Anatomie et cytologie pathologiques

Paris, France

Anatomie et cytologie pathologiques

Paris, France

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Denizot J.,Clermont University | Sivignon A.,Clermont University | Sivignon A.,French National Institute for Agricultural Research | Barreau F.,Institut Universitaire de France | And 9 more authors.
Inflammatory Bowel Diseases | Year: 2012

Background: Abnormal expression of CEACAM6 observed on the ileal epithelium in Crohn's disease (CD) patients allows adherent-invasive Escherichia coli (AIEC) to colonize gut mucosa. Since intestinal permeability is significantly increased in CD patients, we aimed at investigating whether and how AIEC alter barrier function. Methods: Tissue microarray was performed on ileal biopsies from CD patients in quiescent and active phases. CEABAC10 or wildtype mice were orally challenged with 10 9 bacteria. Intestinal permeability was assessed by measuring 4 kDa dextran-FITC flux in serum, barrier integrity was analyzed using biotin tracer experiment, and claudin-2 protein immunostaining. Bacterial translocation was analyzed in Ussing chambers. Results: Pore-forming tight junction protein claudin-2 is strongly expressed in the ileum of 51% patients in quiescent phase and in 49% of the patients with active CD. Infection of CEABAC10 transgenic mice expressing human CEACAMs with AIEC, but not with nonpathogenic E. coli, led to a significant 3.0-fold increase in intestinal permeability and to disruption of mucosal integrity in a type 1 pili-dependent mechanism. This is consistent with the claudin-2 abnormal expression at the plasma membrane of intestinal epithelial cells observed in AIEC-infected CEABAC10 mice. AIEC bacteria were able to translocate through CEABAC10 intestinal mucosa. Conclusions: These findings strongly support the hypothesis that AIEC type 1 pili-mediated interaction with CEACAM6 abnormally expressed in the quiescent phase of CD may disrupt intestinal barrier integrity before the onset of inflammation. Thus, therapeutic targeting claudin-2 induced by AIEC infection could be a new clinical strategy for preserving intestinal barrier function in CD patients. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.


Canella C.,Federal University of Rio de Janeiro | Demondion X.,Laboratoire dAnatomie | Marchiori E.,Federal University of Rio de Janeiro | Cotten H.,Anatomie et Cytologie Pathologiques
European Journal of Radiology | Year: 2013

Objective: The purpose of our study was to demonstrate that ultrasonography may allow a precise assessment of the course and relationships of the spinal accessory nerve (SAN). Material and methods: This study, initially undertaken in 7 cadavers, was followed by high-resolution ultrasonographic study in 15 volunteers (30 nerves) by two radiologists in consensus. The location, course and relations to the adjacent anatomic structures of the SAN were analyzed. Results: The precise course of the SAN between the lateroposterior border of the sternocleidomastoid muscle and the anterior border of the trapezius muscle could be identified by high-resolution ultrasonography. In contrast, clinical bone landmarks were not found helpful for the identification of the nerve. Conclusion: The SAN can be clearly depicted by means of ultrasonography. Knowledge of the nerve's precise location, which may evidence individual variations, may have useful clinical applications. © 2012 Elsevier Ireland Ltd. All rights reserved.


Vuillaumier-Barrot S.,Assistance Publique Hopitaux de Paris | Vuillaumier-Barrot S.,French Institute of Health and Medical Research | Bouchet-Seraphin C.,Assistance Publique Hopitaux de Paris | Chelbi M.,Assistance Publique Hopitaux de Paris | And 29 more authors.
American Journal of Human Genetics | Year: 2012

