102 results on '"Bouvier R"'
Search Results
2. Dark Matter Search in the EDELWEISS experiment
- Author
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Juillard, A., Benoit, A., Berge, L., Bonnevaux, A., Bouvier, R., Broniatowski, A., Chambon, B., Chapellier, M., Chardin, G., Charvin, P., Cluzel, P., De Jesus, M., Di Stefano, P., Drain, D., Dumoulin, L., Gascon, J., Gerbier, G., Goldbach, C., Goyot, M., Gros, M., Hadjout, J. P., De Lesquen, A., Loidl, M., Loiseau, D., Mallet, J., Marnieros, S., Martineau, O., Mirabolfathi, N., Mosca, L., Navick, X-F., Nollez, G., Pari, P., Pastor, C., Simon, E., Stern, M., and Vagneron, L.
- Subjects
Astrophysics - Abstract
The EDELWEISS Dark Matter Search uses low-temperature Ge detectors with heat and ionisation read-out to identify nuclear recoils induced by elastic collisions with WIMPs from the galactic halo. Preliminary results obtained with 320g bolometers are described. After a few weeks of data taking, data accumulated with one of these detectors already allow to reach the upper part of the DAMA region. Prospects for the present run and the second stage of the experiment, EDELWEISS-II, using an innovative reversed cryostat allowing data taking with 100 detectors, are briefly described., Comment: 4 pages, LaTeX, 3 figures, contribution to " Very High Energy Phenomena in the Universe ", Les Arcs, France (January 20-27, 2001)
- Published
- 2001
3. 778TiP A phase I/II trial investigating safety and efficacy of autologous TAC T-cells targeting HER2 in relapsed or refractory solid tumors
- Author
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Schlechter, B.L., primary, Ileana Dumbrava, E.E., additional, Olson, D., additional, Saibil, S., additional, Pieke, B., additional, Bouvier, R., additional, Moss, K., additional, Turnus, N., additional, Bader, A., additional, and Adib, D., additional
- Published
- 2022
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- View/download PDF
4. Prevalence of liver complications in children receiving long-term parenteral nutrition
- Author
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Peyret, B, Collardeau, S, Touzet, S, Loras-Duclaux, I, Yantren, H, Michalski, M C, Chaix, J, Restier-Miron, L, Bouvier, R, Lachaux, A, and Peretti, N
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- 2011
- Full Text
- View/download PDF
5. P-31 A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors
- Author
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Dumbrava, E., Olson, D., George, M., Saibil, S., Antonio, G., Bouvier, R., Gavriliuc, M., Pieke, B., Lichtenstein, E., Geisberger, J., Apostolopoulou, M., Moss, K., Ternus, N., Adib, D., and Schlechter, B.
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- 2023
- Full Text
- View/download PDF
6. Clinical, morphological, and molecular aspects of sialic acid storage disease manifesting in utero
- Author
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Froissart, R, Cheillan, D, Bouvier, R, Tourret, S, Bonnet, V, Piraud, M, and Maire, I
- Published
- 2005
7. Effects of brisk walking on autonomic nervous system reactivation in nursing home residents
- Author
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Raffin, J., primary, Barthélémy, J.C., additional, Busso, T., additional, Calmels, P., additional, Féasson, L., additional, Terrat, P., additional, Diana, M.C., additional, Montuy-Coquard, C., additional, Bouvier, R., additional, Poillerat, R., additional, Roche, F., additional, and Hupin, D., additional
- Published
- 2018
- Full Text
- View/download PDF
8. Scientia (1928 et 1929)
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Bouvier, R.
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- 1931
9. Correlation of serum prostate specific antigen and semi quantitative tissue RT-PCR from prostate cancer samples
- Author
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Colombel, M, Marechal, JM, Gelet, A, Pangaud, C, Bouvier, R, Martin, X, Dubernard, JM, and Lasne, Y
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- 2000
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10. Differential RNA expression of the pS2 gene in the human benign and malignant prostatic tissue
- Author
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Colombel, M, Dante, R, Bouvier, R, Ribieras, S, Pangaud, C, Marechal, J-M, and Lasne, Y
- Published
- 1999
- Full Text
- View/download PDF
11. Comparaison of the Plusoptix A12 and the 2WIN with the Retinomax K-plus 3 in a pediatric population
- Author
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Bouvier, R., primary, Heripret, A., additional, Promelle, V., additional, and Milazzo, S., additional
- Published
- 2016
- Full Text
- View/download PDF
12. A study of new NEK8 mutations in patients with severe renal cystic hypodysplasia and ciliopathy-associated defects
- Author
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Grampa, V, primary, Delous, M, additional, Silbermann, F, additional, Oyde, G, additional, Krug, P, additional, Filhol, E, additional, Alessandri, JL, additional, Sigaudy, S, additional, Bouvier, R, additional, Zabot, MT, additional, Antignac, C, additional, Gubler, M, additional, Attié-Bitach, T, additional, Benmerah, A, additional, Jeanpierre, C, additional, and Saunier, S, additional
- Published
- 2015
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- View/download PDF
13. Dark Matter Search in the EDELWEISS experiment
- Author
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Martineau, O., Benoit, Angélique, Bergé, L., Bouvier, R., Broniatowski, A., Caussignac, M., Chabert, L., Chambon, B., Chapellier, M., Chardin, G., Charvin, P., De Jésus, M., Di Stefano, P., Drain, D., Dumoulin, L., Gascon, J., Gerbier, G., Goldbach, C., Goyot, M., Gros, M., Hadjout, J.-P., Herve, S., Juillard, A., De Lesquen, A., Loidl, M., Mallet, J., Marnieros, S., Martin, M., Mirabolfathi, N., Mosca, L., Navick, X.F., Nollez, G., Pari, P., Riccio, C., Rodenas, H., Shoeffel, L., Stern, M., Vagneron, L., Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Centre de Spectrométrie Nucléaire et de Spectrométrie de Masse (CSNSM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), EDELWEISS, and Flores, Sylvie
- Subjects
010302 applied physics ,[SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph] ,010308 nuclear & particles physics ,Physics::Instrumentation and Detectors ,Astrophysics (astro-ph) ,Astrophysics::Instrumentation and Methods for Astrophysics ,FOS: Physical sciences ,Astrophysics::Cosmology and Extragalactic Astrophysics ,[SDU.ASTR] Sciences of the Universe [physics]/Astrophysics [astro-ph] ,Astrophysics ,01 natural sciences ,[PHYS.ASTR.CO]Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO] ,[PHYS.ASTR.CO] Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO] ,0103 physical sciences - Abstract
The EDELWEISS Dark Matter Search uses low-temperature Ge detectors with heat and ionisation read-out to identify nuclear recoils induced by elastic collisions with WIMPs from the galactic halo. Preliminary results obtained with 320g bolometers are described. After a few weeks of data taking, data accumulated with one of these detectors already allow to reach the upper part of the DAMA region. Prospects for the present run and the second stage of the experiment, EDELWEISS-II, using an innovative reversed cryostat allowing data taking with 100 detectors, are briefly described., 4 pages, LaTeX, 3 figures, contribution to " Very High Energy Phenomena in the Universe ", Les Arcs, France (January 20-27, 2001)
- Published
- 2001
14. BBS10 mutations are common in 'Meckel'-type cystic kidneys
- Author
