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Your search keyword '"Velu, T."' showing total 26 results
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26 results on '"Velu, T."'

1. Overexpression of mouse IsK protein fused to green fluorescent protein induces apoptosis of human astroglioma cells.

Author

Stathopoulos, A., Melas, C., Attali, B., Blum, D., Levivier, M., Brotchi, J., Velu, T., and Tenenbaum, L.

Abstract

Intracellular K+ plays an important role in controlling ion homeostasis for maintaining cell volume and inhibiting activity of pro-apoptotic enzymes. Cytoplasmic K+ concentration is regulated by K+ uptake via Na+-K+-ATPase and K+ efflux through K+ channels in the plasma membrane. The IsK (KCNE1) protein is known to co-assemble with KCNQ1 (KvLQT1) protein to form a K+ channel underlying the slowly activating delayed rectifier K+ outward current which delays voltage activation. In order to further study the activity and cellular localization of IsK protein, we constructed a C-terminal fusion of IsK with EGFP (enhanced green fluorescent protein). Expression of the fusion protein appeared as clusters located in the plasma membrane and induced degeneration of both transiently or stably transfected cells. [Neurol Res 2007; 29: 628–631] [ABSTRACT FROM AUTHOR]

Published
2007
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2. Efficient Early and Sustained Transduction of Human Fetal Mesencephalon Using Adeno-Associated Virus Type 2 Vectors

Author

Tenenbaum, L., Peschanski, M., Melas, C., Rodesh, F., Lehtonen, E., Stathopoulos, A., Velu, T., Brotchi, J., and Levivier, M.

Abstract

The success of transplantation of human fetal mesencephalic tissue into the putamen of patients with Parkinson's disease (PD) is still limited by the poor survival of the graft. In animal models of fetal transplantation for PD, antiapoptotic agents, such as growth factors or caspase inhibitors, or agents counteracting oxidative stress enhance the survival and reinnervation potential of the graft. Genetic modification of the transplant could allow a local and continuous delivery of these factors at physiologically relevant doses. The major challenge remains the development of strategies to achieve both early and sustained gene delivery in the absence of vector-mediated toxicity. We recently reported that E14 rat fetal mesencephalon could be efficiently tranduced by adeno-associated virus type 2 (AAV2) vectors and that gene expression was maintained until at least 3 months after transplantation in the adult rat striatum. Here we report that an AAV2 vector can mediate the expression of the EGFP reporter gene under the control of a CMV promoter in organotypic cultures of freshly explanted solid fragments of human fetal mesencephalic tissue as early as 3 days to at least 6 weeks postinfection. These results suggest that AAV2 vectors could be used to genetically modify the human fetal tissue prior to transplantation to Parkinson's patients to promote graft survival and integration.

Published
2004
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3. AAV2 vectors mediate efficient and sustained transduction of rat embryonic ventral mesencephalon

Author

Lehtonen, E., Bonnaud, F., Melas, C., Lubansu, A., Malgrange, B., Chtarto, A., Velu, T., Brotchi, J., Levivier, M., Peschanski, M., and Tenenbaum, L.

Abstract

The success of transplantation of human embryonic mesencephalic tissue to treat parkinsonian patients is limited by the poor survival of the transplant. We show that an AAV2 vector mediates efficient expression of the egfp reporter gene in organotypic cultures of freshly explanted solid fragments of rat embryonic ventral mesencephalon (VM). We observed early and sustained transgene expression (4 days to ≥ 6 weeks). Furthermore, rAAV-infected rat embryonic VM transplanted in the adult striatum continued to express EGFP for ≥ 3 months. More than 95 of the transduced cells were neurons. Dopaminergic neurons were transduced at low frequency at earlier time points. This method of gene delivery could prove useful to achieve local, continuous secretion of neurotrophic factors at physiologically relevant doses to treat Parkinson's disease.

Published
2002

4. Transient expansion of peptide‐specific lymphocytes producing IFN‐γ after vaccination with dendritic cells pulsed with MAGE peptides in patients with mage‐A1/A3‐positive tumors

Author

Toungouz, M., Libin, M., Bulté, F., Faid, L., Lehmann, F., Duriau, D., Laporte, M., Gangji, D., Bruyns, C., Lambermont, M., Goldman, M., and Velu, T.

Abstract

Assessment of T‐cell activation is pivotal for evaluation of cancerimmunotherapy. We initiated a clinical trial in patients with MAGE‐A1and/or ‐A3 tumors using autologous DC pulsed with MAGE peptides aimedat analyzing T‐cell‐derived, IFN‐γ secretion by cytokine flowcytometry and ELISPOT. We also tested whether further KLH additioncould influence this response favorably. Monocyte‐derived DC weregenerated from leukapheresis products. They were pulsed with therelevant MAGE peptide(s) alone in group A (n=10 pts) andadditionally with KLH in group B (n=16 pts). A specific buttransient increase in the number of peripheral blood T lymphocytessecreting IFN‐γ in response to the vaccine peptide(s) was observed in6/8 patients of group A and in 6/16 patients of group B. We concludethat anti‐tumor vaccination using DC pulsed with MAGE peptides inducesa potent but transient anti‐MAGE, IFN‐γ secretion that is notinfluenced by the additional delivery of a nonspecific, T‐cellhelp.

Published
2001
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5. Tropism of AAV2 vectors for neurons of the globus pallidus

Author

Tenenbaum, L, Jurysta, F, Stathopoulos, A, Puschban, Z, Melas, C, Hermens, W T. J. M. C., Verhaagen, J, Pichon, B, Velu, T, and Levivier, M

Abstract

A recombinant AAV-2 vector encoding the green fluorescent protein (gfp) under the control of the cytomegalovirus (CMV) promoter was injected into the striatum at varying antero-posterior coordinates. When the virus was delivered to the anterior part of the striatum, transduction efficiency was low and limited to the vicinity of the needle tract. In contrast, after injection into the posterior part of the striatum, in addition to a localized transduced area in the striatum, efficient and widespread transduction was observed at distance from the injection site, in the globus pallidus. In the latter case, labelled cells were also detected in the internal capsule and in the stria terminalis. The number of transduced cells in the striatum increased up to 1 month and then decreased whereas in the globus pallidus, transduction was maximal as early as 2 weeks post-injection. In the striatum and in the globus pallidus, the labelled cells had a neuron-like morphology. In contrast, in the internal capsule, labelled cells had a glial-like morphology.

Published
2000

6. Sentinel Lymph Node Mapping in the Management of High Risk Malignant Melanoma

Author

Donckier, V., Vereecken, P., Blocklet, D., Laporte, M., Velu, T., Heenen, M., and Geertruyden, J. Van

Abstract

AbstractIn patients with malignant melanoma, the selective biopsy of the first draining lymph node, so-called the sentinel lymph node, allows to identify, with a low morbidity, the patients with nodal metastasis that require radical lymphadenectomy and adjuvant systemic chemotherapy. Herein, we report our initial experience in sentinel lymph node biopsy in 16 patients with malignant melanoma. The sentinel lymph node was localised using preoperative lymphoscintigraphy and injection of dye blue. Intraoperatively, the dissection was guided with a gamma probe and by the recognition of the blue nodes. In the 16 cases the sentinel lymph node was localised. In 50% of the cases, multiple sentinel nodes were demonstrated at lymphoscintigraphy and found during surgery. A limited postoperative morbidity was observed in three cases. Three patients presented nodal metastasis and underwent further radical lymphadenectomy. We conclude that sentinel lymph node mapping is a feasible and reproductive procedure. The preoperative lymphoscintigraphy is essential to identify multiple sentinel nodes and guide surgical dissection. The impact of this approach on the overall survival of patients with high-risk melanoma has still to be demonstrated in studies with a long follow-up.

