41 results on '"Utsunomiya J"'
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2. Germ line mutations of hMSH2 and hMLH1 genes in Japanese families with hereditary nonpolyposis colorectal cancer (HNPCC): usefulness of DNA analysis for screening and diagnosis of HNPCC patients
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Miyaki, M., Konishi, M., Muraoka, M., Kikuchi-Yanoshita, R., Tanaka, K., Iwama, T., Mori, T., Koike, M., Ushio, K., Chiba, M., Nomizu, S., and Utsunomiya, J.
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- 1995
- Full Text
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3. Water and electrolyte balance after ileal J pouch-anal anastomosis in ulcerative colitis and familial adenomatous polyposis
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Okamoto, T., Kusunoki, M., Kusuhara, K., Yamamura, T., and Utsunomiya, J.
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- 1995
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4. Transitory elevation of serum amylase levels after restorative proctocolectomy
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Sakanoue, Y., Kusunoki, M., Shoji, Y., Yanagi, H., Yamamura, T., and Utsunomiya, J.
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- 1992
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5. Reduction of the effluent volume in high-output ileostomy patients by a somatostatin analogue, SMS 201-995
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Kusuhara, K., Kusunoki, M., Okamoto, T., Sakanoue, Y., and Utsunomiya, J.
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- 1992
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- View/download PDF
6. Restorative proctocolectomy with ileal reservoir
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Dozois, R. R., Goldberg, S. M., Rothenberger, D. A., Utsunomiya, J., Nicholls, R. J., Cohen, Z., Hultén, L. A. G., Moskowitz, R. L., and Williams, N. S.
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- 1986
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7. Planning the human variome project: the Spain report.
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Kaput, J., Cotton, R.G., Hardman, L., Watson, M., Aqeel, A.I. Al, Al-Aama, J.Y., Al-Mulla, F., Alonso, S., Aretz, S., Auerbach, A.D., Bapat, B., Bernstein, I.T., Bhak, J., Bleoo, S.L., Blocker, H., Brenner, S.E., Burn, J., Bustamante, M., Calzone, R., Cambon-Thomsen, A., Cargill, M., Carrera, P., Cavedon, L., Cho, Y.S., Chung, Y.J., Claustres, M., Cutting, G., Dalgleish, R., Dunnen, J.T. den, Diaz, C., Dobrowolski, S., Santos, M.R. dos, Ekong, R., Flanagan, S.B., Flicek, P., Furukawa, Y., Genuardi, M., Ghang, H., Golubenko, M.V., Greenblatt, M.S., Hamosh, A., Hancock, J.M., Hardison, R., Harrison, T.M., Hoffmann, R., Horaitis, R., Howard, H.J., Barash, C.I., Izagirre, N., Jung, J., Kojima, T., Laradi, S., Lee, Y.S., Lee, J.Y., Gil-da-Silva-Lopes, V.L., Macrae, F.A., Maglott, D., Marafie, M.J., Marsh, S.G., Matsubara, Y., Messiaen, L.M., Moslein, G., Netea, M.G., Norton, M.L., Oefner, P.J., Oetting, W.S., O'Leary, J.C., Ramirez, A.M. de, Paalman, M.H., Parboosingh, J., Patrinos, G.P., Perozzi, G., Phillips, I.R., Povey, S., Prasad, S., Qi, M., Quin, D.J., Ramesar, R.S., Richards, C.S., Savige, J., Scheible, D.G., Scott, R.J., Seminara, D., Shephard, E.A., Sijmons, R.H., Smith, T.D., Sobrido, M.J., Tanaka, T., Tavtigian, S.V., Taylor, G.R., Teague, J., Topel, T., Ullman-Cullere, M., Utsunomiya, J., Kranen, H.J. van, Vihinen, M., Webb, E., Weber, T.K., Yeager, M., Kaput, J., Cotton, R.G., Hardman, L., Watson, M., Aqeel, A.I. Al, Al-Aama, J.Y., Al-Mulla, F., Alonso, S., Aretz, S., Auerbach, A.D., Bapat, B., Bernstein, I.T., Bhak, J., Bleoo, S.L., Blocker, H., Brenner, S.E., Burn, J., Bustamante, M., Calzone, R., Cambon-Thomsen, A., Cargill, M., Carrera, P., Cavedon, L., Cho, Y.S., Chung, Y.J., Claustres, M., Cutting, G., Dalgleish, R., Dunnen, J.T. den, Diaz, C., Dobrowolski, S., Santos, M.R. dos, Ekong, R., Flanagan, S.B., Flicek, P., Furukawa, Y., Genuardi, M., Ghang, H., Golubenko, M.V., Greenblatt, M.S., Hamosh, A., Hancock, J.M., Hardison, R., Harrison, T.M., Hoffmann, R., Horaitis, R., Howard, H.J., Barash, C.I., Izagirre, N., Jung, J., Kojima, T., Laradi, S., Lee, Y.S., Lee, J.Y., Gil-da-Silva-Lopes, V.L., Macrae, F.A., Maglott, D., Marafie, M.J., Marsh, S.G., Matsubara, Y., Messiaen, L.M., Moslein, G., Netea, M.G., Norton, M.L., Oefner, P.J., Oetting, W.S., O'Leary, J.C., Ramirez, A.M. de, Paalman, M.H., Parboosingh, J., Patrinos, G.P., Perozzi, G., Phillips, I.R., Povey, S., Prasad, S., Qi, M., Quin, D.J., Ramesar, R.S., Richards, C.S., Savige, J., Scheible, D.G., Scott, R.J., Seminara, D., Shephard, E.A., Sijmons, R.H., Smith, T.D., Sobrido, M.J., Tanaka, T., Tavtigian, S.V., Taylor, G.R., Teague, J., Topel, T., Ullman-Cullere, M., Utsunomiya, J., Kranen, H.J. van, Vihinen, M., Webb, E., Weber, T.K., and Yeager, M.
- Abstract
Contains fulltext : 81952.pdf (publisher's version ) (Closed access), The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008.
