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1. p53 immunohistochemistry in endometrial cancer: clinical and molecular correlates in the PORTEC-3 trial

Author

Lisa Vermij, Alicia Léon-Castillo, Naveena Singh, Melanie E. Powell, Richard J. Edmondson, Catherine Genestie, Pearly Khaw, Jan Pyman, C. Meg McLachlin, Prafull Ghatage, Stephanie M. de Boer, Hans W. Nijman, Vincent T.H.B.M. Smit, Emma J. Crosbie, Alexandra Leary, Carien L. Creutzberg, Nanda Horeweg, Tjalling Bosse, N. Horeweg, S.M. de Boer, C.L. Creutzberg, T. Bosse, V.T.H.B.M. Smit, J. Kroep, R.A. Nout, H.W. Nijman, M. de Bruyn, M.E. Powell, N. Singh, H.C. Kitchener, E. Crosbie, R. Edmondson, D.N. Church, A. Leary, L. Mileshkin, P.M. Pollock, H. MacKay, Radiotherapy, Translational Immunology Groningen (TRIGR), and Targeted Gynaecologic Oncology (TARGON)

Subjects
Manchester Cancer Research Centre, SDG 3 - Good Health and Well-being, ResearchInstitutes_Networks_Beacons/mcrc, Mutation, Humans, Female, Tumor Suppressor Protein p53, DNA Mismatch Repair, Immunohistochemistry, Endometrial Neoplasms, Pathology and Forensic Medicine
Abstract

Standard molecular classification of endometrial cancers (EC) is now endorsed by the WHO and identifies p53-abnormal (p53abn) EC as the subgroup with the poorest prognosis and the most likely to benefit from adjuvant chemo(radio)therapy. P53abn EC are POLE wildtype, mismatch repair proficient and show abnormal immunohistochemical (IHC) staining for p53. Correct interpretation of routinely performed p53 IHC has therefore become of paramount importance. We aimed to comprehensively investigate abnormal p53 IHC patterns and their relation to clinicopathological and molecular features. Tumor material of 411 molecularly classified high-risk EC from consenting patients from the PORTEC-3 clinical trial were collected. p53 IHC was successful in 408 EC and was considered abnormal when the tumor showed a mutant expression pattern (including subclonal): overexpression, null or cytoplasmic. The presence of pathogenic mutations was determined by next generation sequencing (NGS). Abnormal p53 expression was observed in 131/408 (32%) tumors. The most common abnormal p53 IHC pattern was overexpression (n = 89, 68%), followed by null (n = 12, 9%) and cytoplasmic (n = 3, 2%). Subclonal abnormal p53 staining was observed in 27 cases (21%), which was frequently but not exclusively, associated with POLE mutations and/or MMRd (n = 22/27; p < 0.001). Agreement between p53 IHC and TP53 NGS was observed in 90.7%, resulting in a sensitivity and specificity of 83.6% and 94.3%, respectively. Excluding POLEmut and MMRd EC, as per the WHO-endorsed algorithm, increased the accuracy to 94.5% with sensitivity and specificity of 95.0% and 94.1%, respectively. Our data shows that awareness of the abnormal p53 IHC patterns are prerequisites for correct EC molecular classification. Subclonal abnormal p53 expression is a strong indicator for POLEmut and/or MMRd EC. No significant differences in clinical outcomes were observed among the abnormal p53 IHC patterns. Our data support use of the WHO-endorsed algorithm and combining the different abnormal p53 IHC patterns into one diagnostic entity (p53abn EC).

Published
2022
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2. Rift Valley fever virus subunit vaccines confer complete protection against a lethal virus challenge

Author

Rob J. M. Moormann, Adriaan F.G. Antonis, Berend Jan Bosch, S.M. de Boer, Peter J. M. Rottier, Jeroen Kortekaas, J.L. van Oploo, and Jet Kant

Subjects
Rift Valley Fever, viruses, Antibodies, Viral, Mice, Viral Envelope Proteins, Virus-like particle, immune-responses, Rift Valley fever, Mice, Inbred BALB C, biology, Virology & Molecular Biology, Vaccination, Infectious Diseases, Vaccines, Subunit, Molecular Medicine, Drosophila, Female, Bunyaviridae, segment, CVI - Division Virology, monoclonal-antibodies, Coronacrisis-Taverne, Enzyme-Linked Immunosorbent Assay, hantaan-virus, DIVA, Subunit vaccine, Virus, Cell Line, CVI - Divisie Virologie, VLP, expression, medicine, Animals, Humans, Hantaan virus, particles, General Veterinary, General Immunology and Microbiology, envelope glycoproteins, Public Health, Environmental and Occupational Health, Insect cell culture, Viral Vaccines, Rift Valley fever virus, biology.organism_classification, medicine.disease, Survival Analysis, Virology, proteins, Virologie & Moleculaire Biologie, immunogenic properties, Vaccines, Virosome, Phlebovirus, adjuvants
Abstract