Published
1999
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7. Disseminated angiosarcoma presenting as a hemophagocytic syndrome in a renal allograft recipient

Author

Dargent, J.‐L., Vermylen, P., Abramowicz, D., Lespagnard, L., Cochaux, P., Capel, P., Velu, T., Vereerstraeten, P., Haot, J., and Wolf‐Peeters, C. De

Abstract

AbstractA case of angiosarcoma arising in the setting of transplantation is reported. This rare and malignant tumor of the endothelial system is seldom observed in allograft recipients, with only seven cases having been previously reported. What is interesting about the present observation is that the tumor is thought to have developed in the vicinity of a Dacron graft and that it showed prominent erythrophago‐cyte‐like activity. This activity was associated with a particular clinical syndrome that shared some attributes with infection‐associated hemophagocytic syndrome.

Published
1997
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8. Gene therapy for glioblestome multiforme: in vivo tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir

Author

Stockhammer, G., Brotchi, J., Leblanc, R., Bernstein, M., Schackert, G., Weber, F., Ostertag, C., Mulder, N. H., Mellstedt, H., Seiler, R., Yonekawa, Y., Twerdy, K., Kostron, H., Witte, O. De, Lambermont, M., Velu, T., Laneuville, P., Villemure, J.-G., Rutka, J. T., Warnke, P., Laseur, M., Mooij, J. J. A., Boëthius, J., Mariani, L., Meyer, M., Brändli, C., Frei, K., Könu, D., and Gianella-Borradori, A.

