Deprecated: Unparenthesized `a ? b : c ? d : e` is deprecated. Use either `(a ? b : c) ? d : e` or `a ? b : (c ? d : e)` in /home/institu2/public_html/bibliographie/ecrire/inc/utils.php on line 2576
Biblio - Bibliographie IAL
Bibliographie IAL

Warning: Use of undefined constant zitems - assumed 'zitems' (this will throw an Error in a future version of PHP) in /home/institu2/public_html/bibliographie/tmp/cache/skel/html_20003158b6f59285b419f8edbafd1db5.php on line 83

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Warning: count(): Parameter must be an array or an object that implements Countable in /home/institu2/public_html/bibliographie/plugins/auto/zotspip/v3.5.0/lib/citeproc-php/CiteProc.php on line 1120

Recherche bibliographique scientifique

Moteur de recherche scientifique en Médecine, Biologie et Sciences

Accueil > Références bibliographiques

biblio

2008


  • Clifford, GM, Rickenbach, M, Polesel, J, Dal Maso, L, Steffen, I, Ledergerber, B, Rauch, A, Probst-Hensch, NM, Bouchardy, C, Levi, F, Franceschi, S & Cohort, SHIV 2008, « Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma », AIDS, vol. 22, no. 16, p. 2135-41, viewed sans date, .
    Résumé : OBJECTIVE: To investigate HIV-related immunodeficiency as a risk factor for hepatocellular carcinoma (HCC) among persons infected with HIV, while controlling for the effect of frequent coinfection with hepatitis C and B viruses. DESIGN: A case-control study nested in the Swiss HIV Cohort Study. METHODS: Twenty-six HCC patients were identified in the Swiss HIV Cohort Study or through linkage with Swiss Cancer Registries, and were individually matched to 251 controls according to Swiss HIV Cohort Study centre, sex, HIV-transmission category, age and year at enrollment. Odds ratios and corresponding confidence intervals were estimated by conditional logistic regression. RESULTS: All HCC patients were positive for hepatitis B surface antigen or antibodies against hepatitis C virus. HCC patients included 14 injection drug users (three positive for hepatitis B surface antigen and 13 for antibodies against hepatitis C virus) and 12 men having sex with men/heterosexual/other (11 positive for hepatitis B surface antigen, three for antibodies against hepatitis C virus), revealing a strong relationship between HIV transmission route and hepatitis viral type. Latest CD4+ cell count [Odds ratio (OR) per 100 cells/mul decrease = 1.33, 95% confidence interval (CI) 1.06-1.68] and CD4+ cell count percentage (OR per 10% decrease = 1.65, 95% CI 1.01-2.71) were significantly associated with HCC. The effects of CD4+ cell count were concentrated among men having sex with men/heterosexual/other rather than injecting drug users. Highly active antiretroviral therapy use was not significantly associated with HCC risk (OR for ever versus never = 0.59, 95% confidence interval 0.18-1.91). CONCLUSION: Lower CD4+ cell counts increased the risk for HCC among persons infected with HIV, an effect that was particularly evident for hepatitis B virus-related HCC arising in non-injecting drug users.
    Note Note
    <p>18832877</p>
    Note Note
    <p>18832877</p>
    Note Note
    <p>18832877</p>
    Note Note
    <p>18832877</p>

  • Clybouw, C, McHichi, BE, Hadji, A, Portier, A, Auffredou, MT, Arnoult, D, Leca, G & Vazquez, A 2008, « TGFbeta-mediated apoptosis of Burkitt's lymphoma BL41 cells is associated with the relocation of mitochondrial BimEL », Oncogene, vol. 27, no. 24, p. 3446-56, viewed sans date, .
    Résumé : In this study, we showed that the transforming growth factor beta (TGFbeta)-mediated apoptosis of Burkitt's lymphoma BL41 cells is dependent on the BH3-only protein Bim. In contrast to what has been observed with other cell types, TGFbeta activation did not promote Bim upregulation in BL41 cells, but instead resulted in Bim release from the mitochondria. Indeed, Bim levels were high in healthy BL41 cells, in which they dimerized with the Bcl-2-like protein Mcl-1 at the mitochondrial surface. In healthy and TGFbeta-activated BL41 cells, unlike in epithelial cells or hepatocytes, Bim did not associate with Bcl-2 or Bcl-xL. TGFbeta activation of BL41 cells triggered the p38-dependent activation of caspase-8, causing the cleavage of Mcl-1 and the transfer of Bim from the mitochondria to the cytoskeleton. In addition to mitochondrial activation, this relocation of Bim may facilitate the complete demise of a cell death that is beyond the commitment point to apoptosis and may represent a hallmark of the TGFbeta-mediated apoptosis of human lymphoma B cells.
    Mots-clés : Apoptosis/*physiology Apoptosis Regulatory Proteins/antagonists & inhibitors/genetics/*metabolism Blotting, Messenger/genetics/metabolism RNA, Western Burkitt Lymphoma/*metabolism/*pathology Caspase 8/metabolism Cell Proliferation Cells.

