclear reactor has been regularly performed since February 1990. As of November 2014, 510 clinical irradiations were carried out using the reactor-based system. The world’s first accelerator-based neutron irradiation system for BNCT clinical irradiation was completed at this institute in early 2009, and the clinical trial using this system was started in 2012. A shift of BCNT from special particle therapy to a general one is now in progress. To promote and support this shift, improvements to the irradiation system, as well as its preparation, and improvements in the physical engineering and the medical physics processes, such as dosimetry systems and quality assurance programs, must be considered. The recent advances in BNCT at KURRI are reported here with a focus on physical engineering and medical physics topics., First online: 28 July 2015

Published
2015

45. Dispersion tailoring of a crystalline whispering gallery mode microcavity for optical Kerr frequency comb generation

Author

Yuta Mizumoto, Ryo Suzuki, Takasumi Tanabe, Wataru Yoshiki, Hiroyuki Sasada, Hiroki Itobe, Shoko Okuda, Yasuhiro Kakinuma, Mika Fuchida, and Yosuke Nakagawa

Subjects
Signal processing, Materials science, business.industry, Physics::Optics, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, Metrology, 010309 optics, Frequency comb, Quality (physics), Optics, Attenuation coefficient, 0103 physical sciences, Dispersion (optics), Optoelectronics, Whispering-gallery wave, 0210 nano-technology, business, Spectroscopy
Abstract

The generation of an optical Kerr comb in whispering gallery mode (WGM) microcavities has been investigated for applications in frequency metrology, precise spectroscopy, and signal processing. Optical Kerr combs are generated via parametric frequency conversion, thus a high quality factor (Q) is essential for lowering the threshold power, and this can be achieved with crystalline microcavities in, for example, calcium fluoride (CaF 2 ) because of the low absorption coefficient of this material. An optical Kerr comb with a wide span is needed to obtain frequency stabilization with the f-2f self-referencing method, which requires an anomalous dispersion [1]. We used a computer controlled precise cutting machine to fabricate a dispersion controlled CaF 2 microcavity with an anomalous dispersion to obtain exactly the same dispersion as we obtained in the numerical simulation.

Published
2017
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46. Evaluation of thermal neutron irradiation field using a cyclotron-based neutron source for alpha autoradiography

Author

Masaru Narabayashi, K. Ono, N. Fujimoto, Shin-ichiro Masunaga, T. Mitsumoto, Yoshinori Sakurai, Hiroki Tanaka, Minoru Suzuki, Natsuko Kondo, Yosuke Nakagawa, Tsubasa Watanabe, Yuko Kinashi, and Akira Maruhashi

Subjects
Neutrons, Radiation, Chemistry, Cyclotron, Radiochemistry, Neutron stimulated emission computed tomography, Boron Neutron Capture Therapy, Equipment Design, Cyclotrons, Alpha Particles, Radiation Dosage, Neutron temperature, law.invention, Equipment Failure Analysis, Neutron capture, Isotopes, Neutron probe, law, Neutron cross section, Autoradiography, Scattering, Radiation, Neutron source, Neutron, Radiometry, Boron
Abstract

It is important to measure the microdistribution of (10)B in a cell to predict the cell-killing effect of new boron compounds in the field of boron neutron capture therapy. Alpha autoradiography has generally been used to detect the microdistribution of (10)B in a cell. Although it has been performed using a reactor-based neutron source, the realization of an accelerator-based thermal neutron irradiation field is anticipated because of its easy installation at any location and stable operation. Therefore, we propose a method using a cyclotron-based epithermal neutron source in combination with a water phantom to produce a thermal neutron irradiation field for alpha autoradiography. This system can supply a uniform thermal neutron field with an intensity of 1.7×10(9) (cm(-2)s(-1)) and an area of 40mm in diameter. In this paper, we give an overview of our proposed system and describe a demonstration test using a mouse liver sample injected with 500mg/kg of boronophenyl-alanine.

Published
2014
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47. Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

Author

Minoru Suzuki, Yoshinori Sakurai, Tsubasa Watanabe, Hiroki Tanaka, Masaru Narabayashi, Shin-ichiro Masunaga, Yosuke Nakagawa, Akira Maruhashi, Koji Ono, Natsuko Kondo, and Keizo Tano

Subjects
Cancer Research, Pathology, medicine.medical_specialty, 10B-carrier, Bevacizumab, Population, nicotinamide, bevacizumab, chemistry.chemical_compound, Immunology and Microbiology (miscellaneous), medicine, education, quiescent cell, education.field_of_study, Nicotinamide, Oncogene, business.industry, Melanoma, Cancer, Articles, General Medicine, Cell cycle, medicine.disease, chemistry, boron neutron capture therapy, mild temperature hyperthermia, business, Bromodeoxyuridine, medicine.drug
Abstract

The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a (10)B-carrier [L-para-boronophenylalanine-(10)B (BPA) or sodium mercaptoundecahydrododecaborate-(10)B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a (10)B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide.