Published
1997
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9. Abstracts

Author

Derlon, J. M., Petit-taboué, M. C., Dauphin, F., Courtheoux, P., Chapon, F., Creissard, P., Darcel, F., Houtteville, J. P., Kaschten, B., Sadzot, B., Stevenaert, A., Tjuvajev, Juri G., Macapinlac, Homer A., Daghighian, Farhad, Ginos, James Z., Finn, Ronald D., Jiaju Zhang, M. S., Beattie, Bradley, Graham, Martin, Larson, Steven M., Blasberg, Ronald G., Levivier, M., Goldman, S., Pirotte, B., Brucher, J. M., Balériaux, D., Luxen, A., Hildebrand, J., Brotchi, J., Go, K. G., Kamman, R. L., Mooyaart, E. L., Heesters, M. A. A. M., Sijens, P. E., Oudksrk, M., van Dijk, P., Levendag, P. C., Vecht, Ch. J., Metz, R. J., Kennedy, D. N., Rosen, B. R., Hochberg, F. H., Fishman, A. J., Filipek, P. A., Caviness, V. S., Gross, M. W., Weinzierl, F. X., Trappe, A. E., Goebel, W. E., Frank, A. M., Becker, Georg, Krone, Andreas, Schmidt, Karsten, Hofmann, Erich, Bogdahn, Ulrich, Bencsch, H., Fclber, S., Finkenstedt, G., Kremser, C., Sfockhammer, G., Aichner, F., Bogdahn, U., Fröhlich, T., Becker, G., Krone, A., Schlief, R., Schürmann, J., Jachimczak, P., Hofmann, E., Roggendorf, W., Roosen, K., Carapella, C. M., Carpinelli, G., Passalacqua, R., Raus, L., Giannini, M., Mastrostefano, R., Podo, F., Tofani, A., Maslrostefano, R., Mottoles, M., Ferraironi, A., Scelsa, M. G., Oppido, P., Riccio, A., Maini, C. L., Collombier, L., Taillandier, L., Dcbouverie, M., Laurens, M. H., Thouvenot, P., Weber, M., Bertrand, A., Cruickshank, G. S., Patterson, J., Hadley, D., De Witte, Olivier, Hildebrand, Jerzy, Luxen, André, Goldman, Serge, Ernestus, R. -I., Bockhorst, K., Eis, M., Els, T., Hoehn-Berlage, M., Gliese, M., Fründ, R., Geissler, A., Woertgen, C., Holzschuh, M., Goldman, Serge, Levivier, M., Pirotte, B., Brucher, J. M., Luxen, A., Brotchi, J., Hildebrand, J., Hausmann, O., Merlo, A., Jerrnann, E., Uirich, J., Chiquet-Ehrismann, R., Müller, J., Mäcke, H., Gratzl, O., Herholz, K., Ghaemi, M., Würker, M., Pietrzyk, U., Heiss, W. -D., Kotitschke, K., Brandl, M., Tonn, J. C., Haase, A., Bogdahn, U., Kotitschke, K., Muigg, S., Felber, S., Aichner, F., Haase, A., Bogdahn, U., Krone, A., Becker, G., Woydt, M., Roggendorf, W., Hofmann, E., Bogdahn, U., Roosen, K., Lanfermann, Heinrich, Heindel, Walter, Kugel, Harald, Erneslus, Ralf -Ingo, Röhn, Gabricle, Lackner, Klaus, Metz, R. J., Kennedy, D. N., Pardo, F. S., Kutke, S., Sorensen, A. G., Hochberg, F. H., Fishman, A. J., Filipek, P. A., Rosen, B. R., Caviness, V. S., Mechtler, L. L., Withiam-Lench, S., Shin, K., Klnkel, W. R., Patel, M., Truax, B., Kinkel, P., Shin, K., Mechtler, L., Ricci, M., Pantano, P., Maleci, A., Pierallini, S., Di Stefano, D., Bozzao, L., Cantore, G. P., Röhn, Gabriele, Els, T., Schröder, R., Hoehn-Berlage, M., Ernestus, R. -I., Ruda, R., Mocellini, C., Soffietti, R., Campana, M., Ropolo, R., Riva, A., de Filippi, P. G., Schiffer, D., Salgado, D., Rodrigues, M., Salgado, L., Fonseca, A. T., Vieira, M. R., Bravo Marques, J. M., Satoh, H., Uozumi, T., Kiya, K., Kurisu, K., Arita, K., Sumida, M., Ikawa, F., Tzuk-Shina, Tz., Gomori, J. M., Rubinstein, R., Lossos, A., Siegal, T., Vaalburg, W., Paans, A. M. J., Willemsen, A. T. M., van Waarde, A., Pruim, J., Visser, G. M., Go, K. G., Valentini, S., Ting, Y. L. T., De Rose, R., Chidichimo, G., Corricro, G., van Lcycn-Pilgram, Karin, Erncslus, Ralf -Ingo, Klug, Norfried, van Leyen-Pilgram, K., Ernestus, R. -I., Schröder, R., Klug, N., Woydt, M., Krone, A., Tonn, J. C., Becker, G., Neumann, U., Roggendorf, W., Roosen, K., Plate, Karl H., Breier, Georg, Millaucr, Birgit, Weich, Herbert A., Ullrich, Axel, Risau, Werner, Roosen, N., Chopra, R. K., Mikkelsen, T., Rosenblum, S. D., Yan, P. S., Knight, R., Windham, J., Rosenblum, M. L., Schiffer, D., Attanasio, A., Cavalla, P., Chio, A., Giordana, M. T., Migheli, A., Amberger, V., Hensel, T., Schwab, M. E., Cervoni, Luigi, Celli, Paolo, Tarantino, Roberto, Huettner, C., Tonn, J. C., Berweiler, U., Roggendorf, W., Salmon, I., Rorive, S., Rombaut, K., Pirotte, B., Haot, J., Brotchi, J., Kiss, R., Maugard-Louboutin, C., Charrier, J., Fayet, G., Sagan, C., Cuillioere, P., Ricolleau, G., Martin, S., Menegalli-Bogeelli, D., Lajat, Y., Resche, F., Molnàr, Péter, Bárdos, Helga, Ádány, Róza, Rogers, J. P., Pilkington, G. J., Pollo, B., Giaccone, G., Allegranza, A., Bugiani, O., Prim, J., Badia, J., Ribas, E., Coello, F., Shezen, E., Lossos, A., Abramsky, O., Siegal, T., Scerrati, M., Roselli, R., Iacoangeli, M., Pompucci, A., Rossi, G. F., Deeb, Saleh M. Al., Koreich, Osama, Yaqub, Basim, Moutaery, Khalaf R. Al., Giordana, M. T., Cavalla, P., Chio, A., Marino, S., Vigliani, M. C., Schiffer, D., Deburghgraeve, V., Darcel, F., Gedouin, D., Hassel, M. Ben, Guegan, Y., Jeremic, B., Grujicic, D., Antunovic, V., Matovic, M., Shibamoto, Y., Kallio, Merja, Huhmar, Helena, Kudoh, Ch., Detta, A., Sugiura, K., Hitchcock, E. R., Mastrostefano, R., Di Russo, R., Cipriani§, M., Occhipinti, E. M., Conti, E. M. S., Clowegeser, A., Ortler, M., Seiwald, M., Kostron, H., Rajan, B., Ross, G., Lim, C., Ashlcy, S., Goode, D., Traish, D., Brada, M., Sanden, G. A. C. vd, Schouten, L. J., Coebergh, J. W. W., Razenberg, P. P. A., Twijnstra, A., Snilders-Keilholz, A., Voormolen, J. H. C., Hermans, J., Leer, J. W. H., Taillandier, L., Baylac, F., Dcbouvcrie, M., Anxionnal, R., Bracard, S., Vignand, J. M., Duprcz, A., Weber, M., Winking, M., Böker, D. K., Simmet, T., Rothbart, David, Strugar, John, Balledux, Jeroen, Criscuolo, Gregory R., Jachimczak, Piotr, Blesch, Armin, Heβdörfer, Birgit, Bogdahn, Ulrich, Ernestus, Ralf -Ingo, Schröder, Roland, Klug, Norfrid, Krouwer, H. G. J., Duinen, S. G. v., Algra, A., Zentner, J., Wolf, H. K., Ostertun, B., Hufnagel, A., Campos, M. G., Solymosi, L., Schramm, J., Newlands, E. S., O'Reilly, S. M., Brampton, M., Soffietti, R., Chio, A., Mocellini, C., Ruda, R., Vigliani, M. C., Schiffer, D., Sciolla, R., Seliak, D., Henriksson, R., Bergenheim, A. T., Björk, P., Gunnarsson, P. -O., Hariz, Ml., Grant, R., Collie, D., Gregor, A., Ebmeier, K. P., Jarvis, G., Lander, F., Cull, A., Sellar, R., Brada, M., Thomas, C., Elyan, S., Hines, F., Ashley, S., Stenning, S., Bernstein, J. J., Goldberg, W. J., Roelcke, U., Von Ammon, K., Hausmann, O., Radu, E. W., Kaech, D., Leenders, K. L., Fitzek, M. M., Aronen, J. Efird, Hochberg, F., Gruber, M., Schmidt, E., Rosen, B., Flschman, A., Pardo, P., Afra, U. M. U., Sipos, L., Slouik, F., Boiardi, A., Salmaggi, A., Pozzi, A., Farinotti, L., Fariselli, L., Silvani, A., Brandes, A., Scelzi, E., Rigon, A., Zampieri, P., Pignataro, M., Amanzo, P. D'., Amista, P., Rotilio, A., Fiorentino, M. V., Thomas, R., Brazil, L., O'Connor, A. M., Ashley, S., Brada, M., Salvati, Maurizio, Cervoni, Luigi, Puzzilli, Fabrizio, Cervoni, Luigi, Salvati, Maurizio, Raguso, Michele, Cruickshank, G. S., Duckworth, R., Rumpling, R., Rottuci, M., Fariselli, L., Boiardi, A., Broggi, G., Plrint, N. G., Sabattini, E., Manetto, V., Gambacorta, H., Poggi, S., Pileri, S., Ferracini, R., Grant, R., Plev, D. V., Hopf, N. J., Knosp, E., Bohl, J., Perncczky, A., Kiss, R., Salmon, I., Catnby, I., Dewitte, O., Brotchi, J., Pasteels, J. L., Camby, I., Salmon, I., Darro, F., Danguy, A., Brotchi, J., Pasteels, J. L., Kiss, R., Kiu, M. C., Lai, G. M., Yang, T. S., Ng, K. T., Chen, J. S., Chang, C. N., Leung, W. M., Ho, Y. S., Rychter, M. Deblec, Klimek, A., Liberski, P. P., Karpinaka, A., Krauseneck, P., Schöffel, V., Müller, B., Kreth, F. W., Faist, M., Warnke, P. C., Ostertag, C. B., Nielen, K. M. B. v., Visscr, M. C., Lebrun, C., Lonjon, M., Desjardin, T., Michiels, J. F., Chanalet, Sa. Lagrange