Groupe Hospitalier Of Luniversite Catholique Of Lille

Lille, France

Groupe Hospitalier Of Luniversite Catholique Of Lille

Lille, France

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Certad G.,University of Lille Nord de France | Certad G.,José María Vargas University | Creusy C.,Groupe Hospitalier Of Luniversite Catholique Of Lille | Guyot K.,University of Lille Nord de France | And 10 more authors.
International Journal for Parasitology | Year: 2010

We recently demonstrated that Cryptosporidium parvum IOWA strain induces in situ ileo-caecal adenocarcinoma in an animal model. Herein, the ability of another C. parvum strain to induce digestive neoplasia in dexamethasone-treated SCID mice was explored. SCID mice infected with C. parvum TUM1 strain developed a fulminant cryptosporidiosis associated with intramucosal adenocarcinoma, which is considered an early histological sign of invasive cancer. Both evidence of a role of C. parvum in adenocarcinoma induction and the extended prevalence of cryptosporidiosis worldwide, suggest that the risk of C. parvum-induced gastro-intestinal cancer in humans should be assessed. © 2010 Australian Society for Parasitology Inc.


Benamrouz S.,University of Lille Nord de France | Conseil V.,University of Lille Nord de France | Chabe M.,University of Lille Nord de France | Praet M.,Ghent University | And 21 more authors.
DMM Disease Models and Mechanisms | Year: 2014

Cryptosporidium species are apicomplexan protozoans that are found worldwide. These parasites constitute a large risk to human and animal health. They cause self-limited diarrhea in immunocompetent hosts and a life-threatening disease in immunocompromised hosts. Interestingly, Cryptosporidium parvum has been related to digestive carcinogenesis in humans. Consistent with a potential tumorigenic role of this parasite, in an original reproducible animal model of chronic cryptosporidiosis based on dexamethasone-treated or untreated adult SCID mice, we formerly reported that C. parvum (strains of animal and human origin) is able to induce digestive adenocarcinoma even in infections induced with very low inoculum. The aim of this study was to further characterize this animal model and to explore metabolic pathways potentially involved in the development of C. parvum-induced ileo-caecal oncogenesis. We searched for alterations in genes or proteins commonly involved in cell cycle, differentiation or cell migration, such as β-catenin, Apc, E-cadherin, Kras and p53. After infection of animals with C. parvum we demonstrated immunohistochemical abnormal localization of Wnt signaling pathway components and p53. Mutations in the selected loci of studied genes were not found after high-throughput sequencing. Furthermore, alterations in the ultrastructure of adherens junctions of the ileo-caecal neoplastic epithelia of C. parvum-infected mice were recorded using transmission electron microscopy. In conclusion, we found for the first time that the Wnt signaling pathway, and particularly the cytoskeleton network, seems to be pivotal for the development of the C. parvum-induced neoplastic process and cell migration of transformed cells. Furthermore, this model is a valuable tool in understanding the host-pathogen interactions associated with the intricate infection process of this parasite, which is able to modulate host cytoskeleton activities and several host-cell biological processes and remains a significant cause of infection worldwide.


Certad G.,University of Lille Nord de France | Certad G.,José María Vargas University | Benamrouz S.,University of Lille Nord de France | Guyot K.,University of Lille Nord de France | And 13 more authors.
Applied and Environmental Microbiology | Year: 2012

In the present work, we report the characterization of a Cryptosporidium parvum strain isolated from a patient who nearly drowned in the Deule River (Lille, France) after being discharged from the hospital where he had undergone allogeneic stem cell transplantation. After being rescued and readmitted to the hospital, he developed fulminant cryptosporidiosis. The strain isolated from the patient's stools was identified as C. parvum II2A15G2R1 (subtype linked to zoonotic exposure) and inoculated into SCID mice. In this host, this virulent C. parvum isolate induced not only severe infection but also invasive gastrointestinal and biliary adenocarcinoma. The observation of adenocarcinomas that progressed through all layers of the digestive tract to the subserosa and spread via blood vessels confirmed the invasive nature of the neoplastic process. These results indicate for the first time that a human-derived C. parvum isolate is able to induce digestive cancer. This study is of special interest considering the exposure of a large number of humans and animals to this waterborne protozoan, which is highly tumorigenic when inoculated in a rodent model. © 2012, American Society for Microbiology.


Tellier G.,Lille University Hospital Center | Lenne A.,Lille University Hospital Center | Cailliau-Maggio K.,French National Center for Scientific Research | Cabezas-Cruz A.,Lille University Hospital Center | And 9 more authors.
Frontiers in Microbiology | Year: 2016

