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  • 151.
    Aberg, Fredrik
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Kozlova, Elena N
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Metastasis-associated Mts1 (S100A4) protein in the developing and adult central nervous system2000In: J Comp Neurology, Vol. 424, p. 269-Article in journal (Refereed)
  • 152. Aberg, H
    et al.
    Morlin, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lithell, Hans
    Department of Public Health and Caring Sciences.
    Different long-term metabolic effects of enalapril and atenolol in patients with mild hypertension. EGTA Group1995In: J Hum Hypertens, Vol. 9, p. 149-Article in journal (Refereed)
  • 153.
    Aberg, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Eriksson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Tissue Factor Noncoagulant Signaling: Mechanisms and Implications for Cell Migration and Apoptosis2015In: Seminars in Thrombosis and Hemostasis, ISSN 0094-6176, E-ISSN 1098-9064, Vol. 41, no 7, p. 691-699Article in journal (Refereed)
    Abstract [en]

    Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also initiates noncoagulant signaling with broad biological implications. In this review, we discuss how TF interacts with other cell-surface proteins, which affect biological functions such as cell migration and cell survival. A vast number of publications have demonstrated the importance of TF-induced activation of protease-activated receptors, but recently published research has indicated a more complicated picture. As it has been discovered that TF interacts with integrins and receptor tyrosine kinases, novel signaling mechanisms for the TF/FVIIa complex have been presented. The knowledge of these new aspects of TF signaling may, for instance, facilitate the development of new treatment strategies for cancer and acute coronary syndromes, two examples of diseases characterized by aberrant TF expression and signaling.