J. L., Roche, J. L., Chatel, M., Mastronardi, L., Puzzilli, F., Osman, Farah J., Lunardi, P., Matsutani, M., Ushio, Y., Takakura, K., Menten, Johan, Hamers, Han, Ribot, Jacques, Dom, René, Tcepen, Hans, Müller, B., Weidner, N., Krauseneck, P., Naujocks, G., van Roost, D., Wiestler, O. D., Kuncz, A., Nieder, C., Setzel-Sesterhein, M., Niewald, M., Schnabel, I., O'Neill, K. S., Kitchen, N. D., Wilkins, P. R., Marsh, H. T., Pierce, E., Doshi, R., Deane, R., Previtali, S., Quattrini, A., Nemni, R., Ducati, A., Wrabetz, L., Canal, N., Punt, C. J. A., Stamatakis, L., Giroux, B., Rutten, E., Quigley, Matthew R., Beth Sargent, P. A. -C., Flores, Nicholas, Simon, Sheryl, Maroon, Joseph C., Quigley, Matthew R., Beth Sargent, P. A. -C., Flores, Nicholas, Maroon, Joseph C., Rocca, A. A., Gervasoni, C., Castagna, A., Picozzi, P., Giugni, E., Rocca, A. A., Tonnarelli, G. P., Ducati, A., Mangili, F., Truci, G., Canal, N., Giovanelli, M., Roelcke, U., Von Ammon, K., Radu, E. W., Leenders, K. L., Sachsenheimer, W., Bimmler, T., Seiwald, M., Eiter, H. Rhomberg W., Ortler, M., Obwegesser, A., Kostron, H., Steilen, H., Henn, W., Moringlane, J. R., Kolles, H., Feiden, W., Zang, K. D., Sleudel, W. I., Steinbrecher, Andreas, Schabet, Martin, Heb, Clemens, Bamberg, Michael, Dichgans, Johannes, Stragliotto, G., Delattre, J. Y., Poisson, M., Zampieri, P., Brandes, A., Rigon, A., Tosatto, L., D'Amanzo, P., Menicucci, N., Rotilio, A., Mingrino, S., Steudel, W. I., Feld, R., Henn, W., Zang, K. D., Maire, J. Ph., Caudry, M., Guerin, J., Celerier, D., Salem, N., Demeaux, H., Fahregat, J. F., Kusak, M. E., Bucno, A., Albisua, J., Jerez, P., Sarasa, J. L., Garefa, R., de Campos, J. M., Kusak, M. E., de Campos, J. M., Bueno, A., García-Delgado, R., Sarasa, J. L., García-Sola, R., Lantsov, A. A., Shustova, T. I., Lcnartz, D., Wellenreuther, R., von Deirnling, A., Köning, W., Menzel, J., Scarpa, S., Manna, A., Reale, M. G., Oppido, P. A., Carapella, C. M., Frati, L., Valery, C. A., Ichen, M., Foncin, J. P., Soubrane, C., Khayat, D., Philippon, J., Vaz, R., Cruz, C., Weis, S., Protopapa, D., März, R., Winkler, P. A., Reulen, H. J., Bise, K., Beuls, E., Berg, J., Deinsberger, W., Böker, D. K., Samii, M., Caudry, M., Darrouzet, V., Guérin, J., Trouette, R., Causse, N., Bébéar, J. P., Parker, F., Vallee, J. N., Carlier, R., Zerah, M., Lacroix-Jousselin, C., Piepmeier, Joseph M., Kveton, John, Czibulka, Agnes, Tigliev, G. S., Chernov, M. P., Maslova, L. N., Valdueza, José M., Jänisch, Werner, Bock, Alexander, Harms, Lutz, Bessell, E. M., Graus, F., Punt, J., Firth, J., Hope, T., Koriech, Osama, Al Deeb, Saleh, Al Moutaery, Khalaf, Yaqub, B., Silvani, A., Salmaggi, A., Pozzi, A., Franzini, A., Boiardi, A., Goldbrunner, R., Warmuth-Metz, M., Paulus, W., Tonn, J. -Ch., Roosen, K., Strik, I. I., Müller, B., Markert, C., Pflughaupt, K. -W., Krauseneck, P., O'Neill, B. P., Dinapoli, R. P., Voges, J., Sturm, V., Deuß, U., Traud, C., Treuer, H., Lehrke, R., Kim, D. G., Müller, R. P., Alexandrov, Yu. S., Moutaery, K., Aabed, M., Koreich, O., Ross, G. M., Rajan, B., Traish, D., Ashley, S., Ford, D., Brada, M., Schmeets, I. L. O., Jager, J. J., Pannebakker, M. A. G., de Jong, J. M. A., van Lindert, E., Knosp, E., Kitz, K., Blond, S., Dubois, F., Assaker, R., Baranzelli, M. C., Sleiman, M., Pruvo, J. P., Coche-Dequeant, B., Matsutani, M., Takakura, K., Sano, K., PetriČ-Grabnar, G., Jereb, B., Župančič, N., Koršič, M., Rainov, N. G., Burkert, W., Ushio, Yukitaka, Kochi, Masato, Itoyama, Youichi, de Campos, J. M., Kusak, M. E., Sarasa, J. L., García, R., Bueno, A., Ferrando, L., Hoang-Xuan, K., Sanson, M., Merel, P., Delattre, J. Y., Poisson, M., Delattre, O., Thomas, G., Hoang-Xuan, K., Delattre, J. Y., Poisson, M., Thomas, G., Haritz, D., Obersen, B., Grochulla, F., Gabel, D., Haselsberger, K., Radner, H., Pendl, G., Brada, M., Laing, R. W., Warrington, A. P., Nowak, P. J. C. M., Kolkman-Deurloo, I. K. K., Visser, A. G., Berge, Hv. d., Niël, C. G. J. H., Levendag, P. C., Bergström, P., Hariz, M., Löfroth, P. -O., Bergenheim, T., Henriksson, R., Blond, S., Assaker, R., Cortet-rudelli, C., Dewailly, D., Coche-dequeant, B., Castelain, B., Dinapoli, R., Shaw, E., Coffey, R., Earle, J., Foote, R., Schomberg, P., Gorman, D., Girard, N., Courel, M. N., Delpech, B., Haselsberger, K., Friehs, G. M., Schröttner, O., Pendl, G., Pötter, R., hawliczek, R., Sperveslage, P., Prott, F. J., Wachter, S., Dieckmann, K., Würker, M., Herholz, K., Pietrzyk, U., Voges, J., Treuer, H., Sturm, V., Bauer, B., Heiss, W. -D., Jund, R., Zimmermann, F., Feldmann, H. J., Gross, M. W., Kneschaurek, P., Molls, M., Lederman, G., Lowry, J., Wertheim, S., Voulsinas, L., Fine, M., Lederman, G., Lowry, J., Wertheim, S., Fine, M., Voutsinas, I., Qian, G., Rashid, H., Lederman, G., Lowry, J., Wertheim, S., Fine, M., Voulsinas, L., Qian, G., Rashid, H., Moutaery, K., Aabed, M., Koreich, O., Scerrati, M., Montemaggi, P., Iacoangeli, M., Pompucci, A., Roselli, R., Trignani, R., Rossi, G. F., Shin, K., Mechtler, L., West, C., Grand, W., Shin, K., Sibata, C., West, C., Mechtler, L., Grand, W., Thomas, R., Guerrero, D., James, N., Ashley, S., Gregor, A., Brada, M., Voges, J., Sturm, V., Bramer, R., Pahlke, H., Lehrke, R., Treuer, H., Banik, N., Kim, D. G., Hövels, M., Bernsen, H. J. J. A., Rijken, P. F. J. W., Van der Sanden, B. P. J., Hagemeier, N. E. M., Van der Kogel, A. J., Koehler, P. J., Verbiest, H., Jager, J., Vecht, Ch. J., Ross, G. M., McIlwrath, A., Brown, R., Mottolesb, C., Pierre'Kahn, A., Croux, M., Roche, J. L., Marchai, J., Delhemes, P., Tremoulet, M., Stilhart, B., Chazai, J., Caillaud, P., Ravon, R., Passacha, J., Bouffet, E., Dirven, C. M. F., Mooy, J. J. A., Molenaar, W. M., Lewandowicz, G. M., Grant, N., Harkness, W., Hayward, R., Thomas, D. G. T., Darling, J. L., Delepine, N., Subovici, I. I., Cornille, B., Markowska, S., Alkallaf, JC. Desbois, KühI, J., Niethammer, D., Spaar, H. J., Gnekow, A., Havers, W., Berthold, F., Graf, N., Lampert, F., Maass, E., Mertens, R., Schöck, V., Aguzzi, A., Boukhny, A., Smirtukov, S., Prityko, A., Hoiodov, B., Geludkova, O., Nikanorov, A., Levin, P., Rothbart, David, Balledux, Jeroen, Criscuolo, Gregory R., D'haen, B., Van Calenbergh, F., Casaer, P., Dom, R., Menten, J., Goffin, J., Plets, C., Hertel, A., Hernaiz, P., Seipp, C., Siegler, K., Baum, R. P., Maul, F. D., Schwabe, D., Jacobi, G., Kornhuber, B., Hör, G., Menten, J., Casaer, P., Pilkington, G. J., Merzak, A., Rooprai, H. K., Bullock, P., van Domburg, P. H. M. F., Wesseling, P., Thijssen, H. O. M., Wolff, J. E. A., Boos, J., Krähling, K. H., Gressner-Brocks, V., Jürgens, H., Schlegel, J., Scherthan, H., Arens, N., Stumm, Gabi, Kiessling, Marika, Merzak, A., Koochekpour, S., Pilkington, G. J., Reifenberger, G., Reifenberger, J., Liu, L., James, C. D., Wechsler, W., Collins, V. P., Fabel-Schulte, Klaus, Jachimczak, Plotr, Heßdörfer, Birgitt, Baur, Inge, Schlingensiepen, Karl -Hermann, Brysch, Wolgang, Bogdahn, Ulrich, Blesch, A., Bosserhoff, A. K., Apfel, R., Lottspeich, F., Jachimczak, P., Büttner, R., Bogdahn, U., Cece, R., Barajon, I., Tazzari, S., Cavaletti, G., Torri-Tarelli, L., Tredici, G., Hecht, B., Turc-Carel, C., Atllas, R., Chatel, M., Gaudray, P., Gioanni, J., Hecht, F., Balledux, Jeroen, Rothbart, David, Criscuolo, Gregory R., de