A Durlach

Hôpital Universitaire Robert Debré, Lutetia Parisorum, Île-de-France, France

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Publications (76)151.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Bullous pemphigoid (BP) is an autoimmune skin disease characterized by the binding of autoantibodies to components of the hemidesmosome structure resulting in an inflammatory response and subepidermal blister formation. To investigate the role of immune orientation in the inflammatory processes associated to disease progression, blister fluid, serum and biopsy specimens were collected from thirty one consecutive BP patients. Blister fluids displayed high level of IL-6, IL-17, IL-22, IL-23, whereas TGF-β was increased in BP sera. However neither immunocytochemistry on a trans-differentiation model of IL-17-producing PBMCs nor immunohistochemistry on BP biopsy specimens could demonstrate the presence of Th17 lymphocytes. Instead innate immune cells, especially neutrophils, produced IL-17 at the skin lesional site. Of note, superpotent topical corticosteroid application quickly and dramatically reduced both IL-17 expression and clinical signs of BP. Consistently, IL-17 upregulated MMP-9 and neutrophil elastase expression, two proteases involved in blister formation, thereof further demonstrating its role in the progress of BP. Finally IL-17-induced matrix degradation originated from neutrophil activation, initiated the formation of an amplification loop of the inflammatory response that could represent the underlying phenomenon leading to the maintenance and even disease extent. Thus, our results could open new therapeutic strategies for BP patients.Journal of Investigative Dermatology accepted article preview online, 19 June 2014; doi:10.1038/jid.2014.263.
    The Journal of investigative dermatology. 06/2014;
  • Annales de Dermatologie et de Vénéréologie 06/2014; 141(6-7 Suppl 2):S84. · 0.60 Impact Factor
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    ABSTRACT: Our previous study demonstrated that the endothelial lipase (EL) C.584C>T polymorphism (rs2000813, p.Thr111Ile) was significantly associated with diabetic retinopathy (DR). The present work was conducted to see if this specific variant of the EL gene was more specifically linked to the severity of DR.
    Diabetes & metabolism. 05/2014;
  • Annales de Dermatologie et de Vénéréologie 01/2014; 141(s 6–7):S84. · 0.60 Impact Factor
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    ABSTRACT: Aim Our previous study demonstrated that the endothelial lipase (EL) C.584C>T polymorphism (rs2000813, p.Thr111Ile) was significantly associated with diabetic retinopathy (DR). The present work was conducted to see if this specific variant of the EL gene was more specifically linked to the severity of DR. Methods This retrospective cohort study was based on a review of the institutional charts of 287 type 2 diabetes patients (mean age = 59.7 years; mean BMI = 29.0 kg/m2; mean HbA1c = 8.4%) genotyped for the EL C.584C>T polymorphism (rs2000813, p.Thr111Ile). The stage of DR was also determined for each genotype (CC, CT, TT). Results On univariate analysis, the minor allele homozygote TT variant was significantly associated with severe DR (OR: 4.3; 95% CI: 1.4, 13.1) compared with the major CC homozygote. No significant result was found for the CT heterozygote. Multivariate analysis revealed an increased risk for TT homozygotes to present with severe non-proliferative DR (OR: 8.09; 95% CI: 1.23, 53.1) or proliferative DR. Other associations were not significant. Conclusion Minor allele homozygosity for this EL variant (c.584C>T) could be a significant risk factor for developing severe, sight-threatening disease due to proliferative DR. Further prospective studies of this EL polymorphism in a larger population sample are needed to confirm these results.
    Diabetes & Metabolism. 01/2014;
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    ABSTRACT: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are the two main subtypes of auto-immune pemphigus, each having different clinical, histological and immunopathological features. We report the case of a patient initially with typical PV who relapsed within 2years, presenting clinically, histologically and immunologically typical PF. A 47-year old man presented in March 2008 with clinically, histologically and serologically typical PV and treated with systemic corticosteroids alone (prednisone: 1mg/kg per day) then combined with a cycle of rituximab, which resulted in complete remission. After discontinuation of therapy (duration: 26months), he relapsed 6 months later with PF presenting clinical, histological and serological characteristics typical of this condition. This is a rare case of complete transition from PV to PF in clinical, histological and serological terms, and the first case occurring after initial treatment with rituximab.