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Putoux, A., primary, Mougou-Zerelli, S., additional, Thomas, S., additional, Elkhartoufi, N., additional, Audollent, S., additional, Le Merrer, M., additional, Lachmeijer, A., additional, Sigaudy, S., additional, Buenerd, A., additional, Fernandez, C., additional, Delezoide, A.-L., additional, Gubler, M.-C., additional, Salomon, R., additional, Saad, A., additional, Cordier, M.-P., additional, Vekemans, M., additional, Bouvier, R., additional, and Attie-Bitach, T., additional
- Published
- 2010
- Full Text
- View/download PDF
15. Malignancy incidence after renal transplantation in children: a 20-year single-centre experience
- Author
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Koukourgianni, F., primary, Harambat, J., additional, Ranchin, B., additional, Euvrard, S., additional, Bouvier, R., additional, Liutkus, A., additional, and Cochat, P., additional
- Published
- 2009
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16. Summary of the Standards, Options and Recommendations for the management of patients with nonmetastatic prostate cancer (2001)
- Author
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Villers, A, primary, Pommier, P, additional, Bataillard, A, additional, Fervers, B, additional, Bachaud, J M, additional, Berger, N, additional, Bertrand, A F, additional, Bouvier, R, additional, Brune, D, additional, Daver, A, additional, Fontaine, E, additional, Haillot, O, additional, Lagrange, J L, additional, Molinie, V, additional, Muratet, J P, additional, Pabot du Chatelard, P, additional, Peneau, M, additional, Prapotnich, D, additional, Ravery, V, additional, Richaud, P, additional, Rossi, D, additional, and Soulie, M, additional
- Published
- 2003
- Full Text
- View/download PDF
17. Microarchitectural and Physical Changes During Fetal Growth in Human Vertebral Bone
- Author
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Nuzzo, S, primary, Meneghini, C, additional, Braillon, P, additional, Bouvier, R, additional, Mobilio, S, additional, and Peyrin, F, additional
- Published
- 2003
- Full Text
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18. Lupus-Like Nephritis in A Child With AIDS
- Author
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Bertrand, Y, primary, Mialou, V, additional, Bouvier, R, additional, Philippe, N, additional, Nochy, D, additional, and Cochat, P, additional
- Published
- 1999
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19. Clinical relevance of TRKA expression on neuroblastoma: comparison with N-MYC amplification and CD44 expression
- Author
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Combaret, V, primary, Gross, N, additional, Lasset, C, additional, Balmas, K, additional, Bouvier, R, additional, Frappaz, D, additional, Beretta-Brognara, C, additional, Philip, T, additional, Favrot, MC, additional, and Coll, J-L, additional
- Published
- 1997
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20. Mutation in the COL2A1 gene in a patient with hypochondrogenesis. Expression of mutated COL2A1 gene is accompanied by expression of genes for type I procollagen in chondrocytes.
- Author
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Freisinger, P., primary, Ala-Kokko, L., additional, LeGuellec, D., additional, Franc, S., additional, Bouvier, R., additional, Ritvaniemi, P., additional, Prockop, D.J., additional, and Bonaventure, J., additional
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- 1994
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21. Découverte de la Personne, Esquisse d'un personnalisme analytique. Nouvelle Encyclopédie philosophique Charles Baudouin
- Author
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Bouvier, R.
- Published
- 1942
22. A new lethal syndrome of exomphalos, short limbs, and macrogonadism
- Author
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Razavi, F., Faivre, L., Bouvier, R., delezoide, A-L., Cormier-Daire, V., Briard, M-L., Lyonnet, S., Vekemans, M., Munnich, A., Merrer, M. Le, and Narcy, F.
- Abstract
We report a new lethal multiple congenital abnormality (MCA) syndrome of exomphalos, short limbs, nuchal web, macrogonadism, and facial dysmorphism in seven fetuses (six males and one female) belonging to three unrelated families. X rays showed enlarged and irregular metaphyses with a heterogeneous pattern of mineralisation of the long bones. Pathological examination showed adrenal cytomegaly, hyperplasia of Leydig cells, ovarian stroma cells, and Langherans cells, and renal microcysts. We suggest that this condition is a new autosomal recessive MCA syndrome different from Beckwith-Wiedemann syndrome, especially as no infracytogenetic deletion or uniparental disomy of chromosome 11 was found.
- Published
- 1999
23. Carbon-13 nuclear magnetic resonance studies on (85% 13C-enriched Gly 9) oxytocin
- Author
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Griffin, John H., Alazard, Robert, Dibello, Carlo, Sala, Ernest, Mermet-Bouvier, R., and Cohen, Paul
- Published
- 1975
- Full Text
- View/download PDF
24. Heavy isotope labeling study of the turnover of forskolin-stimulated adenylate cyclase in BC3H1 cell line.
- Author
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Bouhelal, R, Bockaert, J, Mermet-Bouvier, R, Guillon, G, and Homburger, V
- Abstract
We have used the method of heavy isotope labeling to study the metabolic turnover of adenylate cyclase in a nonfusing muscle cell line, the BC3H1 cells. These cells contains an adenylate cyclase coupled to beta-adrenergic receptors and highly stimulated by forskolin, a potent activator of the enzyme. After transfer of the cells from normal medium to heavy medium (a medium containing heavy labeled amino acids, 2H, 13C, 15N), heavy isotope-labeled adenylate cyclase molecules progressively replace pre-existing light molecules. In sucrose gradient differential sedimentation, after a 5-day switch in heavy medium, the enzyme exhibited a higher mass (s = 8.40 +/- 0.03 S, n = 13) compared to the control enzyme (s = 7.40 +/- 0.04 S, n = 36). Indeed, the increase in the sedimentation coefficient of the heavy molecules was due to the synthesis of new molecules of adenylate cyclase labeled with heavy isotope amino acids since in the presence of cycloheximide, an inhibitor of protein synthesis, no change in the sedimentation pattern of the forskolin-stimulated adenylate cyclase occurred. After incorporation of heavy isotope amino acids in the adenylate cyclase molecules, the kinetics parameters of the enzyme (i.e. Km for ATP and EC50 for Mn2+ or Mg2+) did not change. However, adenylate cyclase from cells incubated with heavy medium exhibits an activity about 2-fold lower than control (cells in light medium). After switching the cells to the heavy medium, the decrease of the activity of the enzyme occurred during the first 24 h and thereafter remained at a steady state for at least 4 days. In contrast, 24 h after the switch, the sedimentation coefficient of forskolin-stimulated adenylate cyclase was progressively shifted to a higher value indicating that the heavy isotope-labeled enzyme replaced the pre-existing light form of the molecule. These observations show that the rapid decrease in adenylate cyclase activity and the synthesis of heavy adenylate cyclase molecules are two separate events. The relative amounts of heavy and light components of forskolin-stimulated adenylate cyclase obtained in sucrose gradient differential sedimentation were determined as a function of time beginning 24 h after the transfer into the heavy medium. The decrease of the pre-existing light form could be represented by simple first order kinetics with a half-time of 40 h. This result suggests that the metabolic renewal of forskolin-stimulated adenylate cyclase is comparable to that of most plasma membrane proteins.