Campos, J. M., Kusak, M. E., Rey, J. A., Bello, M. J., Sarasa, J. L., Dubois, F., Blond, S., Parent, M., Assaker, R., Gosselin, P., Christiaens, J. L., Feld, R., Moringlane, J. R., Steudel, W. I., Schaudies, J. R., Janka, M., Tonn, J. C., Fischer, U., Meese, E., Roosen, K., Remmelink, M., Salmon, I., Cras, P., Pasteels, J. L., Brotchi, J., Kiss, R., Bensadoun, R. J., Frenay, M., Formento, J. L., Milano, G., Lagrange, J. L., Grellier, P., Lee, J. -Y., Ernestus, R. -I., Riese, H. -H., Cervós-Navarro, J., Reutter, W., Lippitz, B., Scheitinger, C., Scholz, M., Weis, J., Gilsbach, J. M., Füzesi, L., Koochekpour, S., Merzak, A., Pilkington, G. J., Sanson, M., Li, Y. J., Hoang-Xuan, K., Delattre, J. Y., Poisson, M., Hamelin, R., Van de Kelft, Erik, Dams, Erna, Martin, Jean -Jacques, Willems, Patrick, Lehrke, R., Voges, J., Treuer, H., Erdmann, J., Müller, R. P., Sturm, V., Wurm, R. E., Warrington, A. P., Laing, R. W., Sardell, S., Hines, F., Graham, J. D., Brada, M., Ushio, Yukitaka, Kuratsu, Jun -ichi, Kochi, Masato, Kitz, K., Aichholzer, M., Rössler, K., Alesch, F., Ertl, A., Sorensen, P. S., Helweg-Larsen, S., Mourldsen, H., Hansen, H. H., El Sharoum, S. Y., Berfelo, M. W., Theunissen, P. H. M. H., Jager, J. J., de Jong, J. M. A., Fedorcsák, I., Nyáry, I., Osztie, É., Horvath, Á., Kontra, G., Frenay, M., Burgoni-chuzel, J., Paquis, P., Lagrange, J. L., Helweg-Larsen, S., Hansen, SW., Sørensen, PS., Salmon, I., Kiss, R., Krauseneck, P., Müller, B., Morche, M., Tonn, J. C., Lagerwaard, F. J., Levendag, P. C., Eijkenboom, W. M. H., Schmilz, P. I. M., Lentzsch, S., Weber, F., Franke, J., Dörken, B., Lunardi, P., Schettini, G., Osman, Farah J., Qasho, R., Mocellini, C., Ruda, R., Soffietti, R., Garabello, D., Sales, S., De Lucchi, R., Vasario, E., Schiffer, D., Muracciole, X., Régis, J., Manera, L., Peragut, J. C., Juin, P., Sedan, R., Nieder, C., Niewald, M., Walter, K., Schnabel, K., Nieder, C., Niewald, N., Nestle, U., Schnabel, K., Berberich, W., Oschmann, P., Theißen, R. D., Reuner, K. H., Kaps, M., Dorndorf, W., Martin, K. K., Akinwunmi, J., Rooprai, H. K., Kennedy, A., Linke, A., Ognjenovic, N., Pilkington, G. J., Svadovsky, A. I., Peresedov, V. V., Bulakov, A. A., Butyalko, M. Y., Zhirnova, I. G., Labunsky, D. A., Gnazdizky, V. V., Gannushkina, I. V., Taphoorn, M. J. B., Potman, R., Barkhof, F., Weerts, J. G., Karim, A. B. M. F., Heimans, J. J., van de Pol, M., van Aalst, V. C., Wilmink, J. T., Twijnstra, A., van der Sande, J. J., Boogerd, W., Kröger, R., Jäger, A., Wismeth, C., Dekant, A., Brysch, W., Schlingensiepen, K. H., Jachimczak, P., Bogdahn, U., Pirolte, B., Cool, V., Gérard, C., Levivier, M., Dargent, J. L., Goldman, S., Brotchi, J., Hildebrand, J., Velu, T., Herrlinger, U., Schabet, M., Ohneseit, P., Buchholz, R., Zhu, Jianhong, Reszka, Regina, Weber, Friedrich, Walther, Wolfgang, Zhang, L. I., Brock, Mario, Roosen, N., Rock, J. P., Zeng, H., Feng, J., Fenstermacher, J. D., Rosenblum, M. L., Siegal, T., Gabizon, A., Beljanski, M., Crochet, S., Bergenheim, A. T., Zackrisson, B., Elfverson, J., Bergström, P., Henriksson, R., Butti, G., Baetta, R., Magrassi, L., De Renzis, M. R., Soma, M. R., Davegna, C., Pezzotta, S., Paoletti, R., Fumagalli, R., Infuso, L., Sankar, A. A., Darling, J. L., Thomas, D. G. T., Defer, G. -L., Brugières, P., Gray, F., Chomienne, C., Poirier, J., Degos, L., Degos, J. D., Colombo, Bruno M., DiDonato, Stefano, Finocchiaro, Gaetano, Hebeda, K. M., Sterenborg, H. J. C. M., Saarnak, A. E., Wolbers, J. G., van Gemert, M. J. C., Kaaijk, P., Troost, D., Leenstra, S., Das, P. K., Bosch, D. A., Kostron, H., Hochleitner, B. W., Obwegeser, A., Ortler, M., Seiwald, M., Vooys, W., Krouwer, H. G. J., de Gast, G. C., Marx, J. J. M., Osman, Farah J., Lunardi, P., Puzzilli, F., Menovsky, T., Beek, J. F., Wolbers, J. G., van Gemert, M. J. C., Naujocks, G., Wiestler, O. D., Schirrmacher, V., Schramm, J., Schmitz, A., Eis-Hübinger, A. M., Piepmeier, p. h., Pedersen, Patricia, Greer, Charles, Quigley, Matthew R., Shih, Tommy, Elrifal, Amr, Rothfus, William, Maroon, Joseph C., Rohertson, L., Rampling, R., Whoteley, T. L., Piumb, J. A., Kerr, D. J., Falina, P. A., Crossan, I. M., Roosen, N., Rock, J. P., Feng, J., Zeng, H., Ho, K. L., Fenstermacher, J. D., Rosenblum, M. L., Ruchoux, M. M., Vincent, S., Jonca, F., Plouet, J., Lecomte, M., Samid, D., Thibault, A., Ram, Z., Oldfield, E. H., Myers, C. E., Reed, E., Schabet, M., Herrlinger, U., Buchholz, R., Shoshan, Y., Siegal, T., Siegal, T., Shezen, E., Siegal, Tz., Stockhammer, G., Rosenblum, M., Samid, D., Lieberman, F., Terzis, A. J. A., Bjerkvig, R., Laerum, O. D., Arnold, H., Thibault, A., Samid, D., Figg, W. D., Myers, C. E., Reed, E., Thomas, R., Flux, G., Chittenden, S., Doshi, P., Brazil, L., Thomas, D. G. T., Bignor, D., Zalutsky, M., Brada, M., Tjuvajev, Juri, Kaplitt, Michael, Desai, Revathi, Bradley, M. S., Bettie, B. S., Gansbacher, Bernd, Blasberg, Ronald, Haugland, H. K., Saraste, J., Rooseni, K., Laerum, O. D., Vincent, A. J. P. E., Avezaat, C. J. J., Bout, A., Noteboom, J. L., Vecht, C. h., Valerio, D., Hoogerbrugge, P. M., Weber, F., Reszka, R., Zhu, J., Walther, W., List, J., Schulz, W., Wolbers, J. G., Sterenborg, I. I. J. C. M., Kamphorst, W., van Gemert, M. J. C., van Alplien, H. A. M., Salander, P., Bergenheim, T., Henriksson, R., Grant, R., Brazil, L., Thomas, R., Guerrero, D., Laing, R., Ashley, S., Brada, M., Schmidt, B., Bauer, B., Grau, G., Bohnstedt, T., Frydrych, A., Franz, K., Lorenz, R., Brandes, A., Amanzo, P. D'., Zampieri, P., Rigon, A., Scelzi, E., Rotilio, A., Berti, F., Paccagnella, A., Fiorentino, M. V., Müller, B., Krauseneck, P., van Deventer, P. L., Dellemijn, P. L. I., van den Bent, M. J., Vecht, Ch. J., Kansen, P. J., Tredici, G., Petruccioli, N. G., Cavaletti, G., Cavalletti, E., Kiburg, B., Müller, L. J., Moorer-van Delft, C. M., Heimans, J. J., Boer, H. H., Pace, A., Bove, L., Pietrangeli, A., Innocenti, P., Aloe, A., Nardi, M., Jandolo, B., Kellie, S. J., De Graaf, S. S. N., Bloemhof, H., Roebuck, D., Dalla, Pozza L., Uges, D. D. R., Johnston, I., Besser, M., Chaseling, R. A., Koeppen, S., Gründemann, S., Lossos, A., Siegal, T., Nitschke, M., Vieregge, P., Reusche, E., Rob, P., Kömpf, D., Postma, T. J., Vermorken, J. B., Heimans, J. J., Rampling, R. P., Dunlop, D. J., Steward, M. S., Campbell, S. M., Roy, S., Hilkens, P. H. E., Verweij, J., van Putten, W. L. J., Vecht, Ch. J., van den Bent, M. J., Hilkens, P. H. E., Moll, J. W. B., van der Burg, M. E. L., Planting, A. S. T., van Putten, W. L. J., Vecht, Ch. J., van den Bent, M. J., Wondrusch, E., Zifko, U., Drlicek, M., Liszka, U., Grisold, W., Zifko, U., Fazeny, B., Dittrich, Ch., Wondrusch, E., Grisold, W., Verschuuren, Jan J., Meneses, Patricio I., Rosenfeld, Myrna R., Kaplitt, Michael G., Posner, Jerome B., Dalmau, Josep, Sillevis Smitt, P. A. E., Manley, G., Posner, J. B., Cavaletti, G., Bogliun, G., Margorati, L., Bianchi, G., Drlicek, M., Liska, U., Casati, B., Kolig, C., Grisold, H., Graus, F., Reñe, R., Uchuya, M., Valldeoriola, F., Delattre, J. Y., Benedetti de Cosentiro, C., Ortale, D., Martinez, R., Lambre, J., Cagnolati, S., Vinai, C., Salmaggi, A., Nemni, R., Silvani, A., Forno, M. G., Luksch, R., Confalonieri, P., Boiardi, A., Nitschke, M., Scholz, J., Vieregge, P., Kömpf, D., Hochberg, F. H., Pfeiffer, G., Netzer, J., Hansen, Ch., Eggers, Ch., Hagel, Ch., Kunze, K., Verschuuren, Jan J., Rosenblum, Marc K., Lieberman, Frank S., Posner, Jerome B., and Dalmau, Josep