  • 154. Aberg-Wistedt, A
    et al.
    Agren, H
    Ekselius, Lisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Bengtsson, F
    Akerblad, AC
    Sertraline vs Paroxetine in major depression: Clinical outcome after6 months of continuation therapy.2000In: J Clin Psychopharmacol. , Vol. 20, p. 645-Article in journal (Refereed)
  • 155.
    Ablikim, M.
    et al.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Achasov, M. N.
    GI Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia..
    Ahmed, S.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Ai, X. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Albayrak, O.
    Carnegie Mellon Univ, Pittsburgh, PA 15213 USA..
    Albrecht, M.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Ambrose, D. J.
    Univ Rochester, Rochester, NY 14627 USA..
    Amoroso, A.
    GI Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia.;Helmholtz Inst Mainz, D-55099 Mainz, Germany.;Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany.;Chinese Acad Sci, Beijing 100049, Peoples R China.;Univ Hawaii, Honolulu, HI 96822 USA.;Univ Punjab, Lahore 54590, Pakistan.;Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    An, F. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    An, Q.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Bai, J. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ferroli, R. Baldini
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Ban, Y.
    Peking Univ, Beijing 100871, Peoples R China..
    Bennett, D. W.
    Indiana Univ, Bloomington, IN 47405 USA..
    Bennett, J. V.
    Carnegie Mellon Univ, Pittsburgh, PA 15213 USA..
    Berger, N. B.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Bertani, M.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Bettoni, D.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy..
    Bian, J. M.
    Univ Minnesota, Minneapolis, MN 55455 USA..
    Bianchi, F.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Boger, E.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Boyko, I.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Briere, R. A.
    Carnegie Mellon Univ, Pittsburgh, PA 15213 USA..
    Cai, H.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Cai, X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Cakir, O.
    Ankara Univ, TR-06100 Ankara, Turkey..
    Calcaterra, A.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy.;Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany.;Chinese Acad Sci, Beijing 100049, Peoples R China.;Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Cao, G. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Cetin, S. A.
    Istanbul Bilgi Univ, TR-34060 Istanbul, Turkey..
    Chang, J. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chelkov, G.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Chen, G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, H. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, H. Y.
    Beihang Univ, Beijing 100191, Peoples R China..
    Chen, J. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, M. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, S.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Chen, S. J.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Chen, X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, X. R.
    Lanzhou Univ, Lanzhou 730000, Peoples R China..
    Chen, Y. B.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Cheng, H. P.
    Huangshan Coll, Huangshan 245000, Peoples R China..
    Chu, X. K.
    Peking Univ, Beijing 100871, Peoples R China..
    Cibinetto, G.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy..
    Dai, H. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Dai, J. P.
    Shanghai Jiao Tong Univ, Shanghai 200240, Peoples R China..
    Dbeyssi, A.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Dedovich, D.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Deng, Z. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Denig, A.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Denysenko, I.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Destefanis, M.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    De Mori, F.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Ding, Y.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Dong, C.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Dong, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Dong, L. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Dong, M. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Dou, Z. L.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Du, S. X.
    Zhengzhou Univ, Zhengzhou 450001, Peoples R China..
    Duan, P. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Fan, J. Z.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Fang, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Fang, S. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Fang, X.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Fang, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Farinelli, R.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy.;Univ Ferrara, I-44122 Ferrara, Italy..
    Fava, L.
    Univ Piemonte Orientale, I-15121 Alessandria, Italy.;INFN, I-10125 Turin, Italy..
    Fedorov, O.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Feldbauer, F.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Felici, G.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Feng, C. Q.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Fioravanti, E.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy..
    Fritsch, M.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany.;Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Fu, C. D.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Gao, Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Gao, X. L.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Gao, X. Y.
    Beihang Univ, Beijing 100191, Peoples R China..
    Gao, Y.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Gao, Z.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Garzia, I.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy..
    Goetzen, K.
    GSI Helmholtzcentre Heavy Ion Res GmbH, D-64291 Darmstadt, Germany..
    Gong, L.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Gong, W. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Gradl, W.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Greco, M.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Gu, M. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Gu, Y. T.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Guan, Y. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Guo, A. Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Guo, L. B.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Guo, R. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Guo, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Guo, Y. P.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Haddadi, Z.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Hafner, A.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Han, S.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Hao, X. Q.
    Henan Normal Univ, Xinxiang 453007, Peoples R China..
    Harris, F. A.
    Univ Hawaii, Honolulu, HI 96822 USA..
    He, K. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Heinsius, F. H.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Held, T.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Heng, Y. K.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Holtmann, T.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Hou, Z. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Hu, C.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Hu, H. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Hu, J. F.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Hu, T.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Hu, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Huang, G. S.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Huang, J. S.
    Henan Normal Univ, Xinxiang 453007, Peoples R China..
    Huang, X. T.
    Shandong Univ, Jinan 250100, Peoples R China..
    Huang, X. Z.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Huang, Y.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Huang, Z. L.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Hussain, T.
    Univ Punjab, Lahore 54590, Pakistan..
    Ji, Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ji, Q. P.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Ji, X. B.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ji, X. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Jiang, L. W.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Jiang, X. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Jiang, X. Y.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Jiao, J. B.
    Shandong Univ, Jinan 250100, Peoples R China..
    Jiao, Z.
    Huangshan Coll, Huangshan 245000, Peoples R China..
    Jin, D. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Jin, S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Johansson, T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Julin, A.
    Univ Minnesota, Minneapolis, MN 55455 USA..
    Kalantar-Nayestanaki, N.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Kang, X. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Kang, X. S.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Kavatsyuk, M.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Ke, B. C.
    Carnegie Mellon Univ, Pittsburgh, PA 15213 USA..
    Kiese, P.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Kliemt, R.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Kloss, B.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Kolcu, O. B.
    Istanbul Bilgi Univ, TR-34060 Istanbul, Turkey..
    Kopf, B.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Kornicer, M.
    Univ Hawaii, Honolulu, HI 96822 USA..
    Kupsc, Andrzej
    Uppsala University, The Svedberg Laboratory. Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Khn, W.
    Justus Liebig Univ Giessen, Phys Inst 2, D-35392 Giessen, Germany..
    Lange, J. S.
    Justus Liebig Univ Giessen, Phys Inst 2, D-35392 Giessen, Germany..
    Lara, M.
    Indiana Univ, Bloomington, IN 47405 USA..
    Larin, P.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Leithoff, H.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Leng, C.
    INFN, I-10125 Turin, Italy..
    Li, Cui
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Li, Cheng
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Li, D. M.
    Zhengzhou Univ, Zhengzhou 450001, Peoples R China..
    Li, F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, F. Y.
    Peking Univ, Beijing 100871, Peoples R China..
    Li, G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, H. B.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, H. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, J. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, Jin
    Seoul Natl Univ, Seoul 151747, South Korea..
    Li, K.
    Hangzhou Normal Univ, Hangzhou 310036, Peoples R China.;Shandong Univ, Jinan 250100, Peoples R China..
    Li, Lei
    Beijing Inst Petrochem Technol, Beijing 102617, Peoples R China..
    Li, P. R.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Li, Q. Y.
    Shandong Univ, Jinan 250100, Peoples R China..
    Li, T.
    Shandong Univ, Jinan 250100, Peoples R China..
    Li, W. D.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, W. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, X. L.
    Shandong Univ, Jinan 250100, Peoples R China..
    Li, X. M.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Li, X. N.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, X. Q.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Li, Y. B.
    Beihang Univ, Beijing 100191, Peoples R China..
    Li, Z. B.
    Sun Yat Sen Univ, Guangzhou 510275, Guangdong, Peoples R China..
    Liang, H.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Liang, J. J.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Liang, Y. F.
    Sichuan Univ, Chengdu 610064, Peoples R China..
    Liang, Y. T.
    Justus Liebig Univ Giessen, Phys Inst 2, D-35392 Giessen, Germany..
    Liao, G. R.
    Guangxi Normal Univ, Guilin 541004, Peoples R China..
    Lin, D. X.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Liu, B.
    Shanghai Jiao Tong Univ, Shanghai 200240, Peoples R China..
    Liu, B. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, C. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, D.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Liu, F. H.
    Shanxi Univ, Taiyuan 030006, Peoples R China..
    Liu, Fang
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, Feng
    Cent China Normal Univ, Wuhan 430079, Peoples R China..
    Liu, H. B.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Liu, H. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China.;Henan Univ Sci & Technol, Luoyang 471003, Peoples R China..
    Liu, H. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, J. B.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Liu, J. P.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Liu, J. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, K.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Liu, K. Y.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Liu, L. D.
    Peking Univ, Beijing 100871, Peoples R China..
    Liu, P. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, Q.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Liu, S. B.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Liu, X.
    Lanzhou Univ, Lanzhou 730000, Peoples R China..
    Liu, Y. B.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Liu, Y. Y.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Liu, Z. A.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, Zhiqing
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Loehner, H.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Lou, X. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Lu, H. J.
    Huangshan Coll, Huangshan 245000, Peoples R China..