    Annales de Dermatologie et de Vénéréologie 12/2013; 140(12):788-92. · 0.60 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 01/2013; 140(12):S359. · 0.60 Impact Factor
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    ABSTRACT: Background Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are the two main subtypes of auto-immune pemphigus, each having different clinical, histological and immunopathological features. We report the case of a patient initially with typical PV who relapsed within 2 years, presenting clinically, histologically and immunologically typical PF. Patients and methods A 47-year old man presented in March 2008 with clinically, histologically and serologically typical PV and treated with systemic corticosteroids alone (prednisone: 1 mg/kg per day) then combined with a cycle of rituximab, which resulted in complete remission. After discontinuation of therapy (duration: 26 months), he relapsed 6 months later with PF presenting clinical, histological and serological characteristics typical of this condition. Discussion This is a rare case of complete transition from PV to PF in clinical, histological and serological terms, and the first case occurring after initial treatment with rituximab.
    Annales de Dermatologie et de Vénéréologie 01/2013; 140(12):788–792. · 0.60 Impact Factor
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    ABSTRACT: Pathological endothelin axis is known to be involved in prostate cancer progression. Our study evaluates immunohistochemical expression of ET-1 and ET-AR on prostate biopsy specimen and the predictive value for biochemical relapse on patients with advanced and metastatic cancer. We also evaluated the impact of ET-1 and ET-AR expression on local progression and metastatic bone progression for these patients. From 1992 to June 2009, 44 patients with clinical T3 stage and metastatic lymph nodes were included. PSA levels, Gleason score in biopsy cores, number of invaded lymph nodes, the existence of nodular capsule transgression and hormonal treatment given to the patient, were analyzed. Biopsy cores were submitted to immunohistochemical study of the expression of ET-1 and ET-AR. Semi-quantitative ET-1 and ET-AR staining assessment was always realised by the same pathologist. The average age of the cohort was 65.6 (standard deviation 6.3), median PSA level was 52.8 ng /ml (3-227), median time of follow-up was 70 months (6-144). Biochemical relapse was observed in 62.8%. Statistically significant stronger ET-1 expression was observed in biopsies of patients with a biochemical relapse (p=0.014). Eighty percent of patients with a biochemical relapse had a high level of ET-AR expression, but no statistical significance has been shown (p=0.109). The relative risk for progression under hormonal therapy was 1.9 in case of high level of ET-1 expression and biochemical relapse was confirmed 8 months earlier in average. High level of ET-AR expression on biopsy cores may indicate earlier local progression and metastatic bone progression but there were no statistical proof. In our study, the strength of ET-1 expression in prostate cancer biopsy cores is a prognostic factor of biochemical relapse for cT3 stage patients with metastatic lymph nodes. We have not been able to prove that ET-1 is an independent prognostic factor. A high level of ET-AR expression on prostate biopsy cores is not, in our study, a prognosis factor for predicting the biochemical relapse.
    Progrès en Urologie 01/2012; 22(1):38-44. · 0.80 Impact Factor
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    ABSTRACT: Introduction Pathological endothelin axis is known to be involved in prostate cancer progression. Our study evaluates immunohistochemical expression of ET-1 and ET-AR on prostate biopsy specimen and the predictive value for biochemical relapse on patients with advanced and metastatic cancer. We also evaluated the impact of ET-1 and ET-AR expression on local progression and metastatic bone progression for these patients. Patients and method From 1992 to June 2009, 44 patients with clinical T3 stage and metastatic lymph nodes were included. PSA levels, Gleason score in biopsy cores, number of invaded lymph nodes, the existence of nodular capsule transgression and hormonal treatment given to the patient, were analyzed. Biopsy cores were submitted to immunohistochemical study of the expression of ET-1 and ET-AR. Semi-quantitative ET-1 and ET-AR staining assessment was always realised by the same pathologist. Results The average age of the cohort was 65.6 (standard deviation 6.3), median PSA level was 52.8 ng /ml (3–227), median time of follow-up was 70 months (6–144). Biochemical relapse was observed in 62.8%. Statistically significant stronger ET-1 expression was observed in biopsies of patients with a biochemical relapse (p = 0.014). Eighty percent of patients with a biochemical relapse had a high level of ET-AR expression, but no statistical significance has been shown (p = 0.109). The relative risk for progression under hormonal therapy was 1.9 in case of high level of ET-1 expression and biochemical relapse was confirmed 8 months earlier in average. High level of ET-AR expression on biopsy cores may indicate earlier local progression and metastatic bone progression but there were no statistical proof. Conclusion In our study, the strength of ET-1 expression in prostate cancer biopsy cores is a prognostic factor of biochemical relapse for cT3 stage patients with metastatic lymph nodes. We have not been able to prove that ET-1 is an independent prognostic factor. A high level of ET-AR expression on prostate biopsy cores is not, in our study, a prognosis factor for predicting the biochemical relapse.