Rift Valley fever virus (RVFV) is an emerging mosquito-borne virus causing significant morbidity and mortality in livestock and humans. Rift Valley fever is endemic in Africa, but also outside this continent outbreaks have been reported. Here we report the evaluation of two vaccine candidates based on the viral Gn and Gc envelope glycoproteins, both produced in a Drosophila insect cell expression system. Virus-like particles (VLPs) were generated by merely expressing the Gn and Gc glycoproteins. In addition, a soluble form of the Gn ectodomain was expressed and affinity-purified from the insect cell culture supernatant. Both vaccine candidates fully protected mice from a lethal challenge with RVFV. Importantly, absence of the nucleocapsid protein in either vaccine candidate facilitates the differentiation between infected and vaccinated animals using a commercial recombinant nucleocapsid protein-based indirect ELISA.

Published
2010
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3. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Author

Lodi, S. Del Amo, J. Moreno, S. Bucher, H.C. Furrer, H. Logan, R. Sterne, J. Pérez-Hoyos, S. Jarrín, I. Phillips, A. Olson, A. Van Sighem, A. Reiss, P. Sabin, C. Jose, S. Justice, A. Goulet, J. Miró, J.M. Ferrer, E. Meyer, L. Seng, R. Vourli, G. Antoniadou, A. Dabis, F. Vandenhede, M.-A. Costagliola, D. Abgrall, S. Hernán, M.A. Hernan, M. Bansi, L. Hill, T. Sabin, C. Dunn, D. Porter, K. Glabay, A. Orkin, C. Thomas, R. Jones, K. Fisher, M. Perry, N. Pullin, A. Churchill, D. Gazzard, B. Nelson, M. Asboe, D. Bulbeck, S. Mandalia, S. Clarke, J. Delpech, V. Anderson, J. Munshi, S. Post, F. Easterbrook, P. Khan, Y. Patel, P. Karim, F. Duffell, S. Gilson, R. Man, S.-L. Williams, I. Gompels, M. Dooley, D. Schwenk, A. Ainsworth, J. Johnson, M. Youle, M. Lampe, F. Smith, C. Grabowska, H. Chaloner, C. Ismajani Puradiredja, D. Bansi, L. Hill, T. Phillips, A. Sabin, C. Walsh, J. Weber, J. Kemble, C. Mackie, N. Winston, A. Leen, C. Wilson, A. Bezemer, D.O. Gras, L.A.J. Kesselring, A.M. Van Sighem, A.I. Zaheri, S. Van Twillert, G. Kortmann, W. Branger, J. Prins, J.M. Kuijpers, T.W. Scherpbier, H.J. Van Der Meer, J.T.M. Wit, F.W.M.N. Godfried, M.H. Reiss, P. Van Der Poll, T. Nellen, F.J.B. Lange, J.M.A. Geerlings, S.E. Van Vugt, M. Pajkrt, D. Bos, J.C. Van Der Valk, M. Grijsen, M.L. Wiersinga, W.J. Brinkman, K. Blok, W.L. Frissen, P.H.J. Schouten, W.E.M. Van Den Berk, G.E.L. Veenstra, J. Lettinga, K.D. Mulder, J.W. Vrouenraets, S.M.E. Lauw, F.N. Van Eeden, A. Verhagen, D.W.M. Van Agtmael, M.A. Perenboom, R.M. Claessen, F.A.P. Bomers, M. Peters, E.J.G. Richter, C. Van Der Berg, J.P. Gisolf, E.H. Schippers, E.F. Van Nieuwkoop, C. Van Elzakker, E.P. Leyten, E.M.S. Gelinck, L.B.S. Pronk, M.J.H. Bravenboer, B. Kootstra, G.J. Delsing, C.E. Sprenger, H.G. Doedens, R. Scholvinck, E.H. Van Assen, S. Bierman, W.F.W. Soetekouw, R. Ten Kate, R.W. Van Vonderen, M.G.A. Van Houte, D.P.F. Kroon, F.P. Van Dissel, J.T. Arend, S.M. De Boer, M.G.J. Jolink, H. Ter Vollaard, H.J.M. Bauer, M.P. Weijer, S. El Moussaoui, R. Lowe, S. Schreij, G. Oude Lashof, A. Posthouwer, D. Koopmans, P.P. Keuter, M. Van Der Ven, A.J.A.M. Ter