Published
1994
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10. Disseminated angiosarcoma presenting as a hemophagocytic syndrome in a renal allograft recipient

Author

Dargent, J., Vermylen, P., Abramowicz, D., Lespagnard, L., Cochaux, P., Capel, P., Velu, T., Vereerstraeten, P., Haot, J., and Wolf-Peeters, C.

Abstract

A case of angiosarcoma arising in the setting of transplantation is reported. This rare and malignant tumor of the endothelial system is seldom observed in allograft recipients, with only seven cases having been previously reported. What is interesting about the present observation is that the tumor is thought to have developed in the vicinity of a Dacron graft and that it showed prominent erythrophagocyte-like activity. This activity was associated with a particular clinical syndrome that shared some attributes with infection-associated hemophagocytic syndrome.

Published
1996
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11. Transmembrane signalling at epidermal growth factor receptors overexpressed in NIH 3T3 cells. Phosphoinositide hydrolysis, cytosolic Ca2+ increase and alkalinization correlate with epidermal-growth-factor-induced cell proliferation

Author

Pandiella, A, Beguinot, L, Velu, T J, and Meldolesi, J

Abstract

NIH 3T3 cells, which express a small number of EGF (epidermal growth factor) receptors, are poorly responsive to EGF. However, when the same cells overexpress the cloned human EGF receptor (EGFR T17 cells), they display EGF-dependent transformation. In EGFR T17 cells (but not in the parental NIH 3T3 cells), EGF is shown here to trigger polyphosphoinositide hydrolysis as well as the generation of the ensuing intracellular signals, the increase in the cytosolic Ca2+ concentration ([Ca2+]i) and pH. EGF induced a large accumulation of inositol 1,4,5-trisphosphate, with a peak at 15-30 s and a slow decline thereafter. Other inositol phosphates (1,3,4-trisphosphate and 1,3,4,5-tetrakisphosphate) increased less rapidly and to a lesser degree. [Ca2+]i increased after a short lag, reached a peak at 25 s and remained elevated for several minutes. By use of incubation media with and without Ca2+, the initial phase of the EGF-induced [Ca2+]i increase was shown to be due largely to Ca2+ release from intracellular stores. In contrast with previous observations in human A431 cells, the concentration-dependence of the EGF-triggered [Ca2+]i increase in EGFR T17 cells paralleled that of [3H]thymidine incorporation. It is concluded that polyphosphoinositide hydrolysis, [Ca2+]i increase and cytoplasmic alkalinization are part of the spectrum of intracellular signals generated by the activation of one single EGF receptor type. These processes might be triggered by the receptor via activation of the intrinsic tyrosine kinase activity. Large stimulation of DNA synthesis and proliferation by EGF in EGFR T17 cells could be due to a synergistic interplay between the two signal pathways initiated by tyrosine phosphorylation and polyphosphoinositide hydrolysis.

Published
1988
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12. Morphologic and phenotypic changes of the leukemic cells in a case of marginal zone B-cell lymphoma

Author

Dargent, J. L., Delville, J. P., Kornreich, A., Pradier, O., Cochaux, P., Velu, T., Capel, P., Feremans, W., and Neve, P.

Abstract

Abstract:  A particular case of marginal zone B-cell lymphoma (MZBCL) presenting with leukemic lymphocytes is reported. In the present observation, the leukemic cells not only displayed a remarkable morphological fluctuation but also had an unusual phenotype, changing with time. These phenotypic features, which have been functionally investigated by in vitro assays, might simply reflect an activation state depending on the microenvironment. Because of its disconcerting similarities with hairy cell leukemia (HCL) and splenic lymphoma with villous lymphocytes (SLVL), this case relaunches the debate about whether close relationships might exist between the splenic marginal zone, SLVL and HCL.