    Progres En Urologie - PROG UROL. 01/2012;
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    ABSTRACT: Vitamin K antagonists (VKAs) are widely used in thromboembolic diseases. We report five cases of necrotic leg ulcers having a particularly severe course and in which withdrawal of VKA treatment alone enabled healing. Five patients presented with necrotic leg ulcers clinically evocative of necrotic angiodermatitis or vasculitis. Histological features were variable, including inconstantly inflammatory lesions (leukocytoclastic vasculitis) and microthrombosis. None of the patients had laboratory signs of autoimmune disease. Healing occurred in all patients only after withdrawal of VKA therapy (fluindione or acenocoumarol). Associated vascular diseases included superficial venous, distal arterial insufficiency and postphlebitic disease. In three cases, thrombotic factors were observed: hyperhomocysteinaemia or heterozygous Factor V Leiden mutation. Although the causative role of VKAs is based solely on chronological criteria, this potential side effect deserves publication because of its practical therapeutic consequences. The physiopathological mechanisms accounting for the role of VKAs, including immunoallergic phenomena and, above all, microcirculatory thrombotic processes, are hypothetical and not universally accepted.
    Annales de Dermatologie et de Vénéréologie 10/2011; 138(10):657-63. · 0.60 Impact Factor
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    ABSTRACT: High-mobility group A1 (HMGA1) protein is a key regulator of insulin receptor (INSR) gene expression. We previously identified a functional HMGA1 gene variant in 2 insulin-resistant patients with decreased INSR expression and type 2 diabetes mellitus (DM). To examine the association of HMGA1 gene variants with type 2 DM. Case-control study that analyzed the HMGA1 gene in patients with type 2 DM and controls from 3 populations of white European ancestry. Italian patients with type 2 DM (n = 3278) and 2 groups of controls (n = 3328) were attending the University of Catanzaro outpatient clinics and other health care sites in Calabria, Italy, during 2003-2009; US patients with type 2 DM (n = 970) were recruited in Northern California clinics between 1994 and 2005 and controls (n = 958) were senior athletes without DM collected in 2004 and 2009; and French patients with type 2 DM (n = 354) and healthy controls (n = 50) were enrolled at the University of Reims in 1992. Genomic DNA was either directly sequenced or analyzed for specific HMGA1 mutations. Messenger RNA and protein expression for HMGA1 and INSR were measured in both peripheral lymphomonocytes and cultured Epstein-Barr virus-transformed lymphoblasts from patients with type 2 DM and controls. The frequency of HMGA1 gene variants among cases and controls. Odds ratios (ORs) for type 2 DM were estimated by logistic regression analysis. The most frequent functional HMGA1 variant, IVS5-13insC, was present in 7% to 8% of patients with type 2 DM in all 3 populations. The prevalence of IVS5-13insC variant was higher among patients with type 2 DM than among controls in the Italian population (7.23% vs 0.43% in one control group; OR, 15.77 [95% confidence interval {CI}, 8.57-29.03]; P < .001 and 7.23% vs 3.32% in the other control group; OR, 2.03 [95% CI, 1.51-3.43]; P < .001). In the US population, the prevalence of IVS5-13insC variant was 7.7% among patients with type 2 DM vs 4.7% among controls (OR, 1.64 [95% CI, 1.05-2.57]; P = .03). In the French population, the prevalence of IVS5-13insC variant was 7.6% among patients with type 2 DM and 0% among controls (P = .046). In the Italian population, 3 other functional variants were observed. When all 4 variants were analyzed, HMGA1 defects were present in 9.8% of Italian patients with type 2 DM and 0.6% of controls. In addition to the IVS5 C-insertion, the c.310G>T (p.E104X) variant was found in 14 patients and no controls (Bonferroni-adjusted P = .01); the c.*82G>A variant (rs2780219) was found in 46 patients and 5 controls (Bonferroni-adjusted P < .001); the c.*369del variant was found in 24 patients and no controls (Bonferroni-adjusted P < .001). In circulating monocytes and Epstein-Barr virus-transformed lymphoblasts from patients with type 2 DM and the IVS5-13insC variant, the messenger RNA levels and protein content of both HMGA1 and the INSR were decreased by 40% to 50%, and these defects were corrected by transfection with HMGA1 complementary DNA. Compared with healthy controls, the presence of functional HMGA1 gene variants in individuals of white European ancestry was associated with type 2 DM.