Hofstede, H.J.M. Dofferhoff, A.S.M. Warris, A. Van Crevel, R. Van Der Ende, M.E. De Vries-Sluijs, T.E.M.S. Schurink, C.A.M. Nouwen, J.L. Nispen Tot Pannerden, M.H. Verbon, A. Rijnders, B.J.A. Van Gorp, E.C.M. Hassing, R.J. Smeulders, A.W.M. Hartwig, N.G. Driessen, G.J.A. Den Hollander, J.G. Pogany, K. Juttmann, J.R. Van Kasteren, M.E.E. Hoepelman, A.I.M. Mudrikova, T. Schneider, M.M.E. Jaspers, C.A.J.J. Ellerbroek, P.M. Oosterheert, J.J. Arends, J.E. Wassenberg, M.W.M. Barth, R.E. Geelen, S.P.M. Wolfs, T.F.W. Bont, L.J. Van Den Berge, M. Stegeman, A. Groeneveld, P.H.P. Alleman, M.A. Bouwhuis, J.W. Barin, F. Burty, C. Duvivier, C. Enel, P. Fredouille-Heripret, L. Gasnault, J. Khuong, M.A. Mahamat, A. Pilorgé, F. Tattevin, P. Salomon, V. Jacquemet, N. Abgrall, S. Costagliola, D. Grabar, S. Guiguet, M. Lanoy, E. Lièvre, L. Mary-Krause, M. Selinger-Leneman, H. Lacombe, J.M. Potard, V. Bricaire, F. Herson, S. Katlama, C. Simon, A. Desplanque, N. Girard, P.M. Meynard, J.L. Meyohas, M.C. Picard, O. Cadranel, J. Mayaud, C. Pialoux, G. Clauvel, J.P. Decazes, J.M. Gerard, L. Molina, J.M. Diemer, M. Sellier, P. Bentata, M. Honoré, P. Jeantils, V. Tassi, S. Mechali, D. Taverne, B. Bouvet, E. Crickx, B. Ecobichon, J.L. Matheron, S. Picard-Dahan, C. Yeni, P. Berthé, H. Dupont, C. Chandemerle, C. Mortier, E. De Truchis, P. Tisne-Dessus, D. Weiss, L. Salmon, D. Auperin, I. Gilquin, J. Roudière, L. Viard, J.P. Boué, F. Fior, R. Delfraissy, J.F. Goujard, C. Jung, C. Lesprit, Ph. Vittecoq, D. Fraisse, P. Lang, J.M. Rey, D. Beck-Wirth, G. Stahl, J.P. Lecercq, P. Gourdon, F. Laurichesse, H. Fresard, A. Lucht, F. Bazin, C. Verdon, R. Chavanet, P. Arvieux, C. Michelet, C. Choutet, P. Goudeau, A. Maître, M.F. Hoen, B. Eglinger, P. Faller, J.P. Borsa-Lebas, F. Caron, F. Reynes, J. Daures, J.P. May, T. Rabaud, C. Berger, J.L. Rémy, G. Arlet-Suau, E. Cuzin, L. Massip, P. Thiercelin Legrand, M.F. Pontonnier, G. Viget, N. Yasdanpanah, Y. Dellamonica, P. Pradier, C. Pugliese, P. Aleksandrowicz, K. Quinsat, D. Ravaux, I. Tissot-Dupont, H. Delmont, J.P. Moreau, J. Gastaut, J.A. Poizot-Martin, I. Retornaz, F. Soubeyrand, J. Galinier, A. Ruiz, J.M. Allegre, T. Blanc, P.A. Bonnet-Montchardon, D. Lepeu, G. Granet-Brunello, P. Esterni, J.P. Pelissier, L. Cohen-Valensi, R. Nezri, M. Chadapaud, S. Laffeuillade, A. Billaud, E. Raffi, F. Boibieux, A. Peyramond, D. Livrozet, J.M. Touraine, J.L. Cotte, L. Trepo, C. Strobel, M. Bissuel, F. Pradinaud, R. Sobesky, M. Cabié, A. Gaud, C. Contant, M. Aubert, V. Barth, J. Battegay, M. Bernasconi, E. Böni, J. Bucher, H.C. Burton-Jeangros, C. Calmy, A. Cavassini, M. Egger, M. Elzi, L. Fehr, J. Fellay, J. Furrer, H. Haerry, D. Fux, C.A. Gorgievski, M. Günthard, H. Hasse, B. Hirsch, H.H. Hösli, I. Kahlert, C. Kaiser, L. Keiser, O. Klimkait, T. Kovari, H. Ledergerber, B. Martinetti, G. Martinez De