    Lu, J. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Lu, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Lu, Y. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Luo, C. L.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Luo, M. X.
    Zhejiang Univ, Hangzhou 310027, Zhejiang, Peoples R China..
    Luo, T.
    Univ Hawaii, Honolulu, HI 96822 USA..
    Luo, X. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Lyu, X. R.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Ma, F. C.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Ma, H. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, L. L.
    Shandong Univ, Jinan 250100, Peoples R China..
    Ma, M. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, Q. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, T.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, X. N.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Ma, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, Y. M.
    Shandong Univ, Jinan 250100, Peoples R China..
    Maas, F. E.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Maggiora, M.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Malik, Q. A.
    Univ Punjab, Lahore 54590, Pakistan..
    Mao, Y. J.
    Peking Univ, Beijing 100871, Peoples R China..
    Mao, Z. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Marcello, S.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Messchendorp, J. G.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Mezzadri, G.
    Univ Ferrara, I-44122 Ferrara, Italy..
    Min, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Mitchell, R. E.
    Indiana Univ, Bloomington, IN 47405 USA..
    Mo, X. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Mo, Y. J.
    Cent China Normal Univ, Wuhan 430079, Peoples R China..
    Morales, C. Morales
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Muchnoi, N. Yu.
    GI Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia..
    Muramatsu, H.
    Univ Minnesota, Minneapolis, MN 55455 USA..
    Musiol, P.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Nefedov, Y.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Nerling, F.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Nikolaev, I. B.
    GI Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia..
    Ning, Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Nisar, S.
    COMSATS Inst Informat Technol, Lahore 54000, Pakistan..
    Niu, S. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Niu, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Olsen, S. L.
    Seoul Natl Univ, Seoul 151747, South Korea..
    Ouyang, Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Pacetti, S.
    INFN, I-06100 Perugia, Italy.;Univ Perugia, I-06100 Perugia, Italy..
    Pan, Y.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Patteri, P.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Pelizaeus, M.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Peng, H. P.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Peters, K.
    GSI Helmholtzcentre Heavy Ion Res GmbH, D-64291 Darmstadt, Germany..
    Pettersson, Jean
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ping, J. L.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Ping, R. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Poling, R.
    Univ Minnesota, Minneapolis, MN 55455 USA..
    Prasad, V.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Qi, H. R.
    Beihang Univ, Beijing 100191, Peoples R China..
    Qi, M.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Qian, S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Qiao, C. F.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Qin, L. Q.
    Shandong Univ, Jinan 250100, Peoples R China..
    Qin, N.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Qin, X. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Qin, Z. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Qiu, J. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Rashid, K. H.
    Univ Punjab, Lahore 54590, Pakistan..
    Redmer, C. F.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Ripka, M.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Rong, G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Rosner, Ch.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Ruan, X. D.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Sarantsev, A.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Savrie, M.
    Univ Ferrara, I-44122 Ferrara, Italy..
    Schnier, C.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Schönning, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics. Uppsala University, The Svedberg Laboratory.
    Schumann, S.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Shan, W.
    Peking Univ, Beijing 100871, Peoples R China..
    Shao, M.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Shen, C. P.
    Beihang Univ, Beijing 100191, Peoples R China..
    Shen, P. X.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Shen, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sheng, H. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Shi, M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Song, W. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Song, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sosio, S.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Spataro, S.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Sun, G. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, J. F.
    Henan Normal Univ, Xinxiang 453007, Peoples R China..
    Sun, S. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, X. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, Y. J.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Sun, Y. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, Z. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, Z. T.
    Indiana Univ, Bloomington, IN 47405 USA..
    Tang, C. J.
    Sichuan Univ, Chengdu 610064, Peoples R China..
    Tang, X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Tapan, I.
    Uludag Univ, TR-16059 Bursa, Turkey..
    Thorndike, E. H.
    Univ Rochester, Rochester, NY 14627 USA..
    Tiemens, M.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Uman, I.
    Near East Univ, Nicosia 10, Turkey..
    Varner, G. S.
    Univ Hawaii, Honolulu, HI 96822 USA..
    Wang, B.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Wang, B. L.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Wang, D.
    Peking Univ, Beijing 100871, Peoples R China..
    Wang, D. Y.
    Peking Univ, Beijing 100871, Peoples R China..
    Wang, K.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, L. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, L. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, M.
    Shandong Univ, Jinan 250100, Peoples R China..
    Wang, P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, P. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, S. G.
    Peking Univ, Beijing 100871, Peoples R China..
    Wang, W.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, W. P.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Wang, X. F.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Wang, Y.
    Soochow Univ, Suzhou 215006, Peoples R China..
    Wang, Y. D.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Wang, Y. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, Y. Q.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Wang, Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, Z. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, Z. H.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Wang, Z. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Weber, T.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Wei, D. H.
    Guangxi Normal Univ, Guilin 541004, Peoples R China..
    Wei, J. B.
    Peking Univ, Beijing 100871, Peoples R China..
    Weidenkaff, P.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Wen, S. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wiedner, U.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Wolke, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Wu, L. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wu, L. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wu, Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xia, L.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Xia, L. G.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Xia, Y.
    Hunan Univ, Changsha 410082, Peoples R China..
    Xiao, D.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xiao, H.
    Univ South China, Hengyang 421001, Peoples R China..
    Xiao, Z. J.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Xie, Y. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xiu, Q. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xu, G. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xu, J. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xu, L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xu, Q. J.
    Hangzhou Normal Univ, Hangzhou 310036, Peoples R China..
    Xu, Q. N.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Xu, X. P.
    Soochow Univ, Suzhou 215006, Peoples R China..
    Yan, L.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Yan, W. B.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Yan, W. C.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Yan, Y. H.
    Hunan Univ, Changsha 410082, Peoples R China..
    Yang, H. J.
    Shanghai Jiao Tong Univ, Shanghai 200240, Peoples R China..
    Yang, H. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yang, L.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Yang, Y. X.
    Guangxi Normal Univ, Guilin 541004, Peoples R China..
    Ye, M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ye, M. H.
    China Ctr Adv Sci & Technol, Beijing 100190, Peoples R China..
    Yin, J. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yu, B. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yu, C. X.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Yu, J. S.
    Lanzhou Univ, Lanzhou 730000, Peoples R China..
    Yuan, C. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yuan, W. L.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Yuan, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yuncu, A.
    Istanbul Bilgi Univ, TR-34060 Istanbul, Turkey..
    Zafar, A. A.
    Univ Punjab, Lahore 54590, Pakistan..
    Zallo, A.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Zeng, Y.
    Hunan Univ, Changsha 410082, Peoples R China..
    Zeng, Z.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhang, B. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, B. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, C.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Zhang, C. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, D. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, H. H.
    Sun Yat Sen Univ, Guangzhou 510275, Guangdong, Peoples R China..
    Zhang, H. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. W.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, K.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, S. Q.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Zhang, X. Y.
    Shandong Univ, Jinan 250100, Peoples R China..
    Zhang, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, Y. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, Y. N.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Zhang, Y. T.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhang, Yu
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Zhang, Z. H.
    Cent China Normal Univ, Wuhan 430079, Peoples R China..
    Zhang, Z. P.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhang, Z. Y.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Zhao, G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, J. W.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, J. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, J. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, Lei
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhao, Ling
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, M. G.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Zhao, Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, Q. W.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, S. J.
    Zhengzhou Univ, Zhengzhou 450001, Peoples R China..
    Zhao, T. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, Y. B.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, Z. G.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhemchugov, A.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Zheng, B.
    Univ South China, Hengyang 421001, Peoples R China..
    Zheng, J. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zheng, W. J.
    Shandong Univ, Jinan 250100, Peoples R China..
    Zheng, Y. H.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Zhong, B.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Zhou, L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhou, X.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Zhou, X. K.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhou, X. R.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhou, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, K.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, K. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, S. H.
    Univ Sci & Technol Liaoning, Anshan 114051, Peoples R China..
    Zhu, X. L.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Zhu, Y. C.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhu, Y. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, Z. A.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhuang, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zotti, L.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Zou, B. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zou, J. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Amplitude analysis of D0 -> K -π+π+π-2017In: Physical Review D: covering particles, fields, gravitation, and cosmology, ISSN 2470-0010, E-ISSN 2470-0029, Vol. 95, no 7, article id 072010Article in journal (Refereed)
    Abstract [en]