Published
2014
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48. The BRCA2 gene is a potential molecular target during 5-fluorouracil therapy in human oral cancer cells

Author

Takeo Ohnishi, Tadaaki Kirita, Natsuko Kondo, Akihisa Takahashi, Eiichiro Mori, Atsuhisa Kajihara, and Yosuke Nakagawa

Subjects
Antimetabolites, Antineoplastic, Cancer Research, Ku80, DNA Repair, Cell Survival, CHO Cells, Biology, medicine.disease_cause, Chinese hamster, XRCC2, Mice, Cricetulus, Cell Line, Tumor, Cricetinae, medicine, Animals, Humans, DNA Breaks, Double-Stranded, RNA, Small Interfering, BRCA2 Protein, Chinese hamster ovary cell, Cancer, General Medicine, Cell cycle, medicine.disease, biology.organism_classification, Oncology, Cancer cell, Cancer research, M Phase Cell Cycle Checkpoints, Mouth Neoplasms, RNA Interference, Fluorouracil, Carcinogenesis
Abstract

5-Fluorouracil (5-FU) is widely used in clinical cancer therapy. It is commonly used either alone or in combination with other drugs and/or radiation for head and neck, and other types of cancers. 5-FU induces DNA double-strand breaks (DSBs). Inhibition of the repair of 5-FU-induced DSBs may improve the therapeutic response in many tumors to this anticancer agent. The aim of the present study was to further our understanding of the pathways which are involved in the repair of 5-FU-induced DSBs. Cell survival after drug treatment was examined with colony forming assays using Chinese hamster lung fibroblast cells or Chinese hamster ovary cell lines which are deficient in DSB repair pathways involving the homologous recombination repair-related genes BRCA2 and XRCC2, and the non-homologous end joining repair-related genes DNA-PKcs and Ku80. It was found that BRCA2 was involved in such repair, and may be effectively targeted to inhibit the repair of 5-FU-induced damage. Observations showed that knockdown of BRCA2 using small interference RNA suppression increased the sensitivity to 5-FU of human oral cancer cell lines (SAS and HSC3). These findings suggest that downregulation of BRCA2 may be useful for sensitizing tumor cells during 5-FU chemotherapy.

Published
2014
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49. Continuous Glucose Monitoring Effects on Blood Glucose Management in Diabetic Patients on Hemodialysis-Results in the Patients from Single Hospital

Author

Masafumi Fukagawa, Yosuke Nakagawa, Nobumichi Saito, Masao Toyoda, and Moritsugu Kimura

Subjects
medicine.medical_specialty, endocrine system diseases, Diet therapy, business.industry, Insulin, medicine.medical_treatment, 030232 urology & nephrology, nutritional and metabolic diseases, 030209 endocrinology & metabolism, Type 2 diabetes, Hypoglycemia, Bioinformatics, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Postprandial, Internal medicine, Diabetes mellitus, medicine, Hemodialysis, business, Glycemic
Abstract

Objective: Diabetic patients on hemodialysis (HD) are prone to develop treatment-related serious hypoglycemia due to poor renal clearance of insulin and augmented drug efficacy, often resulting in withdrawal of insulin. Consequently, many patients are erroneously switched to oral glucose-lowering agents or diet therapy alone, without self-monitoring of blood glucose (SMBG). Therefore, we hypothesized that continuous glucose monitoring (CGM) may be useful for optimizing glycemic control and clinical management in diabetic patients on HD. Methods: In this study, 8 type 2 diabetic patients on HD who did not use SMBG after withdrawal of insulin and start of oral glucose-lowering agents, were recruited to measure and evaluate blood glucose with CGM. These patients thought to be controlled within glycemic control target proposed by the Japanese Society for Dialysis Therapy. Predialysis casual plasma glucose level (or 2-h postprandial plasma glucose level) of 200 mg/dl) after HD. Conclusions: Diabetic patients on HD require careful monitoring with SMBG, CGM, and direct measurement of postprandial blood glucose level during HD before any decision is made regarding withdrawal of insulin and cessation of SMBG.

Published
2017
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50. Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [

Author

Tsubasa, Watanabe, Yoshihide, Hattori, Youichiro, Ohta, Miki, Ishimura, Yosuke, Nakagawa, Yu, Sanada, Hiroki, Tanaka, Satoshi, Fukutani, Shin-Ichiro, Masunaga, Masahiro, Hiraoka, Koji, Ono, Minoru, Suzuki, and Mitsunori, Kirihata

Subjects
inorganic chemicals, Fluorine Radioisotopes, FBPA, Boron Neutron Capture Therapy, Disease Models, Animal, Mice, Boron concentration, Neoplasms, Positron-Emission Tomography, Animals, Female, Tissue Distribution, L-BPA, [18F]-L-FBPA, Research Article
Abstract

Background Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. L-p-Boronophenylalanine (L-BPA) is a boron compound now widely used in clinical situations. Determination of the boron distribution is required for successful BNCT prior to neutron irradiation. Thus, positron emission tomography with [18F]-L-FBPA, an 18F-labelled radiopharmaceutical analogue of L-BPA, was developed. However, several differences between L-BPA and [18F]-L-FBPA have been highlighted, including the different injection doses and administration protocols. The purpose of this study was to clarify the equivalence between L-BPA and [19F]-L-FBPA as alternatives to [18F]-L-FBPA. Methods SCC-VII was subcutaneously inoculated into the legs of C3H/He mice. The same dose of L-BPA or [19F]-L-FBPA was subcutaneously injected. The time courses of the boron concentrations in blood, tumour tissue, and normal tissue were compared between the groups. Next, we administered the therapeutic dose of L-BPA or the same dose of [19F]-L-FBPA by continuous infusion and compared the effects of the administration protocol on boron accumulation in tissues. Results There were no differences between L-BPA and [19F]-L-FBPA in the transition of boron concentrations in blood, tumour tissue, and normal tissue using the same administration protocol. However, the normal tissue to blood ratio of the boron concentrations in the continuous-infusion group was lower than that in the subcutaneous injection group. Conclusions No difference was noted in the time course of the boron concentrations in tumour tissue and normal tissues between L-BPA and [19F]-L-FBPA. However, the administration protocol had effects on the normal tissue to blood ratio of the boron concentration. In estimating the BNCT dose in normal tissue by positron emission tomography (PET), we should consider the possible overestimation of the normal tissue to blood ratio of the boron concentrations derived from the values measured by PET on dose calculation. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2913-x) contains supplementary material, which is available to authorized users.

Published
2016

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