- Published
- 2009
8. Planning the Human Variome Project: The Spain Report
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Kaput, J, Cotton, RGH, Hardman, L, Watson, M, Al Aqeel, AI, Al-Aama, JY, Al-Mulla, F, Alonso, S, Aretz, S, Auerbach, AD, Bapat, B, Bernstein, IT, Bhak, J, Bleoo, SL, Bloecker, H, Brenner, SE, Burn, J, Bustamante, M, Calone, R, Cambon-Thomsen, A, Cargill, M, Carrera, P, Cavedon, L, Cho, YS, Chung, Y-J, Claustres, M, Cutting, G, Dalgleish, R, den Dunnen, JT, Diaz, C, Dobrowolski, S, dos Santos, MRN, Ekong, R, Flanagan, SB, Flicek, P, Furukawa, Y, Genuardi, M, Ghang, H, Golubenko, MV, Greenblatt, MS, Hamosh, A, Hancock, JM, Hardison, R, Harrison, TM, Hoffmann, R, Horaitis, R, Howard, HJ, Barash, CI, Izagirre, N, Jung, J, Kojima, T, Laradi, S, Lee, Y-S, Lee, J-Y, Gil-da-Silva-Lopes, VL, Macrae, FA, Maglott, D, Marafie, MJ, Marsh, SGE, Matsubara, Y, Messiaen, LM, Moeslein, G, Netea, MG, Norton, ML, Oefner, PJ, Oetting, WS, O'Leary, JC, Oller de Ramirez, AM, Paalman, MH, Parboosingh, J, Patrinos, GP, Perozzi, G, Phillips, IR, Povey, S, Prasad, S, Qi, M, Quin, DJ, Ramesar, RS, Richards, CS, Savige, J, Scheible, DG, Scott, RJ, Seminara, D, Shephard, EA, Sijmons, RH, Smith, TD, Sobrido, M-J, Tanaka, T, Tavtigian, SV, Taylor, GR, Teague, J, Toepel, T, Ullman-Cullere, M, Utsunomiya, J, van Kranen, HJ, Vihinen, M, Webb, E, Weber, TK, Yeager, M, Yeom, YI, Yim, S-H, Yoo, H-S, Kaput, J, Cotton, RGH, Hardman, L, Watson, M, Al Aqeel, AI, Al-Aama, JY, Al-Mulla, F, Alonso, S, Aretz, S, Auerbach, AD, Bapat, B, Bernstein, IT, Bhak, J, Bleoo, SL, Bloecker, H, Brenner, SE, Burn, J, Bustamante, M, Calone, R, Cambon-Thomsen, A, Cargill, M, Carrera, P, Cavedon, L, Cho, YS, Chung, Y-J, Claustres, M, Cutting, G, Dalgleish, R, den Dunnen, JT, Diaz, C, Dobrowolski, S, dos Santos, MRN, Ekong, R, Flanagan, SB, Flicek, P, Furukawa, Y, Genuardi, M, Ghang, H, Golubenko, MV, Greenblatt, MS, Hamosh, A, Hancock, JM, Hardison, R, Harrison, TM, Hoffmann, R, Horaitis, R, Howard, HJ, Barash, CI, Izagirre, N, Jung, J, Kojima, T, Laradi, S, Lee, Y-S, Lee, J-Y, Gil-da-Silva-Lopes, VL, Macrae, FA, Maglott, D, Marafie, MJ, Marsh, SGE, Matsubara, Y, Messiaen, LM, Moeslein, G, Netea, MG, Norton, ML, Oefner, PJ, Oetting, WS, O'Leary, JC, Oller de Ramirez, AM, Paalman, MH, Parboosingh, J, Patrinos, GP, Perozzi, G, Phillips, IR, Povey, S, Prasad, S, Qi, M, Quin, DJ, Ramesar, RS, Richards, CS, Savige, J, Scheible, DG, Scott, RJ, Seminara, D, Shephard, EA, Sijmons, RH, Smith, TD, Sobrido, M-J, Tanaka, T, Tavtigian, SV, Taylor, GR, Teague, J, Toepel, T, Ullman-Cullere, M, Utsunomiya, J, van Kranen, HJ, Vihinen, M, Webb, E, Weber, TK, Yeager, M, Yeom, YI, Yim, S-H, and Yoo, H-S
- Abstract
The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008.
- Published
- 2009
9. Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer
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Konishi, M, primary, Kikuchi-Yanoshita, R, additional, Tanaka, K, additional, Muraoka, M, additional, Onda, A, additional, Okumura, Y, additional, Kishi, N, additional, Iwama, T, additional, Mori, T, additional, Koike, M, additional, Ushio, K, additional, Chiba, M, additional, Nomizu, S, additional, Konishi, F, additional, Utsunomiya, J, additional, and Miyaki, M, additional
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- 1996
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10. Thermal design for high-speed high-density multichip module
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Handa, T., primary, Iida, S., additional, and Utsunomiya, J., additional
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- 1993
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11. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients.
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Miyoshi, Y, primary, Ando, H, additional, Nagase, H, additional, Nishisho, I, additional, Horii, A, additional, Miki, Y, additional, Mori, T, additional, Utsunomiya, J, additional, Baba, S, additional, and Petersen, G, additional
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- 1992
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12. Correlation between protein kinase C activity and histopathological criteria in human colorectal adenoma
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Kusunoki, M, primary, Hatada, T, additional, Sakanoue, Y, additional, Yanagi, H, additional, and Utsunomiya, J, additional
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- 1992
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13. Fecal and stomal bile acid composition after ileostomy or ileoanal anastomosis in patients with chronic ulcerative colitis and adenomatosis coli
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Natori, H, primary, Utsunomiya, J, additional, Yamamura, T, additional, Benno, Y, additional, and Uchida, K, additional
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- 1992
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14. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients
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Takesada Mori, Yusuke Nakamura, Utsunomiya J, Yasuo Miyoshi, Shozo Baba, Hiroshi Ando, Gloria M. Petersen, Kenneth W. Kinzler, Stanley R. Hamilton, Yoshio Miki, Isamu Nishisho, Hiroki Nagase, Bert Vogelstein, and Akira Horii
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Adenoma ,Genetic Linkage ,Adenomatous polyposis coli ,Molecular Sequence Data ,Nonsense mutation ,medicine.disease_cause ,Polymerase Chain Reaction ,Frameshift mutation ,Familial adenomatous polyposis ,Japan ,medicine ,Humans ,Missense mutation ,Genes, Tumor Suppressor ,Codon ,Frameshift Mutation ,Genetics ,Mutation ,Multidisciplinary ,Base Sequence ,biology ,Point mutation ,DNA, Neoplasm ,Exons ,medicine.disease ,United States ,Stop codon ,Adenomatous Polyposis Coli ,biology.protein ,Chromosomes, Human, Pair 5 ,Chromosome Deletion ,Research Article - Abstract
We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5' half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis.
15. Urinary II-Deoxy-17-oxosteroids in British and Japanese Women with Reference to the Incidence of Breast Cancer.
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BULBROOK, R. D., THOMAS, B. S., and UTSUNOMIYA, J.
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- 1964
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16. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study