    We present an amplitude analysis of the decay D-0 -> K- pi(+)pi(+)pi(-) based on a data sample of 2.93 fb(-1) acquired by the BESIII detector at the psi(3770) resonance. With a nearly background free sample of about 16000 events, we investigate the substructure of the decay and determine the relative fractions and the phases among the different intermediate processes. Our amplitude model includes the two-body decays D-0 -> (K) over bar*(0)rho(0), D-0 -> K- a(1)(+) (1260) and D-0 -> K-1(-)(1270)pi(+), the three-body decays D-0 -> K-1(-)*(0)pi(+)pi(-) and D-0 -> K- pi(+)rho(0), as well as the four-body nonresonant decay D-0 -> K- pi(+)pi(+)pi(-). The dominant intermediate process is D-0 -> K(-)a(1)(+)(1260)accounting for a fit fraction of 54.6%.

  • 156.
    Abok, Kisia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Free radicals in cellular pathology: effects of ionizing radiation on cultured macrophages, submandibular salivary glands and mesenteric mast cells 1984Doctoral thesis, comprehensive summary (Other academic)
  • 157.
    Abouzayed, Ayman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Yim, Cheng-Bin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Mitran, Bogdan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Rinne, Sara S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Larhed, Mats
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Rosenström, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Synthesis and Preclinical Evaluation of Radio-Iodinated GRPR/PSMA Bispecific Heterodimers for the Theranostics Application in Prostate Cancer2019In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 11, no 7, article id 358Article in journal (Refereed)
    Abstract [en]

    Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are overexpressed in most prostate cancers. GRPR expression is higher in early stages while PSMA expression increases with progression. The possibility of targeting both markers with a single theranostics radiotracer could improve patient management. Three GRPR/PSMA-targeting bispecific heterodimers (urea derivative PSMA-617 and bombesin-based antagonist RM26 linked via X-triazolyl-Tyr-PEG2, X = PEG2 (BO530), (CH2)(8) (BO535), none (BO536)) were synthesized by solid-phase peptide synthesis. Peptides were radio-iodinated and evaluated in vitro for binding specificity, cellular retention, and affinity. In vivo specificity for all heterodimers was studied in PC-3 (GRPR-positive) and LNCaP (PSMA-positive) xenografts. [I-125]I-BO530 was evaluated in PC-3pip (GRPR/PSMA-positive) xenografts. Micro single-photon emission computed tomography/computed tomography (microSPECT/CT) scans were acquired. The heterodimers were radiolabeled with high radiochemical yields, bound specifically to both targets, and demonstrated high degree of activity retention in PC-3pip cells. Only [I-125]I-BO530 demonstrated in vivo specificity to both targets. A biodistribution study of [I-125]I-BO530 in PC-3pip xenografted mice showed high tumor activity uptake (30%-35%ID/g at 3 h post injection (pi)). Activity uptake in tumors was stable and exceeded all other organs 24 h pi. Activity uptake decreased only two-fold 72 h pi. The GRPR/PSMA-targeting heterodimer [I-125]I-BO530 is a promising agent for theranostics application in prostate cancer.

