La Louvière, Belgium
La Louvière, Belgium

Time filter

Source Type

Decock A.,Ghent University | Ongenaert M.,Ghent University | Hoebeeck J.,Ghent University | Hoebeeck J.,University College Ghent | And 15 more authors.
Genome Biology | Year: 2012

Background: Accurate outcome prediction in neuroblastoma, which is necessary to enable the optimal choice of risk-related therapy, remains a challenge. To improve neuroblastoma patient stratification, this study aimed to identify prognostic tumor DNA methylation biomarkers.Results: To identify genes silenced by promoter methylation, we first applied two independent genome-wide methylation screening methodologies to eight neuroblastoma cell lines. Specifically, we used re-expression profiling upon 5-aza-2'-deoxycytidine (DAC) treatment and massively parallel sequencing after capturing with a methyl-CpG-binding domain (MBD-seq). Putative methylation markers were selected from DAC-upregulated genes through a literature search and an upfront methylation-specific PCR on 20 primary neuroblastoma tumors, as well as through MBD- seq in combination with publicly available neuroblastoma tumor gene expression data. This yielded 43 candidate biomarkers that were subsequently tested by high-throughput methylation-specific PCR on an independent cohort of 89 primary neuroblastoma tumors that had been selected for risk classification and survival. Based on this analysis, methylation of KRT19, FAS, PRPH, CNR1, QPCT, HIST1H3C, ACSS3 and GRB10 was found to be associated with at least one of the classical risk factors, namely age, stage or MYCN status. Importantly, HIST1H3C and GNAS methylation was associated with overall and/or event-free survival.Conclusions: This study combines two genome-wide methylation discovery methodologies and is the most extensive validation study in neuroblastoma performed thus far. We identified several novel prognostic DNA methylation markers and provide a basis for the development of a DNA methylation-based prognostic classifier in neuroblastoma. © 2012 Decock et al.; licensee BioMed Central Ltd.


Hachulla E.,Medecine Interne | Rose C.,Hematologie | Gressin V.,Actelion Pharmaceuticals | Cherin P.,Medecine Interne | And 8 more authors.
Osteoporosis International | Year: 2011

Summary: Gaucher disease type 1 (GD1), results in a range of skeletal complications including osteopenia, osteoporosis, and osteonecrosis, but there is little published information regarding vertebral fractures. Findings from this observational study indicated that the prevalence of vertebral fractures in a cohort of adult French GD1 patients is approximately 15%. Introduction: The aim of the study was to assess the prevalence and characteristics of vertebral fractures in a cohort of adult patients with GD1. Methods: This study was performed in adult patients with GD1 based on a detailed and complete clinical examination. For all patients for whom vertebral fractures were reported, a specific questionnaire was sent to physicians, and imaging data were collected, when available, for centralized analysis. Results: Data were collected from a total of 105 adult GD1 patients. Bone complications were reported in 85% of patients, among whom vertebral fractures were diagnosed in 16 (15%); seven women and nine men (mean age, 45 years). We observed five patients with multiple vertebral fractures and one patient in whom the T3 vertebra was fractured. Most of these patients did not report fracture-related back pain. Conclusions: The prevalence of vertebral fractures in this cohort of adult patients with GD1 was 15%. Greater awareness of the natural history of vertebral fractures in GD1, and rigorous monitoring of bone fragility and spine involvement in affected patients, should allow earlier detection and initiation of treatment tailored toward improving bone status. © 2010 International Osteoporosis Foundation and National Osteoporosis Foundation.


Ghannam A.,Joseph Fourier University | Fauquert J.-L.,Pediatrie | Thomas C.,Nantes University Hospital Center | Kemper C.,King's College London | Drouet C.,Joseph Fourier University
Molecular Immunology | Year: 2014

Human T helper type 1 (Th1) responses are essential in defense. Although T cell receptor (TCR) and co-stimulator engagement are indispensable for T cell activation, stimulation of additional receptor pathways are also necessary for effector induction. For example, engagement of the complement regulator CD46 by its ligand C3b generated upon TCR activation is required for IFN-γ production as CD46-deficient patients lack Th1 responses. Utilizing T cells from two C3-deficient patients we demonstrate here that normal Th1 responses also depend on signals mediated by the anaphylatoxin C3a receptor (C3aR). Importantly, and like in CD46-deficient patients, whilst Th1 induction are impaired in C3-deficient patients in vitro, their Th2 responses are unaffected. Furthermore, C3-deficient CD4+ T cells present with reduced expression of CD25 and CD122, further substantiating the growing notion that complement fragments regulate interleukin-2 receptor (IL-2R) assembly and that disturbance of complement-guided IL-2R assembly contributes to aberrant Th1 effector responses. Lastly, sustained intrinsic production of complement fragments may participate in the Th1 contraction phase as both C3a and CD46 engagement regulate IL-10 co-expression in Th1 cells. These data suggest that C3aR and CD46 activation via intrinsic generation of their respective ligands is an integral part of human Th1 (but not Th2) immunity. © 2013 Elsevier Ltd.


