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1. Cover

Author

Kenneth L. Caneva

Published
2015

5. Part I

Author

Kenneth L. Caneva

Published
2015

18. Notes

Author

Kenneth L. Caneva

Published
2015

20. Helmholtz, the conservation of force and the conservation of vis viva

Author

Kenneth L. Caneva

Subjects
Conservation of energy, Vis viva, Physics, History, 19th Century, 06 humanities and the arts, Physical Phenomena, symbols.namesake, Classical mechanics, 060105 history of science, technology & medicine, History and Philosophy of Science, Germany, Helmholtz free energy, symbols, 0601 history and archaeology, Mechanical Phenomena, Mathematics
Abstract

This paper investigates the relationship between Helmholtz's formulation of the principle of the conservation of force and the two principles well known in rational mechanics as the principle of vis viva and the principle of the conservation of vis viva. An examination of the relevant literature from Leibniz to Duhamel reveals both Helmholtz's indebtedness to that tradition and his creative refashioning of it as he endeavoured to craft an argument that would both prohibit the construction of a perpetuum mobile and the efficacy of a supposed vital force and demonstrate the necessity of an ontology of mass points subject to attractive and repulsive central forces depending solely on distance.

Published
2019
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21. Helmholtz and the Conservation of Energy : Contexts of Creation and Reception

Author

Kenneth L. Caneva and Kenneth L. Caneva

Subjects
Force and energy--History, Physicists--Germany--Biography
Abstract

An examination of the sources Helmholtz drew upon for his formulation of the conservation of energy and the impact of his work on nineteenth-century physics.In 1847, Herman Helmholtz, arguably the most important German physicist of the nineteenth century, published his formulation of what became known as the conservation of energy--unarguably the most important single development in physics of that century, transforming what had been a conglomeration of separate topics into a coherent field unified by the concept of energy. In Helmholtz and the Conservation of Energy, Kenneth Caneva offers a detailed account of Helmholtz's work on the subject, the sources that he drew upon, the varying responses to his work from scientists of the era, and the impact on physics as a discipline.Caneva describes the set of abiding concerns that prompted Helmholtz's work, including his rejection of the idea of a work-performing vital force, and investigates Helmholtz's relationship to both an older generation of physicists and an emerging community of reformist physiologists. He analyzes Helmholtz's indebtedness to Johannes Müller and Justus Liebig and discusses Helmholtz's tense and ambivalent relationship to the work of Robert Mayer, who had earlier proposed the uncreatability, indestructibility, and transformability of'force.'Caneva examines Helmholtz's continued engagement with the subject, his role in the acceptance of the conservation of energy as the central principle of physics, and the eventual incorporation of the principle in textbooks as established science.

Published
2021

22. 37th International Symposium on Intensive Care and Emergency Medicine (part 2 of 3)