Tejada, B. Metzner, K. Müller, N. Nadal, D. Pantaleo, G. Rauch, A. Regenass, S. Rickenbach, M. Rudin, C. Schmid, P. Schultze, D. Schöni-Affolter, F. Schüpbach, J. Speck, R. Taffé, P. Tarr, P. Telenti, A. Trkola, A. Vernazza, P. Weber, R. Yerly, S. Casabona, J. Gallois, A. Esteve, A. Podzamczer, D. Murillas, J. Gatell, J.M. Manzardo, C. Tural, C. Clotet, B. Ferrer, E. Riera, M. Segura, F. Navarro, G. Force, L. Vilaró, J. Masabeu, A. García, I. Guadarrama, M. Cifuentes, C. Dalmau, D. Jaen, À. Agustí, C. Montoliu, A. Pérez, I. Gargoulas, F. Blanco, J.L. Garcia-Alcaide, F. Martínez, E. Mallolas, J. López-Dieguez, M. García-Goez, J.F. Sirera, G. Romeu, J. Jou, A. Negredo, E. Miranda, C. Capitan, M.C. Saumoy, M. Imaz, A. Tiraboschi, J.M. Murillo, O. Bolao, F. Peña, C. Cabellos, C. Masó, M. Vila, A. Sala, M. Cervantes, M. Jose Amengual, Ma. Navarro, M. Penelo, E. Barrufet, P. Bejarano, G. Molina, J. Guadarrama, M. Alvaro, M. Mercadal, J. Fernandez, J. Ospina, J.E. Muñoz, M.A. Caro-Murillo, A.M. Sobrino, P. Jarrín, I. Gomez Sirvent, J.L. Rodríguez, P. Aleman, M.R. Alonso, M.M. Lopez, A.M. Hernandez, M.I. Soriano, V. Labarga, P. Barreiro, P. Medrano, J. Rivas, P. Herrero, D. Blanco, F. Vispo, M.E. Martín, L. Ramírez, G. De Diego, M. Rubio, R. Pulido, F. Moreno, V. Cepeda, C. Hervás, Rl. Iribarren, J.A. Arrizabalaga, J. Aramburu, M.J. Camino, X. Rodrí-guez-Arrondo, F. Von Wichmann, M.A. Pascual, L. Goenaga, M.A. Gutierrez, F. Masia, M. Ramos, J.M. Padilla, S. Sanchez-Hellín, V. Bernal, E. Escolano, C. Montolio, F. Peral, Y. Berenguer, J. Lopez, J.C. Miralles, P. Cosín, J. Sanchez, M. Gutierrez, I. Ramírez, M. Padilla, B. Vidal, F. Sanjuan, M. Peraire, J. Veloso, S. Vilades, C. Lopez-Dupla, M. Olona, M. Vargas, M. Aldeguer, J.L. Blanes, M. Lacruz, J. Salavert, M. Montero, M. Cuéllar, S. De Los Santos, I. Sanz, J. Oteo, J.A. Blanco, J.R. Ibarra, V. Metola, L. Sanz, M. Pérez-Martínez, L. Sola, J. Uriz, J. Castiello, J. Reparaz, J. Arriaza, M.J. Irigoyen, C. Moreno, S. Antela, A. Casado, J.L. Dronda, F. Moreno, A. Pérez, M.J. López, D. Gutiérrez, C. Hernández, B. Pumares, M. Martí, P. García, L. Page, C. García, F. Hernández, J. Peña, A. Muñoz, L. Parra, J. Viciana, P. Leal, M. López-Cortés, L.F. Trastoy, M. Mata, R. Justice, A.C. Fiellin, D.A. Rimland, D. Jones-Taylor, C. Oursler, K.A. Titanji, R. Brown, S. Garrison, S. Rodriguez-Barradas, M. Masozera, N. Goetz, M. Leaf, D. Simberkoff, M. Blumenthal, D. Leung, J. Butt, A. Hoffman, E. Gibert, C. Peck, R. Mattocks, K. Braithwaite, S. Brandt, C. Bryant, K. Cook, R. Conigliaro, J. Crothers, K. Chang, J. Crystal, S. Day, N. Erdos, J. Freiberg, M. Kozal, M. Gandhi, N. Gaziano, M. Gerschenson, M. Good, B. Gordon, A. Goulet, J.L. Kraemer, K. Lim, J. Maisto, S. Miller, P. Mole, L. O'Connor, P. Papas, R. Robins, J.M. Rinaldo, C. Roberts, M. Samet, J. Tierney, B. Whittle, J. Babiker, A. Brettle, R. Darbyshire, J. Gilson, R. Goldberg, D. Hawkins, D. Jaffe, H. Johnson, A. McLean, K. Pillay, D. Cursley, A. Ewings, F. Fairbrother, K. Louisa Gnatiuc, S.L. Murphy, B. Douglas, G. Kennedy, N. Pritchard, J. Andrady, U. Rajda, N. Maw, R. McKernan, S. Drake, S. Gilleran, G. White, D. Ross, J. Toomer, S. Hewart, R. Wilding, H. Woodward, R. Dean, G. Heald, L. Horner, P. Glover, S. Bansaal, D. Eduards, S. Carne, C. Browing, M. Das, R. Stanley, B. Estreich, S. Magdy, A. O'Mahony, C. Fraser, P. Hayman, B. Jebakumar, S.P.R. Joshi, U. Ralph, S. Wade, A. Mette, R. Lalik, J. Summerfield, H. El-Dalil, A. France, J.A. White, C. Robertson, R. Gordon, S. McMillan, S. Morris, S. Lean, C. Vithayathil, K. McLean, L. Winter, A. Gale, D. Jacobs, S. Tayal, S. Short, L. Roberts, M. Green, S. Williams, G. Sivakumar, K. Bhattacharyya, N.D. Monteiro, E. Minton, J. Dhar, J. Nye, F. De