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Seçil Aksoy, Michael O. Woods, Heinric Williams, Bruno Buecher, Finlay A. Macrae, Lotte N. Krogh, Jay Qiu, Wan K.W. Juhari, Jan T. Lowery, Anne-Marie Gerdes, Magnus von Knebel Doeberitz, Luigi Ricciardiello, Karsten Schulmann, Jose Luis Soto, Kristina Lagerstedt-Robinson, Kiwamu Akagi, Raj Ramesar, Uffe Birk Jensen, Angel Alonso, Robert Hüneburg, Olivier Caron, Michel Longy, Jan Lubinski, Kate Green, Annabel Goodwin, D. Gareth Evans, Julie Wods, Leigha Senter, Matthew F. Kalady, Mark Clendenning, Barbara A. Leggett, Ravindran Ankathil, Swati G. Patel, Julian Barwell, Katherine M. Tucker, Grant Lee, Pascaline Berthet, Dawn M. Nixon, Sonia S. Kupfer, Naohiro Tomita, Susan Parry, Trinidad Caldés, Robert W. Haile, Edenir Inêz Palmero, Karin Alvarez, Cassandra B. Nichols, Mark A. Jenkins, N. Jewel Samadder, Loic LeMarchand, John Burn, Francisco Lopez, Rodney J. Scott, Pierre Laurent-Puig, Julie Arnold, Christina Therkildsen, Hans K. Schackert, Pilar Garre, Reinhard Buettner, Adriana Della Valle, Patricia Esperon, Wolff Schmiegel, Karl Heinimann, Inge Bernstein, Matthias Kloor, Nicoline Hoogerbrugge, Rui Manuel Reis, Fränzel J.B. Van Duijnhoven, Christoph Engel, Mohd Nizam Zahary, Sylviane Olschwang, Sapna Syngal, Valérie Bonadona, Nicholas Pachter, Matilde Navarro, Albert de la Chapelle, Beate Betz, Jukka-Pekka Mecklin, Catherine Noguès, Elena M. Stoffel, Toni T. Seppälä, Chrystelle Colas, Anneke Lucassen, Allan D. Spigelman, Youenn Drouet, Elisa J. Cops, Uri Ladabaum, Steve Thibodeau, Jeffrey N. Weitzel, Fiona Lalloo, Patrick J. Morrison, Maurizio Genuardi, Kohji Tanakaya, Patrick M. Lynch, Frederik J. Hes, William D. Foulkes, Carmen Guillén-Ponce, Jenny von Salomé, Emilia Rogoża-Janiszewska, Andrew Latchford, John L. Hopper, Carrie Snyder, Verónica Barca-Tierno, Gabriela Möslein, Lauren M. Gima, Melissa C. Southey, Paul A. James, Marion Dhooge, Claudia Perne, Steven Gallinger, Heather Hampel, Amanda B. Spurdle, Ingrid Winship, Emmanuelle Fourme, Rish K. Pai, Daniela Turchetti, Marta Pineda, Jürgen Weitz, James Hill, Daniel D. Buchanan, Carlos A. Vaccaro, Noralane M. Lindor, Rachel Pearlman, Pål Møller, Christian P. Strassburg, Jane C. Figueiredo, Aída Falcón de Vargas, Silke Zachariae, Karolin Bucksch, Joanne Ngeow, Silke Redler, Henrik Okkels, Maija R.J. Kohonen-Corish, Hans F. A. Vasen, Verena Steinke-Lange, Roselyne Guimbaud, Deepak Vangala, Isabelle Coupier, Nils Rahner, Berrin Tunca, Sanne W. Bajwa-ten Broeke, Niels de Wind, Sophie Lejeune, José Gaston Guillem, Karin Wadt, Polly A. Newcomb, Elke Holinski-Feder, Florencia Neffa, Rodrigo Santa Cruz Guindalini, Paul E. Wise, Julian R. Sampson, Graham Casey, Lene Juel Rasmussen, Rolf H. Sijmons, Tadeusz Dębniak, Ann-Sofie Backman, Joji Utsunomiya, Melyssa Aronson, Aung Ko Win, Yves-Jean Bignon, Judy W. C. Ho, Robyn L. Ward, Mev Dominguez-Valentin, Karolina Malińska, Elizabeth E. Half, John-Paul Plazzer, Marjolijn J. L. Ligtenberg, Rachel Austin, Nicola K. Poplawski, Marcia Cruz-Correa, Nagahide Matsubara, Charlotte Kvist Lautrup, Thomas Hansen, Tatsuro Yamaguchi, Thomas John, David J. Amor, Ilana Solomon, Yun-Hee Choi, Meghan J. van Wanzeele, Rakefet Shtoyerman, Vanessa Huntley, Maartje Nielsen, Deborah Neklason, Kevin J. Monahan, Gülçin Tezcan, Stefan Aretz, Talya Boisjoli, Sophie Giraud, Thierry Frebourg, Christophe Rosty, Heike Görgens, Lone Sunde, Allyson Templeton, Jacob Nattermann, Mala Pande, Joan Brunet, Nancy Uhrhammer, James M. Church, Florencia Spirandelli, Laurent Briollais, James G. Dowty, Jeanette C. Reece, Rachel Susman, Fay Kastrinos, Kirsi Pylvänäinen, Gabriel Capellá, Helène Schuster, Min H. Chew, Markus Loeffler, Christine Lasset, Michael J. Hall, Capuccine Delnatte, Floor A. Duijkers, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Digital Precision Cancer Medicine (iCAN), ATG - Applied Tumor Genomics, HUS Abdominal Center, Clinical sciences, Medical Genetics, Win A.K., Dowty J.G., Reece J.C., Lee G., Templeton A.S., Plazzer J.-P., Buchanan D.D., Akagi K., Aksoy S., Alonso A., Alvarez K., Amor D.J., Ankathil R., Aretz S., Arnold J.L., Aronson M., Austin R., Backman A.-S., Bajwa-ten Broeke S.W., Barca-Tierno V., Barwell J., Bernstein I., Berthet P., Betz B., Bignon Y.-J., Boisjoli T., Bonadona V., Briollais L., Brunet J., Bucksch K., Buecher B., Buettner R., Burn J., Caldes T., Capella G., Caron O., Casey G., Chew M.H., Choi Y.-H., Church J., Clendenning M., Colas C., Cops E.J., Coupier I., Cruz-Correa M., de la Chapelle A., de Wind N., Debniak T., Della Valle A., Delnatte C., Dhooge M., Dominguez-Valentin M., Drouet Y., Duijkers F.A., Engel C., Esperon P., Evans D.G., Falcon de Vargas A., Figueiredo J.C., Foulkes W., Fourme E., Frebourg T., Gallinger S., Garre P., Genuardi M., Gerdes A.-M., Gima L.M., Giraud S., Goodwin A., Gorgens H., Green K., Guillem J., Guillen-Ponce C., Guimbaud R., Guindalini R.S.C., Half E.E., Hall M.J., Hampel H., Hansen T.V.O., Heinimann K., Hes F.J., Hill J., Ho J.W.C., Holinski-Feder E., Hoogerbrugge N., Huneburg R., Huntley V., James P.A., Jensen U.B., John T., Juhari W.K.W., Kalady M., Kastrinos F., Kloor M., Kohonen-Corish M.R., Krogh L.N., Kupfer S.S., Ladabaum U., Lagerstedt-Robinson K., Lalloo F., Lasset C., Latchford A., Laurent-Puig P., Lautrup C.K., Leggett B.A., Lejeune S., LeMarchand L., Ligtenberg M., Lindor N., Loeffler M., Longy M., Lopez F., Lowery J., Lubinski J., Lucassen A.M., Lynch P.M., Malinska K., Matsubara N., Mecklin J.-P., Moller P., Monahan K., Morrison P.J., Nattermann J., Navarro M., Neffa F., Neklason D., Newcomb P.A., Ngeow J., Nichols C., Nielsen M., Nixon D.M., Nogues C., Okkels H., Olschwang S., Pachter N., Pai R.K., Palmero E.I., Pande M., Parry S., Patel S.G., Pearlman R., Perne C., Pineda M., Poplawski N.K., Pylvanainen K., Qiu J., Rahner N., Ramesar R., Rasmussen L.J., Redler S., Reis R.M., Ricciardiello L., Rogoza-Janiszewska E., Rosty C., Samadder N.J., Sampson J.R., Schackert H.K., Schmiegel W., Schulmann K., Schuster H., Scott R., Senter L., Seppala T.T., Shtoyerman R., Sijmons R.H., Snyder C., Solomon I.B., Soto J.L., Southey M.C., Spigelman A., Spirandelli F., Spurdle A.B., Steinke-Lange V., Stoffel E.M., Strassburg C.P., Sunde L., Susman R., Syngal S., Tanakaya K., Tezcan G., Therkildsen C., Thibodeau S., Tomita N., Tucker K.M., Tunca B., Turchetti D., Uhrhammer N., Utsunomiya J., Vaccaro C., van Duijnhoven F.J.B., van Wanzeele M.J., Vangala D.B., Vasen H.F.A., von Knebel Doeberitz M., von Salome J., Wadt K.A.W., Ward R.L., Weitz J., Weitzel J.N., Williams H., Winship I., Wise P.E., Wods J., Woods M.O., Yamaguchi T., Zachariae S., Zahary M.N., Hopper J.L., Haile R.W., Macrae F.A., Moslein G., and Jenkins M.A.
- Subjects
0301 basic medicine ,Proband ,Oncology ,Male ,Heredity ,DNA mismatch repair ,[SDV]Life Sciences [q-bio] ,SUSCEPTIBILITY ,Settore MED/03 - GENETICA MEDICA ,0302 clinical medicine ,Residence Characteristics ,Risk Factors ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,PMS2 ,ComputingMilieux_MISCELLANEOUS ,MLH1 ,Age Factors ,Middle Aged ,Penetrance ,Lynch syndrome ,3. Good health ,Pedigree ,Phenotype ,030220 oncology & carcinogenesis ,Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis ,Female ,Adult ,medicine.medical_specialty ,PENETRANCE ,congenital, hereditary, and neonatal diseases and abnormalities ,GENES ,3122 Cancers ,colorectal cancer ,BREAST ,Risk Assessment ,03 medical and health sciences ,Sex Factors ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Retrospective Studies ,business.industry ,MUTATIONS ,Cancer ,medicine.disease ,digestive system diseases ,MSH2 ,MSH6 ,MODEL ,INDIVIDUALS ,030104 developmental biology ,Lynch Syndrome ,Gene-Environment Interaction ,business - Abstract
Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (p 0 center dot 0001 for each of the three three continents). These familial risk factors resulted in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and onlyBackground Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence. Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero. Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and only 10-19% having a penetrance of 40-60%. Interpretation Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessments for precision prevention and early detection of colorectal cancer for people with Lynch syndrome. Funding National Health and Medical Research Council, Australia. Copyright (c) 2021 Elsevier Ltd. All rights reserved.Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.