- Published
- 1987
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25. Carbon‐13 nuclear magnetic resonance studies on (85% 13C‐enriched Gly9) oxytocin
- Author
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Griffin, John H., Alazard, Robert, Dibello, Carlo, Sala, Ernest, Mermet-Bouvier, R., and Cohen, Paul
- Published
- 1975
- Full Text
- View/download PDF
26. A new lethal syndrome of exomphalos, short limbs, and macrogonadism
- Author
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Faivre L, Al, Delezoide, Narcy F, Razavi F, Bouvier R, valerie cormier-daire, Ml, Briard, Lyonnet S, Vekemans M, Munnich A, and Le Merrer M
- Subjects
Original Articles - Abstract
We report a new lethal multiple congenital abnormality (MCA) syndrome of exomphalos, short limbs, nuchal web, macrogonadism, and facial dysmorphism in seven fetuses (six males and one female) belonging to three unrelated families. X rays showed enlarged and irregular metaphyses with a heterogeneous pattern of mineralisation of the long bones. Pathological examination showed adrenal cytomegaly, hyperplasia of Leydig cells, ovarian stroma cells, and Langherans cells, and renal microcysts. We suggest that this condition is a new autosomal recessive MCA syndrome different from Beckwith-Wiedemann syndrome, especially as no infracytogenetic deletion or uniparental disomy of chromosome 11 was found. Keywords: MCA syndrome; exomphalos; short limbs; abnormal metaphyses
27. Carbon-13 nuclear magnetic resonance studies on (85% 13 C-enriched Gly9 ) oxytocin
- Author
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Griffin, John H., primary, Alazard, Robert, additional, Dibello, Carlo, additional, Sala, Ernest, additional, Mermet-Bouvier, R., additional, and Cohen, Paul, additional
- Published
- 1975
- Full Text
- View/download PDF
28. First report of rapidly progressive glomerulonephritis in tumor necrosis factor receptor-associated periodic syndrome.
- Author
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Harambat J, Desjonqueres M, Garaix F, Cochat P, Ranchin B, Cimaz R, Dodé C, and Bouvier R
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- 2008
- Full Text
- View/download PDF
29. A study of new NEK8mutations in patients with severe renal cystic hypodysplasia and ciliopathy-associated defects
- Author
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Grampa, V, Delous, M, Silbermann, F, Oyde, G, Krug, P, Filhol, E, Alessandri, JL, Sigaudy, S, Bouvier, R, Zabot, MT, Antignac, C, Gubler, M, Attié-Bitach, T, Benmerah, A, Jeanpierre, C, and Saunier, S
- Published
- 2015
- Full Text
- View/download PDF
30. Risk factors associated with Crimean-Congo hemorrhagic fever virus circulation among human, livestock and ticks in Mauritania through a one health retrospective study.
- Author
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El Ghassem A, Apolloni A, Vial L, Bouvier R, Bernard C, Khayar MS, Cheikh Ahmed M, Fausther-Bovendo H, Beyit AD, Yahya B, Ould El Mamy MB, Elbara A, Bollahi MA, Cêtre-Sossah C, and Ould Mohamed Salem Boukhary A
- Subjects
- Humans, Animals, Cattle, Sheep, Livestock, Retrospective Studies, Mauritania, Goats, Antibodies, Viral, RNA, Risk Factors, Seroepidemiologic Studies, Hemorrhagic Fever Virus, Crimean-Congo, Ticks, Hemorrhagic Fever, Crimean epidemiology, One Health, Ixodidae
- Abstract
Background: Crimean Congo hemorrhagic fever (CCHF) is endemic in Southern Mauritania where recurrent outbreaks have been constantly observed since the 1980's. The present study is the first to assess CCHFV antibodies and RNA in humans., Methods: A retrospective study was conducted using 263 humans and 1380 domestic animals serum samples, and 282 tick specimens of Hyalomma genus collected from 54 settings in 12 provinces across Mauritania. Antibodies targeting CCHF viral nucleoprotein were detected in animal and human sera using double-antigen ELISA. CCHFV specific RNA was detected in human and animal sera as well as tick supernatants using a CCHFV real time RT-PCR kit. Individual characteristics of sampled hosts were collected at the same time and data were geo-referenced. Satellite data of several environmental and climatic factors, were downloaded from publicly available datasets, and combined with data on livestock mobility, animal and human density, road accessibility and individual characteristics to identify possible risk factors for CCHFV spatial distribution. To this end, multivariate logistic models were developed for each host category (human, small and large ruminants)., Results: The overall CCHFV antibody prevalence was 11.8% [95% CI: 8.4-16.3] in humans (17.9% in 2020 and 5.4% in 2021; p = 0.0017) and 33.1% (95% CI: 30.1-36.3) in livestock. CCHFV-specific antibodies were detected in 91 (18.1%) out of 502 sheep, 43 (9.0%) out of 477 goats, 144 (90.5%) out of 161 dromedaries and 179 (74.6%) out of 240 cattle. CCHFV RNA was detected in only 2 (0.7%) sera out of 263 animals herders samples from Hodh El Gharbi province and in 32 (11.3%) out of 282 Hyalomma ticks. In humans as well as in animals, seropositivity was not associated with sex or age groups. The multivariate analysis determined the role of different environmental, climatic and anthropic factors in the spatial distribution of the disease with animal mobility and age being identified as risk factors., Conclusion: Results of the present study demonstrate the potential risk of CCHF for human population in Mauritania primarily those living in rural areas in close vicinity with animals. Future studies should prioritize an integrative human and veterinary approach for better understanding and managing Crimean-Congo hemorrhagic fever., (© 2023. The Author(s).)
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- 2023
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31. Bardet-Biedl syndrome: Antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes.
- Author
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Mary L, Chennen K, Stoetzel C, Antin M, Leuvrey A, Nourisson E, Alanio-Detton E, Antal MC, Attié-Bitach T, Bouvagnet P, Bouvier R, Buenerd A, Clémenson A, Devisme L, Gasser B, Gilbert-Dussardier B, Guimiot F, Khau Van Kien P, Leroy B, Loget P, Martinovic J, Pelluard F, Perez MJ, Petit F, Pinson L, Rooryck-Thambo C, Poch O, Dollfus H, Schaefer E, and Muller J
- Subjects
- Alleles, Amino Acid Substitution, Autopsy, Bardet-Biedl Syndrome genetics, Biopsy, Genotype, Humans, Mutation, Prenatal Diagnosis, Exome Sequencing, Bardet-Biedl Syndrome diagnosis, Genetic Association Studies, Genetic Predisposition to Disease, Phenotype
- Abstract
Bardet-Biedl syndrome (BBS) is an emblematic ciliopathy associated with retinal dystrophy, obesity, postaxial polydactyly, learning disabilities, hypogonadism and renal dysfunction. Before birth, enlarged/cystic kidneys as well as polydactyly are the hallmark signs of BBS to consider in absence of familial history. However, these findings are not specific to BBS, raising the problem of differential diagnoses and prognosis. Molecular diagnosis during pregnancies remains a timely challenge for this heterogeneous disease (22 known genes). We report here the largest cohort of BBS fetuses to better characterize the antenatal presentation. Prenatal ultrasound (US) and/or autopsy data from 74 fetuses with putative BBS diagnosis were collected out of which molecular diagnosis was established in 51 cases, mainly in BBS genes (45 cases) following the classical gene distribution, but also in other ciliopathy genes (6 cases). Based on this, an updated diagnostic decision tree is proposed. No genotype/phenotype correlation could be established but postaxial polydactyly (82%) and renal cysts (78%) were the most prevalent symptoms. However, autopsy revealed polydactyly that was missed by prenatal US in 55% of the cases. Polydactyly must be carefully looked for in pregnancies with apparently isolated renal anomalies in fetuses., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
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32. DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma.