  • 158. Aboyans, Victor
    et al.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Naylor, A Ross
    Roffi, Marco
    Tendera, Michal
    Vlachopoulos, Charalambos
    Ricco, Jean-Baptiste
    Questions and answers on diagnosis and management of patients with Peripheral Arterial Diseases: a companion document of the 2017 ESC Guidelines for the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 9, p. E35-E41Article in journal (Refereed)
  • 159. Aboyans, Victor
    et al.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Naylor, A Ross
    Roffi, Marco
    Tendera, Michal
    Vlachopoulos, Charalambos
    Ricco, Jean-Baptiste
    Document Reviewers,
    Widimsky, Petr
    Kolh, Philippe
    Dick, Florian
    de Ceniga, Melina Vega
    Piepoli, Massimo Francesco
    Sievert, Horst
    Sulzenko, Jakub
    Esc Committee For Practice Guidelines Cpg,
    Windecker, Stephan
    Aboyans, Victor
    Agewall, Stefan
    Barbato, Emanuele
    Bueno, Héctor
    Coca, Antonio
    Collet, Jean-Philippe
    Coman, Ioan Mircea
    Dean, Veronica
    Delgado, Victoria
    Fitzsimons, Donna
    Gaemperli, Oliver
    Hindricks, Gerhard
    Iung, Bernard
    Jüni, Peter
    Katus, Hugo A
    Knuuti, Juhani
    Lancellotti, Patrizio
    Leclercq, Christophe
    McDonagh, Theresa
    Piepoli, Massimo Francesco
    Ponikowski, Piotr
    Richter, Dimitrios J
    Roffi, Marco
    Shlyakhto, Evgeny
    Simpson, Iain A
    Zamorano, Jose Luis
    Questions and Answers on Diagnosis and Management of Patients with Peripheral Arterial Diseases: A Companion Document of the 2017 ESC Guidelines for the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).2018In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 55, no 4, p. 457-464, article id S1078-5884(17)30516-6Article in journal (Refereed)
  • 160. Aboyans, Victor
    et al.
    Ricco, Jean-Baptiste
    Bartelink, Marie-Louise
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Cohner, Tina
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Debus, Sebastian
    Espinola-Klein, Christine
    Kahan, Thomas
    Kownator, Serge
    Mazzolai, Lucia
    Naylor, Ross
    Roffi, Marco
    Röther, Joachim
    Sprynger, Muriel
    Tendera, Michal
    Tepe, Gunnar
    Venermo, Maarit
    Vlachopoulos, Charalambos
    Desormais, Ileana
    [2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)]2017In: Kardiologia polska, ISSN 0022-9032, E-ISSN 1897-4279, Vol. 75, no 11, p. 1065-1160Article in journal (Refereed)
  • 161. Aboyans, Victor
    et al.
    Ricco, Jean-Baptiste
    Bartelink, Marie-Louise E L
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Cohnert, Tina
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Debus, Sebastian
    Espinola-Klein, Christine
    Kahan, Thomas
    Kownator, Serge
    Mazzolai, Lucia
    Naylor, A Ross
    Roffi, Marco
    Röther, Joachim
    Sprynger, Muriel
    Tendera, Michal
    Tepe, Gunnar
    Venermo, Maarit
    Vlachopoulos, Charalambos
    Desormais, Ileana
    2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 9, p. 763-816Article in journal (Refereed)
  • 162. Aboyans, Victor
    et al.
    Ricco, Jean-Baptiste
    Bartelink, Marie-Louise E L
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Cohnert, Tina
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Debus, Sebastian
    Espinola-Klein, Christine
    Kahan, Thomas
    Kownator, Serge
    Mazzolai, Lucia
    Naylor, A Ross
    Roffi, Marco
    Röther, Joachim
    Sprynger, Muriel
    Tendera, Michal
    Tepe, Gunnar
    Venermo, Maarit
    Vlachopoulos, Charalambos
    Desormais, Ileana
    Widimsky, Petr
    Kolh, Philippe
    Agewall, Stefan
    Bueno, Héctor
    Coca, Antonio
    De Borst, Gert J
    Delgado, Victoria
    Dick, Florian
    Erol, Cetin
    Ferrini, Marc
    Kakkos, Stavros
    Katus, Hugo A
    Knuuti, Juhani
    Lindholt, Jes
    Mattle, Heinrich
    Pieniazek, Piotr
    Piepoli, Massimo Francesco
    Scheinert, Dierk
    Sievert, Horst
    Simpson, Iain
    Sulzenko, Jakub
    Tamargo, Juan
    Tokgozoglu, Lale
    Torbicki, Adam
    Tsakountakis, Nikolaos
    Tuñón, José
    de Ceniga, Melina Vega
    Windecker, Stephan
    Zamorano, Jose Luis
    2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)2018In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 55, no 3, p. 305-368Article in journal (Refereed)
  • 163. Aboyans, Victor
    et al.
    Ricco, Jean-Baptiste
    Bartelink, Marie-Louise E L
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Cohnert, Tina
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Debusa, Sebastian
    Espinola-Klein, Christine
    Kahan, Thomas
    Kownator, Serge
    Mazzolai, Lucia
    Naylora, A Ross
    Roffi, Marco
    Rotherb, Joachim
    Sprynger, Muriel
    Tendera, Michal
    Tepe, Gunnar
    Venermoa, Maarit
    Vlachopoulos, Charalambos
    Desormais, Ileana
    2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).2018In: Revista espanola de cardiologia (English ed.), ISSN 1885-5857, Vol. 71, no 2, article id 111Article in journal (Refereed)
  • 164. Abraham-Nordling, Mirna
    et al.
    Byström, Kristina
    Törring, Ove
    Lantz, Mikael
    Berg, Gertrud
    Calissendorff, Jan
    Nyström, Helena Filipsson
    Jansson, Svante
    Jörneskog, Gun
    Karlsson, F Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nyström, Ernst
    Ohrling, Hans
    Orn, Thomas
    Hallengren, Bengt
    Wallin, Göran
    Incidence of hyperthyroidism in Sweden2011In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 165, no 6, p. 899-905Article in journal (Refereed)
    Abstract [en]

    Introduction The incidence of hyperthyroidism has been reported in various countries to be 23-93/100 000 inhabitants per year. This extended study has evaluated the incidence for ∼40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. Methods All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows: clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. Results A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. Conclusion The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.

  • 165. Abrahamsson, Christina
    et al.
    Ahlund, Catherine
    Nordlander, Margareta
    Lind, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    A method for heart rate-corrected estimation of baroreflex sensitivity.2003In: J Hypertens, ISSN 0263-6352, Vol. 21, no 11, p. 2133-40Article in journal (Refereed)
  • 166.
    Abrahamsson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Quick, Linnéa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Datorbaserad fonologisk lästräning för barn med hörselnedsättning: En undersökning av fonologisk medvetenhet och ordavkodning2015Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Randomized controlled trials evaluating the effect of various forms of literacy training with reliable tests are lacking in Sweden today. The aim of the present study was to investigate whether a cross-over design and the use of phonologically matched wordlists specifically designed to detect transfer, would yield a more thorough method and reliable results. Six children with hearing impairment using hearing aids between 7 and 9 years of age took part in the study. The schools in which the children had their education were randomized into either an intervention group that started to practice phonics by means of a computer-assisted program after the first testing, or a control group that, continued as usual in school. Children were informed to practice daily with the program during four weeks in school. Children were tested with a battery of tests for phonological awareness, letter knowledge and word decoding at three occasions separated by four weeks. Results showed that the wordlists seemed reliable in establishing children’s decoding strategies as well as how word length affected reading speed. Both children who took part in the intervention and the control group improved their scores at the second testing. Thus, the computer-assisted reading intervention did not prove to be more effective than usual school activities. Due to a small number of participants, a large heterogeneity of the group and insufficient practice time, effects were difficult to detect. The present investigation should be considered a pilot study towards the use of more careful testing methods with adapted wordlists that enables the detection of transfer. But, to accomplish this, it is crucial to use a larger number of participants.

    Randomiserade kontrollerade studier som utvärderar effekten av olika former av läs- och skrivträning med tillförlitliga tester saknas i Sverige idag. Syftet med denna undersökning var att genomföra en interventionsstudie med cross-over design och använda fonologiskt matchade ordlistor specifikt utformade för att upptäcka transfer, för att ge utdelning för en mer grundlig metod och reliabla resultat. Sex barn mellan 7 och 9 års ålder som använde hörapparat deltog i studien. Skolorna som barnen gick i randomiserades till att antingen utgöra en interventionsgrupp, som började träna med ett ljudbaserat lästräningsprogram via dator efter första testningen, eller kontrollgrupp som fortsatte med vanlig skolundervisning. Barnen informerades att träna med programmet under fyra veckor dagligen i skolan. Barnen utförde ett testbatteri innehållande tester för fonologisk medvetenhet, bokstavskännedom och ordavkodning vid tre tillfällen med fyra veckors mellanrum. Resultaten visade att ordlistorna på ett reliabelt sätt kunde fastställa barns avkodningsstrategier samt hur ordlängd påverkade läshastigheten. Både interventions- och kontrollgruppen påvisade förbättring vid andra testningen. Dock kunde det inte påvisas att den datorbaserade lästräningen var mer effektiv än sedvanlig skolundervisning. Då deltagarantalet var litet, spridningen stor och träningstiden vid datorn var låg kan detta ha bidragit till att effekterna uteblev. Studien bör ses som en pilotstudie som går mot en noggrannare form av testmetod där användandet av anpassade ordlistor möjliggör upptäckt av transfer. För att åstadkomma detta är det emellertid avgörande att det ingår ett större deltagarantal.