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- 2021
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17. Surgery for ulcerative colitis in 1,000 patients.
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Ikeuchi H, Uchino M, Matsuoka H, Bando T, Matsumoto T, Tomita N, Syoji Y, Kusunoki M, Yamamura T, and Utsunomiya J
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- Adolescent, Adult, Aged, Aged, 80 and over, Cause of Death, Child, Colitis, Ulcerative physiopathology, Colonic Pouches pathology, Elective Surgical Procedures statistics & numerical data, Female, Humans, Male, Middle Aged, Postoperative Complications etiology, Time Factors, Treatment Outcome, Young Adult, Anastomosis, Surgical statistics & numerical data, Colitis, Ulcerative surgery, Colonic Pouches statistics & numerical data
- Abstract
Background and Aims: Ileal pouch-anal anastomosis (IPAA) has become the standard treatment for patients with ulcerative colitis (UC) who ultimately require a colectomy. Herein, we report results of our 24-year experience with that surgical method at our hospital., Patients and Methods: Data were collected regarding surgical procedures and postoperative pathologic diagnoses for 1,000 UC patients, with early and late complications also noted. The pouch functioning rate was calculated using the Kaplan-Meier method., Results: We performed 1,000 operations for UC over a 24-year period. The mean patient age at the time of operation was 35 years, and the most frequent indication for a colectomy was intractable disease. The overall rates of pouch success after 10 and 20 years were 97% and 89%, respectively. During the study period, 944 patients underwent IPAA at our hospital, of whom 12 (1.3%) were eventually diagnosed with Crohn's disease (CD). Pouch success was higher in patients with UC, with a functioning ileal pouch after 10 and 20 years found in 97% and 92%, respectfully, whereas the proportions of patients with CD and a functioning ileal pouch were lower at 82% and 20%, respectively (p < 0.01)., Conclusion: A restorative proctocolectomy with an IPAA is a safe procedure, with low rates of mortality and major morbidity. We do not recommend routine application of IPAA in any subset of patients with known CD.
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- 2010
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18. GENETICS. The Human Variome Project.
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Cotton RG, Auerbach AD, Axton M, Barash CI, Berkovic SF, Brookes AJ, Burn J, Cutting G, den Dunnen JT, Flicek P, Freimer N, Greenblatt MS, Howard HJ, Katz M, Macrae FA, Maglott D, Möslein G, Povey S, Ramesar RS, Richards CS, Seminara D, Smith TD, Sobrido MJ, Solbakk JH, Tanzi RE, Tavtigian SV, Taylor GR, Utsunomiya J, and Watson M
- Subjects
- Databases, Factual, Human Genome Project, Humans, Interdisciplinary Communication, International Cooperation, Databases, Genetic, Genetic Variation, Genome, Human, Mutation, Nervous System Diseases genetics
- Abstract
An ambitious plan to collect, curate, and make accessible information on genetic variations affecting human health is beginning to be realized.
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- 2008
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19. Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome.
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Miyaki M, Iijima T, Hosono K, Ishii R, Yasuno M, Mori T, Toi M, Hishima T, Shitara N, Tamura K, Utsunomiya J, Kobayashi N, Kuroki T, and Iwama T
- Subjects
- AMP-Activated Protein Kinase Kinases, Adenoma genetics, Adenoma pathology, Carcinoma genetics, Carcinoma pathology, Gastrointestinal Neoplasms genetics, Gastrointestinal Neoplasms pathology, Germ-Line Mutation, Hamartoma genetics, Hamartoma pathology, Humans, Loss of Heterozygosity, Peutz-Jeghers Syndrome complications, Peutz-Jeghers Syndrome pathology, beta Catenin, Cytoskeletal Proteins genetics, Mutation, Peutz-Jeghers Syndrome genetics, Protein Serine-Threonine Kinases genetics, Trans-Activators
- Abstract
Peutz-Jeghers syndrome (PJS) is characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous melanin deposition, and increased risk of cancer, mainly in the gastrointestinal tract. We examined mutations of the LKB1, beta-catenin, APC, K-ras, and p53 genes in 27 gastrointestinal hamartomatous polyps from 10 patients in nine PJS families. Of these hamartomatous polyps, one intestinal polyp had an adenomatous lesion, and one gastric polyp contained adenomatous and carcinomatous lesions. Germ-line mutations of the LKB1 gene were detected in six PJS families. Somatic mutations of the LKB1 gene were found in 5 polyps, whereas loss of heterozygosity (LOH) at the LKB1 locus at 19p was seen in 14 other polyps. In adenomatous lesions microdissected from hamartomatous polyps, both beta-catenin mutation and 19p LOH were detected. Furthermore, a carcinomatous lesion in a gastric hamartomatous polyp was found to contain a mutation of the p53 gene and LOH at the p53 locus in addition to LOH at the LKB1 locus and a beta-catenin mutation. K-ras mutations were detected in a few polyps, whereas no APC mutation or 5q LOH was detected in hamartomatous polyps. These results suggest that gastrointestinal hamartomatous polyps in PJS patients develop through inactivation of the LKB1 gene by germ-line mutation plus somatic mutation or LOH of the unaffected LKB1 allele, and that additional mutations of the beta-catenin gene and p53 gene convert hamartomatous polyps into adenomatous and carcinomatous lesions.
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- 2000
20. Anticipation phenomenon in familial adenomatous polyposis:an analysis of its origin.
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Iwama T and Utsunomiya J
- Abstract
AIM:To analyze the origin of the anticipation phenomenon, which means earlier death in successive generation in familial adenomatous polyposis.METHODS:The study subjects were 2161 patients with familial adenomatous polyposis and their 7465 first degree relatives who were members of 750 families registered at our Polyposis Registry. The ages at death and cumulative mortality rates in theparent, the proband, and the child generations were compared for both all subjects and the patients alone.RESULTS:In the patients over 5 years of age, the mean age at death was 50.9 years for the parent, 42.3 years for the proband, and 33.3 years for the child generations, respectively a(c)(P < 0.001). The deceased rates in the three generations were 90.7%, 51.3% and 23.1% of the patients, respectively, and this difference was the main cause of the anticipation measured by parent-child paring method. The cumulative mortality rates for all subjects failed to show anticipation, however the cumulative mortality rates for the patients showed the anticipation. The anticipation phenomenon was shown by any parent-child pairing methods for the deceased patients. Other important causes of the anticipation were different proportion of causes of death between generations a(c)(P <0.001), and a low proportion of detected or deceased patients (P < 0.001) in the child generation.CONCLUSION:Anticipation in familial adenomatous polyposis may be caused by parent child paring methods as well as several intergenerational biases.
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- 2000
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21. The relationship between frequencies of extracolonic manifestations and the position of APC germline mutation in patients with familial adenomatous polyposis.
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Enomoto M, Konishi M, Iwama T, Utsunomiya J, Sugihara KI, and Miyaki M
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- Adenoma etiology, Adenomatous Polyposis Coli complications, Adenomatous Polyposis Coli pathology, Adolescent, Adult, DNA Mutational Analysis, Duodenal Diseases etiology, Female, Genotype, Humans, Male, Middle Aged, Pedigree, Phenotype, Polyps, Stomach Neoplasms etiology, Adenoma genetics, Adenomatous Polyposis Coli genetics, Cytoskeletal Proteins genetics, DNA, Neoplasm genetics, Duodenal Diseases genetics, Genes, APC, Germ-Line Mutation, Stomach Neoplasms genetics
- Abstract
Background: Familial adenomatous polyposis (FAP) patients develop various extracolonic lesions; however, the relationship between germline mutation of the APC gene and extracolonic manifestations is mostly unknown. To examine the genotype-phenotype relationship, we compared the APC mutation and clinical data., Methods: Germline mutations from codon 157 to 1465 of the APC gene were identified in 39 families of FAP and clinical data were collected from 80 patients of these families. Germline mutations were classified into two groups: mutations from exon 4 to 9 (codon 157 to 416, Group 1) and those from exon 10 to 15H (codon 564 to 1465, Group 2). The complication rates of extracolonic manifestations were compared between these two groups., Results: Frequencies of duodenal polyps and gastric adenomas in Group 2 were higher than those in Group 1 (p < 0.0001 and p < 0.0004, respectively) and development of osteoma was more frequent in Group 2 (p = 0.01). The number of colorectal polyps and retinal pigments also correlated with the germline mutation, which was consistent with previous reports. However, such correlations were less obvious with regard to gastric fundic polyps, desmoid tumors, soft tissue tumors and colorectal cancer., Conclusion: There are two types with regard to extracolonic manifestations of FAP: one is more severely affected according to the position of germline mutation of the APC gene and the other is not affected.