Cherin P.,Medecine Interne | Rose C.,Hematologie | De Roux-Serratrice C.,Medecine Interne | Tardy D.,Actelion Pharmaceuticals | And 9 more authors.
Journal of Inherited Metabolic Disease | Year: 2010

Background: Gaucher disease (GD), the most prevalent inherited lysosomal storage disorder, is caused by deficient glucocerebrosidase activity. Type 1 GD (GD1), the most common variant, is classically considered non-neuronopathic. Methods: We performed a national cross-sectional observational survey-the French Observatoire on Gaucher Disease (FROG)-in patients with GD1 between March 2005 and September 2006. The study included all patients over 18 years of age with confirmed GD1 who attended participating centers for regular follow-up. Results: One hundred and five patients were included, in whom we studied the prevalence and characteristics of relevant neurological symptoms associated with the neuraxis. Of these, 51 (49%) GD1 patients presented at least one neurological symptom. Four patients (4%) had Parkinson disease and 22 (21%) presented with at least one parkinsonian sign or at least one sign frequently associated with Parkinson disease. Five patients (5%) had a previous diagnosis of peripheral neuropathy. Other central nervous system symptoms were recorded in 20 (19%) patients and other peripheral nervous system symptoms in 39 (37%) patients. Conclusions: These data challenge the current classification of GD, and suggest that the three forms of GD each involve a different profile of neurological manifestations. © 2010 SSIEM and Springer.


PubMed | Pediatrie, King's College London, Joseph Fourier University and Nantes University Hospital Center
Type: Journal Article | Journal: Molecular immunology | Year: 2014

Human T helper type 1 (Th1) responses are essential in defense. Although T cell receptor (TCR) and co-stimulator engagement are indispensable for T cell activation, stimulation of additional receptor pathways are also necessary for effector induction. For example, engagement of the complement regulator CD46 by its ligand C3b generated upon TCR activation is required for IFN- production as CD46-deficient patients lack Th1 responses. Utilizing T cells from two C3-deficient patients we demonstrate here that normal Th1 responses also depend on signals mediated by the anaphylatoxin C3a receptor (C3aR). Importantly, and like in CD46-deficient patients, whilst Th1 induction are impaired in C3-deficient patients in vitro, their Th2 responses are unaffected. Furthermore, C3-deficient CD4(+) T cells present with reduced expression of CD25 and CD122, further substantiating the growing notion that complement fragments regulate interleukin-2 receptor (IL-2R) assembly and that disturbance of complement-guided IL-2R assembly contributes to aberrant Th1 effector responses. Lastly, sustained intrinsic production of complement fragments may participate in the Th1 contraction phase as both C3a and CD46 engagement regulate IL-10 co-expression in Th1 cells. These data suggest that C3aR and CD46 activation via intrinsic generation of their respective ligands is an integral part of human Th1 (but not Th2) immunity.


Ben Salah F.Z.,Institute Superieur Of Leducation Speciale | Dzirib C.,Institute national dorthopedie | Ben Dridic M.F.,Pediatrie
Journal de Readaptation Medicale | Year: 2014

The disabled people constitute a major concern in Tunisia; their care is considerable for the society and especially the concerned families. Among them, the multi-handicapped people represent a more dependent, more vulnerable group, deserving to be individualized and better known to specify their real needs and improve their global coverage (care), without neglecting that of their family. The authors present the results of the reflection organized on this theme in Tunisia within the framework of a federal research project, the report of which was published in a book appeared in June 2013. © 2014.


Leuret O.,French Institute of Health and Medical Research | Leuret O.,Reseau Maladies Metaboliques Hopitaux Universitaires du Grand Ouest | Barth M.,Angers University Hospital Center | Barth M.,Reseau Maladies Metaboliques Hopitaux Universitaires du Grand Ouest | And 12 more authors.
Journal of Inherited Metabolic Disease | Year: 2012