Author

D. Rob, R. Špunda, J. Lindner, J. Šmalcová, O. Šmíd, T. Kovárník, A. Linhart, J. Bìlohlávek, M. M. Marinoni, G. Cianchi, S. Trapani, M. L. Migliaccio, L. Gucci, M. Bonizzoli, A. Cramaro, M. Cozzolino, S. Valente, A. Peris, E. Grins, E. Kort, M. Weiland, N. Manandhar Shresta, P. Davidson, L. Algotsson, S. Fitch, G. Marco, J. Sturgill, S. Lee, M. Dickinson, T. Boeve, A. Khaghani, P. Wilton, S. Jovinge, A. N. Ahmad, R. Loveridge, S. Vlachos, S. Patel, E. Gelandt, L. Morgan, S. Butt, M. Whitehorne, V. Kakar, C. Park, M. Hayes, C. Willars, T. Hurst, T. Best, A. Vercueil, G. Auzinger, B. Adibelli, N. Akovali, A. Torgay, P. Zeyneloglu, A. Pirat, Z. Kayhan, S. S. Schmidbauer, J. Herlitz, T. Karlsson, H. Friberg, R. Knafelj, P. Radsel, F. Duprez, T. Bonus, G. Cuvelier, S. Mashayekhi, M. Maka, S. Ollieuz, G. Reychler, R. Mosaddegh, S. Abbasi, S. Talaee, V. Z. Zotzmann, D. S. Staudacher, T. W. Wengenmayer, D. D. Dürschmied, C. B. Bode, A. Nelskylä, J. Nurmi, M. Jousi, A. Schramko, E. Mervaala, G. Ristagno, M. Skrifvars, G. Ozsoy, T. Kendirli, E. Azapagasi, O. Perk, U. Gadirova, E. Ozcinar, M. Cakici, C. Baran, S. Durdu, A. Uysalel, M. Dogan, M. Ramoglu, T. Ucar, E. Tutar, S. Atalay, R. Akar, M. Kamps, G. Leeuwerink, J. Hofmeijer, O. Hoiting, J. Van der Hoeven, C. Hoedemaekers, A. Konkayev, V. Kuklin, T. Kondratyev, M. Konkayeva, N. Akhatov, M. Sovershaev, T. Tveita, V. Dahl, L. Wihersaari, M. B. Skrifvars, S. Bendel, K. M. Kaukonen, J. Vaahersalo, J. Romppanen, V. Pettilä, M. Reinikainen, A. Lybeck, T. Cronberg, N. Nielsen, M. Rauber, K. Steblovnik, A. Jazbec, M. Noc, P. Kalasbail, F. Garrett, E. Kulstad, D. J. Bergström, H. R. Olsson, S. Schmidbauer, I. Mandel, S. Mikheev, Y. Podoxenov, I. Suhodolo, A. Podoxenov, J. Svirko, A. Sementsov, L. Maslov, V. Shipulin, L. V. Vammen, S. R. Rahbek, N. S. Secher, J. P. Povlsen, N. J. Jessen, B. L. Løfgren, A. G. Granfeldt, A. Grossestreuer, S. Perman, P. Patel, S. Ganley, J. Portmann, M. Cocchi, M. Donnino, Y. Nassar, S. Fathy, A. Gaber, S. Mokhtar, Y. C. Chia, R. Lewis-Cuthbertson, K. Mustafa, A. Sabra, A. Evans, P. Bennett, W. Eertmans, C. Genbrugge, W. Boer, J. Dens, C. De Deyne, F. Jans, A. Skorko, M. Thomas, M. Casadio, A. Coppo, A. Vargiolu, J. Villa, M. Rota, L. Avalli, G. Citerio, J. B. Moon, J. H. Cho, C. W. Park, T. G. Ohk, M. C. Shin, M. H. Won, P. Papamichalis, V. Zisopoulou, E. Dardiotis, S. Karagiannis, D. Papadopoulos, T. Zafeiridis, D. Babalis, A. Skoura, I. Staikos, A. Komnos, S. Silva Passos, F. Maeda, L. Silva Souza, A. Amato Filho, T. Araújo Guerra Granjeia, M. Schweller, D. Franci, M. De Carvalho Filho, T. Martins Santos, P. De Azevedo, R. Wall, I. Welters, P. Tansuwannarat, P. Sanguanwit, T. Langer, M. Carbonara, A. Caccioppola, C. Ferraris Fusarini, E. Carlesso, E. Paradiso, M. Battistini, E. Cattaneo, F. Zadek, R. Maiavacca, N. Stocchetti, A. Pesenti, A. Ramos, F. Acharta, J. Toledo, M. Perezlindo, L. Lovesio, A. Dogliotti, C. Lovesio, N. Schroten, B. Van der Veen, M. C. De Vries, J. Veenstra, Y. B. Abulhasan, S. Rachel, M. Châtillon-Angle, N. Alabdulraheem, I. Schiller, N. Dendukuri, M. Angle, C. Frenette, S. Lahiri, K. Schlick, S. A. Mayer, P. Lyden, M. Akatsuka, J. Arakawa, M. Yamakage, J. Rubio, J. A. Rubio Mateo-Sidron, R. Sierra, M. Celaya, L. Benitez, S. Alvarez-Ossorio, A. Fernandez, O. Gonzalez, H. Engquist, E. Rostami, P. Enblad, L. Canullo, J. Nallino, M. Perreault, J. Talic, A. J. Frenette, L. Burry, F. Bernard, D. R. Williamson, D. Adukauskiene, J. Cyziute, A. Adukauskaite, L. Malciene, L. Luca, A. Rogobete, O. Bedreag, M. Papurica, M. Sarandan, C. Cradigati, S. Popovici, C. Vernic, D. Sandesc, V. Avakov, I. Shakhova, H. Trimmel, M. Majdan, G. H. Herzer, C. S. Sokoloff, M. Albert, D. Williamson, C. Odier, J. Giguère, E. Charbonney, Z. Husti, T. Kaptás, Z. Fülep, Z. Gaál, M. Tusa, J. Donnelly, M. Aries, M. Czosnyka, C. Robba, M. Liu, A. Ercole, D. Menon, P. Hutchinson, P. Smielewski, R. López, J. Graf, J. M. Montes, M. Kenawi, A. Kandil, K. Husein, A. Samir, J. Heijneman, J. Huijben, F. Abid-Ali, M. Stolk, J. Van Bommel, H. Lingsma, M. Van der Jagt, R. C. Cihlar, G. Mancino, P. Bertini, F. Forfori, F. Guarracino, D. Pavelescu, I. Grintescu, L. Mirea, S. Alamri, M. Tharwat, N. Kono, H. Okamoto, H. Uchino, T. Ikegami, T. Fukuoka, M. Simoes, E. Trigo, P. Coutinho, J. Pimentel, A. Franci, D. Basagni, M. Boddi, V. Anichini, A. Cecchi, D. Markopoulou, K. Venetsanou, I. Papanikolaou, T. Barkouri, D. Chroni, I. Alamanos, E. Cingolani, M. G. Bocci, L. Pisapia, A. Tersali, S. L. Cutuli, V. Fiore, A. Palma, G. Nardi, M. Antonelli, R. Coke, A. Kwong, D. J. Dwivedi, M. Xu, E. McDonald, J. C. Marshall, A. E. Fox-Robichaud, P. C. Liaw, I. Kuchynska, I. R. Malysh, L. V. Zgrzheblovska, L. Mestdagh, E. F. Verhoeven, I. Hubloue, J. Ruel-laliberte, R. Zarychanski, F. Lauzier, P. Lessard Bonaventure, R. Green, D. Griesdale, R. Fowler, A. Kramer, D. Zygun, T. Walsh, S. Stanworth, C. Léger, A. F. Turgeon, D. M. Baron, J. Baron-Stefaniak, G. C. Leitner, R. Ullrich, O. Tarabrin, A. Mazurenko, Y. Potapchuk, D. Sazhyn, P. Tarabrin, A. González Pérez, J. Silva, V. Artemenko, A. Bugaev, I. Tokar, S. Konashevskaya, I. M. Kolesnikova, E. V. Roitman, T. Rengeiné Kiss, Z. Máthé, L. Piros, E. Dinya, E. Tihanyi, A. Smudla, J. Fazakas, R. Ubbink, P. Boekhorst te, E. Mik, L. Caneva, G. Ticozzelli, S. Pirrelli, D. Passador, F. Riccardi, F. Ferrari, E. M. Roldi, M. Di Matteo, I. Bianchi, G. A. Iotti, G. Zurauskaite, A. Voegeli, M. Meier, D. Koch, S. Haubitz, A. Kutz, M. Bargetzi, B. Mueller, P. Schuetz, G. Von Meijenfeldt, M. Van der