Protein phosphatase 1 (PP1c) is one of the main phosphatases whose function is shaped by many regulators to confer a specific location and a selective function for this enzyme. Here, we report that eukaryotic initiation factor 2β of Plasmodium falciparum (PfeIF2β) is an interactor of PfPP1c. Sequence analysis of PfeIF2β revealed a deletion of 111 amino acids when compared to its human counterpart and the presence of two potential binding motifs to PfPP1 (29FGEKKK34, 103KVAW106). As expected, we showed that PfeIF2β binds PfeIF2γ and PfeIF5, confirming its canonical interaction with partners of the translation complex. Studies of the PfeIF2β-PfPP1 interaction using wild-type, single and double mutated versions of PfeIF2β revealed that both binding motifs are critical. We next showed that PfeIF2β is able to induce Germinal Vesicle Break Down (GVBD) when expressed in Xenopus oocytes, an indicator of its capacity to regulate PP1. Only combined mutations of both binding motifs abolished the interaction with PP1 and the induction of GVBD. In P. falciparum, although the locus is accessible for genetic manipulation, PfeIF2β seems to play an essential role in intraerythrocytic cycle as no viable knockout parasites were detectable. Interestingly, as for PfPP1, the subcellular fractionation of P. falciparum localized PfeIF2β in cytoplasm and nuclear extracts, suggesting a potential effect on PfPP1 in both compartments and raising the question of a non-canonical function of PfeIf2β in the nucleus. Hence, the role played by PfeIF2β in blood stage parasites could occur at multiple levels involving the binding to proteins of the translational complex and to PfPP1. © 2016 Tellier, Lenne, Cailliau-Maggio, Cabezas-Cruz, Valdés, Martoriati, Aliouat, Gosset, Delaire, Fréville, Pierrot and Khalife.


Certad G.,Institute Pasteur Of Lille | Creusy C.,Groupe Hospitalier Of Luniversite Catholique Of Lille | Ngouanesavanh T.,Institute Pasteur Of Lille | Guyot K.,Lille 2 University of Health and Law | And 10 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2010

We reported previously that Cryptosporidium parvum was able to induce intestinal tumors in severe combined immunodeficiency (SCID) mice treated with corticoids. To further characterize this Cryptosporidium-induced cell transformation, SCID mice treated with dexamethasone were challenged with C.parvum oocysts, and euthanatized sequentially after infection for histologic examination. Ki-67 was used as a marker of cellular proliferation. Our previous results were confirmed, and it was also found that mice receiving higher inocula (106-107) experienced more severe neoplastic development. Additionally, neoplastic changes were observed not only in the caecum but also in the stomach and duo-denum of some animals. Interestingly, SCID mice (6/6) inoculated with 105-107 oocysts showed high grade intraepithelial neoplasia or adenomas with high grade dysplasia in the caecum after Day 46 post-infection (PI). Immunohistochemistry for Ki-67 staining indicated the neoplastic process associated to cryptosporidiosis, and evidenced the first immunohistochemical alterations at early stages of the process, even at 3 weeks PI. © 2010 by The American Society of Tropical Medicine and Hygiene.


Jimenez J.C.,University of Lille Nord de France | Jimenez J.C.,Central University of Venezuela | Fontaine J.,French Institute of Health and Medical Research | Creusy C.,Groupe Hospitalier Of Luniversite Catholique Of Lille | And 5 more authors.
Parasitology Research | Year: 2014

The humoral and cellular responses against excretory/secretory proteins and soluble extracts of Giardia intestinalis were evaluated in the course of experimental G. intestinalis infection in BALB/c mice. Production of IgG1, IgG2a, IgA, and IgE antibodies against excreted/secreted proteins and soluble extract was detected after infection by G. intestinalis. Specific IgA antibody against E/S proteins and soluble extract form intestinal fluids in infected mice was detected by ELISA. The Western blotting identified proteins of 30, 58, 63, and 83 kDa for IgA and IgG, respectively. High proliferation rate in vitro of spleen cell and secretion of interleukin-4 (IL-4) at 21 days p.i. after stimulation with excreted/secreted proteins and low proliferative response in the presence of soluble extract in infected BALB/c mice was observed. High production of interferon gamma (IFN-γ) and interleukin-5 (IL-5) at the time of decreasing cyst output (14-21 days p.i.) in infected mice was recorded, suggesting the important role of these cytokines in the control of the infection. Interestingly, progressive and gradual increase of the interleukin-10 after stimulation with both preparations was recorded from 7 days until 28 days after infection, indicating the possible regulatory effect of these antigens on the immune response during Giardia infection. Therefore, the infection by Giardia duodenalis stimulates a mixed response Th1 and Th2, mainly stimulated by excretory/secretory antigens. The immunogenicity of these antigens may be a suitable for identification of the proteins related with the effective immune response in the course of infection by G. duodenalsis. © 2014 Springer-Verlag.