- Author
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Sheffield NC, Pierron G, Klughammer J, Datlinger P, Schönegger A, Schuster M, Hadler J, Surdez D, Guillemot D, Lapouble E, Freneaux P, Champigneulle J, Bouvier R, Walder D, Ambros IM, Hutter C, Sorz E, Amaral AT, de Álava E, Schallmoser K, Strunk D, Rinner B, Liegl-Atzwanger B, Huppertz B, Leithner A, de Pinieux G, Terrier P, Laurence V, Michon J, Ladenstein R, Holter W, Windhager R, Dirksen U, Ambros PF, Delattre O, Kovar H, Bock C, and Tomazou EM
- Subjects
- Adolescent, Adult, Cell Line, Tumor, Child, Child, Preschool, Epigenesis, Genetic, Female, Genetic Heterogeneity, Humans, Male, Middle Aged, Promoter Regions, Genetic genetics, Young Adult, Bone Neoplasms genetics, DNA Methylation genetics, Gene Expression Regulation, Neoplastic, Oncogene Proteins, Fusion genetics, Proto-Oncogene Protein c-fli-1 genetics, RNA-Binding Protein EWS genetics, Sarcoma, Ewing genetics
- Abstract
Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.
- Published
- 2017
- Full Text
- View/download PDF
33. Increasing diversion of household hazardous wastes and materials through mandatory retail take-back.
- Author
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Wagner TP, Toews P, and Bouvier R
- Subjects
- Environmental Monitoring, Hazardous Waste analysis, Refuse Disposal methods
- Abstract
The disposal of household hazardous waste and materials as municipal solid waste (MSW) remains a vexing problem for solid waste managers and policymakers. A major underlying factor is the inconvenience of special collection programs compared to general disposal. A properly designed, mandatory retail take-back program can significantly improve user convenience compared to centralized or periodic, voluntary special collection programs. San Luis Obispo County, California, population 271,960, was the first county in the US to establish a mandatory retail take-back program for specific household hazardous waste and materials (HHWM): fluorescent lamps, household batteries, medical sharps, and latex paint. This program uses retail locations as collection points for subsequent transport by the county to its transfer facility. This shared responsibility program has been highly effective at diverting HHWM from disposal as MSW. Between April 2009 and October 2012 the estimated collection/diversion rates increased dramatically from near zero percent to approximately 36.44% for fluorescent lamps, 21.4% for household batteries, 28.43% for latex paint, and 72.65% for used medical sharps. For household batteries and fluorescent lamps, the convenience of the collection container and the type of store were statistically significant predictors of the number of batteries and lamps collected., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
34. Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes.
- Author
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Madariaga L, Morinière V, Jeanpierre C, Bouvier R, Loget P, Martinovic J, Dechelotte P, Leporrier N, Thauvin-Robinet C, Jensen UB, Gaillard D, Mathieu M, Turlin B, Attie-Bitach T, Salomon R, Gübler MC, Antignac C, and Heidet L
- Subjects
- Abortion, Therapeutic, Autopsy, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Heredity, Humans, Male, Pedigree, Phenotype, Predictive Value of Tests, Pregnancy, Retrospective Studies, Severity of Illness Index, Ultrasonography, Prenatal, Urogenital Abnormalities, Hepatocyte Nuclear Factor 1-beta genetics, Mutation, PAX2 Transcription Factor genetics, Prenatal Diagnosis methods, Vesico-Ureteral Reflux diagnosis, Vesico-Ureteral Reflux genetics
- Abstract
Background and Objectives: Congenital anomalies of the kidney and urinary tract (CAKUT) are a frequent cause of renal failure in children, and their detection in utero is now common with fetal screening ultrasonography. The clinical course of CAKUT detected before birth is very heterogeneous and depends on the level of nephron reduction. The most severe forms cause life-threatening renal failure, leading to perinatal death or the need for very early renal replacement therapy., Design, Setting, Participants, & Measurements: This study reports the screening of two genes (HNF1B and PAX2) involved in monogenic syndromic CAKUT in a cohort of 103 fetuses from 91 families with very severe CAKUT that appeared isolated by fetal ultrasound examination and led to termination of pregnancy., Results: This study identified a disease-causing mutation in HNF1B in 12 cases from 11 families and a mutation in PAX2 in 4 unrelated cases. Various renal phenotypes were observed, but no case of bilateral agenesis was associated with HNF1B or PAX2 mutations. Autopsy identified extrarenal abnormalities not detected by ultrasonography in eight cases but confirmed the absence of extrarenal defects in eight other cases. A positive family history of renal disease was not significantly more frequent in cases with an identified mutation. Moreover, in cases with an inherited mutation, there was a great phenotypic variability regarding the severity of the renal disease within a single family., Conclusions: Our results suggest that mutations in genes involved in syndromic CAKUT with Mendelian inheritance are not rare in fetal cases with severe CAKUT appearing isolated at prenatal ultrasound, a finding of clinical importance because of genetic counseling.
- Published
- 2013
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35. First de novo mutation in RPS19 gene as the cause of hydrops fetalis in Diamond–Blackfan anemia.
- Author
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Da Costa L, Chanoz-Poulard G, Simansour M, French M, Bouvier R, Prieur F, Couque N, Delezoide AL, Leblanc T, Mohandas N, and Touraine R
- Subjects
- Anemia, Diamond-Blackfan embryology, Female, Fetal Death, Humans, Pregnancy, Anemia, Diamond-Blackfan genetics, Hydrops Fetalis genetics, Mutation, Ribosomal Proteins genetics