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- 2000
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22. Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis.
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Miyaki M, Iijima T, Konishi M, Sakai K, Ishii A, Yasuno M, Hishima T, Koike M, Shitara N, Iwama T, Utsunomiya J, Kuroki T, and Mori T
- Subjects
- Colorectal Neoplasms pathology, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Humans, Liver Neoplasms genetics, Smad4 Protein, Colorectal Neoplasms genetics, DNA-Binding Proteins genetics, Liver Neoplasms secondary, Mutation, Trans-Activators genetics
- Abstract
We have previously detected an increased frequency of loss of heterozygosity (LOH) on chromosome 18q during progression of colorectal carcinomas. To clarify the target of 18qLOH, mutation of Smad4 and Smad2 genes was analysed in 176 colorectal tumors with different stages, including liver metastasis, from 111 sporadic, 52 familial adenomatous polyposis (FAP) and nine hereditary nonpolyposis colorectal cancer (HNPCC) patients. Mutation of other Smad gene families in the TGF-beta signaling pathway was also examined. Twenty-one Smad4 mutations and one Smad2 mutation were detected, whereas mutation of Smad3, 6 and 7 genes was not detected. Smad4 mutations included seven frameshift, one inframe deletion, four nonsense and nine missense mutations, 95% of which resulted in alteration of Smad4 protein regions included in homo-oligomer and hetero-oligomer formation. Frequencies of tumors with Smad4 mutation were 0/40 (0%) in adenoma, 4/39 (10%) in intramucosal carcinoma, 3/44 (7%) in primary invasive carcinoma without distant metastasis, 6/17 (35%) in primary invasive carcinoma with distant metastasis, and 11/36 (31%) in distant metastasis (metastatic/non-metastatic: P=0.006 approximately 0.01). Loss of the other allele was observed in 19 of 20 (95%) invasive and metastasized carcinomas with Smad4 mutations. In four cases both primary and metastasized carcinomas in the same patients showed the same mutations. The present results suggest that Smad4 gene is one of true targets of 18qLOH, and that its inactivation is involved in advanced stages, such as distant metastasis, in human colorectal carcinogenesis.
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- 1999
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23. Extrinsic neural control of nitric oxide synthase expression in the myenteric plexus of rat jejunum.
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Nakao K, Takahashi T, Utsunomiya J, and Owyang C
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- Animals, Autonomic Nervous System drug effects, Autonomic Nervous System physiology, Blotting, Northern, Blotting, Western, Denervation, Electric Stimulation, Enzyme Inhibitors pharmacology, Ganglionectomy, Immunohistochemistry, Jejunum drug effects, Jejunum innervation, Male, Myenteric Plexus drug effects, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide Synthase antagonists & inhibitors, Oxidopamine toxicity, Rats, Rats, Sprague-Dawley, Thiolester Hydrolases metabolism, Ubiquitin Thiolesterase, Vagotomy, Jejunum enzymology, Myenteric Plexus enzymology, Nitric Oxide Synthase biosynthesis
- Abstract
1. The role of extrinsic innervation in the expression of nitric oxide synthase (NOS) in the myenteric plexus remains unknown. In this study, we investigated the effect of extrinsic denervation on NOS expression in rat jejunum. 2. NG-nitro-L-arginine methyl ester (L-NAME)-sensitive non-adrenergic, non-cholinergic (NANC) relaxations induced by transmural nerve stimulation were significantly increased in muscle strips obtained from rats treated with splanchnic ganglionectomy or 6-hydroxydopamine (6-OH-dopamine). Truncal vagotomy or treatment of the coeliac ganglia with capsaicin did not significantly affect NANC relaxations. 3. The number of NOS-immunopositive cells in the myenteric plexus was significantly increased in tissues obtained from rats treated with splanchnic ganglionectomy or 6-OH-dopamine. 4. Western blot analysis and Northern blot analysis showed a significant increase in the density of the immunoreactive NOS band and the NOS mRNA band, respectively, of the tissues obtained from rats treated with splanchnic ganglionectomy or 6-OH-dopamine. 5. Truncal vagotomy or treatment of the coeliac ganglia with capsaicin did not significantly affect the density of NOS band or NOS mRNA band. 6. It is concluded that neuronal NOS expression in the myenteric plexus is independent of vagus nerve and is negatively regulated by the splanchnic nerves in the rat small intestine.
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- 1998
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24. Drastic genetic instability of tumors and normal tissues in Turcot syndrome.
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Miyaki M, Nishio J, Konishi M, Kikuchi-Yanoshita R, Tanaka K, Muraoka M, Nagato M, Chong JM, Koike M, Terada T, Kawahara Y, Fukutome A, Tomiyama J, Chuganji Y, Momoi M, and Utsunomiya J
- Subjects
- Adenocarcinoma genetics, Adenoma genetics, Adenomatous Polyposis Coli genetics, Adolescent, Astrocytoma genetics, Child, Colonic Neoplasms genetics, Fibroma genetics, Genes, APC, Humans, Lymphoma genetics, Male, Germ-Line Mutation, Neoplasms, Multiple Primary genetics, Neoplastic Syndromes, Hereditary genetics
- Abstract
Turcot syndrome is characterized by an association of malignant brain tumors and colon cancer developing in the patient's teens. Since the mechanism of carcinogenesis in Turcot syndrome is still unclear, we analysed genetic changes in tumors from a Turcot patient with no family history of the condition. All tumors, including one astrocytoma, three colon carcinomas, and two colon adenomas, exhibited severe replication error (RER), and all colon tumors showed somatic mutations at repeated regions of TGFbetaRII, E2F-4, hMSH3, and/or hMSH6 genes. Somatic APC mutations were detected in three of three colon carcinomas, and somatic p53 mutations were detected in the astrocytoma and two of three colon carcinomas, both of which showed two mutations without allele loss. We also found that normal colon mucosa, normal skin fibroblasts and normal brain tissue from this patient showed respective high frequencies of RER, in contrast to usual HNPCC patients in which RER was very rare in normal tissues. These results suggest that extreme DNA instability in normal tissues causes the early development of multiple cancer in Turcot syndrome. A missense mutation (GAG to AAG) at codon 705 of hPMS2 gene was detected in one allele of this patient, which was inherited from his mother without tumors. Additional unknown germline mutation may contribute to the genetic instability in normal tissues.
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- 1997
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25. DNA damage-associated dysregulation of the cell cycle and apoptosis control in cells with germ-line p53 mutation.