Cobblestone lissencephaly is a peculiar brain malformation with characteristic radiological anomalies. It is defined as cortical dysplasia that results when neuroglial overmigration into the arachnoid space forms an extracortical layer that produces agyria and/or a "cobblestone" brain surface and ventricular enlargement. Cobblestone lissencephaly is pathognomonic of a continuum of autosomal-recessive diseases characterized by cerebral, ocular, and muscular deficits. These include Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama muscular dystrophy. Mutations in POMT1, POMT2, POMGNT1, LARGE, FKTN, and FKRP identified these diseases as alpha-dystroglycanopathies. Our exhaustive screening of these six genes, in a cohort of 90 fetal cases, led to the identification of a mutation in only 53% of the families, suggesting that other genes might also be involved. We therefore decided to perform a genome-wide study in two multiplex families. This allowed us to identify two additional genes: TMEM5 and ISPD. Because TMEM has a glycosyltransferase domain and ISPD has an isoprenoid synthase domain characteristic of nucleotide diP-sugar transferases, these two proteins are thought to be involved in the glycosylation of dystroglycan. Further screening of 40 families with cobblestone lissencephaly identified nonsense and frameshift mutations in another four unrelated cases for each gene, increasing the mutational rate to 64% in our cohort. All these cases displayed a severe phenotype of cobblestone lissencephaly A. TMEM5 mutations were frequently associated with gonadal dysgenesis and neural tube defects, and ISPD mutations were frequently associated with brain vascular anomalies. © 2012 The American Society of Human Genetics.


Collet J.-F.,Anatomie et Cytologie Pathologiques | Collet J.-F.,Institute Of Pathologie | Lacave R.,Unite de Genomique des Tumeurs Solides | Hugonin S.,Unite de Genomique des Tumeurs Solides | And 3 more authors.
Head and Neck | Year: 2016

Background Whether preoperative knowledge of the BRAF mutation status would help to determine the extent of surgery for thyroid nodules is still under investigation. Methods We developed a method to state the V600E mutation before surgery on fine-needle aspiration (FNA) stained smears checked to contain tumor cells. We evaluated the interest of the preoperative assessment of the mutation for surgical strategy of nodules, diagnosed as malignant, suspicious for malignancy or follicular neoplasms. Results The mutation was found in 81% (79 of 97) malignant, 59% (20 of 34) suspicious nodules, and in none of follicular neoplasms (n = 29). Overall, the mutation was detected in 82% of papillary carcinomas. The sensitivity, specificity, and positive and negative predictive values for the diagnosis of malignancy were 75%, 100%, 100%, and 46%, respectively. Conclusion The preoperative knowledge of the V600E mutation status is fundamental to plan total thyroidectomy with certainty and should be part of the decision tree for the management of thyroid nodules. © 2016 Wiley Periodicals, Inc.


Guyader C.,University Pierre and Marie Curie | Ceraline J.,University of Strasbourg | Gravier E.,University Pierre and Marie Curie | Gravier E.,French Institute of Health and Medical Research | And 10 more authors.
PLoS ONE | Year: 2012

Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape -frequency and delay- are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH) antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR) antagonists (bicalutamide or flutamide). Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration), but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR) as compared to continuous castration (RRintermittent: 14.5, RRcomplete blockade: 6.5 and 1.35). All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17) and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent tumors displayed genetic instability, AR mutations, and alterations of phosphorylation pathways. We postulated that Her-2/AKT pathways allowed salvage of tumor cells under castration and we demonstrated that their inhibition prevented tumor recurrence in our model. © 2012 Guyader et al.


Cochand-Priollet B.,Anatomie et Cytologie Pathologiques | Schmitt F.C.,University of Porto | Totsch M.,Medical University of Graz | Vielh P.,Institute Gustave Roussy
Acta Cytologica | Year: 2011

Objectives: A 2007 conference held at the National Cancer Institute, Bethesda, Md., USA, proposed a new terminology for classifying the results of thyroid fine-needle aspiration (FNA)-The Bethesda System for Reporting Thyroid Cytology (TBSRTC). The need to standardize thyroid FNA terminology was emphasized during the 35th European Congress of Cytology in 2009. An interobserver review study to assess the new terminology for analyzing the results of thyroid FNA was organized by the scientific committee of the European Federation of Cytology Societies. Study Design: Four experts in thyroid FNA examined and classified 116 FNAs according to the 6 levels of TBSRTC which are: nondiagnostic (ND); benign; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN), with those of Hürthle cell type reported as follicular neoplasm, Hürthle cell type/suspicious for a follicular neoplasm, Hürthle cell type (FNHCT/SFNHCT); suspicious (SUS), and malignant. Results: The total consensus was 62.1%; the cytopathologists disagreed on 44 cases, including 8 cases of AUS/FLUS and 18 of FN/SFN; 59% of the cases had no consensus. They agreed on 73 and 80% of the cases classified as benign and malignant, respectively, and on 58.3% of the SUS cases. The percentage of no consensus for each expert was between 32 and 39%. Conclusions: Disagreement regarding the use of TBSRTC terminology for classifying the results of thyroid FNA mainly occurred in the most-often criticized categories of AUS/FLUS and FN/SFN. © 2011 S. Karger AG, Basel.