  • 167. Abrahamsson, Hasse
    et al.
    Ostlund-Lindqvist, Ann-Margret
    Nilsson, Ralf
    Simren, Magnus
    Gillberg, Per-Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Altered bile acid metabolism in patients with constipation-predominant irritable bowel syndrome and functional constipation2008In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 43, no 12, p. 1483-1488Article in journal (Refereed)
    Abstract [en]

    Objective. Bile acids are derived from cholesterol and are potent physiological laxatives. The aim of this study was to investigate whether bile acid synthesis is altered in constipation. Material and methods. Female patients with constipation (23 IBS-C, 4 functional constipation (FC)) were studied and compared with non-constipated subjects (16 IBS-D, 20 healthy women). Body mass index (BMI), blood lipids, lanosterol, sitosterol, colonic transit (oro-anal transit time (OATT), reference=4.3 days) and stool frequency were measured. C4 (7--hydroxy-4-cholesten-3-one) levels reflecting bile acid synthesis were measured at 0800 h and 1300 h. Results. When all the groups of constipated and non-constipated subjects were compared, it was found that only stool frequency and OATT differed between groups (p 0.001). When constipated patients were categorized according to OATT, absence of the usual C4 increase at lunchtime was noted in 82% of patients with delayed OATT compared with 17% in subjects with normal OATT (p 0.001). Symptom severity did not differ between groups. A subset of the patients with severely delayed OATT had markedly elevated C4 levels. Conclusions. Patients with IBS-C and FC have marked changes in bile acid synthesis in relation to colonic transit. The diurnal rhythm is altered in the slow transit colon when there is no C4 peak at lunchtime. Alterations in bile acid metabolism may be implicated in the pathophysiology of constipation.

  • 168.
    Abrahamsson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Characterization of calcium transport in mouse and clonal rat pancreatic ß-cells 1985Doctoral thesis, comprehensive summary (Other academic)
  • 169.
    Abrahamsson, Jonas
    et al.
    Queen Silvia Children’s Hospital, Gothenburg.
    Forestier, Erik
    Heldrup, Jesper
    Jahnukainen, Kirsi
    Jónsson, Olafur G.
    Lausen, Birgitte
    Palle, Josefine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Zeller, Bernward
    Hasle, Henrik
    Aarhus University Hospital Skejby, Aarhus.
    Response-Guided Induction Therapy in Pediatric Acute Myeloid Leukemia With Excellent Remission Rate2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 3, p. 310-315Article in journal (Refereed)
    Abstract [en]

    Purpose

    To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.

    Patients and Methods

    All Nordic children with AML younger than 15 years (n = 151) were treated on the Nordic Society for Pediatric Hematology and Oncology (NOPHO) AML 2004 protocol. After the first course of idarubicin, cytarabine, etoposide, and 6-thioguanin, patients with good response were allowed hematologic recovery before the second course, whereas patients with a poor (>= 15% blasts) or intermediate (5% to 14.9% blasts) were recommended to proceed immediately with therapy. Patients not in remission after the second course received fludarabine, cytarabine, and granulocyte colony-stimulating factor. Poor responders received allogeneic stem-cell transplantation (SCT) as consolidation.

    Results

    Seventy-four percent of patients had good response, 17% had intermediate response, and 7% had poor response after the first course. The overall remission frequency was 97.4%, with 92% in remission after the second course. The rate of induction death was 1.3%. Patients with an intermediate response had a lower event-free survival of 35% compared with good (61%) and poor responders (82%).

    Conclusion

    The NOPHO-AML 2004 induction strategy gives an excellent remission rate with low toxic mortality in an unselected population. Outcome is worse in patients with intermediate response but may be improved by intensifying consolidation in this group using SCT.

  • 170.
    Abrahamsson, Lillemor
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Domestic Sciences.
    Andersson, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Domestic Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Principles of nutritional assessment2006In: Scandinavian Journal of Food and Nutrition, ISSN 1748-2976, E-ISSN 1748-2984, Vol. 50, no 4, p. 177-177Article, book review (Other (popular science, discussion, etc.))
  • 171.
    Abrahamsson, Lillemor
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Domestic Sciences. kost.
    Andersson, Agneta
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Domestic Sciences. Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Becker, Wulf
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition och metabolism.
    Nilsson, Gerd
    Näringslära för högskolan2006Book (Other (popular scientific, debate etc.))
  • 172.
    Abrahamsson, Lotta
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Ljung, Ida-Karin
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Bliss i interaktion: - En samtalsanalytisk fallstudie av hur blissanvändare och tolkare tillsammans bygger upp yttranden2008Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 173.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    On the Impact of Bariatric Surgery on Glucose Homeostasis2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI>50 kg/m2.

    In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery.

    In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS).

    In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day <3.3mmol/l and 20 and 40 minutes < 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms.

    In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response.

    In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.

    List of papers
    1. Gastric Bypass Surgery Elevates NT-ProBNP Levels
    Open this publication in new window or tab >>Gastric Bypass Surgery Elevates NT-ProBNP Levels
    2013 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 23, no 9, p. 1421-1426Article in journal (Refereed) Published
    Abstract [en]

    Background

    Brain natriuretic peptide (BNP) is produced in the heart in response to stretching of the myocardium. BNP levels are negatively correlated to obesity, and in obese subjects, a reduced BNP responsiveness has been described. Diet-induced weight loss has been found to lower or to have no effect on BNP levels, whereas gastric banding and gastric bypass have reported divergent results. We studied obese patients undergoing gastric bypass (GBP) surgery during follow-up of 1 year.

    Methods

    Twenty patients, 18 women, mean 41 (SD 9.5) years old, with a mean preoperative BMI of 44.6 (SD 5.5) kg/m2 were examined. N-terminal pro-brain natriuretic peptide (NT-ProBNP), glucose and insulin were measured preoperatively, at day 6 and months 1, 6 and 12. In 14 of the patients, samples were also taken at days 1, 2 and 4.