Laan, C. Zeebregts, K. B. Christopher, P. Vernikos, T. Melissopoulou, G. Kanellopoulou, M. Panoutsopoulou, D. Xanthis, K. Kolovou, T. Kypraiou, J. Floros, H. Broady, C. Pritchett, M. Marshman, N. Jannaway, C. Ralph, C. L. Lehane, C. K. Keyl, E. Z. Zimmer, D. T. Trenk, A. S. Ducloy-Bouthors, M. J. Jonard, F. Fourrier, F. Piza, T. Correa, A. Marra, J. Guerra, R. Rodrigues, A. Vilarinho, V. Aranda, S. Shiramizo, M. R. Lima, E. Kallas, A. B. Cavalcanti, M. Donoso, P. Vargas, J. McCartney, S. Ramsay, K. McDowall, I. Novitzky-Basso, C. Wright, M Grgic Medic, L Bielen, V Radonic, O Zlopasa, N Gubarev Vrdoljak, V Gasparovic, R Radonic, G. Narváez, D. Cabestrero, L. Rey, M. Aroca, S. Gallego, J. Higuera, R. De Pablo, L. Rey González, G. Narváez Chávez, J. Higuera Lucas, D. Cabestrero Alonso, M. Aroca Ruiz, L. Jaramillo Valarezo, R. De Pablo Sánchez, A. Quinza Real, T. W. Wigmore, I. Bendavid, J. Cohen, I. Avisar, I. Serov, I. Kagan, P. Singer, J Hanison, U Mirza, D Conway, A. Takasu, H. Tanaka, N. Otani, S. Ohde, S. Ishimatsu, F Coffey, P Dissmann, K Mirza, M Lomax, P. Dissmann, F. Coffey, K. Mirza, M. Lomax, JR Miner, R Leto, AM Markota, PG Gradišek, VA Aleksejev, AS Sinkovič, S. Romagnoli, C. Chelazzi, G. Zagli, F. Benvenuti, P. Mancinelli, P. Boninsegni, L. Paparella, A. T. Bos, O. Thomas, T. Goslar, A. Martone, P. R. Sandu, V. A. Rosu, A. Capilnean, P. Murgoi, A. Lecavalier, D. Jayaraman, P. Rico, P. Bellemare, C. Gelinas, T. Nishida, T. Kinoshita, N. Iwata, K. Yamakawa, S. Fujimi, L. Maggi, F. Sposato, G. Citterio, C. Bonarrigo, M. Rocco, V. Zani, R. A. De Blasi, D Alcorn, L Barry, M. A. Riedijk, D. M. Milstein, J. Caldas, R. Panerai, L. Camara, G. Ferreira, E. Bor-Seng-Shu, M. Lima, F. Galas, N. Mian, R. Nogueira, G. Queiroz de Oliveira, J. Almeida, J. Jardim, T. G. Robinson, F. Gaioto, L. A. Hajjar, I. Zabolotskikh, T. Musaeva, W. Saasouh, J. Freeman, A. Turan, S. Saseedharan, E. Pathrose, S. Poojary, J. Messika, Y. Martin, N. Maquigneau, M. Henry-Lagarrigue, C. Puechberty, A. Stoclin, L. Martin-Lefevre, F. Blot, D. Dreyfuss, A. Dechanet, D. Hajage, J. Ricard, E. Almeida, G. Landoni, J. Fukushima, E. Fominskiy, C. De Brito, L. Cavichio, L. Almeida, U. Ribeiro, E. Osawa, R. Boltes, L. Battistella, L. Hajjar, P. Fontela, T. Lisboa, L. Forgiarini Junior, G. F. Friedman, F. Abruzzi, J. Azevedo Peixoto Primo, P. Marques Filho, J. Stormorvski de Andrade, K. Matos Brenner, M. Scorsato boeira, C. Leães, C. Rodrigues, A. Vessozi, A. SantAnna Machado, M. Weiler, H. Bryce, A. Hudson, T. Law, R. Reece-Anthony, A. Molokhia, F. Abtahinezhadmoghaddam, E. Cumber, L. Channon, A. Wong, R. Groome, D. Gearon, J. Varley, A. Wilson, J. Reading, F. G. Zampieri, F. A. Bozza, M. Ferez, H. Fernandes, A. Japiassú, J. Verdeal, A. C. Carvalho, M. Knibel, J. I. Salluh, M. Soares, J. Gao, E. Ahmadnia, B. Patel, A. MacKay, S. Binning, R. J. Pugh, C. Battle, C. Hancock, W. Harrison, T. Szakmany, F. Mulders, J. Vandenbrande, J. Dubois, B. Stessel, K. Siborgs, D. Ramaekers, U. V. Silva, W. S. Homena, G. C. Fernandes, A. P. Moraes, L. Brauer, M. F. Lima, F. De Marco, N. Maric, M. Mackovic, N. Udiljak, CE Bosso, RD Caetano, AP Cardoso, OA Souza, R Pena, MM Mescolotte, IA Souza, GM Mescolotte, H. Bangalore, E. Borrows, D. Barnes, V. Ferreira, L. Azevedo, G. Alencar, A. Andrade, A. Bierrenbach, L. Tadini Buoninsegni, L. Cecci, J. Lindskog, K. Rowland, P. Sturgess, A. Ankuli, R Rosa, T Tonietto, A Ascoli, L Madeira, W Rutzen, M Falavigna, C Robinson, J Salluh, A Cavalcanti, L Azevedo, R Cremonese, D Da Silva, A Dornelles, Y Skrobik, J Teles, T Ribeiro, C Eugênio, C Teixeira, M. Zarei, H. Hashemizadeh, M. Eriksson, G. Strandberg, M. Lipcsey, A. Larsson, M. Lignos, E. Crissanthopoulou, K. Flevari, P. Dimopoulos, A. Armaganidis, JG Golub, AS Stožer, H. Rüddel, C. Ehrlich, C. M. Burghold, C. Hohenstein, J. Winning, W. Sellami, Z. Hajjej, M. Bousselmi, H. Gharsallah, I. Labbene, M. Ferjani, J. Sattler, D. Steinbrunner, H. Poppert, G. Schneider, M. Blobner, K. G. Kanz, S. J. Schaller, K. Apap, G. Xuereb, L. Massa, N. Delvau, A Penaloza, G Liistro, F Thys, I. K. Delattre, P. Hantson, P. M. Roy, P. Gianello, L Hadîrcă, A Ghidirimschi, N Catanoi, N Scurtov, M Bagrinovschi, Y. S. Sohn, Y. C. Cho, B. Golovin, O. Creciun, A. Ghidirimschi, M. Bagrinovschi, R. Tabbara, J. Z. Whitgift, A. Ishimaru, A. Yaguchi, N. Akiduki, M. Namiki, M. Takeda, J. N. Tamminen, A. Uusaro, C. G. Taylor, E. D. Mills, A. D. Mackay, C. Ponzoni, R. Rabello, A. Serpa, M. Assunção, A. Pardini, G. Shettino, T. Corrêa, P. V. Vidal-Cortés, L. Álvarez-Rocha, P. Fernández-Ugidos, A. Virgós-Pedreira, M. A. Pérez-Veloso, I. M. Suárez-Paul, L. Del Río-Carbajo, S. Pita Fernández, A. Castro-Iglesias, A. Butt, A. A. Alghabban, S. K. Khurshid, Z. A. Ali, I. N. Nizami, N. S. Salahuddin, M. Alshahrani, A. W. Alsubaie, A. S. Alshamsy, B. A. Alkhiliwi, H. K. Alshammari, M. B. Alshammari, N. K. Telmesani, R. B. Alshammari, L. P. Asonto, L. P. Damiani, F Bozza, A. El Khattate, M. Bizrane, N. Madani, J. Belayachi, R. Abouqal, D. Ramnarain, B. Gouw-Donders, C. Benstoem, A. Moza, P. Meybohm, C. Stoppe, R. Autschbach, D. Devane, A. Goetzenich, L. U. Taniguchi, L. Araujo, G. Salgado, J. M. Vieira, J. Viana, N. Ziviani, I. Pessach, A. Lipsky, A. Nimrod, M. O´Connor, I. Matot, E. Segal, A. Kluzik, A. Gradys, P. Smuszkiewicz, I. Trojanowska, M. Cybulski, A. De Jong, M. Sebbane, G. Chanques, S. Jaber, R. Rosa, C. Robinson, M. Bessel, L. Cavalheiro, L. Madeira, W. Rutzen, R. Oliveira, J. Maccari, M. Falavigna, E. Sanchez, F. Dutra, C. Dietrich, P. Balzano, J. Rezende, C. Teixeira, S. Sinha, K. Majhi, J. G. Gorlicki, F. P. Pousset, J. Kelly, J. Aron, A. Crerar Gilbert, N. Prevec Urankar, M. Irazabal, M. Bosque, J. Manciño, A. Kotsopoulos, N. Jansen, W. Abdo, Ú. M. Casey, B. O’Brien, R. Plant, and B. Doyle