  • Cordier, AG, Braidy, C, Levaillant, JM, Brisset, S, Maurin, ML, Mas, AE, Frydman, R, Tachdjian, G & Picone, O 2008, « Correlation between ultrasound and pathological examination in a prenatal diagnosis of Cri du Chat syndrome associated with partial trisomy 17q », Prenat Diagn, vol. 28, no. 5, p. 463-5, viewed sans date, .
    Note Note
    <p>18444226</p>
    Note Note
    <p>18444226</p>
    Note Note
    <p>18444226</p>
    Note Note
    <p>18444226</p>
  • Corpechot, C, Abenavoli, L, Rabahi, N, Chretien, Y, Andreani, T, Johanet, C, Chazouilleres, O & Poupon, R 2008, « Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis », Hepatology, vol. 48, no. 3, p. 871-7.
    Résumé : Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. It has been recently proposed that an alkaline phosphatase (ALP) decline of more than 40% in baseline value or a normal level after 1 year of UDCA treatment (Barcelona criteria) could serve as a good marker of long-term prognosis. Our aim was to define the best efficient set of biochemistries able to identify UDCA-treated patients at risk of death or liver transplantation (LT). The efficiency of several combinations of serum bilirubin, ALP, and aspartate aminotransferase (AST) threshold values to predict outcome was assessed after 1 year of treatment in 292 patients with PBC. Patients showing ALP <3 upper limit of normal (ULN), AST <2 ULN, and bilirubin </=1 mg/dL after 1 year of UDCA had a 10-year transplant-free survival rate of 90% (95% confidence interval, 81%-95%), compared to 51% (95% confidence interval, 38%-64%) for those who did not (P < 0.001). Patients were less well discriminated by the Barcelona criteria (79% versus 63%). Independent predictive factors of death or LT were baseline serum bilirubin level >1 mg/dL (relative risk [RR], 1.7), histologic stage >/=3 (RR, 1.5), interface hepatitis (RR, 1.9), and the absence of biochemical response (ALP >3 ULN or AST >2 ULN, or bilirubin >1 mg/dL) (RR, 2.3). Antinuclear antibodies against gp210 or Sp100 proteins were associated with death or LT in univariate but not in multivariate analysis. CONCLUSION: This study defines the best efficient biochemical response to UDCA, which, independent of baseline predictive factors, identifies patients with PBC with a good long-term prognosis. Patients who fail to achieve this response and those with interface hepatitis or advanced histological stage should be targeted for further therapeutic research.
    Mots-clés : Adult Aged Alkaline Phosphatase/ blood Aspartate Aminotransferases/ blood Bilirubin/ blood Biological Markers/blood Cholagogues and Choleretics/ therapeutic use Dose-Response Relationship, Biliary/ blood/diagnosis/ drug therapy Longitudinal Studies Male Middle Aged Multivariate Analysis Predictive Value of Tests Prognosis Treatment Outcome Ursodeoxycholic Acid/ therapeutic use, Drug Female Follow-Up Studies Humans Kaplan-Meier Estimate Liver Cirrhosis.