- Published
- 2013
- Full Text
- View/download PDF
36. Hepatocyte nuclear factor 1β controls nephron tubular development.
- Author
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Massa F, Garbay S, Bouvier R, Sugitani Y, Noda T, Gubler MC, Heidet L, Pontoglio M, and Fischer E
- Subjects
- Animals, Calcium-Binding Proteins, Chromatin Immunoprecipitation, Gene Expression Regulation, Developmental genetics, Hepatocyte Nuclear Factor 1-beta genetics, Homeodomain Proteins metabolism, Immunohistochemistry, In Situ Hybridization, Intercellular Signaling Peptides and Proteins metabolism, Mice, Microscopy, Electron, Nephrons abnormalities, Nephrons ultrastructure, Nerve Tissue Proteins metabolism, Organogenesis genetics, POU Domain Factors metabolism, Real-Time Polymerase Chain Reaction, Transcription Factors metabolism, Gene Expression Regulation, Developmental physiology, Hepatocyte Nuclear Factor 1-beta metabolism, Nephrons embryology, Organogenesis physiology
- Abstract
Nephron morphogenesis is a complex process that generates blood-filtration units (glomeruli) connected to extremely long and patterned tubular structures. Hepatocyte nuclear factor 1β (HNF1β) is a divergent homeobox transcription factor that is expressed in kidney from the first steps of nephrogenesis. Mutations in HNF1B (OMIM #137920) are frequently found in patients with developmental renal pathologies, the mechanisms of which have not been completely elucidated. Here we show that inactivation of Hnf1b in the murine metanephric mesenchyme leads to a drastic tubular defect characterized by the absence of proximal, distal and Henle's loop segments. Nephrons were eventually characterized by glomeruli, with a dilated urinary space, directly connected to collecting ducts via a primitive and short tubule. In the absence of HNF1β early nephron precursors gave rise to deformed S-shaped bodies characterized by the absence of the typical bulge of epithelial cells at the bend between the mid and lower segments. The lack of this bulge eventually led to the absence of proximal tubules and Henle's loops. The expression of several genes, including Irx1, Osr2 and Pou3f3, was downregulated in the S-shaped bodies. We also observed decreased expression of Dll1 and the consequent defective activation of Notch in the prospective tubular compartment of comma- and S-shaped bodies. Our results reveal a novel hierarchical relationship between HNF1β and key genes involved in renal development. In addition, these studies define a novel structural and functional component of S-shaped bodies at the origin of tubule formation.
- Published
- 2013
- Full Text
- View/download PDF
37. Long-term critical issues in pediatric renal transplant recipients: a single-center experience.
- Author
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Harambat J, Ranchin B, Bertholet-Thomas A, Mestrallet G, Bacchetta J, Badet L, Basmaison O, Bouvier R, Demède D, Dubourg L, Floret D, Martin X, and Cochat P
- Subjects
- Adolescent, Child, Child, Preschool, Female, Graft Survival, Humans, Immunosuppressive Agents therapeutic use, Kidney Transplantation adverse effects, Kidney Transplantation mortality, Living Donors, Male, Models, Statistical, Proportional Hazards Models, Retrospective Studies, Treatment Outcome, Kidney Transplantation statistics & numerical data, Renal Insufficiency therapy
- Abstract
Data on long-term outcomes after pediatric renal transplantation (Tx) are still limited. We report on a 20-year single-center experience. Medical charts of all consecutive pediatric Tx performed between 1987 and 2007 were reviewed. Data of patients who had been transferred to adult units were extracted from the French databases of renal replacement therapies. Outcomes were assessed using Kaplan-Meier and Cox models. Two hundred forty Tx were performed in 219 children (24.1% pre-emptive and 17.5% living related donor Tx). Median age at Tx was 11.1 years and median follow-up was 10.4 years. Patient survival was 94%, 92%, and 91% at 5, 10, and 15 years post-Tx, respectively. Overall, transplant survival was 92%, 82%, 72%, and 59% at 1, 5, 10, and 15 years post-Tx, respectively. The expected death-censored graft half-life was 20 years. Sixteen patients developed malignancies during follow-up. Median height at 18 years of age was 166 cm in boys and 152 cm in girls with 68% of patients being in the normal range. The proportion of socially disadvantaged young people was higher than in general population. Excellent long-term outcomes can be achieved in pediatric renal Tx, but specific problems such as malignancies, growth, and social outcome remain challenging., (© 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
38. NEK1 and DYNC2H1 are both involved in short rib polydactyly Majewski type but not in Beemer Langer cases.
- Author
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El Hokayem J, Huber C, Couvé A, Aziza J, Baujat G, Bouvier R, Cavalcanti DP, Collins FA, Cordier MP, Delezoide AL, Gonzales M, Johnson D, Le Merrer M, Levy-Mozziconacci A, Loget P, Martin-Coignard D, Martinovic J, Mortier GR, Perez MJ, Roume J, Scarano G, Munnich A, and Cormier-Daire V
- Subjects
- Consanguinity, Female, Fetus abnormalities, Genetic Association Studies, Genetic Heterogeneity, Genotype, Humans, Male, Mutation, NIMA-Related Kinase 1, Pregnancy, Cell Cycle Proteins genetics, Cytoplasmic Dyneins genetics, Protein Serine-Threonine Kinases genetics, Short Rib-Polydactyly Syndrome genetics
- Abstract
Background: The lethal short rib polydactyly syndromes (SRP type I-IV) are characterised by notably short ribs, short limbs, polydactyly, multiple anomalies of major organs, and autosomal recessive mode of inheritance. Among them, SRP type II (Majewski; MIM 263520) is characterised by short ovoid tibiae or tibial agenesis and is radiographically closely related to SRP type IV (Beemer-Langer; MIM 269860) which is distinguished by bowed radii and ulnae and relatively well tubulated tibiae. NEK1 mutations have been recently identified in SRP type II. Double heterozygosity for mutations in both NEK1 and DYNC2H1 in one SRP type II case supported possible digenic diallelic inheritance., Methods: The aim of this study was to screen DYNC2H1 and NEK1 in 13 SRP type II cases and seven SRP type IV cases. It was not possible to screen DYNC2H1 in two patients due to insufficient amount of DNA., Results: The study identified homozygous NEK1 mutations in 5/13 SRP type II and compound heterozygous DYNC2H1 mutations in 4/12 cases. Finally, NEK1 and DYNC2H1 were excluded in 3/12 SRP type II and in all SRP type IV cases. The main difference between the mutation positive SRP type II group and the mutation negative SRP type II group was the presence of holoprosencephaly and polymycrogyria in the mutation negative group., Conclusion: This study confirms that NEK1 is one gene causing SRP type II but also reports mutations in DYNC2H1, expanding the phenotypic spectrum of DYNC2H1 mutations. The exclusion of NEK1 and DYNC2H1 in 3/12 SRP type II and in all SRP type IV cases further support genetic heterogeneity.
- Published
- 2012
- Full Text
- View/download PDF
39. Occurrence of inflammatory bowel disease during treatment of juvenile idiopathic arthritis with etanercept: a French retrospective study.
- Author
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Dallocchio A, Canioni D, Ruemmele F, Duquesne A, Scoazec JY, Bouvier R, Paraf F, Languepin J, Wouters CH, Guillot M, Quartier P, and Bader-Meunier B
- Subjects
- Adolescent, Arthritis, Juvenile physiopathology, Child, Child, Preschool, Female, France, Humans, Inflammatory Bowel Diseases physiopathology, Male, Retrospective Studies, Surveys and Questionnaires, Time Factors, Tumor Necrosis Factor-alpha adverse effects, Antirheumatic Agents adverse effects, Arthritis, Juvenile drug therapy, Inflammatory Bowel Diseases chemically induced, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Objectives: To identify juvenile idiopathic arthritis (JIA) patients who developed IBD during treatment with anti-TNF-alpha agents and better characterize the IBD clinical and pathological presentation., Methods: A retrospective French multicentre study included patients with a diagnosis of JIA according to the ILAR criteria who developed IBD while under anti-TNF-alpha therapy before 18 years of age. Intestinal biopsies were collected and reviewed by the same pathologist., Results: Eight patients were included. They had been treated with etanercept from 11 to 78 months before IBD onset. Gastro-intestinal symptoms included abdominal pain (six patients), diarrhoea (four patients), anorexia (four patients), anal abscess (three patients) and oral ulcers (one patient). Five patients presented with Crohn's disease (CD) and three with indeterminate IBD, of whom four had severe pancolitis. Clinical remission of IBD was obtained in all patients after discontinuation of etanercept and initiation of IBD-specific therapy, including infliximab in six patients., Conclusion: IBD must be suspected in JIA patients treated with etanercept who develop intestinal symptoms, including anal abscess. This series raises the possibility of a relationship between etanercept therapy and the occurrence of IBD in a subset of patients with JIA.