Subjects
Fatal outcome, business.industry, Traumatic brain injury, 030208 emergency & critical care medicine, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, Outcome (game theory), 03 medical and health sciences, 0302 clinical medicine, Anesthesia, Medicine, business, Acute subdural hematoma
Published
2017
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24. Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

Author

null Author et al, R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis, J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez Gallego, F. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. Tuzun, R. Riff, O. Naamani, A. Douvdevani, R. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. Shimazu, S. Ono, T. Kubo, S. Suda, T. Ueno, T. Ikeda, H. Ogura, H. Takahashi, J. Kang, Y. Nakamura, T. Kojima, Y. Izutani, T. Taniguchi, M. O, C. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. Lott, M. M. Meili, P. S. Schuetz, H. Hawa, M. Sharshir, M. Aburageila, N. Salahuddin, V. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. Michaloudis, A. Kodaira, H. Imaizumi, M. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-Alcantara, N. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. Nee, G. Nicolaes, M. Wiewel, M. Schultz, K. Wildhagen, J. Horn, R. Schrijver, T. Van der Poll, C. Reutelingsperger, S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans, E. G. Gayat, J. Struck, A. Cariou, N. Deye, B. Guidet, S. Jabert, J. Launay, M. Legrand, M. Léone, M. Resche-Rigon, E. Vicaut, A. Vieillard-Baron, A. Mebazaa, R. Arnold, M. Capan, A. Linder, P. Akesson, M. Popescu, D. Tomescu, C. L. Sprung, R. Calderon Morales, G. Munteanu, E. Orenbuch-Harroch, P. Levin, H. Kasdan, A. Reiter, T. Volker, Y. Himmel, Y. Cohen, J. Meissonnier, L. Girard, F. Rebeaud, I. Herrmann, B. Delwarde, E. Peronnet, E. Cerrato, F. Venet, A. Lepape, T. Rimmelé, G. Monneret, J. Textoris, N. Beloborodova, V. Moroz, A. Osipov, A. Bedova, Y. Sarshor, A. Pautova, A. Sergeev, E. Chernevskaya, J. Odermatt, R. Bolliger, L. Hersberger, M. Ottiger, M. Christ-Crain, B. Mueller, P. Schuetz, N. K. Sharma, A. K. Tashima, M. K. Brunialti, F. R. Machado, M. Assuncao, O. Rigato, R. Salomao, S. C. Cajander, G. Rasmussen, E. Tina, B. Söderquist, J. Källman, K. Strålin, A. L. Lange, J. S. Sundén-Cullberg, A. M. Magnuson, O. H. Hultgren, P. Van der Geest, M. Mohseni, J. Linssen, R. De Jonge, S. Duran, J. Groeneveld, R. Miller, B. K. Lopansri, L. C. McHugh, A. Seldon, J. P. Burke, J. Johnston, R. Reece-Anthony, A. Bond, A. Molokhia, C. Mcgrath, E. Nsutebu, P. Bank Pedersen, D. Pilsgaard Henriksen, S. Mikkelsen, A. Touborg Lassen, R. Tincu, C. Cobilinschi, Z. Ghiorghiu, R. Macovei, M. A. Wiewel, M. B. Harmon, L. A. Van Vught, B. P. Scicluna, A. J. Hoogendijk, A. H. Zwinderman, O. L. Cremer, M. J. Bonten, M. J. Schultz, N. P. Juffermans, W. J. Wiersinga, G. Eren, Y. Tekdos, M. Dogan, O. Acicbe, E. Kaya, O. Hergunsel, S. Alsolamy, G. Ghamdi, L. Alswaidan, S. Alharbi, F. Alenezi, Y. Arabi, J. Heaton, A. Boyce, L. Nolan, A. Dukoff-Gordon, A. Dean, T. Mann Ben Yehudah, C. Fleischmann, D. Thomas-Rueddel, C. Haas, U. Dennler, K. Reinhart, O. Suntornlohanakul, B. Khwannimit, F. Breckenridge, A. Puxty, P. Szturz, P. Folwarzcny, J. Svancara, R. Kula, P. Sevcik, L. Caneva, A. Casazza, E. Bellazzi, S. Marra, L. Pagani, M. Vetere, R. Vanzino, D. Ciprandi, R. Preda, R. Boschi, L. Carnevale, V. Lopez, M. Aguilar Arzapalo, L. Barradas, A. Escalante, J. Gongora, M. Cetina, B Adamik, D Jakubczyk, A Kübler, A. Radford, T. Lee, J. Singer, J. Boyd, D. Fineberg, M. Williams, J. Russell, E. Scarlatescu, G. Droc, S. Arama, M. Müller, M. Straat, S. S. Zeerleder, C. F. Fuchs, C. S. Scheer, S. W. Wauschkuhn, M. V. Vollmer, K. M. Meissner, S. K. Kuhn, K. H. Hahnenkamp, S. R. Rehberg, M. G. Gründling, S. Hamaguchi, E. Gómez-Sánchez, M. Heredia-Rodríguez, E. Álvarez-Fuente, M. Lorenzo-López, E. Gómez-Pesquera, M. Aragón-Camino, P. Liu-Zhu, A. Sánchez-López, A. Hernández-Lozano, M. T. Peláez-Jareño, E. 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Kongkamol, B. Xavier, C. Koutsogiannidis, M. Moschopoulou, G. Taskin, M. Çakir, AK Güler, A. Taskin, N. Öcal, S. Özer, L. Yamanel, J. M. Wong, C. Fitton, S. Anwar, S. Stacey, M. Aggou, B. Fyntanidou, S. Patsatzakis, E. Oloktsidou, K. Lolakos, E. Papapostolou, V. Grosomanidis, S. Gaudry, V. Desailly, P. Pasquier, PB Brun, AT Tesnieres, JD Ricard, D. Dreyfuss, A. Mignon, J. C White, A. Stilwell, G. Friedlaender, M. Peters, S. Stipulante, A. Delfosse, AF Donneau, A. Ghuysen, C. Feldmann, D. Freitag, W. Dersch, M. Irqsusi, D. Eschbach, T. Steinfeldt, H. Wulf, T. Wiesmann, J. Cholkraisuwat, S. Beitland, E. Nakstad, H. Stær-Jensen, T. Drægni, G. Andersen, D. Jacobsen, C. Brunborg, B. Waldum-Grevbo, K. Sunde, K. Hoyland, D. Pandit, K. Hayakawa, K. Kotzampassi, L. Loukipoudi, E. Doumaki, M. M. Admiraal, M. Van Assen, M. J. Van Putten, M. Tjepkema-Cloostermans, A. F. Van Rootselaar, F. Ragusa, A. Marudi, S. Baroni, A. Gaspari, E. Bertellini, T. Abdullah, S. Abdel Monem, S. Alcorn, S. McNeill, S. Russell, W. Eertmans, C. Genbrugge, I. Meex, J. Dens, F. Jans, C. De Deyne, B Avard, R Burns, A. Patarchi, T. Spina, H. Tanaka, N. Otani, S. Ode, S. Ishimatsu, J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin, M. H. Won, S. Dakova, Z. Ramsheva, K. Ramshev, A Marudi, S Baroni, A Gaspari, E Bertellini, P. E. Ozcan, S. Sencer, C. Ulusoy, M. Fallenius, M. B. Skrifvars, M. Reinikainen, S. Bendel, R. Raj, M. Abu-Habsa, C. Hymers, A. Borowska, H. Sivadhas, S. Sahiba, S. Perkins, J. Rubio, J. A. Rubio, R. Sierra, S. English, M. Chasse, A. Turgeon, F. Lauzier, D. Griesdale, A. Garland, D. Fergusson, R. Zarychanski, A. Tinmouth, C. Van