Souza, C.B. Isaksen, A. McDonald, L. McLean, K. Franca, A. Hawkins, D. William, L. Jendrulek, I. Peters, B. Shaunak, S. El-Gadi, S. Easterbrook, P.J. Mazhude, C. Gilson, R. Johnstone, R. Fakoya, A. McHale, J. Waters, A. Kegg, S. Mitchell, S. Byrne, P. Johnson, M. Rice, P. Fidler, S. Mullaney, S.A. McCormack, S. David, D. Melville, R. Phillip, K. Balachandran, T. Mabey-Puttock, S. Sukthankar, A. Murphy, C. Wilkins, E. Ahmad, S. Tayal, S. Haynes, J. Evans, E. Ong, E. Das, R. Grey, R. Meaden, J. Bignell, C. Loay, D. Peacock, K. Girgis, M.R. Morgan, B. Palfreeman, A. Wilcox, J. Tobin, J. Tucker, L. Saeed, A.M. Chen, F. Deheragada, A. Williams, O. Lacey, H. Herman, S. Kinghorn, D. Devendra, V.S. Wither, J. Dawson, S. Rowen, D. Harvey, J. Wilkins, E. Bridgwood, A. Singh, G. Chauhan, M. Kellock, D. Young, S. Dannino, S. Kathir, Y. Rooney, G. Currie, J. Fitzgerald, M. Devendra, S. Keane, F. Booth, G. Green, T. Arumainayyagam, J. Chandramani, S. Rajamanoharan, S. Robinson, T. Curless, E. Gokhale, R. Tariq, A. Roberts, M. Williams, O. Luzzi, G. FitzGerald, M. Fairley, I. Wallis, F. Smit, E. Ward, F. Molina, J.M. Loze, B. Morlat, P. Bonarek, M. Bonnet, F. Nouts, C. Louis, I. Raffi, F. Reliquet, V. Sauser, F. Biron, C. Mounoury, O. Hue, H. Brosseau, D. Delfraissy, J.F. Goujard, C. Ghosn, J. Rannou, M.T. Bergmann, J.F. Badsi, E. Rami, A. Diemer, M. Parrinello, M. Girard, P.M. Samanon-Bollens, D. Campa, P. Tourneur, M. Desplanques, N. Livrozet, J.M. Jeanblanc, F. Chiarello, P. Makhloufi, D. Blanc, A.P. Allègre, T. Reynes, J. Baillat, V. Lemoing, V. Merle De Boever, C. Tramoni, C. Cabié, A. Sobesky, G. Abel, S. Beaujolais, V. Pialoux, G. Slama, L. Chakvetadze, C. Berrebi, V. Yeni, P. Bouvet, E. Fournier, I. Gerbe, J. Trepo, C. Koffi, K. Augustin-Normand, C. Miailhes, P. Thoirain, V. Brochier, C. Thomas, R. Souala, F. Ratajczak, M. Beytoux, J. Jacomet, C. Gourdon, F. Rouveix, E. Morelon, S. Dupont, C. Olivier, C. Lortholary, O. Dupont, B. Viard, J.P. Maignan, A. Ragnaud, J.M. Raymond, I. Leport, C. Jadand, C. Jestin, C. Longuet, P. Boucherit, S. Sereni, D. Lascoux, C. Prevoteau, F. Sobel, A. Levy, Y. Lelièvre, J.D. Lascaux, A.S. Dominguez, S. Dumont, C. Aumâitre, H. Delmas, B. Saada, M. Medus, M. Guillevin, L. Salmon, D. Tahi, T. Yazdanpanah, Y. Pavel, S. Marien, M.C. Drenou, B. Beck-Wirth, G. Beck, C. Benomar, M. Katlama, C. Tubiana, R. Ait Mohand, H. Chermak, A. Ben Abdallah, S. Bentata, M. Touam, F. Hoen, B. Drobacheff, C. Folzer, A. Massip, P. Obadia, M. Prudhomme, L. Bonnet, E. Balzarin, F. Pichard, E. Chennebault, J.M. Fialaire, P. Loison, J. Galanaud, P. Boué, F. Bornarel, D. Verdon, R. Bazin, C. Six, M. Ferret, P. Weiss, L. Batisse, D. Gonzales-Canali, G. Tisne-Dessus, D. Devidas, A. Chevojon, P. Turpault, I. Lafeuillade, A. Cheret, A. Philip, G. Morel, P. Timsit, J. Herson, S. Amirat, N. Simon, A. Brancion, C. Cabane, J. Picard, O. Tredup, J. Stein, A. Ravault, I. Chavanet, C. Buisson, M. Treuvetot, S. Choutet, P. Nau, P. Bastides, F. May, T. Boyer, L. Wassoumbou, S. Oksenhendeler, E. Gérard, L. Bernard, L. De