Background: Sapropterin dihydrochloride, an EMEA-approved synthetic formulation of BH4, has been available in Europe since 2009 for PKU patients older than 4 years, but its use with younger children is allowed in France based on an expert recommendation. We report the cases of 15 patients treated under the age of 4 years and demonstrate the safety and efficacy of this treatment for patients in this age group. Patients and method: We report the use of BH4 in 15 PKU patients treated before the age of 4 years. Results: Fifteen patients were enrolled in this retrospective study. Mean phenylalaninemia at diagnosis was 542±164 μM and all patients had mild PKU (maximal phenylalaninemia: 600-1200 μM). BH4 responsiveness was assessed using a 24-hour BH4 loading test (20 mg/kg), performed during the neonatal period (n = 11) or before 18 months of age (n = 4). During the test, these patients exhibited an 80±12% decrease in phenylalaninemia. Long-term BH4 therapy was initiated during the neonatal period (n = 7) or at the age of 13±12 months (n = 8). The median duration of treatment was 23 months [min 7; max 80]. BH4 therapy drastically improved dietary phenylalanine tolerance (456±181 vs 1683±627 mg/day, p < 0.0001) and allowed a phenylalanine-free amino acid mixture to be discontinued or not introduced in 14 patients. Additionally, in the eight patients treated after a few months of diet therapy, BH4 treatment significantly decreased mean phenylalaninemia (352±85 vs 254±64μM, p < 0.05), raised the percentage of phenylalaninemia tests within therapeutic targets [120-300 μM] (35±25 vs 64±16%, p < 0.05), and reduced phenylalaninemia variance (130±21 vs 93±27μM, p < 0.05). No side effects were reported. Conclusion: BH4-therapy is efficient and safe before the age of 4 years in mild PKU, BH4-responsive patients. © 2012 SSIEM and Springer.


Richard-Lenoble D.,IAcademie Nationale de Medecine | Kombila M.,Pararasitologie Medecine Tropicale e i USS Libreville | Gendrel D.,Pediatrie
Bulletin de l'Academie Nationale de Medecine | Year: 2010

Etiologic investigations of hypereosinophilia, often accompanied by IgE elevation, depends on the patient's geographic origin and travel history. In France, helminth diseases are the only parasitoses associated with hypereosinophilia. Some, such as oxyurosis in children, are frequent but generally mild. More severe but less frequent infections include distomatoses, trichinellosis, taeniasis, echinococcosis and visceral larva migrans. Among subjects originating from or having travelled to tropical areas with poor hygiene, eosinophilia may be due to early intense polyparasitism and has little etiologic value. In Gabon, a warm, humid country in equatorial Africa, schoolchildren harbor an average of three different parasites capable of inducing hypereosinophilia or serum IgE elevation. These children's eosinophil counts start to rise at very young age, after weaning and contact with soil, and continue to increase rapidly until adulthood Average values across all age groups are 1580 eosinophils/mm3 and 3300 kU IgEIL. Direct diagnosis of chronic parasitic infections is often possible in this setting, and specific treatments can be prescribed. In contrast, hypereosinophilia has less etiologic significance in patients originating from or having travelled to the tropics and who present to European parasitology units. Direct examination is rarely positive, and the etiologic diagnosis will thus be guided by epidemiologic, clinical and serologic findings. These findings are sometimes sufficient to initiate probabilistic treatment with albendazole, ivermectin and praziquentel.


Ben Salah F.Z.,Institute Superieur Of Lgeducation Speciale | Dzirib C.,Institute National Dgorthopedie | Ben Dridic M.F.,Pediatrie
Journal de Readaptation Medicale | Year: 2014

The disabled people constitute a major concern in Tunisia; their care is considerable for the society and especially the concerned families. Among them, the multi-handicapped people represent a more dependent, more vulnerable group, deserving to be individualized and better known to specify their real needs and improve their global coverage (care), without neglecting that of their family. The authors present the results of the reflection organized on this theme in Tunisia within the framework of a federal research project, the report of which was published in a book appeared in June 2013. © 2014 Published by Elsevier Masson SAS.


Cow's milk is a common cause of food allergy in children. Children usually outgrow cow's milk allergy by 6 years of age, but recent studies have found that a considerable number of children will have persistent symptoms until adolescence. Strict elimination of cow's milk is difficult. Accidental ingestion of cow's milk is frequent, with a high risk of a severe allergic reaction. Different types of immunotherapy have been studied in patients with IgE-mediated allergy to cow's milk proteins, aiming to induce tolerance; these methods involve oral, sublingual, or epicutaneous immunotherapy. Oral immunotherapy seems to be the most promising approach. It involves drinking increasing doses of cow's milk during an induction phase followed by a maintenance phase with daily intake of a maximum tolerated amount. No uniform protocol has yet been developed. When raw milk is not tolerated, baked milk represents a possible alternative in some cases. © 2014 Elsevier Masson SAS.

Loading Pediatrie collaborators
Loading Pediatrie collaborators