    JAMA The Journal of the American Medical Association 03/2011; 305(9):903-12. · 29.98 Impact Factor
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    ABSTRACT: Endothelial lipase (EL) is a key enzyme in lipid metabolism, and a polymorphism in the EL gene may be a candidate for modulating lipid parameters in type 2 diabetic (T2D) patients. In 396 T2D patients (age: 59.5 ± 10.7 years; BMI: 28.9 ± 5.3 kg/m(2); HbA(1c): 8.2 ± 1.9%), the c.584C>T polymorphism (rs2000813, p.Thr111Ile) was studied in 225 men (frequency of c.584T: 0.351) and 171 women (frequency of c.584T: 0.304). Patients' metabolic parameters, and macrovascular and microvascular complications, were assessed at baseline and at follow-up (mean: 4.2 years). Patients who were homozygous for the minor allele displayed modestly decreased low-density lipoprotein (LDL) cholesterol and raised apolipoprotein B at baseline, and raised systolic blood pressure and high-density lipoprotein (HDL) cholesterol on follow-up. Homozygosity for the minor allele was significantly associated with frequency of retinopathy (P=0.025), with TT homozygous patients more likely to have diabetic retinopathy (OR: 3.505; 95% CI: 1.491-8.239) both initially and at follow-up. The c.584C>T EL polymorphism is associated with a higher risk of diabetic retinopathy that could be linked to modifications in HDL-cholesterol metabolism and blood pressure levels.
    Diabetes & Metabolism 02/2011; 37(1):64-71. · 2.39 Impact Factor
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    ABSTRACT: This study aims to develop a new FT-IR spectral imaging of tumoral tissue permitting a better characterization of tumor heterogeneity and tumor/surrounding tissue interface. Infrared (IR) data were acquired on 13 biopsies of paraffin-embedded human skin carcinomas. Our approach relies on an innovative fuzzy C-means (FCM)-based clustering algorithm, allowing the automatic and simultaneous estimation of the optimal FCM parameters (number of clusters K and fuzziness index m). FCM seems more suitable than classical 'hard' clusterings, as it permits the assignment of each IR spectrum to every cluster with a specific membership value. This characteristic allows differentiating the nuances in the assignment of pixels, particularly those corresponding to tumoral tissue and those located at the tumor/peritumoral tissue interface. FCM images permit to highlight a marked heterogeneity within the tumor and characterize the interconnection between tissular structures. For the infiltrative tumors, a progressive gradient in the membership values of the pixels of the invasive front was also revealed.
    Laboratory Investigation 02/2011; 91(5):799-811. · 3.96 Impact Factor
  • Annales De Pathologie - ANN PATHOL. 01/2011; 31(5).