- Published
- 2010
- Full Text
- View/download PDF
40. Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.
- Author
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Denamur E, Delezoide AL, Alberti C, Bourillon A, Gubler MC, Bouvier R, Pascaud O, Elion J, Grandchamp B, Michel-Calemard L, Missy P, Zaccaria I, Le Nagard H, Gerard B, Loirat C, Barbet J, Beaufrère AM, Berchel C, Bessières B, Boudjemaa S, Buenerd A, Carles D, Clemenson A, Dechelotte P, Devisme L, Dijoud F, Espérandieu O, Fallet C, Gonzalès M, Hillion Y, Jacob B, Joubert M, Kermanach P, Lallemand A, Laquerrière A, Laurent N, Liprandi A, Loeuillet L, Loget P, Martinovic J, Ménez F, Narcy F, Roux JJ, Rouleau-Dubois C, Sinico M, Tantau J, and Wann AR
- Subjects
- Genotype, Humans, Infant, Newborn, Phenotype, Fetal Diseases genetics, Fetal Diseases pathology, Mutation, Polycystic Kidney, Autosomal Recessive genetics, Polycystic Kidney, Autosomal Recessive pathology, Receptors, Cell Surface genetics
- Abstract
The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.
- Published
- 2010
- Full Text
- View/download PDF
41. Malignancy incidence after renal transplantation in children: a 20-year single-centre experience.
- Author
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Koukourgianni F, Harambat J, Ranchin B, Euvrard S, Bouvier R, Liutkus A, and Cochat P
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Incidence, Infant, Male, Retrospective Studies, Risk Factors, Time Factors, Kidney Transplantation adverse effects, Neoplasms epidemiology, Neoplasms etiology
- Abstract
Background: Cancer is a well-recognized complication of organ transplantation. The pattern of malignancies that occur in the paediatric graft population is different from that in the general paediatric population and in the population of adult organ transplant recipients., Methods: We reviewed medical records from 240 consecutive paediatric renal transplantations performed in 219 children, aged less than 19 years, in our centre between April 1987 and March 2007. Data from patients who had been transferred into adult units were extracted from the French registries of dialysis and transplantation., Results: Among the 219 children who underwent renal transplantation during the study period, 16 (7.3%) developed malignancy. The cumulative incidence of cancer was 1.9, 4.0, 6.9 and 10.2% at 1, 5, 10 and 15 years post-transplantation, respectively. The 10-year incidence of post-transplantation lymphoproliferative disorder (PTLD) was 4.5%. Other identified cancers were Hodgkin lymphoma, Burkitt lymphomas, renal papillary carcinoma, thyroid papillary carcinoma, recurrent ovarian seminoma and skin cancer. The mortality rate was 25% (4/16)., Conclusion: Early detection of cancer in transplant recipients is of great importance. Regular screening for persistent Epstein-Barr virus (EBV) DNA viral load in patients at risk for developing PTLD is recommended. The occurrence of skin cancer in transplanted children is extremely rare during childhood, but cases can develop in early adulthood.
- Published
- 2010
- Full Text
- View/download PDF
42. Elevated aminotransaminases as the first manifestation of sarcoidosis.
- Author
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Nawfal G, Budin C, Bouvier R, and Lachaux A
- Abstract
Sarcoidose is a rare disease in children. The aminotransaminase level is often normal to moderately elevated (2 to 3 folds of the normal level). We report the case of a child who presented an aminotransaminase level that was 10 times the normal level, as the first manifestation of sarcoidosis.
- Published
- 2009
- Full Text
- View/download PDF
43. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer.
- Author
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Cairo S, Armengol C, De Reyniès A, Wei Y, Thomas E, Renard CA, Goga A, Balakrishnan A, Semeraro M, Gresh L, Pontoglio M, Strick-Marchand H, Levillayer F, Nouet Y, Rickman D, Gauthier F, Branchereau S, Brugières L, Laithier V, Bouvier R, Boman F, Basso G, Michiels JF, Hofman P, Arbez-Gindre F, Jouan H, Rousselet-Chapeau MC, Berrebi D, Marcellin L, Plenat F, Zachar D, Joubert M, Selves J, Pasquier D, Bioulac-Sage P, Grotzer M, Childs M, Fabre M, and Buendia MA
- Subjects
- Animals, Child, DNA Mutational Analysis, Humans, Mice, Nucleic Acid Hybridization, Oligonucleotide Array Sequence Analysis, Phenotype, Reproducibility of Results, Signal Transduction, Liver metabolism, Liver Neoplasms metabolism, Proto-Oncogene Proteins c-myc metabolism, Wnt Proteins metabolism, beta Catenin metabolism
- Abstract
Hepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/beta-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. beta-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy.
- Published
- 2008
- Full Text
- View/download PDF
44. Androgens repress the expression of the angiogenesis inhibitor thrombospondin-1 in normal and neoplastic prostate.
- Author
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Colombel M, Filleur S, Fournier P, Merle C, Guglielmi J, Courtin A, Degeorges A, Serre CM, Bouvier R, Clézardin P, and Cabon F
- Subjects
- Angiogenesis Inhibitors therapeutic use, Animals, Antineoplastic Agents therapeutic use, Cell Line, Tumor, Humans, Male, Mice, Mice, Nude, Orchiectomy, Prostate, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology, Rats, Rats, Sprague-Dawley, Thrombospondin 1 drug effects, Vascular Endothelial Growth Factor A analysis, Androgens pharmacology, Gene Expression Regulation drug effects, Gene Expression Regulation, Neoplastic drug effects, Neovascularization, Pathologic prevention & control, Neovascularization, Physiologic drug effects, Prostatic Neoplasms blood supply, Thrombospondin 1 genetics
- Abstract
In order to understand why the angiogenesis inhibitor thrombospondin-1 (TSP1) is often, although not always, associated with prostatic tumors, we have investigated its relationship with the testosterone and the vasculature on which both normal and tumorigenic prostatic epithelia depend. In vivo, androgen withdrawal led to increased TSP1 production and decreased vascularization in the normal rat prostate which was reversed by androgen replacement. Androgen repression of TSP1 production occurred at the transcriptional level and was dependent on the presence of the first intron of the TSP1 gene. In an experimental model of prostate tumorigenesis, TSP1, when delivered by admixed stromal fibroblasts, markedly delayed LNCaP tumor growth and limited tumor vascularization. However, prolonged exposure to TSP1 resulted in the growth of tumors secreting high levels of vascular endothelial growth factor in the bloodstream of tumor-bearing animals and tumor growth was no longer sensitive to TSP1 inhibitory effects. Clinical evidence also suggested that prostate carcinomas are able to adapt to escape the antiangiogenic effects of TSP1. In human androgen-dependent localized prostate carcinomas, TSP1 expression was inversely correlated with blood vessel density. Androgen deprivation in patients with hormone-responsive tumors led to increased TSP1 expression and vascular regression. In contrast, despite a sustained expression in the tumor bed, TSP1 was no longer associated with decreased vascularization in hormone-refractory prostate tumors. Overall, these results suggest that the high in situ TSP1 exposure triggered by androgen deprivation in patients with prostate cancer could lead to early tumor resistance. Such patients could benefit from a combination of androgen deprivation and antiangiogenic therapy in order to minimize the induction of such tumor escape.