Published
1997
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13. Harvey murine sarcoma virus: influences of coding and noncoding sequences on cell transformation in vitro and oncogenicity in vivo

Author

Velu, T J, Vass, W C, Lowy, D R, and Tambourin, P E

Abstract

The rat-derived Harvey murine sarcoma virus (Ha-MuSV) contains a transduced ras oncogene activated by two missense mutations and flanked by rat retroviruslike VL30 sequences. Ha-MuSV induces focal transformation of mouse NIH 3T3 cells in vitro and tumors (fibrosarcomas and splenic erythroleukemias) in newborn mice. We have used these two assays to study the contribution of coding and noncoding viral sequences to the biological activity of Ha-MuSV. A good correlation was found between the in vitro and in vivo assays. In several different isogenic Ha-MuSV variants, those with a rasH gene that had one or both of the Ha-MuSV missense mutations were much more active biologically than the corresponding proto-oncogene. A Ha-MuSV variant that encoded the proto-oncogene protein induced lymphoid leukemias (with thymomas), with a relatively long latent period, rather than the fibrosarcomas and erythroleukemias characteristic of Ha-MuSV with one or both missense mutations. A VL30-derived segment with enhancer activity was identified downstream from v-rasH. A mutant Ha-MuSV from which this 3' noncoding segment was deleted expressed lower levels of the wild-type viral protein, displayed impaired transforming activity in vitro, and induced lymphoid leukemias (with thymomas). 5' noncoding rat c-rasH sequences were found to increase the biological activity of the virus when substituted for the corresponding segment of v-rasH. We conclude that (i) the biological activity of Ha-MuSV can be influence significantly by noncoding sequences located outside the long terminal repeat as well as by coding sequences, (ii) VL30 sequences positively regulate the expression of v-rasH, (iii) relatively low biological levels of ras, whether resulting from low-level expression of wild type v-rasH or high-levels of ras proto-oncogene protein, induce a type of tumor that differs from tumors induced by high biological levels of ras, and (iv) the in vivo pathogenicity of the Ha-MuSV variants correlated with their transforming activity on NIH 3T3 cells.

Published
1989
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14. In vivo induction of interleukin 10 by anti-CD3 monoclonal antibody or bacterial lipopolysaccharide: differential modulation by cyclosporin A.

Author

Durez, P, Abramowicz, D, Gérard, C, Van Mechelen, M, Amraoui, Z, Dubois, C, Leo, O, Velu, T, and Goldman, M

Abstract

We investigated the in vivo effects of cyclosporin A (CsA) on the production of interleukin (IL) 10, a cytokine with major immunosuppressive properties. To elicit IL-10 production in vivo, BALB/c mice were injected either with the anti-mouse CD3 145-2C11 monoclonal antibody (mAb) (25 micrograms) or with bacterial lipopolysaccharide (LPS) (20 micrograms). A systemic release of IL-10 was observed in both models, IL-10 serum levels reaching 1.60 +/- 0.32 U/ml (mean +/- SEM) and 0.67 +/- 0.09 U/ml 6 h after injection of 145-2C11 mAb and LPS, respectively. Experiments in nude mice indicated that T cells are involved in the induction of IL-10 by anti-CD3 mAb, but not by LPS. Pretreatment with CsA (total dose: 50 mg/kg) before injection of 145-2C11 mAb completely prevented the release of IL-10 in serum as well as IL-10 mRNA accumulation in spleen cells. In contrast, CsA markedly enhanced LPS-induced IL-10 release (IL-10 serum levels at 6 h: 8.31 +/- 0.43 vs. 0.71 +/- 0.15 U/ml in mice pretreated with CsA vehicle-control, p < 0.001), as well as IL-10 mRNA accumulation in spleen. We conclude that CsA differentially affects IL-10 production in vivo depending on the nature of the eliciting agent. This observation might be relevant to clinical settings, especially in organ transplantation.

Published
1993
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15. Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia.

Author

Gérard, C, Bruyns, C, Marchant, A, Abramowicz, D, Vandenabeele, P, Delvaux, A, Fiers, W, Goldman, M, and Velu, T

Abstract

Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (TNF) release in the circulation was observed after IL-10 pretreatment at doses at low as 10 U. IL-10 also efficiently prevented the hypothermia generated by the injection of 100 micrograms LPS. Finally, pretreatment with a single injection of 1,000 U IL-10 completely prevented the mortality consecutive to the challenge with 500 micrograms LPS, a dose that was lethal in 50% of the control mice. We conclude that IL-10 inhibits in vivo TNF secretion and protects against the lethality of endotoxin in a murine model of septic shock.

Published
1993
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16. The bovine papillomavirus E5 oncogene can cooperate with ras: identification of p21 amino acids critical for transformation by c-rasH but not v-rasH

Author

Willumsen, B M, Vass, W C, Velu, T J, Papageorge, A G, Schiller, J T, and Lowy, D R

Abstract

We have previously used a series of insertion-deletion mutants of the mutationally activated v-rasH gene to identify several regions of the encoded protein that are dispensable for cellular transformation (B. M. Willumsen, A. G. Papageorge, H.-F. Kung, E. Bekesi, T. Robins, M. Johnsen, W. C. Vass, and D. R. Lowy, Mol. Cell. Biol. 6:2646-2654, 1986). To determine if some of these amino acids are more important for the biological activity of c-rasH, we have now tested many of the same insertion-deletion mutants in the c-rasH form for their ability to transform NIH 3T3 cells. Since the transforming activity of c-rasH is low, we have used cotransfection with the bovine papillomavirus (BPV) genome to develop a more sensitive transformation assay for c-rasH mutants. The increased sensitivity of the assay, which is seen both in focal transformation and in anchorage-independent growth, is mediated by cooperation between the BPV E5 gene and ras. E5-dependent cooperation was seen for v-rasH as well as for c-rasH, which suggests that the major effect of E5 was to increase the susceptibility of the cell to transformation to a given level of ras activity. The cooperation assay was used to test the potential importance, in c-rasH, of codons 93 to 108, 123 to 130, and 166 to 183, which were nonessential for v-rasH transformation. Relative to the respective transforming activity of wild-type c-rasH and v-rasH, mutants with lesions in codons 102 and 103 were significantly less active in their c-rasH forms than in their v-rasH forms. We conclude that a region including amino acids 102 and 103 encodes a function that is more critical to c-rasH than to v-rasH. Guanine nucleotide exchange is one function that is compatible with such a phenotype.

Published
1991
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17. A highly efficient retroviral vector allows detection of the transforming activity of the human c-fps/fes proto-oncogene

Author

Feldman, R A, Lowy, D R, Vass, W C, and Velu, T J

Abstract

We have constructed an efficient new retroviral vector containing strong promoting elements derived from the Friend murine leukemia virus (F-MuLV) long terminal repeat (LTR) and have used the vector to demonstrate that overexpression of human c-fps/fes can transform established mouse cells. When a c-fps/fes cDNA was cloned into the vector, this viral DNA and the recovered virus induced very high levels of the c-fps/fes product NCP92 and tumorigenic transformation of NIH 3T3 cells. Compared with an isogenic vector under control of a Moloney MuLV-derived LTR, the vector driven by the F-MuLV LTR induced 3- to 10-times-higher levels of expression of c-fps/fes, a higher level of phosphotyrosine in cellular proteins, and a virus whose transforming activity was 2 orders of magnitude greater. We conclude (i) that normal c-fps/fes can induce morphologic transformation and that its transforming activity is a function of the level of expression of NCP92 and (ii) that the vector based on the F-MuLV LTR is more efficient than the vector driven by a Moloney MuLV LTR in inducing high levels of expression and measurable biological activity.