Truchis, P. Berthé, H. Domart, Y. Merrien, D. Greder Belan, A. Gayraud, M. Bodard, L. Meudec, A. Beuscart, C. Daniel, C. Pape, E. Vinceneux, P. Simonpoli, A.M. Zeng, A. Fournier, L. Fuzibet, J.G. Sohn, C. Rosenthal, E. Quaranta, M. Dellamonica, P. Chaillou, S. Sabah, M. Audhuy, B. Schieber, A. Moreau, P. Niault, M. Vaillant, O. Huchon, G. Compagnucci, A. De Lacroix Szmania, I. Richier, L. Lamaury, I. Saint-Dizier, F. Garipuy, D. Gastaut, J.A. Drogoul, M.P. Poizot Martin, I. Fabre, G. Lambert De Cursay, G. Abraham, B. Perino, C. Lagarde, P. David, F. Roche-Sicot, J. Saraux, J.L. Leprêtre, A. Fampin, B. Uludag, A. Morin, A.S. Bletry, O. Zucman, D. Regnier, A. Girard, J.J. Quinsat, D.T. Heripret, L. Grihon, F. Houlbert, D. Ruel, M. Chemlal, K. Caron, F. Debab, Y. Tremollieres, F. Perronne, V. Lepeu, G. Slama, B. Perré, P. Miodovski, C. Guermonprez, G. Dulioust, A. Boudon, P. Malbec, D. Patey, O. Semaille, C. Deville, J. Remy, G. Béguinot, I. Galanaud, P. Boue, F. Chambrin, V. Pignon, C. Estocq, G.A. Levy, A. Delfraissy, J.F. Goujard, C. Duracinsky, M. Le Bras, P. Ngussan, M.S. Peretti, D. Medintzeff, N. Lambert, T. Segeral, O. Lezeau, P. Laurian, Y. Weiss, L. Buisson, M. Piketty, C. Karmochkine, M. Batisse, D. Eliaszewitch, M. Jayle, D. Tisne-Dessus, D. Kazatchkine, M. Leport, C. Colasante, U. Jadand, C. Jestin, C. Duval, X. Nouaouia, W. Boucherit, S. Vilde, J.L. Girard, P.M. Bollens, D. Binet, D. Diallo, B. Meyohas, M.C. Fonquernie, L. Lagneau, J.L. Salmon, D. Guillevin, L. Tahi, T. Launay, O. Pietrie, M.P. Sicard, D. Stieltjes, N. Michot, J. Sobel, A. Levy, Y. Bourdillon, F. Lascaux, A.S. Lelievre, J.D. Dumont, C. Dupont, B. Obenga, G. Viard, J.P. Maignan, A. Vittecoq, D. Escaut, L. Bolliot, C. Bricaire, F. Katlama, C. Schneider, L. Herson, S. Simon, A. Iguertsira, M. Stein, A. Tomei, C. Ravaux, I. Dhiver, C. Tissot Dupont, H. Vallon, A. Gallais, J. Gallais, H. Gastaut, J.A. Drogoul, M.P. Fabre, G. Dellamonica, P. Durant, J. Mondain, V. Perbost, I. Cassuto, J.P. Karsenti, J.M. Venti, H. Fuzibet, J.G. Rosenthal, E. Ceppi, C. Quaranta, M. Krivitsky, J.A. Bentata, M. Bouchaud, O. Honore, P. Sereni, D. Lascoux, C. Delgado, J. Rouzioux, C. Burgard, M. Boufassa, L. Peynet, J. Pérez-Hoyos, S. Del Amo, J. Alvarez, D. Monge, S. Muga, R. Sanvisens, A. Clotet, B. Tor, J. Bolao, F. Rivas, I. Vallecillo, G. Del Romero, J. Raposo, P. Rodríguez, C. Vera, M. Hurtado, I. Belda, J. Fernandez, E. Alastrue, I. Santos, C. Tasa, T. Juan, A. Trullen, J. Garcia De Olalla, P. Cayla, J. Masdeu, E. Knobel, H. Mirò, J.M. Sambeat, M.A. Guerrero, R. Rivera, E. Guerrero, R. Marco, A. Quintana, M. Gonzalez, C. Castilla, J. Guevara, M. De Mendoza, C. Zahonero, N. Ortíz, M. Paraskevis, D. Touloumi, G. Pantazis, N. Bakoyannis, G. Gioukari, V. Antoniadou, A. Papadopoulos, A. Petrikkos, G. Daikos, G. Psichogiou, M. Gargalianos-Kakolyris, P. Xylomenos, G. Katsarou, O. Kouramba, A. Ioannidou, P. Kordossis, T. Kontos, A. Lazanas, M. Chini, M. Tsogas, N. Panos, G. Paparizos, V. Leuow, K. Kourkounti, S. Sambatakou, H. Mariolis, I. Skoutelis, A. Papastamopoulos, V. Baraboutis, I. The HIV-CAUSAL Collaboration