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Goi K, Takagi M, Iwata S, Delia D, Asada M, Donghi R, Tsunematsu Y, Nakazawa S, Yamamoto H, Yokota J, Tamura K, Saeki Y, Utsunomiya J, Takahashi T, Ueda R, Ishioka C, Eguchi M, Kamata N, and Mizutani S
- Subjects
- Adolescent, Adult, Alleles, Apoptosis radiation effects, Cell Cycle physiology, Cell Death radiation effects, Cell Transformation, Viral, Child, Preschool, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases metabolism, Cyclins biosynthesis, Cyclins metabolism, Disease Susceptibility, Female, Gene Expression, Herpesvirus 4, Human, Humans, Li-Fraumeni Syndrome blood, Lymphocytes cytology, Lymphocytes physiology, Lymphocytes radiation effects, Male, Phenotype, Protein Serine-Threonine Kinases metabolism, Transcriptional Activation, Tumor Suppressor Protein p53 biosynthesis, Tumor Suppressor Protein p53 physiology, Apoptosis physiology, CDC2-CDC28 Kinases, DNA Damage, Genes, p53, Germ-Line Mutation, Li-Fraumeni Syndrome genetics, Li-Fraumeni Syndrome pathology
- Abstract
Lymphoblastoid cell lines (LCLs) with heterozygous p53 mutations at residues 286A, 133R, 282W, 132E, and 213ter were established from five independent Li-Fraumeni syndrome families. When cell cycle regulation in response to gamma-irradiation was studied, these LCLs showed an abnormal G1 checkpoint associated with defective inhibition of cyclin E/cyclin-dependent kinase 2 activity in all cases except for 282W LCL, which showed a normal G1 checkpoint. On the other hand, the control of S-phase-G2 as determined by cyclin A/cyclin-dependent kinase 2 activity was defective in all these LCLs. The mitotic checkpoint was also defective in the two LCLs analyzed as either competent or incompetent for G1 arrest. When radiation-induced apoptosis, which requires wild-type p53 function under optimal conditions, was studied, all of these LCLs showed significant failure compared to normal LCLs. These findings indicate that although p53-dependent transactivation and G1-S-phase cell cycle control are variably dysregulated, the induction of apoptosis and control of the cell cycle at S-phase-G2 and the mitotic checkpoint in response to DNA-damaging agents are consistently dysregulated in heterozygous mutant LCLs. This suggests that these dysfunctions underlie, at least in part, the susceptibility of Li-Fraumeni syndrome families to cancer. Furthermore, the approach presented is a potentially useful method for studying individual carriers of different germ-line p53 mutations and different biological features.
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- 1997
26. Germline p53 mutation at codon 133 in a cancer-prone family.
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Saeki Y, Tamura K, Yamamoto Y, Hatada T, Furuyama J, and Utsunomiya J
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- Adult, Codon, Exons, Female, Germ Cells, Humans, Male, Pedigree, Breast Neoplasms genetics, Point Mutation, Tumor Suppressor Protein p53 genetics
- Abstract
We identified four families in which we suspected the presence of genetic factors predisposing them to cancer. We examined one family with features suggesting Li-Fraumeni syndrome for the presence of a germline p53 mutation in 13 of its members. To detect germline p53 mutations we performed polymerase chain reaction/nonradioisotopic single-strand conformation polymorphism and DNA sequencing analysis on exons 4-9 of the p53 gene. Mutated polymerase chain reaction-restriction fragment length polymorphism analysis was also performed on exon 5 to confirm the mutation identified by the sequencing analysis. A novel germline p53 mutation was identified at codon 133 (ATG-->AGG) in exon 5, resulting in the substitution of arginine for methionine, in all four cancer-affected individuals and in three apparently healthy individuals. We also analyzed tumor specimens for additional p53 mutations in the wild-type alleles using the same methods. However, heterozygosity was retained, and no other additional mutations in the wild-type allele were identified in any of the tumor tissues. It is possible that additional mutations in the wild-type allele are not always necessary for the loss of tumor suppressor functions. This study presents serious clinical and ethical problems about the predictive value of identifying germline p53 mutations in presymptomatic carriers. However, accurate predictive testing will be very useful in identifying unaffected individuals who are at increased risk of developing cancer and in detecting cancer at an early stage.
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- 1997
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27. Frequent microsatellite instabilities and analyses of the related genes in familial gastric cancers.
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Akiyama Y, Nakasaki H, Nihei Z, Iwama T, Nomizu T, Utsunomiya J, and Yuasa Y
- Subjects
- Adaptor Proteins, Signal Transducing, Base Sequence, DNA Repair genetics, DNA-Binding Proteins genetics, Female, Fungal Proteins genetics, Humans, Male, Molecular Sequence Data, MutL Protein Homolog 1, MutS Homolog 2 Protein, Mutation, Pedigree, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Saccharomyces cerevisiae Proteins, Transforming Growth Factor beta genetics, Microsatellite Repeats, Stomach Neoplasms genetics
- Abstract
Microsatellite instability or replication error seems to be related to defective DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2, which have been identified as causative genes of hereditary nonpolyposis colorectal cancers (HNPCC). Recently, it was reported that mutations at the simple repeated sequences in the transforming growth factor-beta type II receptor (TGF-beta RII) gene occurred in replication error-positive colorectal cancers. To determine genetic alterations in familial gastric cancers (FGC, we examined replication error using eight microsatellite DNA markers, and screened mutations in the hMSH2, hMLH1 and TGF-beta RII genes in six cases from four FGC kindreds. Moreover, hMTH1, a human homolog of the bacterial mutT gene, was also screened. Four of six (67%) cancers showed the replication error-positive phenotype, indicating that microsatellite instability is highly associated with not only HNPCC, but also FGC. No germline mutation was found in the whole coding sequences of hMSH2 and hMTH1, or in the conservative regions of hMLH1 in any patient, while one cancer DNA showed a somatic mutation at codon 682 (threonine to alanine) in hMSH2. No alteration was found at the small repeated sequences in TGF-beta RII in FGC tumor DNA. These results indicate that the carcinogenetic process of FGC may be different from that of HNPCC.
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- 1996
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28. The impact of familial adenomatous polyposis on the tumorigenesis and mortality at the several organs. Its rational treatment.
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Iwama T, Mishima Y, and Utsunomiya J
- Subjects
- Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli surgery, Adult, Colectomy, Colorectal Neoplasms epidemiology, Female, Gastrointestinal Neoplasms epidemiology, Humans, Incidence, Japan epidemiology, Male, Morbidity, Prevalence, Proctocolectomy, Restorative, Registries, Risk Factors, Thyroid Neoplasms epidemiology, Adenomatous Polyposis Coli epidemiology
- Abstract
The authors reviewed the case records of 1050 familial adenomatous polyposis (FAP) patients who were registered at their institution. The organ-specific morbidity and mortality rates of malignant tumor in FAP patients were compared with those of the general population of Japan, and the prognosis after rectum-preserving operation also was calculated. The cumulative prevalence of colorectal carcinoma at the age of 44 years was 0.52 for men and 0.61 for women. The observed/expected morbidity ratio was 20.9 (95% confidence interval, 10.8-36.6) for thyroid carcinoma, 3.08 (2.03-7.75) for gastric carcinoma, and 295 (263-330) for colorectal carcinoma. The observed/expected mortality ratios was 250 (112-447) for periampullary and small intestinal carcinoma, 3.43 (1.77-6.0) for gastric carcinoma, and 210 (183-241) for colorectal carcinoma. The risk of rectal carcinoma after ileorectal anastomosis was 13% (8.5-17.5%) at 10 years and 37% at 20 years. The results clarified the impact of FAP on the carcinogenesis in several organs as a whole including preserved rectum, and suggested a direction of the rational treatment of FAP.
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- 1993
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29. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients.
- Author
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Nagase H, Miyoshi Y, Horii A, Aoki T, Ogawa M, Utsunomiya J, Baba S, Sasazuki T, and Nakamura Y
- Subjects
- Adolescent, Adult, Chromosome Deletion, Humans, Middle Aged, Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli pathology, Genes genetics, Mutation genetics
- Abstract
Recently we have isolated the adenomatous polyposis coli (APC) gene which causes familial adenomatous polyposis (FAP), and its germ-line mutations in a substantial number of FAP patients have been identified. On the basis of this information, we compared the location of germ-line mutations in the APC gene in 22 unrelated patients (12 of whom have been reported previously) with the number of colorectal polyps developed in FAP patients; 17 were sparse types and five were profuse types. All but one of the mutations were considered to cause truncation of the gene product by frame-shift due to deletion (14 cases) or nonsense mutation (seven cases). The location of the germ-line mutations seems to correlate with the two clinical types; germ-line mutations in five FAP patients with profuse polyps were observed between codon 1250 and codon 1464, whereas mutations in 17 FAP patients with fewer polyps were observed in the other regions of the APC gene. The result suggests that the number of colorectal polyps in FAP patients may be associated with a difference in the stability or biological function of the truncated APC protein.