- Published
- 2005
45. Mitochondrial complex I is deficient in renal oncocytomas.
- Author
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Simonnet H, Demont J, Pfeiffer K, Guenaneche L, Bouvier R, Brandt U, Schagger H, and Godinot C
- Subjects
- Electron Transport Complex I, Humans, Mitochondrial Diseases, NADH Dehydrogenase deficiency, NADH, NADPH Oxidoreductases deficiency, Oxidative Phosphorylation, Adenoma, Oxyphilic metabolism, Kidney Neoplasms metabolism, Mitochondria metabolism
- Abstract
Renal oncocytomas are benign tumors characterized by dense accumulation of mitochondria the cause of which remains unknown so far. Consistently, mitochondrial DNA content and the amounts and catalytic activities of several oxidative phosphorylation (OXPHOS) complexes were known to be increased in these tumors, but it was not ascertained that the OXPHOS system was functional. Here we investigated mitochondrial complex I and found that its NADH dehydrogenase activity and protein content were specifically decreased in oncocytomas, in stark contrast with the parallel decrease of all respiratory chain complexes in other, malignant, renal tumors. We conclude that deficiency of complex I in oncocytomas might be the early event causing the increased mitochondrial biogenesis, attempting to compensate for the loss of OXPHOS function. Since other tumors were found to be linked to mitochondrial deficiencies like genetic alterations of fumarate hydratase or succinate dehydrogenase, oncocytoma could be the third type of benign tumor associated with impairment of mitochondrial ATP production in an oxidative, quiescent tissue. Besides, complex I enzyme activity was moderately decreased in the vicinity of oncocytomas, when compared with normal tissue adjacent to other renal tumors. This suggested that oncocytomas are the result of at least two serial modifications altering the mitochondrial respiratory chain.
- Published
- 2003
- Full Text
- View/download PDF
46. A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23).
- Author
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Argani P, Lui MY, Couturier J, Bouvier R, Fournet JC, and Ladanyi M
- Subjects
- Adolescent, Artificial Gene Fusion, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Chromosomes, Human, Pair 17, Chromosomes, Human, X, Humans, Immunohistochemistry, Male, Adenocarcinoma genetics, Clathrin Heavy Chains genetics, DNA-Binding Proteins genetics, Kidney Neoplasms genetics, Transcription Factors genetics, Translocation, Genetic
- Abstract
A distinctive subset of renal carcinomas is associated with Xp11. 2 translocations and resulting TFE3 gene fusions (PRCC-TFE3, PSF-TFE3, NONO-TFE3, ASPL-TFE3), encoding related aberrant transcription factors. We report the cloning of a novel clathrin heavy-chain gene (CLTC)-TFE3 gene fusion resulting from a t(X;17)(p11.2;q23) in a renal carcinoma arising in a 14-year-old boy. The fusion transcript joined the 5' exons of CLTC on chromosome band 17q23 to the 3' exons of TFE3. CLTC encodes a major subunit of clathrin, a multimeric protein on cytoplasmic organelles, and is a known recurrent fusion partner of the ALK tyrosine kinase gene in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors. The predicted CLTC-TFE3 product retains the nuclear localization and DNA-binding domains of TFE3, but lacks the multimerization domain of CLTC. The present renal tumor demonstrated morphologic and immunohistochemical features of both PRCC-TFE3 and ASPL-TFE3 carcinomas, including strong nuclear immunoreactivity for the TFE3 C-terminal and only minimal expression of epithelial proteins. However, unlike most renal carcinomas, it also focally expressed melanocytic proteins. The present report highlights the promiscuity of certain genes involved in chromosomal translocations. Further analysis of the shared features of CLTC and other TFE3 fusion partners may shed light on the essential biology of TFE3 fusion proteins.
- Published
- 2003
- Full Text
- View/download PDF
47. Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma.
- Author
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Simonnet H, Alazard N, Pfeiffer K, Gallou C, Béroud C, Demont J, Bouvier R, Schägger H, and Godinot C
- Subjects
- Base Sequence, Carcinoma, Renal Cell pathology, DNA Primers, DNA, Mitochondrial metabolism, Humans, Kidney Neoplasms pathology, Mutation, Oxidative Phosphorylation, Carcinoma, Renal Cell metabolism, Electron Transport, Kidney Neoplasms metabolism, Mitochondria metabolism
- Abstract
A mechanism decreasing oxidative metabolism during normal cell division and growth is expected to direct substrates toward biosyntheses rather than toward complete oxidation to CO(2). Hence, any event decreasing oxidative phosphorylations (OXPHOS) could provide a proliferating advantage to a transformed or tumor cell in an oxidative tissue. To test this hypothesis, we studied mitochondrial enzymes, DNA and OXPHOS protein content in three types of renal tumors from 25 patients. Renal cell carcinomas (RCCs) of clear cell type (CCRCCs) originate from the proximal tubule and are most aggressive. Chromophilic RCCs, from similar proximal origin, are less aggressive. The benign renal oncocytomas originate from collecting duct cells. Mitochondrial enzyme and DNA contents in all tumor types or grades differed significantly from normal tissue. Mitochondrial impairment increased from the less aggressive to the most aggressive RCCs, and correlated with a considerably decreased content of OXPHOS complexes (complexes II, III, and IV of the respiratory chain, and ATPase/ATP synthase) rather than to the mitochondrial content (citrate synthase and mitochondrial (mt)DNA). In benign oncocytoma, some mitochondrial parameters (mtDNA, citrate synthase, and complex IV) were increased 4- to 7-fold, and some were slightly increased by a factor of 2 (complex V) or close to normal (complexes II and III). A low content of complex V protein was found in all CCRCC and chromophilic tumors studied. However F(1)-ATPase activity was not consistently decreased and its impairment was associated with increased aggressiveness in CCRCCs. Immunodetection of free F(1)-sector of complex V demonstrated a disturbed assembly/stability of complex V in several CCRCC and chromophilic tumors. All results are in agreement with the hypothesis that a decreased OXPHOS capacity favors faster growth or increased invasiveness.
- Published
- 2002
- Full Text
- View/download PDF
48. Expression of hMLH1 and hMSH2 and assessment of microsatellite instability in testicular and mediastinal germ cell tumours.