Subjects
virus diseases
Abstract

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting. Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis. Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Published
2014

4. Acid-activated structural reorganization of the Rift Valley fever virus Gc fusion protein

Author

Peter J. M. Rottier, Berend Jan Bosch, S.M. de Boer, Lotte Spel, Jeroen Kortekaas, Rob J. M. Moormann, and LS Virologie

Subjects
Protein Conformation, viruses, mammalian-cells, cell-fusion, conserved histidine-residues, influenza-virus, Cricetinae, Microscopy, Cell fusion, Blotting, Hydrogen-Ion Concentration, Flow Cytometry, Endocytosis, Virus-Cell Interactions, Virology & Molecular Biology, Drosophila, Electrophoresis, Polyacrylamide Gel, Western, Electrophoresis, Immunology, Blotting, Western, Coronacrisis-Taverne, Biology, mediated endocytosis, Microbiology, Virus, Fluorescence, Cell Line, Viral envelope, Viral entry, Virology, triggering membrane-fusion, uukuniemi-virus, Animals, Dynamin, DNA Primers, Polyacrylamide Gel, Base Sequence, Lipid bilayer fusion, Rift Valley fever virus, Fusion protein, Molecular biology, Virologie & Moleculaire Biologie, enveloped viruses, Microscopy, Fluorescence, Insect Science, Acids, Viral Fusion Proteins, hemorrhagic-fever, semliki-forest-virus
Abstract

The entry of the enveloped Rift Valley fever virus (RVFV) into its host cell is mediated by the viral glycoproteins Gn and Gc. We investigated the RVFV entry process and, in particular, its pH-dependent activation mechanism using our recently developed nonspreading-RVFV-particle system. Entry of the virus into the host cell was efficiently inhibited by lysosomotropic agents that prevent endosomal acidification and by compounds that interfere with dynamin- and clathrin-dependent endocytosis. Exposure of plasma membrane-bound virions to an acidic pH (

Published
2012

5. Intramuscular inoculation of calves with an experimental Newcastle disease virus-based vector vaccine elicits neutralizing antibodies against Rift Valley fever virus

Author

S.M. de Boer, Aldo Dekker, Jeroen Kortekaas, R.P.M. Vloet, A.A.C. de Wit, Ben Peeters, K. Weerdmeester, and Rob J. M. Moormann

Subjects
respiratory-tract, replication, Paramyxoviridae, animal diseases, viruses, Genetic Vectors, Newcastle disease virus, i interferon, Antibodies, Viral, immunization, Injections, Intramuscular, Newcastle disease, Virus, Microbiology, CVI - Divisie Virologie, expression, medicine, fusion protein, Animals, Rift Valley fever, Mononegavirales, humans, Administration, Intranasal, Vaccines, Synthetic, General Veterinary, General Immunology and Microbiology, biology, Public Health, Environmental and Occupational Health, Viral Vaccines, Vector vaccine, Rift Valley fever virus, biology.organism_classification, medicine.disease, Antibodies, Neutralizing, Virology, Virology & Molecular Biology, Virologie & Moleculaire Biologie, Vaccination, Infectious Diseases, Phlebovirus, foreign gene, Molecular Medicine, Cattle, avian influenza, Wageningen Livestock Research, CVI - Division Virology, cloned cdna
Abstract

In the past decade, the use of Newcastle disease virus (NDV) as a vaccine vector for the prevention of economically important livestock diseases as well as for human diseases has been extensively explored. In this study, we have constructed a recombinant NDV vaccine virus, named NDFL-Gn, that produces the Rift Valley fever virus (RVFV) Gn glycoprotein. Calves were immunized via either the intranasal route or the intramuscular route. Delivery via the intranasal route elicited no detectable antibody responses, whereas delivery via the intramuscular route elicited antibodies against both NDV and the Gn protein. The RVFV-neutralizing activity of the antisera from intramuscularly vaccinated calves was demonstrated, suggesting that NDV is a promising vaccine vector for the prevention of RVF in calves.

