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17 results on '"Kraemer, D. M."'

5. Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia

Author

Cornely, O. A., Leguay, T., Maertens, J., Vehreschild, M. J. G. T., Anagnostopoulos, A., Castagnola, C., Verga, L., Rieger, C., Kondakci, M., Harter, G., Duarte, R. F., Allione, B., Cordonnier, C., Heussel, C. P., Morrissey, C. O., Agrawal, S. G., Peter Donnelly, J., Bresnik, M., Hawkins, M. J., Garner, W., Gokbuget, N., Jarchum, G., Dictar, M., Ramirez Borga, S., Valledor, A., Knoebl, P., Greil, R., Linkesch, W., Sill, H., De Prijck, B., Sonet, A., Theunissen, K., Selleslag, D., Vargas Schwarzbold, A., Nucci, M. L. M., Lopes de Castro Lobo, C., Fogliatto, L., Bonmati, C., Turlure, P., Herbrecht, R., Thiebaut, A., Michallet, M., Egerer, G., Silling, G., Pfreundschuh, M., Hasenkamp, J., Kraemer, D. M., Topp, M., Heinz, W., Junghanss, C., Schaich, M. A., Parmentier, S., Roellig, C., Beck, H. J., Huttmann, A., Mousset, S., Duenzinger, U. N., Schwartz, S., Haerter, G., Ostermann, H., Tsirigotis, P., Matsouka, P., Angelopoulou, M. K., Karakantza, M., Spyridonidis, A., Kolomansky, A., Moses, A., Horowitz, N., Rahav, G., Aversa, F., Velardi, A., Pagano, Livio, Gentile, Giuseppe, Gobbi, M., Luppi, M., Nosari, A. M., Rambaldi, A., Candoni, A., Marbello, L., Rossi, G., Pogliani, E., Moreira, I., Nunes, A., Botelho de Sousa, A., Rubio Tejero, A. I., Vallejo, C., Vazquez, L., Besalduch Vidal, J., Gomez-Garcia de Soria, V., Jurado Chacon, M., Gonzalez Campos, J., Olavarria, E., Barba, P., de la Serna Torroba, J., Duarte, R., Heim, D., Zimmerli, S., Gerber, B., Akova, M., Bolaman, A. Z., Tabak, F., Akan, H., Senol, E., and Gilead Sciences

Subjects
0301 basic medicine, Male, Antifungal Agents, Administration, Intravenous, Adolescent, Adult, Aged, Aged, 80 and over, Amphotericin B, Chemoprevention, Double-Blind Method, Europe, Female, Humans, Invasive Fungal Infections, Middle Aged, Placebos, Precursor Cell Lymphoblastic Leukemia-Lymphoma, South America, Treatment Outcome, Young Adult, Medizin, law.invention, Randomized controlled trial, law, hemic and lymphatic diseases, Clinical endpoint, 80 and over, Pharmacology (medical), Original Research, hemic and immune systems, Chemotherapy regimen, Infectious Diseases, Tolerability, Administration, Intravenous, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Neutropenia, Placebo, 03 medical and health sciences, Internal medicine, medicine, Pharmacology, Surrogate endpoint, business.industry, medicine.disease, Surgery, Regimen, Settore MED/15 - MALATTIE DEL SANGUE, business
Abstract

[Objectives] To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL)., [Patients and methods] In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB., [Results] Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB (n = 237) or placebo (n = 118). Rates of proven and probable IFD assessed independently were 7.9% (18/228) in the L-AMB group and 11.7% (13/111) in the placebo group (P = 0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group (P = 0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo (P = 1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB., [Conclusions] The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7% in the placebo group, and was not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL., This study was funded by Gilead Sciences, Inc. M. B., W. G. and M. J. H. are employees of Gilead Sciences. All other authors or their institutions have received compensation for study participation from Gilead Sciences International Ltd.

Published
2017

8. The essential yeast nucleoporin NUP159 is located on the cytoplasmic side of the nuclear pore complex and serves in karyopherin-mediated binding of transport substrate.

Author

Kraemer, D M, Strambio-de-Castillia, C, Blobel, G, and Rout, M P

Abstract

We have identified a new yeast nucleoporin of 159 kDa that we term NUP159. Immunofluorescence microscopy with a monospecific monoclonal antibody against NUP159 gave the punctate nuclear rim staining characteristic of nucleoporins. Immunogold electron microscopy with isolated yeast NEs yielded decoration of only the cytoplasmic side of the nuclear pore complex. The gene encoding NUP159 is essential, and, like some other nucleoporins, NUP159 contains a coiled-coil domain as well as a domain of repeated motifs. Five segments of NUP159, covering its entire length, were expressed in Escherichia coli. The repeat motif-containing segment was found to bind a nuclear transport substrate in the presence of vertebrate cytosolic extract containing nuclear transport factors. This segment also bound 35S-labeled mammalian karyopherin beta, one such transport factor that mediates the docking of substrates to the nuclear pore complex. These data establish a direct biochemical link between the repeat motif domain of a yeast nucleoporin, transport factors, (specifically karyopherin beta), and nuclear transport substrates. Its cytoplasmic aspect implies a role for NUP159 in nuclear import.

Published
1995

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