- Author
-
Devouassoux-Shisheboran M, Mauduit C, Bouvier R, Berger F, Bouras M, Droz JP, and Benahmed M
- Subjects
- Adaptor Proteins, Signal Transducing, Adult, Base Pair Mismatch genetics, Carrier Proteins, DNA Repair, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Endodermal Sinus Tumor genetics, Endodermal Sinus Tumor metabolism, Endodermal Sinus Tumor pathology, Germinoma metabolism, Germinoma pathology, Humans, Immunohistochemistry, Male, Mediastinal Neoplasms metabolism, Mediastinal Neoplasms pathology, MutL Protein Homolog 1, MutS Homolog 2 Protein, Neoplasm Proteins genetics, Nuclear Proteins, Proto-Oncogene Proteins genetics, Testicular Neoplasms metabolism, Testicular Neoplasms pathology, Germinoma genetics, Mediastinal Neoplasms genetics, Microsatellite Repeats genetics, Neoplasm Proteins metabolism, Proto-Oncogene Proteins metabolism, Testicular Neoplasms genetics
- Abstract
The aim of this study was to investigate DNA mismatch repair deficiency in male germ cell tumours. We analysed the expression of two mismatch repair proteins, human mutL homologue 1 (hMLH1) and human mutS homologue 2 (hMSH2), and evaluated the frequency of microsatellite instability with 10 mononucleotide and two dinucleotide repeat sequences, in 39 paired tumour/normal DNA samples obtained from 17 testicular and two mediastinal germ cell tumours. In all 19 cases, hMLH1 and hMSH2 both showed nuclear immunolocalization in invasive and testicular in-situ tumours. In non-neoplastic seminiferous tubules, hMLH1 was expressed only in premeiotic germ cells, while hMSH2 was seen in all stages of spermatogenesis. Genetic analysis of dinucleotide markers revealed loss of heterozygosity in one of two testicular yolk sac tumours at D18S58 and an allelic shift at D2S123 in two of three testicular embryonal carcinomas, while none of the 12 seminomas exhibited a genetic abnormality at these loci. No abnormalities were demonstrated with the 10 mononucleotide markers. The two mediastinal germ cell tumours showed no genetic instability or allelic loss with all 12 markers. We suggest that genetic alterations as assessed by microsatellite analysis in germ cell tumours may reflect tissue maturation and phenotypic differentiation rather than tumour progression. In addition, we suggest that hMLH1 and hMSH2 genes may not be implicated in the genesis of germ cell tumours.
- Published
- 2001
- Full Text
- View/download PDF
49. A novel SMAD4 gene mutation in seminoma germ cell tumors.
- Author
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Bouras M, Tabone E, Bertholon J, Sommer P, Bouvier R, Droz JP, and Benahmed M
- Subjects
- Amino Acid Sequence, Base Sequence, DNA-Binding Proteins analysis, DNA-Binding Proteins physiology, Humans, Immunohistochemistry, Molecular Sequence Data, Mutation, Polymorphism, Single-Stranded Conformational, Reverse Transcriptase Polymerase Chain Reaction, Smad2 Protein, Smad4 Protein, Trans-Activators analysis, Trans-Activators physiology, Transforming Growth Factor beta physiology, DNA-Binding Proteins genetics, Seminoma genetics, Trans-Activators genetics
- Abstract
Transforming growth factor (TGF)-beta is known as an antiproliferative factor in the majority of mammalian cells, including stem germ cells. Lack of TGF-beta-induced growth inhibition has been associated with disruptions of TGF-beta receptors and SMADs. In the present study, we performed a mutational analysis of the TGF-beta signaling system, including TGF-beta receptor type I and type II and SMADs (SMAD1-SMAD7), in 20 seminoma germ cell tumors. Using reverse transcription-PCR, single-strand conformational polymorphism, and sequencing analysis, the COOH-terminal domain of SMAD4 was found to be mutated: a single thymine was inserted between nt 1521 and 1522 in 2 of 20 tumors analyzed. This addition of a thymine creates a frameshift and a new stop signal at codon 492, which leads to premature termination of the encoded protein. Such a mutation potentially abrogates signaling from TGF-beta as well as the other TGF-beta family members, including activin and bone morphogenetic protein, which all use the SMAD pathway. Immunohistological analysis confirmed the loss of expression of SMAD4 protein in the seminoma tissues with the insertional mutation. To our knowledge, this is the first description of a novel SMAD4 insertional mutation in seminoma testicular germ cell tumors. This mutational inactivation of SMAD4/COOH-terminal domain may cause TGF-beta unresponsiveness. It could thus provide a basis for understanding the potential role of the TGF-beta system in germ cell tumorigenesis.
- Published
- 2000
50. Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes.
- Author
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Longuemaux S, Deloménie C, Gallou C, Méjean A, Vincent-Viry M, Bouvier R, Droz D, Krishnamoorthy R, Galteau MM, Junien C, Béroud C, and Dupret JM
- Subjects
- Adult, Alleles, Arylamine N-Acetyltransferase genetics, Carcinoma, Renal Cell enzymology, Case-Control Studies, Cytochrome P-450 CYP1A1 genetics, Cytochrome P-450 CYP2D6 genetics, Female, Gene Frequency, Genotype, Glutathione Transferase genetics, Humans, Inactivation, Metabolic, Kidney Neoplasms enzymology, Male, Middle Aged, Polymerase Chain Reaction, Risk Factors, Carcinoma, Renal Cell genetics, Cytochrome P-450 Enzyme System genetics, Genetic Predisposition to Disease, Kidney Neoplasms genetics, Polymorphism, Restriction Fragment Length, Xenobiotics metabolism
- Abstract
The steady increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the notion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence of RCC. Many of the enzymes dealing with such environmental factors are polymorphic and may, therefore, confer variable susceptibility to RCC. This case-control study was designed to test for an association between genetic polymorphism of enzymes involved in xenobiotic metabolism and the risk of sporadic RCC. Genomic DNA was obtained from 173 patients with RCC and 211 controls of Caucasian origin. We used PCR-RFLP to investigate polymorphism for the most common alleles at two cytochrome-P450 mono-oxygenases (CYP1A1 and CYP2D6), one NAD[P]H:quinone oxidoreductase (NQO1), three glutathione S-transferases (GSTM1, GSTT1, and GSTP1), and one N-acetyltransferase (NAT2) loci. The CYP1A1 (m) "variant" genotype, which contains at least one copy of the CYP1A1 variant alleles, was found to be associated with a 2.1-fold [95% confidence interval (CI), 1.1-3.9] increase in the risk of RCC. There was also a higher risk of RCC for subjects with the CYP1A1 (m) variant genotype combined with any of the following genotypes: GSTT1 (+) "active" [odds ratio (OR), 2.3; 95% CI, 1.2-4.5], GSTP1 (m) variant (OR, 2.4; 95% CI, 1.0-5.4), or NAT2 (-) "slow acetylator" (OR, 2.5; 95% CI, 1.1-5.5). A significant association was also found for the GSTM1 (-) "null" and GSTP1 (m) genotypes combined with either NAT2 (-) (OR, 2.6; 95% CI, 1.2-5.8) or CYP1A1 (m) (OR, 3.5; 95% CI, 1.1-11.2). The CYP2D6 (-) "poor metabolizer " and the NQO1 (-) "defective" genotypes were not clearly associated with a higher risk of RCC. Our data demonstrate for the first time a significant association between a group of pharmacogenetic polymorphisms and RCC risk. These positive findings suggest that interindividual variation in the metabolic pathways involved in the functionalization and detoxification of specific xenobiotics is an important susceptibility factor for RCC in Caucasians.
- Published
- 1999
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