Galmiche L.,University of Paris Descartes | Serre V.,University of Paris Descartes | Beinat M.,University of Paris Descartes | Assouline Z.,University of Paris Descartes | And 10 more authors.
Human Mutation | Year: 2011

By combining exome sequencing in conjunction with genetic mapping, we have identified the first mutation in large mitochondrial ribosomal protein MRPL3 in a family of four sibs with hypertrophic cardiomyopathy, psychomotor retardation, and multiple respiratory chain deficiency. Affected sibs were compound heterozygotes for a missense MRPL3 mutation (P317R) and a large-scale deletion, inherited from the mother and the father, respectively. These mutations were shown to alter ribosome assembly and cause a mitochondrial translation deficiency in cultured skin fibroblasts resulting in an abnormal assembly of several complexes of the respiratory chain. This observation gives support to the view that exome sequencing combined with genetic mapping is a powerful approach for the identification of new genes of mitochondrial disorders. ©2011 Wiley Periodicals, Inc.


PubMed | Anatomie et cytologie pathologiques, Service de Nephrologie et Transplantation Adulte, University of Paris Descartes and Columbia University
Type: Journal Article | Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2016

Persistent CD4 T-cell lymphopenia after kidney transplantation has been associated with an increased occurrence of opportunistic infections, malignancies and even mortality, but studies have focussed only on the first few years after kidney transplantation. In this study, we investigated the risk factors and clinical significance of long-term profound CD4 lymphopenia detected 10 years after renal transplantation.Between 2007 and 2010, 6206 CD4 T-cell counts, including 1507 counts <300/mm(3), were identified in an active cohort of 1876 kidney transplant patients. We identified 27 HIV-negative lymphopenic kidney transplant recipients out of 513 patients with graft survival over 10 years. We compared this cohort to 54 non-lymphopenic controls matched for the date of kidney transplantation.The prevalence of CD4 lymphopenia 10 years after transplantation was 5.3%. CD4 T-cell lymphopenia was associated with significantly lower thymic output and with B-cell lymphopenia (P < 0.05). The duration of pre-transplant dialysis, but not the use of lymphopenic induction or recipient age, was significantly associated with a persistent CD4 lymphopenia (6.1 versus 3.0 years, P = 0.008). CD4 lymphopenia was associated with a higher frequency of cancer (50 versus 29.6%, P = 0.047). Most strikingly, long-term lymphopenia was significantly and independently associated with an accelerated decline in renal allograft function (P = 0.005), despite a similar rate of biopsy-proven acute rejection and comparable immunosuppression.Our study shows an association between long-term CD4 T-cell lymphopenia in kidney recipients and malignancy and an accelerated decline of kidney allograft function.


PubMed | Unite de Genomique des Tumeurs Solides, Radiologie and Anatomie et Cytologie Pathologiques
Type: Journal Article | Journal: Head & neck | Year: 2016

Whether preoperative knowledge of the BRAF mutation status would help to determine the extent of surgery for thyroid nodules is still under investigation.We developed a method to state the V600E mutation before surgery on fine-needle aspiration (FNA) stained smears checked to contain tumor cells. We evaluated the interest of the preoperative assessment of the mutation for surgical strategy of nodules, diagnosed as malignant, suspicious for malignancy or follicular neoplasms.The mutation was found in 81% (79 of 97) malignant, 59% (20 of 34) suspicious nodules, and in none of follicular neoplasms (n = 29). Overall, the mutation was detected in 82% of papillary carcinomas. The sensitivity, specificity, and positive and negative predictive values for the diagnosis of malignancy were 75%, 100%, 100%, and 46%, respectively.The preoperative knowledge of the V600E mutation status is fundamental to plan total thyroidectomy with certainty and should be part of the decision tree for the management of thyroid nodules. 2016 Wiley Periodicals, Inc. Head Neck 38: 1017-1021, 2016.

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