PubMed | Institute Superieur Dagriculture Of Lille, French Institute of Health and Medical Research, Groupe Hospitalier Of Luniversite Catholique Of Lille, CNRS Institute of Electronics, Microelectronics and Nanotechnology and 5 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Cryptosporidium, a protozoan parasite that can cause severe diarrhea in a wide range of vertebrates including humans, is increasingly recognized as a parasite of a diverse range of wildlife species. However, little data are available regarding the identification of Cryptosporidium species and genotypes in wild aquatic environments, and more particularly in edible freshwater fish. To evaluate the prevalence of Cryptosporidiumspp. in fish from Lake Geneva (Lac Lman) in France, 41 entire fish and 100 fillets (cuts of fish flesh) were collected from fishery suppliers around the lake. Nested PCR using degenerate primers followed by sequence analysis was used. Five fish species were identified as potential hosts of Cryptosporidium: Salvelinus alpinus, Esox lucius, Coregonus lavaretus, Perca fluviatilis, and Rutilus rutilus. The presence of Cryptosporidium spp. was found in 15 out of 41 fish (37%), distributed as follows: 13 (87%) C. parvum, 1 (7%) C. molnari, and 1 (7%) mixed infection (C. parvum and C. molnari). C. molnari was identified in the stomach, while C. parvum was found in the stomach and intestine. C. molnari was also detected in 1 out of 100 analyzed fillets. In order to identify Cryptosporidium subtypes, sequencing of the highly polymorphic 60-kDa glycoprotein (gp60) was performed. Among the C. parvum positive samples, three gp60 subtypes were identified: IIaA15G2R1, IIaA16G2R1, and IIaA17G2R1. Histological examination confirmed the presence of potential developmental stages of C. parvum within digestive epithelial cells. These observations suggest that C. parvum is infecting fish, rather than being passively carried. Since C. parvum is a zoonotic species, fish potentially contaminated by the same subtypes found in terrestrial mammals would be an additional source of infection for humans and animals, and may also contribute to the contamination of the environment with this parasite. Moreover, the risk of human transmission is strengthened by the observation of edible fillet contamination.


Peyrodie L.,School of Advanced Engineering Studies | Gallois P.,Groupe Hospitalier Of Luniversite Catholique Of Lille | Gallois P.,Lille Catholic University | Boudet S.,School of Advanced Engineering Studies | And 3 more authors.
Journal of Clinical Neurophysiology | Year: 2014

OBJECTIVE:: Further developments in EEG monitoring necessitate new methods of filtering to eliminate artifacts, without transforming relevant signals. This article presents an automatic filtering of EEG recordings, based on a spatio-temporal method called Adaptive Filtering by Optimal Projection or Dual Adaptive Filtering by Optimal Projection. Evaluation of filtering methods is difficult, and comparisons between methods remain a challenge; here, we present a method to score the visual assessment of the EEG. The aim of this study was to evaluate an automatic filtering method, called Adaptive Filtering by Optimal Projection, improved by Dual Adaptive Filtering by Optimal Projection, of EEG recordings of patients with epilepsy. METHODS:: Two hundred forty-eight nonfiltered EEG segments of 20 seconds each were selected from 35 EEG recordings of 27 different patients by 3 clinical neurophysiologists based on their content. The reading quality as well as the proportions of artifacts and of cerebral activity removed after filtering were evaluated on a scale of 0 to 4. The mean square difference of amplitude before and after filtering was computed in specific spectral band. RESULTS:: The artifacts were largely removed (82% for muscular, 72% for ocular, and 71% for electrode artifacts). The readability was improved on an average by two points for pages containing epileptic seizures, and by one point for those containing alpha rhythms, slow waves, and spikes. After filtering, consistency tests showed a consensus (Spearman correlation [0.69-0.79]) on the removal of the artifact versus loss of information. The spectral analysis showed equivalent results (0.16% mean square difference in the alpha band). CONCLUSIONS:: Our filtering method is effective in removing artifacts without altering relevant signals. The significance is that we evaluated a new automated method of filtering EEG that is easy to use for both for the analysis of routine EEG and in the field of epilepsy at large. © 2014 by the American Clinical Neurophysiology Society.


Zanati J.,Groupe Hospitalier Of Luniversite Catholique Of Lille | Resch B.,Service de Maternite | Roman H.,Service de Maternite | Brabant G.,Groupe Hospitalier Of Luniversite Catholique Of Lille | And 7 more authors.
Journal de Gynecologie Obstetrique et Biologie de la Reproduction | Year: 2010

Post-partum haemorrhage remains a major cause of maternal mortality. Surgical management may be needed in patients with hemodynamic instability. Arterial embolization may be needed in case of persisting haemorrhage despite initial surgical management. We report a case of buttock necrosis occurring after pelvic embolization to control refractory post-partum haemorrhage and failed subtotal hysterectomy with bilateral internal iliac arteries ligation. To the best of our knowledge, this is the first case of buttock necrosis complicating a severe post-partum haemorrhage reported in the literature. © 2009 Elsevier Masson SAS. All rights reserved.


PubMed | Groupe Hospitalier Of Luniversite Catholique Of Lille
Type: Case Reports | Journal: Journal de gynecologie, obstetrique et biologie de la reproduction | Year: 2010

Post-partum haemorrhage remains a major cause of maternal mortality. Surgical management may be needed in patients with hemodynamic instability. Arterial embolization may be needed in case of persisting haemorrhage despite initial surgical management. We report a case of buttock necrosis occurring after pelvic embolization to control refractory post-partum haemorrhage and failed subtotal hysterectomy with bilateral internal iliac arteries ligation. To the best of our knowledge, this is the first case of buttock necrosis complicating a severe post-partum haemorrhage reported in the literature.

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