Walraven, K. Montroy, J. Ziegler, R. Dupont Chouinard, R. Carignan, A. Dhaliwal, C. Lum, J. Sinclair, G. Pagliarello, L. McIntyre, T. Groza, N. Moreau, D. Castanares-Zapatero, P. Hantson, M. Carbonara, F. Ortolano, T. Zoerle, S. Magnoni, S. Pifferi, V. Conte, N. Stocchetti, L. Carteron, T. Suys, C. Patet, H. Quintard, M. Oddo, V. Spatenkova, E. Pokorna, P. Suchomel, N. Ebert, T. Bylinski, C. Hawthorne, M. Shaw, I. Piper, J. Kinsella, A. K. Kink, I. R. Rätsep, A. Boutin, L. Moore, J. Lacroix, P. Lessard-Bonaventure, A. F. Turgeon, R. Green, M. Erdogan, M. Butler, P. Desjardins, D. A. Fergusson, B. Goncalves, B. Vidal, C. Valdez, A. C. Rodrigues, L. Miguez, G. Moralez, T. Hong, A. Kutz, P. Hausfater, D. Amin, T. Struja, S. Haubitz, A. Huber, T. Brown, J. Collinson, C. Pritchett, T. Slade, M. Le Guen, S. Hellings, R. Ramsaran, A. Alsheikhly, T. Abe, L. Kanapeckaite, R. Bahl, M. Q. Russell, K. J. Real, R. M. Lyon, N. P. Oveland, J. Penketh, M. Mcdonald, F. Kelly, M. Alfafi, W. Almutairi, B. Alotaibi, A. E Van den Berg, Y. Schriel, L. Dawson, I. A. Meynaar, D. Silva, S. Fernandes, J. Gouveia, J. Santos Silva, J. Foley, A. Kaskovagheorgescu, D. Evoy, J. Cronin, J. Ryan, M. Huck, C. Hoffmann, J. Renner, P. Laitselart, N. Donat, A. Cirodde, J. V. Schaal, Y. Masson, A. Nau, O. Howarth, K. Davenport, P. Jeanrenaud, S. Raftery, P. MacTavish, H. Devine, J. McPeake, M. Daniel, T. Quasim, S. Alrabiee, A. Alrashid, O. Gundogan, C. Bor, E. Akýn Korhan, K. Demirag, M. Uyar, F. Frame, C. Ashton, L. Bergstrom Niska, P. Dilokpattanamongkol, T. Suansanae, C. Suthisisang, S. Morakul, C. Karnjanarachata, V. Tangsujaritvijit, S. Mahmood, H. Al Thani, A. Almenyar, S. E. Morton, Y. S. Chiew, C. Pretty, J. G. Chase, G. M. Shaw, P. Kordis, V. Grover, I. Kuchyn, K. Bielka, Z. Aidoni, G. Stavrou, C. Skourtis, S. D. Lee, K. Williams, I. D. Weltes, S. Berhane, C. Arrowsmith, C. Peters, S. Robert, R. B. Panerai, T. G. Robinson, E. Borg-Seng-Shu, M. De Lima Oliveira, N. C. Mian, R. Nogueira, S. P. Zeferino, M. Jacobsen Teixeira, P. Killeen, M. McPhail, W. Bernal, J. Maggs, J. Wendon, T. Hughes, L. U. Taniguchi, E. M. Siqueira, J. M. Vieira Jr, L. C. Azevedo, A. N. Ahmad, E. Helme, S. Hadfield, J. Shak, C. Senver, R. Howard-Griffin, P. Wacharasint, P. Fuengfoo, N. Sukcharoen, R. Rangsin, D. Sbiti-Rohr, H. Na, S. Song, S. Lee, E. Jeong, K. Lee, E. Zoumpelouli, E. A Volakli, V. Chrysohoidou, K. Charisopoulou, E. Kotzapanagiotou, K. Manavidou, Z. Stathi, B. AlGhamdi, Q. Marashly, K. Zaza, M. Khurshid, Z. Ali, M. Malgapo, M. Jamil, A. Shafquat, M. Shoukri, M. Hijazi, F. A. Rocha, K. Ebecken, L. S. Rabello, M. F. Lima, R. Hatum, F. V. De Marco, A. Alves, J. E. Pinto, M. Godoy, P. E. Brasil, F. A. Bozza, J. I. Salluh, M. Soares, J. Krinsley, G. Kang, J. Perry, H. Hines, K. M. Wilkinson, C. Tordoff, B. Sloan, M. C. Bellamy, E. Moreira, F. Verga, M. Barbato, G. Burghi, M Soares, U. V. Silva, A. P. Torelly, J. M. Kahn, D. C. Angus, M. F. Knibel, R. Marshall, T. Gilpin, D. Mota, B. Loureiro, J. Dias, O. Afonso, F. Coelho, A. Martins, F. Faria, H. Al Orainni, F. AlEid, H. Tlaygeh, A. Itani, A. Hejazi, J. Messika, J. D. Ricard, S. Guillo, B. Pasquet, E. Dubief, F. Tubach, K. James, P. Temblett, L. Davies, C. Lynch, S. Pereira, S. Cavaco, J. Fernandes, I. Moreira, E. Almeida, F. Seabra Pereira, M. Malheiro, F. Cardoso, I. Aragão, T. Cardoso, M. Fister, P. Muraray Govind, N. Brahmananda Reddy, R. Pratheema, E. D. Arul, J. Devachandran, N. Chin-Yee, G. D’Egidio, K. Thavorn, K. Kyeremanteng, A. G. Murchison, K. Swalwell, J. Mandeville, D. Stott, I. Guerreiro, C. Goossens, M. B. Marques, S. Derde, S. Vander Perre, T. Dufour, S. E. Thiessen, F. Güiza, T. Janssens, G. Hermans, I. Vanhorebeek, K. De Bock, G. Van den Berghe, L. Langouche, B. Miles, S. Madden, M. Weiler, P. Marques, C. Rodrigues, M. Boeira, K. Brenner, C. Leães, A. Machado, R. Townsend, J. Andrade, R. Kishore, C. Fenlon, T. Fiks, A. Ruijter, M. Te Raa, P. Spronk, P. Docherty, J. Dickson, E. Moltchanova, C. Scarrot, T. Hall, W. C. Ngu, J. M. Jack, A. Pavli, X. Gee, E. Akin Korhan, M. Shirazy, A. Fayed, S. Gupta, A. Kaushal, S. Dewan, A. Varma, E. Ghosh, L. Yang, L. Eshelman, B. Lord, E. Carlson, R. Broderick, J. Ramos, D. Forte, F. Yang, J. Feeney, K. Wilkinson, K. Shuker, M. Faulds, D. Bryden, L. England, K Shuker, A Tridente, M Faulds, A Matheson, J. Gaynor, D Bryden, S South Yorkshire Hospitals Researc ᅟ, B. Peroni, R. Daglius-Dias, L. Miranda, C. Cohen, C. Carvalho, I. Velasco, J. M. Kelly, A. Neill, G. Rubenfeld, N. Masson, A. Min, E. Boezeman, J. Hofhuis, A. Hovingh, R. De Vries, G. Cabral-Campello, M. Van Mol, M. Nijkamp, E. Kompanje, P. Ostrowski, K. Kiss, B. Köves, V. Csernus, Z. Molnár, Y. Hoydonckx, S. Vanwing, V. Medo, R. Galvez, J. P. Miranda, C. Stone, T. Wigmore, Y. Arunan, A. Wheeler, Y. Wong, C. Poi, C. Gu, P. Molmy, N. Van Grunderbeeck, O. Nigeon, M. Lemyze, D. Thevenin, J. Mallat, M. Correa, R. T. Carvalho, A. Fernandez, C. McBride, E. Koonthalloor, C. Walsh, A. Webber, M. Ashe, K. Smith, E. A. Volakli, M. Dimitriadou, P. Mantzafleri, O. Vrani, A. Arbouti, T. Varsami, J. A. Bollen, T. C. Van Smaalen, W. C. De Jongh, M. M. Ten Hoopen, D. Ysebaert, L. W. Van Heurn, W. N. Van Mook, A. Roze des Ordons, P. Couillard, C. Doig, R. V. Van Keer, R. D. Deschepper, A. F. Francke, L. H. Huyghens, J. B. Bilsen, B. Nyamaizi, C. Dalrymple, A. Dobru, E. Marrinan, A. Ankuli, R. Struthers, R. Crawford, P. Mactavish, P. Morelli, M. Degiovanangelo, F. Lemos, V. MArtinez, J. Cabrera, A. Rutten, S. Van Ieperen, S. De Geer, M. Van Vugt, E. Der Kinderen, A. Giannini, G Miccinesi, T Marchesi, and E Prandi