- Published
- 1992
30. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer.
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Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler KW, Vogelstein B, and Nakamura Y
- Subjects
- Base Sequence, Blotting, Southern, DNA genetics, DNA isolation & purification, DNA, Neoplasm genetics, DNA, Neoplasm isolation & purification, Exons, Humans, Intestinal Mucosa physiopathology, Molecular Sequence Data, Repetitive Sequences, Nucleic Acid, Retroviridae genetics, Sequence Homology, Nucleic Acid, Adenomatous Polyposis Coli genetics, Colonic Neoplasms genetics, DNA Transposable Elements, Genes, Tumor Suppressor, Mutagenesis, Insertional
- Abstract
The APC gene is responsible for familial adenomatous polyposis and is considered to be a tumor suppressor gene associated with development of sporadic colorectal tumors. Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer. The inserted sequence was composed of a 3' portion of the LINE-1 consensus sequence and nearly 180 base pairs of polyadenylate tract. Furthermore, since an 8-base pair target site duplication was observed, retrotranscriptional insertion of an active LINE-1 sequence is suspected as the cause of this insertion event. This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element.
- Published
- 1992
31. Frequent loss of heterozygosity at the MCC locus on chromosome 5q21-22 in sporadic colorectal carcinomas.
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Miki Y, Nishisho I, Miyoshi Y, Horii A, Ando H, Nakajima T, Utsunomiya J, and Nakamura Y
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- Chromosome Mapping, DNA, Neoplasm genetics, Genes, Suppressor genetics, Humans, Polymorphism, Restriction Fragment Length, Chromosomes, Human, Pair 5 physiology, Colorectal Neoplasms genetics, Heterozygote
- Abstract
Recent studies have identified a gene on chromosome 5q, designated MCC (mutated in colorectal cancers), as a candidate for the putative colorectal tumor suppressor gene that is located at 5q21. We examined loss of heterozygosity (LOH) at the MCC locus and its vicinity in sporadic colorectal carcinomas, using 12 RFLP (restriction fragment length polymorphism) markers. One clone, L5.71, had been used to identify the MCC gene; all 12 markers also had tight linkage to the gene responsible for adenomatous polyposis coli. All 40 cases studied were informative with at least one marker, and 22 of them (55%) showed LOH at one or more loci. LOH in the tumors was more frequent in the immediate vicinity of L5.71 than in distant parts of the chromosome, and a common region of deletion was detected between markers L5.62 and 15A6. In one case, alleles were retained at L5.71 and at loci proximal to L5.71, but alleles were lost at loci distal to L5.71. In another case, both alleles were retained at L5.71 but alleles were lost at loci proximal and distal to L5.71. These results support the conclusion that a tumor suppressor gene for colorectal carcinoma is located within or around locus L5.71.
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- 1991
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32. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.
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Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, and Hedge P
- Subjects
- Amino Acid Sequence, Base Sequence, Chromosome Mapping, Codon genetics, DNA, Neoplasm genetics, DNA, Neoplasm isolation & purification, Genetic Linkage, Genetic Variation, Humans, Molecular Sequence Data, Oligonucleotide Probes, Polymerase Chain Reaction methods, Adenomatous Polyposis Coli genetics, Chromosomes, Human, Pair 5, Colonic Neoplasms genetics, Mutation, Rectal Neoplasms genetics
- Abstract
Previous studies suggested that one or more genes on chromosome 5q21 are responsible for the inheritance of familial adenomatous polyposis (FAP) and Gardner's syndrome (GS), and contribute to tumor development in patients with noninherited forms of colorectal cancer. Two genes on 5q21 that are tightly linked to FAP (MCC and APC) were found to be somatically altered in tumors from sporadic colorectal cancer patients. One of the genes (APC) was also found to be altered by point mutation in the germ line of FAP and GS patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS. The identification of these genes should aid in understanding the pathogenesis of colorectal neoplasia and in the diagnosis and counseling of patients with inherited predispositions to colorectal cancer.
- Published
- 1991
- Full Text
- View/download PDF
33. Molecular nature of chromosome 5q loss in colorectal tumors and desmoids from patients with familial adenomatous polyposis.
- Author
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Okamoto M, Sato C, Kohno Y, Mori T, Iwama T, Tonomura A, Miki Y, Utsunomiya J, Nakamura Y, and White R
- Subjects
- Alleles, Blotting, Southern, Chromosome Deletion, DNA Probes, Humans, Restriction Mapping, Adenomatous Polyposis Coli genetics, Chromosomes, Human, Pair 5, Colorectal Neoplasms genetics, Fibroma genetics
- Abstract
Familial adenomatous polyposis (FAP), which includes familial polyposis coli (FPC) and the Gardner syndrome (GS), is a genetically determined premalignant disease of the colon inherited by a locus (APC) mapping within 5q15-q22. To elucidate the role of 5q loss in FAP tumorigenesis, we analysed 51 colorectal tumors and seven desmoids from 19 cases of FPC and five GS patients, as well as 15 sporadic colon cancers. RFLP analysis revealed a high incidence of allelic deletion in hereditary colon cancers as well as in sporadic colon cancers with a peak at the APC locus. APC loss resulted primarily from interstitial deletion or mitotic recombination. Combined tumor and pedigree analysis in a GS family revealed loss of normal 5q alleles in three tumors, including a desmoid tumor, which suggests the involvement of hemizygosity or homozygosity of the defective APC gene in colon carcinogenesis and, possibly, in extracolonic neoplasms associated with FAP.
- Published
- 1990
- Full Text
- View/download PDF
34. Frequency of adenomatosis coli in Japan.
- Author
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Murata M, Utsunomiya J, Iwama T, and Tanimura M
- Subjects
- Adenocarcinoma epidemiology, Adolescent, Adult, Aged, Child, Child, Preschool, Colonic Neoplasms epidemiology, Female, Humans, Japan, Male, Middle Aged, Probability, Adenocarcinoma genetics, Colonic Neoplasms genetics
- Published
- 1981
- Full Text
- View/download PDF
35. The Paneth cell in the adenoma of familial polyposis coli.
- Author
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Iwama T, Utsunomiya J, and Hamaguchi E
- Subjects
- Adult, Aged, Epithelial Cells, Epithelium pathology, Female, Humans, Intestinal Mucosa, Intestine, Large cytology, Male, Middle Aged, Adenoma pathology, Colonic Neoplasms pathology, Intestinal Polyps pathology, Rectal Neoplasms pathology
- Abstract
It is said that the Paneth cells are found in the large intestine in a pathological state such as ulcerative colitis or adenoma. We examined the Paneth cells in the adenomas of familial polyposis coli. Nine cases including one case of Gardner's syndrome comprised the material for the examination of the Paneth cells because the caecum was available for the examination. The remaining one case had no Paneth cells. In two cases, the Paneth cells were found among the adenomas in the areas beyond the caecum and the proximal part of the colon ascendens. In one remarkable case, the Paneth cells were found in 43% of the adenomas in the caecum. Seven cases were carcinomas but no Paneth cells were found in or near the carcinoma. In the control cases, which were taken from the resected colon with a disease other than familial polyposis coli, the Paneth cells were found confined to the caecum. We concluded that the distribution of the Paneth cell-bearing adenomas reflects the distribution of the Paneth cells in the normal mucosa of the large intestine and that the Paneth cells in the adenoma may have differentiated in the adenoma.