Published
1989
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18. Intrathyroidal cytokine gene expression profiles in autoimmune thyroiditis

Author

Paschke, R, Schuppert, F, Taton, M, and Velu, T

Abstract

Cytokines are thought to mediate the initiation and perpetuation of autoimmune thyroiditis. However, this concept is mainly based on in vitrofindings and to date only interleukin (IL)-6 and interferon-γ (IFN-γ) have been detected in Graves' disease in vivo. The cytokine pattern produced by T-helper (Th) cells has important regulatory effects on the nature of the immune response. We therefore determined these cytokine mRNAs in Graves' disease and Hashimoto's thyroiditis.RNA was extracted by cesium chloride gradient centrifugation from the thyroid tissue of 12 patients undergoing thyroid resection for Graves' disease and from two patients being treated for Hashimoto's thyroiditis. Two patients with parathyroid adenomas and one patient with a goiter were used as controls. RNA was also extracted from normal human thyroid epithelial cells in primary culture. The cDNAs were prepared by reverse transcription and amplified for IL-2, -4, -5, -6 and -10 and IFN-γ by polymerase chain reaction.All the cytokine mRNAs were detected in the Hashimoto's thyroid glands in large quantities. Six of the 12 Graves' disease thyroid glands showed, when compared with controls, an increased accumulation of transcripts for: IFN-γ, IL-2, -4 and -10 or IL-2, -4 and IFN-γ or IL-2 and IFN-γ or IFN-γ alone, each in one case or IL-2 alone in two cases. These cytokine profiles were not representative of a Th1 or Th2 phenotype. Increased amounts of cytokine mRNA in thyroid glands from Graves' disease patients were mostly associated with high microsomal antibody titres and/or prominent intrathyroidal lymphocytic infiltration. IL-6 and/or IL-10 mRNAs were detectable in all Graves' disease thyroid glands and in control thyroid tissue. IL-10 mRNA was not detectable in normal human thyroid epithelial cells in primary culture.Graves' disease and Hashimoto's thyroiditis clearly differ with respect to the number of positive intrathyroidal cytokine mRNAs and their levels. The different cytokine patterns in Graves' disease and in Hashimoto's thyroiditis could reflect the clinical spectrum of autoimmune thyroiditis which is characterized by thyroid tissue destruction and/or thyroid autoantibody production. These data suggest that the course of autoimmune thyroiditis is regulated by the interplay of several cytokines.Journal of Endocrinology(1994) 141,309–315

Published
1994
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19. A Case of Pleomorphic T-Cell Lymphoma with a High Content of Reactive Histiocytes Presented with Hypereosinophilia

Author

Dargent, J.L., Jacobovitz, D., Pradier, O., Velu, T., Martiat, P., Delplace, J., Neve, P., and Diebold, J.

Abstract

A case of peripheral T-cell lymphoma classified, according to the updated Kiel classification, as a large pleomorphic T-cell lymphoma with a high content of reactive histiocytes and blood hypereosinophilia is reported. Light microscopic examination revealed a diffuse effacement of the lymph node structure by large pleomorphic lymphoma cells mixed with eosino phils and many histiocytes, some of them presenting discrete features of hemo phagocytosis. The neoplastic cells were CD3, CD5, CD8 and HLA-DR positive but failed to show CD30 antigen. DNA molecular analysis displayed simultaneous rearrangements o f the genes coding for the delta chain of the T-cell receptor and for the Ig heavy chain. Increased serum levels of angiotensin converting enzyme and ferritin were found and probably induced by the reactive histiocytes. Immunoassays (ELISA) with antibodies directed against some cytokines and against the Tac peptide (sIL-2R) were performed. They demonstrated high serum levels of sIL-2R and a slight increase in GM-CSF, but neither IL-5 nor IL-3. The association of blood hypereosinophilia and histiocytic hyperplasia with a peripheral T-cell lymphoma is discussed.

Published
1995
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20. Signal Transduction in Hamster Fibroblasts Overexpressing the Human EGF Receptor

Author

L'allemain, G., Seuwen, K., Velu, T., and Pouyssegur, J.

Abstract

Human EGF receptors (HERs) were expressed in CCL39 hamster fibroblasts, a cell line responding only weakly to EGF despite the presence of 10-20,000 EGF receptors per cell. High expression of HERs (800,000 per cell) conferred EGF responsiveness. In these cells EGF is a potent mitogen, induces strong receptor autophosphorylation, phosphorylation of cellular substrates on tyrosine, activates the Na+/H+ exchanger, and weakly stimulates phosphoinositide (PI) turnover. Activation of PI turnover by a mitogen activating a receptor tyrosine kinase has not been observed previously in CCL39 cells. We present evidence, however, that the activation of this signaling pathway which is insensitive to pertussis toxin does not mediate the proliferative response. Unlike NIH 3T3 cells, CCL39 fibroblasts over-expressing HERs are not transformed nor can a transformed phenotype be observed in response to EGF or TGFα.

Published
1989
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22. Functional heterogeneity of proto-oncogene tyrosine kinases: the C terminus of the human epidermal growth factor receptor facilitates cell proliferation

Author

Velu, T J, Vass, W C, Lowy, D R, and Beguinot, L

Abstract

Previous reports have indicated that the C termini of the membrane-associated tyrosine kinases encoded by c-src and c-fms proto-oncogenes have a negative effect on their biological activity and that this effect is mediated by their C-terminal tyrosine residue. To determine whether this was true for the human epidermal growth factor (EGF) receptor, which is also a membrane-associated tyrosine kinase proto-oncogene, we have constructed two premature termination mutants, dc19 and dc63, that delete the C-terminal 19 and 63 amino acids, respectively, from the human full-length receptor (hEGFR). The smaller deletion removes the C-terminal tyrosine residue, while the larger deletion removes the two most C-terminal tyrosines; similar deletions are found in v-erbB. As previously shown for the gene encoding the full-length EGF receptor, the two C-terminal mutants induced EGF-dependent focal transformation and anchorage-independent growth of NIH 3T3 cells. However, both dc19 and dc63 were quantitatively less efficient than the gene encoding the full-length receptor, with dc63 being less active than dc19. Although the C-terminal mutants displayed lower biological activity than the gene encoding the full-length receptor, the mutant receptors were found to be similar in several respects to the full-length receptor. These parameters included receptor localization, stability in the absence of EGF, receptor half-life in the presence of EGF, EGF binding, extent of EGF-dependent autophosphorylation in vitro, and EGF-dependent phosphorylation of an exogenous substrate in vitro. Therefore, the C-terminal 63 amino acids of the human receptor have no detectable influence on EGF-dependent early events. We conclude that in contrast

Published
1989
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23. Chorioretinal post-transplant lymphoproliferative disorder induced by the Epstein-Barr virus

Author

demols, P.F., Cochaux, P.M., Velu, T., and Caspers-Velu, L.

Abstract

BACKGROUND: The Epstein-Barr virus (EBV) is responsible for the lymphoproliferative disorders observed in transplanted patients. METHODS: The case history is described of a 59 year old man with a chorioretinal lesion who had received a single lung transplant and was on immunosuppressive treatment. Immunoglobulin gene rearrangement and EBV detection by polymerase chain reaction (PCR) with semiquantification were used on the vitreous material. RESULTS: A proliferation of B lymphocytes with a monoclonal subpopulation was found by PCR on the vitreous sample. The large amounts of EBV genomes found in the vitreous suggest that EBV was the cause of the lymphoproliferation. Healing of the lesion was achieved by a decrease in immunosuppressive treatment and the use of nucleotide analogues. CONCLUSION: The diagnosis of ocular post-transplant lymphoproliferative disorder (PTLD) can be made by PCR on vitreous material. Early diagnosis and treatment can lead to regression of limited monoclonal lesions.

Published
2001

26. Dendritic cells generated in the presence of IL-13 and GM-CSF in a GMP large scale production process are potent tumor antigen stimulators and are well tolerated by cancer patients

Author

Bercovici, N., Massicard, S., Agrawal, S., Pauillac, F., Duffour, M.T., Boccaccio, C., Boyer, A., Nardin, A., Chauvet, I., Prigent, D., Fabbro, M.-O., Goxe, B., Latour, N., Heshmati, F., Duriau, D., Lehmann, F., Bruyns, C., Velu, T., Romet-Lemonne, J.-L., Abastado, J.-P., and Salcedo, M.

Published
2001
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