    Results

    The NT-ProBNP levels showed a marked increase during the postoperative week (from 54 pg/mL preop to 359 pg/mL on day 2 and fell to 155 on day 6). At 1 year, NT-ProBNP was 122 pg/mL (125 % increase, p = 0.01). Glucose, insulin and HOMA indices decreased shortly after surgery without correlation to NT-ProBNP change. Mean BMI was reduced from 44.6 to 30.5 kg/m2 at 1 year and was not related to NT-ProBNP change.

    Conclusions

    The data indicate that GBP surgery rapidly alters the tone of BNP release, by a mechanism not related to weight loss or to changes in glucometabolic parameters. The GBP-induced conversion of obese subjects, from low to high NT-ProBNP responders, is likely to influence the evaluation of cardiac function in GBP operated individuals.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-199870 (URN)10.1007/s11695-013-0889-z (DOI)000322494800011 ()23456799 (PubMedID)
    Available from: 2013-05-17 Created: 2013-05-17 Last updated: 2017-12-06Bibliographically approved
    2. GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?
    Open this publication in new window or tab >>GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?
    2013 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 169, no 6, p. 885-889Article in journal (Refereed) Published
    Abstract [en]

    Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-213465 (URN)10.1530/EJE-13-0504 (DOI)000327539100021 ()
    Available from: 2014-01-02 Created: 2013-12-23 Last updated: 2017-12-06Bibliographically approved
    3. Hypoglycemia in everyday life after gastric bypass and duodenal switch
    Open this publication in new window or tab >>Hypoglycemia in everyday life after gastric bypass and duodenal switch
    2015 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 173, no 1, p. 91-100Article in journal (Refereed) Published
    Abstract [en]

    Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-261313 (URN)10.1530/EJE-14-0821 (DOI)000358947700018 ()25899582 (PubMedID)
    Available from: 2015-09-03 Created: 2015-09-01 Last updated: 2017-12-04Bibliographically approved
    4. Gastric bypass reduces symptoms and hormonal responses to hypoglycemia
    Open this publication in new window or tab >>Gastric bypass reduces symptoms and hormonal responses to hypoglycemia
    Show others...
    2016 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2667-2675Article in journal (Refereed) Published
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

    Keywords
    Gastric bypass, hypoglycemia
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-276380 (URN)10.2337/db16-0341 (DOI)000382099800021 ()27313315 (PubMedID)
    Funder
    Swedish Diabetes Association
    Available from: 2016-02-12 Created: 2016-02-12 Last updated: 2017-11-30Bibliographically approved
  • 174.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlund, Lovisa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ahrin, Elsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Alfonsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Video-based CBT-E improves eating patterns in obese patients with eating disorder: A single case multiple baseline study2018In: Journal of Behavior Therapy and Experimental Psychiatry, ISSN 0005-7916, E-ISSN 1873-7943, Vol. 61, p. 104-112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES:

    Cognitive Behavioral Therapy (CBT) is effective for treating eating disorders but it may be difficult to reach patients living far from urban centers. Mobile video-based psychotherapy may potentially improve service reach but has not yet been evaluated. The purpose of this study was to investigate the effects of mobile video-based CBT for eating disorder and to explore the feasibility to use this technology in clinical care.

    METHODS:

    A controlled single case multiple baseline design was used which allowed for statistical analyses with randomization tests and non-overlap of all pairs (NAP). Five patients in the first stage of eating disorder treatment were included and the main outcome variable was daily meal frequency. Secondary outcome variables included eating disorder symptoms, psychological distress and treatment satisfaction.

    RESULTS:

    The treatment resulted in a significant (p < .01) increase in daily meal frequency with medium to large effect sizes (combined NAP = .89). Four participants reported reliable improvements in eating disorder symptoms and three reported improvements in mood. The participants reported high satisfaction with the treatment and with the mobile video-application despite some technical problems.

    LIMITATIONS:

    Self-reported data on eating behavior is prone to be biased and the results of single case studies may have limited generalizability.

    CONCLUSION:

    CBT can be delivered effectively via a mobile video application and, despite some technological issues, can be well received by patients. All participants in this study had previous low access to mental health services and reported high satisfaction with the treatment format.

  • 175.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Gastric Bypass Surgery Elevates NT-ProBNP Levels2013In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 23, no 9, p. 1421-1426Article in journal (Refereed)
    Abstract [en]

    Background

    Brain natriuretic peptide (BNP) is produced in the heart in response to stretching of the myocardium. BNP levels are negatively correlated to obesity, and in obese subjects, a reduced BNP responsiveness has been described. Diet-induced weight loss has been found to lower or to have no effect on BNP levels, whereas gastric banding and gastric bypass have reported divergent results. We studied obese patients undergoing gastric bypass (GBP) surgery during follow-up of 1 year.

    Methods

    Twenty patients, 18 women, mean 41 (SD 9.5) years old, with a mean preoperative BMI of 44.6 (SD 5.5) kg/m2 were examined. N-terminal pro-brain natriuretic peptide (NT-ProBNP), glucose and insulin were measured preoperatively, at day 6 and months 1, 6 and 12. In 14 of the patients, samples were also taken at days 1, 2 and 4.

    Results

    The NT-ProBNP levels showed a marked increase during the postoperative week (from 54 pg/mL preop to 359 pg/mL on day 2 and fell to 155 on day 6). At 1 year, NT-ProBNP was 122 pg/mL (125 % increase, p = 0.01). Glucose, insulin and HOMA indices decreased shortly after surgery without correlation to NT-ProBNP change. Mean BMI was reduced from 44.6 to 30.5 kg/m2 at 1 year and was not related to NT-ProBNP change.

    Conclusions

    The data indicate that GBP surgery rapidly alters the tone of BNP release, by a mechanism not related to weight loss or to changes in glucometabolic parameters. The GBP-induced conversion of obese subjects, from low to high NT-ProBNP responders, is likely to influence the evaluation of cardiac function in GBP operated individuals.

  • 176.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?2013In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 169, no 6, p. 885-889Article in journal (Refereed)
    Abstract [en]

    Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.