Published
2010

6. Rift Valley fever virus immunity provided by a paramyxovirus vaccine vector

Author

S.M. de Boer, Adriaan F.G. Antonis, R.P.M. Vloet, Jeroen Kortekaas, Jet Kant, and Rob J. M. Moormann

Subjects
respiratory-tract, Rift Valley Fever, viruses, monoclonal-antibodies, Newcastle disease virus, i interferon, protects mice, medicine.disease_cause, Virus, Microbiology, Mice, CVI - Divisie Virologie, saudi-arabia, medicine, Animals, neutralizing antibodies, Rift Valley fever, Mononegavirales, Mice, Inbred BALB C, lethal infection, Sheep, General Veterinary, General Immunology and Microbiology, biology, envelope glycoproteins, Public Health, Environmental and Occupational Health, Viral Vaccines, Vector vaccine, Rift Valley fever virus, biology.organism_classification, medicine.disease, Virology, Influenza A virus subtype H5N1, Virology & Molecular Biology, Virologie & Moleculaire Biologie, Vaccination, Infectious Diseases, Phlebovirus, Paramyxovirus vaccine, Molecular Medicine, Female, avian influenza, newcastle-disease-virus, CVI - Division Virology
Abstract

Rift Valley fever virus (RVFV) causes recurrent large outbreaks among humans and livestock. Although the virus is currently confined to the African continent and the Arabian Peninsula, there is a growing concern for RVFV incursions into countries with immunologically naive populations. The RVFV structural glycoproteins Gn and Cc are preferred targets in the development of subunit vaccines that can be used to control future outbreaks. We here report the production of Gn and Cc by a recombinant vaccine strain of the avian paramyxovirus Newcastle disease virus (NDV) and demonstrate that intramuscular vaccination with this experimental NDV-based vector vaccine provides complete protection in mice. We also demonstrate that a single intramuscular vaccination of lambs, the main target species of RVFV, is sufficient to elicit a neutralizing antibody response. (C) 2010 Elsevier Ltd. All rights reserved.

Published
2010

7. Effects of amphetamine and β-endorphin fragments on maze performance in rats

Author

S.M. de Boer and Béla Bohus

Subjects
Male, medicine.medical_specialty, Dextroamphetamine, Peptide fragment, Clinical Biochemistry, Neuropeptide, Toxicology, Biochemistry, β-Endorphin-(2-9), Behavioral Neuroscience, chemistry.chemical_compound, Internal medicine, medicine, Animals, Amphetamine, Hebb-Williams mazes, Biological Psychiatry, Rat maze behavior, Pharmacology, Behavior, Animal, beta-Endorphin, Rats, Inbred Strains, Space perception, β-Endorphin-(2-16), Peptide Fragments, Rats, β-Endorphin fragments, Endocrinology, chemistry, α-Type endorphins, Psychology, psychological phenomena and processes, medicine.drug
Abstract

Fragments of beta-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two beta-endorphin fragments [beta-endorphin (beta E)-(2-9) and beta E-(2-16)] on maze behavior in more detail. In Experiment I no significant effects of amphetamine and the peptides on behavioral performance in three selected Davenport configurations were found. In Experiment II amphetamine increased the frequency of errors and of returns to the start box, but only in the first trial. This effect was dependent on the rats' experience and on the maze configuration. In the next 11 trials, amphetamine slightly decreased the overall frequency of errors and of returns to the start box. Therefore, the effects of amphetamine on maze behavior depend upon the extent of training experience and on the structure of the test mazes. The peptides did not significantly affect maze performance. It is concluded that the effects of amphetamine and the beta-endorphin fragments on maze behavior are not comparable in this maze test.

Published
1990
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8. A Controlled Trial of Senna Preparations and Other Laxatives Used for Bowel Cleansing Prior to Radiological Examination

Author

W.P.L. van Ouwerkerk, S.M de Boer, J.R.B.J. Brouwers, and Loes Thoman

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Nursing staff, Adolescent, Colon, Senna, Enema, Pharmacology, law.invention, Randomized controlled trial, law, Simethicone, medicine, Humans, Bowel cleansing, Palatability, Defecation, Intensive care medicine, Aged, Muscle Cramp, Clinical Trials as Topic, biology, Cathartics, business.industry, Senna Extract, General Medicine, Middle Aged, Radiological examination, biology.organism_classification, Diet, Radiography, Low residue diet, Female, business
Abstract

Film quality of PP, X-P and HP methods shows only small differences. 1-day preparation reduces the burden on nursing staff. The standardized sennoside preparations have a good palatability. HP was significantly better than X-P and is safe in diabetic patients. PP gives fewer side effects (cramps) than HP and X-P. Low residue dietary measures are essential for a good result.

Published
1980
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