Subjects
0301 basic medicine, 03 medical and health sciences, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, 030104 developmental biology, 0302 clinical medicine, business.industry, Intensive care, Emergency medicine, Medicine, Critical Care and Intensive Care Medicine, business
Published
2016
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36. ‘Discovery’ as a site for the collective construction of scientific knowledge

Author

Kenneth L. Caneva

Subjects
Sociology of scientific knowledge, Process (engineering), media_common.quotation_subject, Philosophy, General Physics and Astronomy, Consensus formation, Historiography, Plant Science, Social constructionism, Epistemology, Embodied cognition, Perception, Animal Science and Zoology, Attribution, media_common
Abstract

Hans Christian Ørsted and Thomas Johann Seebeck are recognized as the discoverers of electromagnetism and thermoelectricity. Yet what each man believed he had discovered differed markedly from what many contemporaries saw in those discoveries and from subsequent canonized representations of them. The central historical concern of this paper is to track the details of how scientists' understanding of what was discovered in these two cases, as embodied in their preferred language, evolved over time in response to different interests, conceptual preferences, and ontological beliefs. The very concept of discovery, in accordance with which scientists bestow recognition only on someone who has discovered something held to be true of the world, plays an important role in the process of consensus formation by the interacting collectivity of scientists. In its historiographical assessment of such episodes, this study builds upon Thomas Kuhn's recognition that “discovering a new sort of phenomena is necessarily a complex process which includes recognizing both that something is and what it is”; upon augustine Brannigan's analysis of the social construction of discovery accounts, whereby “the attribution of discovery is structured…by the perception that the achievement is coherent with existing knowledge in the field”; and upon Ludwik Fleck's analysis of the creative role of an interacting “thought collective” in the “genesis and development of a scientific fact.”