  • 177.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hypoglycemia in everyday life after gastric bypass and duodenal switch2015In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 173, no 1, p. 91-100Article in journal (Refereed)
    Abstract [en]

    Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

  • 178.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umea Univ, Biomed Engn, Dept Radiat Sci, Umea, Sweden.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gastric bypass reduces symptoms and hormonal responses to hypoglycemia2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2667-2675Article in journal (Refereed)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 179. Abrahamsson, P
    et al.
    Andersen, K
    Grip, L
    Wallentin, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Dellborg, M
    Early assessment of long-term risk with continuous ST-segment monitoringamong patients with unstable coronary syndromes. Results from 1-yearfollow-up in the TRIM study.2001In: J Electrocardiol, Vol. 34, p. 103-Article in journal (Refereed)
  • 180.
    Abramenkovs, Andris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Induction and repair of clustered DNA damage sites after exposure to ionizing radiation2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The mechanisms that maintain genomic stability safeguard cells from constant DNA damage produced by endogenous and external stressors. Therefore, this thesis aimed to specifically address questions regarding the requirement and involvement of DNA repair proteins in the repair of various types of radiation-induced DNA damage.

    The first aim was to determine whether the phosphorylation of DNA-PKcs, a major kinase involved in non-homologous end joining pathway, can be utilized to score the DNA double-strand break (DSB) content in cells. DNA-PKcs phosphorylated (pDNA-PKcs) at T2609 was more sensitive to the cellular DSB content than ɣH2AX, as analyzed by flow cytometry. Further, pDNA-PKcs at T2609 could discriminate between DSB repair-compromised and normal cells, confirming that the pDNA-PKcs can be used as a DSB repair marker. In paper II, the DSB repair was assessed in cells with reduced levels of DNA-PKcs. The reduction in DNA-PKcs resulted in decreased cell survival and unaffected DSB repair. These results clearly indicate that DNA-PKcs plays an additional role in promoting cell survival in addition to its function in DSB repair.

    The second part of the thesis focused on the characterization of complex DNA damage. DNA damage was investigated after exposure to α-particles originating from Ra-223. The Ra-223 treatment induced a nonrandom DSB distribution consistent with damage induced by high-linear energy transfer radiation. The exposure to Ra-223 significantly reduced cell survival in monolayers and 3D cell structures. The last paper unraveled the fate of heat-sensitive clustered DNA damage site (HSCS) repair in cells. HSCS repair was independent of DSB repair, and these lesions did not contribute to the generation of additional DSBs during repair. Prolonged heating of DNA at relatively low temperatures induced structural changes in the DNA that contributed to the production of DNA artifacts.

    In conclusion, these results demonstrate that DNA-PKcs can be used to monitor DSB repair in cells after exposure to ionizing radiation. However, the functions of DNA-PKcs are not limited to DSB repair, as it can promote cell survival through other mechanisms. The complexity of the DNA damage produced by high-LET radiation is a major contributor to cell death. However, not all clusters produced in irradiated cells are converted into DSBs during repair.

    List of papers
    1. Measurement of DNA-Dependent Protein Kinase Phosphorylation Using Flow Cytometry Provides a Reliable Estimate of DNA Repair Capacity
    Open this publication in new window or tab >>Measurement of DNA-Dependent Protein Kinase Phosphorylation Using Flow Cytometry Provides a Reliable Estimate of DNA Repair Capacity
    2017 (English)In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 188, no 6, p. 597-604Article in journal (Refereed) Published
    Abstract [en]

    Uncontrolled generation of DNA double-strand breaks (DSBs) in cells is regarded as a highly toxic event that threatens cell survival. Radiation-induced DNA DSBs are commonly measured by pulsed-field gel electrophoresis, microscopic evaluation of accumulating DNA damage response proteins (e.g., 53BP1 or gamma-H2AX) or flow cytometric analysis of gamma-H2AX. The advantage of flow cytometric analysis is that DSB formation and repair can be studied in relationship to cell cycle phase or expression of other proteins. However, gamma-H2AX is not able to monitor repair kinetics within the first 60 min postirradiation, a period when most DSBs undergo repair. A key protein in non-homologous end joining repair is the catalytic subunit of DNA-dependent protein kinase. Among several phosphorylation sites of DNA-dependent protein kinase, the threonine at position 2609 (T2609), which is phosphorylated by ataxia telangiectasia mutated (ATM) or DNA-dependent protein kinase catalytic subunit itself, activates the end processing of DSB. Using flow cytometry, we show here that phosphorylation at T2609 is faster in response to DSBs than gamma-H2AX. Furthermore, flow cytometric analysis of T2609 resulted in a better representation of fast repair kinetics than analysis of gamma-H2AX. In cells with reduced ligase IV activity, and wild-type cells where DNA-dependent protein kinase activity was inhibited, the reduced DSB repair capacity was observed by T2609 evaluation using flow cytometry. In conclusion, flow cytometric evaluation of DNA-dependent protein kinase T2609 can be used as a marker for early DSB repair and gives a better representation of early repair events than analysis of gamma-H2AX.

    Place, publisher, year, edition, pages
    RADIATION RESEARCH SOC, 2017
    National Category
    Biophysics
    Identifiers
    urn:nbn:se:uu:diva-343567 (URN)10.1667/RR14693.1 (DOI)000416744600001 ()
    Funder
    Swedish Cancer SocietySwedish Radiation Safety Authority
    Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2019-03-08Bibliographically approved
    2. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair
    Open this publication in new window or tab >>Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair
    2014 (English)In: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 769, p. 1-10Article in journal (Refereed) Published
    Abstract [en]

    Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80-95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or gamma-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure which is uncoupled from its essential function in DSB repair. This could have implications for the development of therapeutic strategies aiming to radiosensitize tumors by affecting the DNA-PKcs function.

    Keywords
    DNA repair, DNA-PKcs, Ionizing radiation, DNA-PK deficiency, NU7441
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:uu:diva-237292 (URN)10.1016/j.mrfmmm.2014.06.004 (DOI)000343625700001 ()
    Available from: 2014-12-03 Created: 2014-12-01 Last updated: 2019-03-08Bibliographically approved
    3. The α-emitter Ra-223 induces clustered DNA damage and significantly reduces cell survival
    Open this publication in new window or tab >>The α-emitter Ra-223 induces clustered DNA damage and significantly reduces cell survival