- Published
- 1975
36. Site-directed chromosome rearrangements in skin fibroblasts from persons carrying genes for hereditary neoplasms.
- Author
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Sasaki MS, Tsunematsu Y, Utsunomiya J, and Utsumi J
- Subjects
- Cells, Cultured, Fibroblasts, Genes, Dominant, Humans, Karyotyping, Pedigree, Chromosome Aberrations, Leukemia genetics, Thyroid Neoplasms genetics
- Abstract
Chromosomal variability was studied in cultured skin fibroblasts in members of two unrelated families associated with hereditary neoplasms, one with familial childhood leukemia and the other with medullary thyroid cancer syndrome. Nonconstitutional chromosome rearrangements occurred with consistent frequency in the patients and obligate carriers. The G-banding analysis showed that th chromosome rearrangements were not random, and site of rearrangements tended to cluster to band p22 of chromosome 1 in the carriers of childhood leukemia gene and to band q23 of chromosome 17 in the patient with medullary thyroid cancer. The de novo rearrangements of chromosomes and their tendency to cluster to particular chromosomal sites strongly point to the possibility that the procancer type-dominant mutations responsible for these diseases have a mutator function analogous to the property of some insertion mutations or transposable elements.
- Published
- 1980
37. Studies with carcinogen-induced mammary carcinoma of the rat. The trial of auto-immunization to inhibit tumor formation after the surgical removal of tumors.
- Author
-
Utsunomiya J
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene, Animals, Carcinoma, Papillary chemically induced, Carcinoma, Papillary surgery, Female, Hemagglutination Tests, Mammary Neoplasms, Experimental chemically induced, Mammary Neoplasms, Experimental surgery, Methylcholanthrene, Rabbits immunology, Rats, Sheep immunology, Antigens, Neoplasm administration & dosage, Antigens, Neoplasm isolation & purification, Carcinoma, Papillary immunology, Immunization, Mammary Neoplasms, Experimental immunology, Neoplasm Recurrence, Local prevention & control
- Abstract
Auto-immunization treatment of carcinogen-fed rats using homogenates of carcinogen-induced tumors did not have any adverse effect on new tumor formation and growth as well as local recurrences. Auto-immunization treatments did not change the degree or nature of the inflammatory reaction observed in carcinogen-induced tumors. Auto-antibodies against carcinogen-infiltration of various intensity in the stroma of the tumor suggested that host definsi mechanism may involve in the course of development this authochtonous tumor.
- Published
- 1975
38. Sex hormone binding globulin as a reliable indicator of hormone dependence in human breast cancer.
- Author
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Murayama Y, Utsunomiya J, Takahashi I, Kitamura M, and Tominaga T
- Subjects
- Adult, Aged, Breast Neoplasms drug therapy, Cytosol analysis, Female, Humans, Menopause, Middle Aged, Neoplasms, Hormone-Dependent drug therapy, Receptors, Estrogen analysis, Testosterone blood, Breast Neoplasms metabolism, Neoplasms, Hormone-Dependent metabolism, Sex Hormone-Binding Globulin metabolism
- Abstract
One hundred nine pre- and postmenopausal mammary carcinoma cases were studied to elucidate the role of sex hormone binding globulin (SHBG) in the hormone dependence of human breast cancer. Our findings indicate that there is a significant negative correlation between SHBG binding capacity and plasma testosterone concentration. All patients with high SHBG titers were found to be cytosol estrogen receptor (CER) positive and the plasma SHBG binding capacity of CER positive was significantly higher than that of CER negative patients. We also found that the level of pretherapy plasma SHBG concentration is a reliable indicator in predicting the efficacy of hormone therapy. Our findings also confirm that, for a tumor to be hormone dependent, high plasma SHBG concentration and estrogen receptors must be present simultaneously. The present pretherapy determination of SHBG titers is easier and more reliable than previous methods for determining the hormone dependence of human breast tumors.
- Published
- 1979
- Full Text
- View/download PDF
39. Lack of association and linkage between HLA and familial polyposis coli.
- Author
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Sasaki M, Sugio K, Soejima J, Ikeuchi T, Tonomura A, Iwama T, Utsunomiya J, and Sasazuki T
- Subjects
- Female, Gene Frequency, Genetic Markers, Genotype, Humans, Male, Pedigree, Adenomatous Polyposis Coli genetics, Genetic Linkage, HLA Antigens genetics
- Abstract
We investigated possible association of and linkage between HLA and familial polyposis coli (FPC). In 182 individuals from 66 pedigrees of FPC and 108 individuals from a normal population, HLA-A, -B, and -C antigens were determined. When the frequencies of HLA antigens in 66 unrelated patients and in normal controls were compared, no association of FPC with HLA was observed. For the linkage analysis, HLA haplotypes of 17 affected sib pairs were investigated by the affected sib pair method. The number of pairs which shared two, one, and no haplotypes identical by descent was not significantly different from the number expected with random occurrence (P greater than 0.95). Finally, seven families were analyzed using Morton's sequential test. A maximum lod score of -0.056 at a recombination fraction of 0.4, and a lod of -3.089 at a recombination fraction of 0.05 were obtained. Therefore, there is neither an association of nor linkage between FPC and HLA.
- Published
- 1987
- Full Text
- View/download PDF
40. Argyrophil cells in adenomas of familial polyposis coli.
- Author
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Okayasu I, Hatakeyama S, Iwama T, and Utsunomiya J
- Subjects
- Adult, Female, Humans, Intestinal Mucosa pathology, Male, Middle Aged, Adenoma pathology, Colon pathology, Colonic Neoplasms pathology, Intestinal Polyps pathology
- Abstract
The presence of argyrophil cell was demonstrated in the adenomas of familial polyposis coli (FPC) with the Sevier-Munger method. Usually, argyrophil cells were distributed sparsely near the base of the crypts, rather close to the normal mucosa. But, adenomas with severe or moderate dysplasia did not contain argyrophil cells. The frequency of argyrophil cells in the adenoma was remarkably higher in the sigmoid than in the ascending colon. Because this phenomenon was found both in the non-adenomatous mucosal crypts of FPC and of normal control cases, it is conceivable that the appearance of the argyrophil cells in the adenomas of FPC is affected by the structural arrangement of the original non-tumorous mucosa, as a background. Furthermore, a tendency, that many argyrophil cells were located within the adenomas, was observed in one of the seven families examined. It showed that the argyrophil cell which is thought to be one of the elements constituting the adenoma might actively participate in the growth of the adenoma.
- Published
- 1981
41. Dual action of cholecystokinin-octapeptide on the guinea pig antrum.
- Author
-
Kantoh M, Takahashi T, Kusunoki M, Yamamura T, and Utsunomiya J
- Subjects
- Animals, Female, Guinea Pigs, Male, Muscle Contraction drug effects, Receptors, Cholinergic drug effects, Gastrointestinal Motility drug effects, Muscle, Smooth drug effects, Pyloric Antrum drug effects, Sincalide pharmacology
- Abstract
We examined the mechanism of action of cholecystokinin-octapeptide (CCK-OP) on longitudinal strips of the lesser and greater curvatures of the guinea pig antrum. In the strips of the lesser curvature, CCK-OP produced a concentration-dependent tonic contraction, which was significantly reduced by atropine, but not by tetrodotoxin. In contrast, CCK-OP caused a relaxation of the preparation of the greater curvature in a concentration-dependent manner. The relaxation induced by the peptide was enhanced by atropine, whereas it was blocked by tetrodotoxin. Propranolol, phentolamine, desensitization to adenosine-5'-triphosphate, and desensitization to vasoactive intestinal polypeptide had no effect on CCK-OP-induced relaxation. Cholecystokinin-octapeptide evoked the release of acetylcholine from strips of both sides, and it was not blocked by tetrodotoxin. These findings indicate that the mechanism of action of CCK-OP on the lesser curvature differs from that on the greater curvature. The peptide seems to act directly on smooth muscle cells and to stimulate cholinergic neural activity by sodium channel-independent mechanisms. Additionally, nonadrenergic inhibitory neurons appear to be activated by CCK-OP in the greater curvature.
- Published
- 1987
- Full Text
- View/download PDF
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