Published
2005
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37. The Ecology of Romantic BiologyRobert J. Richards. The Romantic Conception of Life: Science and Philosophy in the Age of Goethe. (Science and Its Conceptual Foundations.) xix+587 pp., frontis., illus., bibl., index. Chicago: University of Chicago Press, 2002. $35 (cloth)

Author

Kenneth L. Caneva

Subjects
History, media_common.quotation_subject, Ecology (disciplines), Context (language use), Patience, Biology, Romance, language.human_language, German, History and Philosophy of Science, Evolutionary biology, Aesthetics, Earth and Planetary Sciences (miscellaneous), language, Abstraction, Period (music), media_common
Abstract

In its exhaustive survey of essential primary sources, its sympathetic yet incisive analysis, and its masterful interweaving of the lives and ideas of his dozen protagonists, the bulk of Robert Richards’s Romantic Conception of Life constitutes the best synthetic account I have ever read of the scientific—especially biological—aspects of German Romantic philosophy. The author has explored all imaginable sources and mined them for every relevant nugget of information. Focusing roughly on the period 1770–1830, Richards has charted the philosophical and scientific ideas of German Romantic thinkers “as their ideas emerged from the intellectual legacy to which they were heir, from their immediate scientific experiences, and especially from their more intimate personal relationships” (p. xviii). The amount of biographical detail may tax the patience of the reader who wants to know what the significance is of this or that fact, but the picture that results is all the richer for having been so fleshed out, and it well illustrates Richards’s point that an adequate understanding of German Romantic philosophy cannot be divorced from the interconnected lives of the people who created it. “Out of these intellectual and personal interactions came a mode of thought that emphasized creative becoming, development, and self-realization” (p. 200). Richards is especially good, for example, in showing the connections between Goethe’s art and science in the context of his lived life, in particular his aesthetic response to both women in the flesh and the female as an abstraction. Nor did he thereby ignore the importance of Goethe’s response to both Kant’s and Schelling’s philosophical enterprises. Indeed, the book invites reflection on what it means to understand a philosophical system like Schelling’s, which evolved from work to work without ever achieving canonical form, which employed concepts and modes of thought largely alien to most of us, and which

Published
2003
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38. The best of times, the worst of times

Author

Kenneth L. Caneva and Barry Barnes

Subjects
History, Philosophy of biology, Philosophy of sport, Philosophy of science, Philosophy of design, History and Philosophy of Science, Philosophy, General Social Sciences, Western philosophy, Philosophy education, History general, Philosophy of technology, Epistemology
Published
2001
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41. Physics and Naturphilosophie: A Reconnaissance

Author

N. Kenneth L. Caneva

Subjects
History, Natural philosophy, 060105 history of science, technology & medicine, History and Philosophy of Science, 0602 languages and literature, Naturphilosophie, Art history, 0601 history and archaeology, 06 humanities and the arts, 060202 literary studies, Humanities
Abstract

Les idees du mouvement intellectuel de la philosophie naturelle ont influence les physiciens du XIX e siecle, particulierement les physiciens allemands dont l'A. decrit les travaux

Published
1997
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42. Colding, Ørsted, and the Meanings of Force

Author

Kenneth L. Caneva

Subjects
Human spirit, Conservation of energy, Philosophy, General Physics and Astronomy, Quality (philosophy), Metaphysics, Conviction, Animal Science and Zoology, Plant Science, Epistemology
Abstract

THE DANISH PHYSICIST and engineer Ludvig August Colding (1815-1888) is known to historians of nineteenth-century physics as the author of one of several formulations, during the 1840s, of the concept that eventually gained currency as the principle of the conservation of energy. Thanks largely to the work of Per Dahl, the substance of Colding's work and a rough idea of the route he followed has been known for several decades.1 In brief, Colding sought experimental corroboration, in terms of the frictional heat produced via the expenditure of a measured amount of mechanical work, of a rough notion of the general imperishability of the forces of nature that he derived from an originally metaphysical conviction concerning the imperishability of the human spirit regarded as a species of force. Nor has the importance gone unnoticed of (Holding's relationship to Hans Christian Orsted (1777-1851), to whom Colding was attached for many years as student and protege Orsted had disclosed the interactive relationship between electricity and magnetism in 1820 and was a highly visible proponent of the notion of the unity of nature, as showcased in particular in the collection of essays he entitled The spirit in nature? Yet some of the important details in this overall picture remain unclear. The quality of Colding's metaphysical beliefs has not been explored in appropriate depth, nor has the significance been established of his brief reference to the role played in the development of his ideas by the antimateri alistic pronouncements of zoologist and physiologist Daniel Frederik Eschricht (1798-1863).3 Nor have we been adequately enlightened as to the significance of what he referred to as d'Alembert's principle of lost forces, or to the status of such a principle in the mechanics of the period.4 And his relationship to Orsted is problematic. Although there would appear to be some important con nection between Colding's and Orsted's general views on nature and its forces, and Orsted occasionally asserted some kind of unity among the forces of nature, he failed signally to appreciate the significance of Colding's work when it was given him to evaluate.5 The solution to this apparent paradox will be sought through an understanding of Orsted's changing conception of force and its relationship to the "activities" of heat, light, electricity, magnetism, and chemical activity.6 Without paying proper attention to language, historians have tended to read back into Orsted's usages meanings of "force" that came to it in large part as a result of the work of Colding and his generation.7

Published
1997
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45. Ørsted's Presentation Of Others'—And His Own—Work

Author

Kenneth L. Caneva

Subjects
Sociology of scientific knowledge, media_common.quotation_subject, language.human_language, Epistemology, Body of knowledge, German, Presentation, Work (electrical), Action (philosophy), Agency (sociology), language, Chemistry (relationship), Sociology, media_common
Abstract