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    ABSTRACT: Introduction La protéine HMGA1 (High Mobility Group A1) est un régulateur clé de l’expression du gène du récepteur de l’insuline (RINS). Nous avons antérieurement décrit un variant génétique d’HMGA1 chez 2 patients insulino-résistants présentant une diminution de l’expression du RINS et un diabéte de type 2 (D.Foti et al. Nat Med. 2005 ; 11(7):765–773). Dans cette étude nous avons évalué l’association de plusieurs variants génétiques d’HMGA1 sur une large cohorte de diabétique de type 2 (DT2). Matériels et méthodes Le gène d’HMGA1 a été analysé chez 4602 DT2 issus de 3 populations italienne, américaine et française) et comparé à des témoins non diabétiques. L’ADN génomique a été soit directement séquencé, soit analysé pour des mutations spécifiques. L’expression des ARNm et des protéines d’HMGA1 et du RINS ont été mesurés sur des lympho-monocytes circulants et sur des lymphoblastes en cultures (EBV-transformed). La fréquence des variants génétiques d’HMGA1 a été évaluée chez les DT2 et les témoins, les odd ratios estimés par analyse de régression logistique. Résultats Le variant fonctionnel le plus frequent d’HMGA1 (IVS5 -13insC), était présent chez 7–8 % des DT2. Dans les monocytes circulants et les lymphoblastes transformés de ces patients, les expressions génique et protéique d’HMGA1 et du RINS étaient diminuées de 50–60 %. Ces anomalies étaient corrigées par transfection du cDNA d’HMGA1. Dans la population la plus importante (italienne), 3 autres variants fonctionnels ont été observés : des anomalies d’HMGA1 étaient présentes chez près de 10 % de ces patients. Conclusion Les variants fonctionnels d’HMGA1 qui affectent l’expression du RINS, sont assez fréquents chez les DT2 (7–10 %) et sont susceptibles de participer à la pathogénie de la maladie. Ils peuvent être envisagés non seulement comme des marqueurs précoces de l’insulino-résistance et du DT2, mais permettre de mieux comprendre la réponse clinique aux thérapeutiques actuelles aidant à l’identification de nouvelles cibles thérapeutiques.
    Diabetes & Metabolism - DIABETES METAB. 01/2011; 37(1).
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    ABSTRACT: To assess the value of endothelin-1 (ET-1) expression in predicting extracapsular extension (ECE) in clinically localized prostate cancer (PCa). ET-1 expression was determined by immunohistochemistry on archival needle biopsies (NBs) from 94 patients (49 pT2 and 45 pT3a) who underwent radical prostatectomy (RP) for clinical T1-T2 PCa. Each sample was analysed independently by two pathologists blinded to the clinical data. In univariate analysis, high ET-1 expression in NBs, pre-operative prostate-specific antigen (PSA) level >10 ng/ml, percentage of positive biopsy cores and NB Gleason score ≥7 were significantly associated with ECE as determined on subsequent RP. No significant association was found between clinical stage and ECE. In multivariate analysis, there was a significant association with high ET-1 expression in NBs (p = 0.006), pre-operative PSA level >10 ng/ml (p = 0.049), and NB Gleason score ≥7 (p = 0.002). These three pre-operative factors combined provided the best model for predicting ECE with 93.3% sensitivity, 49% specificity, 62.5% positive predictive value, 88.9% negative predictive value. The combination yielded a higher concordance index (0.760 vs 0.720) and offered a higher log partial likelihood than the same model without ET1 (112.8 vs 105.7, p = 0.01). ET-1 expression was strongly associated with ECE and, when combined with pre-operative PSA level and Gleason score, improved the predictive accuracy of pre-operative NBs. Its assessment in patients with localized PCa might be useful when making treatment decisions. Further studies with standardisation of immunohistochemical staining and multi-institutional validation are now needed to establish the appropriate use of ET-1 staining in PCa staging and to evaluate inter-observer reproducibility.
    BJU International 11/2010; 108(2 Pt 2):E104-9. · 3.05 Impact Factor
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  • 07/2010; 1267:336-337.
  • Journal of Urology - J UROL. 01/2010; 183(4).

Publication Stats

666 Citations
151.22 Total Impact Points

Institutions

  • 2011
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France
  • 2008–2009
    • Université de Reims Champagne-Ardenne
      Rheims, Champagne-Ardenne, France
  • 2005
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2003
    • Centre Hospitalier Universitaire de Reims
      Rheims, Champagne-Ardenne, France
  • 1996
    • Hôpital Saint-Vincent-de-Paul – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France