Orsted is best known for his discovery of electromagnetism in 1820, clearly his most important and arguably h is only significant contribution to ‘science’ understood as a body of knowledge pertaining to a canonical set of fundamental phenomena. Yet if by ‘science’ one understands the flesh-and-blood, words-on-paper world of ongoing human activity that produces such knowledge, then Orsted’s contemporary significance looms much larger. It turns out that a striking amount of the work of other scientists became known principally through his agency, sometimes becoming so transformed in the process that what the larger world of science took, and continues to take, as others’ work in fact bears the strong stamp of Orsted’s transmission. His fluency in German and French, his extensive European travels, and his wide circle of acquaintances all facilitated his personal influence. This paper examines in detail Orsted’s role in presenting—and significantly transforming—Winterl’s dualistic chemistry, in bringing before a Parisian audience Ritter’s experiments on the chemical action of light and his construction of a storage column for galvanic electricity, and in recasting Seebeck’s discovery of the “magnetic polarization of metals by temperature difference” in terms of his conception of thermoelectricity. It further examines some of the changes Orsted made in the presentation of his own work to different audiences—changes that throw in particular relief Orsted’s complex relationship to German Naturphilosophie—as it identifies some of the peculiar aspects of his presentation of his electrodynamical work of 1820. The result is an enhanced appreciation of Orsted’s important place in the science of his day, a deeper understanding of Orsted’s own scientific work, and an illustration of the complex interrelationship between individuals and the scientific community in the creation of generally accepted scientific knowledge.

Published
2007
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46. Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells

Author

N, Quirici, D, Soligo, L, Caneva, F, Servida, P, Bossolasco, and G L, Deliliers

Subjects
Neovascularization, Physiologic, Antigens, CD34, Cell Differentiation, Cell Separation, Flow Cytometry, Hematopoietic Stem Cells, Immunohistochemistry, Coculture Techniques, Colony-Forming Units Assay, Microscopy, Electron, Antigens, CD, Humans, Microscopy, Phase-Contrast, AC133 Antigen, Endothelium, Vascular, Peptides, Glycoproteins
Abstract

We report a method of purifying, characterizing and expanding endothelial cells (ECs) derived from CD133(+) bone marrow cells, a subset of CD34(+) haematopoietic progenitors. Isolated using immunomagnetic sorting (mean purity 90 +/- 5%), the CD133(+) bone marrow cells were grown on fibronectin-coated flasks in M199 medium supplemented with fetal bovine serum (FBS), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and insulin growth factor (IGF-1). The CD133(+) fraction contained 95 +/- 4% CD34(+) cells, 3 +/- 2% cells expressing VEGF receptor (VEGFR-2/KDR), but did not express von Willebrand factor (VWF), VE-cadherin, P1H12 or TE-7. After 3 weeks of culture, the cells formed a monolayer with a typical EC morphology and expanded 11 +/- 5 times. The cells were further purified using Ulex europaeus agglutinin-1 (UEA-1)-fluorescein isothiocyanate (FITC) and anti-FITC microbeads, and expanded with VEGF for a further 3 weeks. All of the cells were CD45(-) and CD14(-), and expressed several endothelial markers (UEA-1, VWF, P1H12, CD105, E-selectin, VCAM-1 and VE-cadherin) and typical Weibel-Palade bodies. They had a high proliferative potential (up to a 2400-fold increase in cell number after 3 weeks of culture) and the capacity to modulate cell surface antigens upon stimulation with inflammatory cytokines. Purified ECs were also co-cultivated with CD34(+) cells, in parallel with a purified fibroblastic cell monolayer. CD34(+) cells (10 x 10(5)) gave rise to 17,951 +/- 2422 CFU-GM colonies when grown on endothelial cells, and to 12,928 +/- 4415 CFU-GM colonies on fibroblast monolayers. The ECs also supported erythroid blast-forming unit (BFU-E) colonies better. These results suggest that bone marrow CD133(+) progenitor cells can give rise to highly purified ECs, which have a high proliferative capacity, can be activated by inflammatory cytokines and are superior to fibroblasts in supporting haematopoiesis. Our data support the hypothesis that endothelial cell progenitors are present in adult bone marrow and may contribute to neo-angiogenesis.

Published
2001

47. The apoptogenic response of human myeloid leukaemia cell lines and of normal and malignant haematopoietic progenitor cells to the proteasome inhibitor PSI

Author

D, Soligo, F, Servida, D, Delia, E, Fontanella, G, Lamorte, L, Caneva, R, Fumiatti, and G, Lambertenghi Deliliers

Subjects
Membrane Glycoproteins, Time Factors, Dose-Response Relationship, Drug, Paclitaxel, Blotting, Western, Fusion Proteins, bcr-abl, Gene Expression, Apoptosis, HL-60 Cells, Genes, p53, Hematopoietic Stem Cells, Genes, bcl-2, Cytoskeletal Proteins, Microscopy, Electron, Leucine, Leukemia, Myeloid, Antineoplastic Combined Chemotherapy Protocols, Trans-Activators, Humans, Protease Inhibitors, Cisplatin, beta Catenin, Cell Line, Transformed
Abstract

Degradation of several intracellular proteins involved in cell cycle control and tumour growth is regulated by the ubiquitin-dependent multicatalytic protease complex (proteasome). We report that proteasome inhibitor Z-Ile-Glu(OtBu)-Ala-Leucinal (PSI) was cytotoxic on most human myeloid leukaemia cell lines at IC50 doses ranging from 5 to 25 nmol/l. Additionally, PSI pre-treatment enhanced cytotoxicity by taxol and cisplatinum. PSI was more active on leukaemic than on normal CD34(+) bone marrow progenitors because the 50% growth inhibition of colony-forming unit granulocyte macrophage (CFU-GM) from cases of chronic myelogenous leukaemia (CML) and normal subjects was achieved by 15 nmol/l and 50 nmol/l PSI respectively. PSI killed cells by apoptosis as revealed by ultrastructural changes, nuclear DNA fragmentation, cleavage of poly (ADP-ribose) polymerase (PARP) and of beta-catenin, and was antagonized by ectopic expression of Bcl-2 but not by inactivating mutations of p53. This event was associated with a slight accumulation of Bcl-2, a decrease of Bax but no changes in Bcl-X(L) protein expression at any time point. In Ph(+) cell lines BCR-ABL protein was only down-regulated after 48 h of treatment with 10 nmol/l PSI. Altogether, these results indicate that PSI, alone or in association with other cytotoxic agents, has anti-tumour activity against myeloid malignancies and is more effective on leukaemic than on normal haematopoietic progenitor cells.

Published
2001

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