  • Coudert, B, Focan, C, Genet, D, Giacchetti, S, Cvickovic, F, Zambelli, A, Fillet, G, Chollet, P, Amoroso, D, Van Der Auwera, J, Lentz, MA, Marreaud, S, Baron, B, Gorlia, T, Biville, F & Lévi, F 2008, « A randomized multicenter study of optimal circadian time of vinorelbine combined with chronomodulated 5-fluorouracil in pretreated metastatic breast cancer patients: EORTC trial 05971 », Chronobiol Int, vol. 25, no. 5, p. 680-96, viewed sans date, .
    Résumé : Studies in animals synchronized with an alternation of 12 h of light and 12 h of darkness have showed that hematological and systemic toxicities could be reduced if vinorelbine were administered 19 or 23 hours after light onset (HALO), corresponding to 17:00 and 21:00 h in diurnally active humans. This trial aimed to define the least toxic time of vinorelbine administration in metastatic breast cancer patients. Initially, the study treatment consisted of three courses of vinorelbine of 30 mg/m(2)/d on D1 and D6 and chronomodulated 5-fluorouracil of 850 mg/m(2) from D2 to D5 every 21 days. Ninety metastatic breast cancer patients were randomized to receive vinorelbine at one of the eight possible dosing times. Further to the recommendations of the Independent Data Monitoring Committee, the vinorelbine dose was reduced to 25 mg/m(2)/d midway through the study. The primary objective of the study was detection of the least toxic time based on the incidence of grade 3-4 (G3-4) neutropenia. To show a significant result, the 90% confidence interval width of the least toxic time had to be<6 h. The least toxic time detection based on the incidence of other toxicities was also analyzed. The time of least drug toxic was estimated using a logistic regression model assuming that the logit transformation of the toxicity rate follows a sinusoidal distribution over 24 h. The bootstrap technique was used to obtain the 90% confidence interval. The least toxic time of G3-4 neutropenia was observed at 21:00 h with a non-significant 90% CI. Secondary endpoint analyses indicated the least toxic time could differ when based on other toxicity parameters (e.g., a significant least toxic time of 17:00 h was observed for G3-4 leucopenia), in agreement with animal data. The least toxic time of 10:30 h was estimated for any G3-4 gastrointestinal toxicity. This results of this study do not allow us to recommend an optimal time for vinorelbine administration. It has highlighted, however, the inherent methodological difficulties in the conduct of such a trial in the human setting. It indicates that future optimal time-finding trials should have tolerability and/or activity as the primary endpoint in place of a particular toxicity. The randomized optimal time-finding design may be used to identify the best time of chemotherapy administration.
    Note Note
    <p>18780198</p>
    Note Note
    <p>18780198</p>
    Note Note
    <p>18780198</p>
    Note Note
    <p>18780198</p>
  • Couty, JP, Crain, AM, Gerbaud, S, Labasque, M, Marchiol, C, Fradelizi, D, Boudaly, S, Guettier, C, Vignuzzi, M, van der Werf, S, Escriou, N & Viguier, M 2008, « Delivery of mengovirus-derived RNA replicons into tumoural liver enhances the anti-tumour efficacy of a peripheral peptide-based vaccine », Cancer Immunol Immunother, vol. 57, no. 8, p. 1161-71.
    Résumé : Hepatocellular carcinoma is a deadly cancer with growing incidence for which immunotherapy is one of the most promising therapeutic approach. Peptide-based vaccines designed to induce strong, sustained CD8+ T cell responses are effective in animal models and cancer patients. We demonstrated the efficacy of curative peptide-based immunisation against a unique epitope of SV40 tumour antigen, through the induction of a strong CD8+ T cell-specific response, in our liver tumour model. However, as in human clinical trials, most tumour antigen epitopes did not induce a therapeutic effect, despite inducing strong CD8+ T cell responses. We therefore modified the tumour environment to enhance peptide-based vaccine efficacy by delivering mengovirus (MV)-derived RNA autoreplicating sequences (MV-RNA replicons) into the liver. The injection of replication-competent RNA replicons into the liver converted partial tumour regression into tumour eradication, whereas non-replicating RNA had no such effect. Replicating RNA replicon injection induced local recruitment of innate immunity effectors (NK and NKT) to the tumour and did not affect specific CD8+ T cell populations or other myelolymphoid subsets. The local delivery of such RNA replicons into tumour stroma is therefore a promising strategy complementary to the use of peripheral peptide-based vaccines for treating liver tumours.
    Mots-clés : Animal Flow Cytometry Histocompatibility Antigens Class I/immunology Immunotherapy Liver Neoplasms/immunology/pathology/ therapy Male Mengovirus/ immunology Mice Mice, Animals Cancer Vaccines/ administration & dosage/immunology Carcinoma, Hepatocellular/immunology/pathology/ therapy Disease Models, Inbred C57BL Peptides/ administration & dosage/immunology RNA, Viral/ immunology Replicon/immunology Treatment Outcome.

  • de Haas, RJ, Wicherts, DA & Adam, R 2008, « Resection of colorectal liver metastases with extrahepatic disease », Dig Surg, vol. 25, no. 6, p. 461-6, viewed sans date, .
    Résumé : Extrahepatic disease in combination with colorectal liver metastases has long been considered an absolute contraindication for surgery. However, in many reported series, long-term survival is achieved in selected patients with concomitant extrahepatic disease as long as the resection of all metastatic sites is complete. Owing to these results, an increasing number of patients with advanced metastatic colorectal disease are now being referred for surgery. For patients with concomitant liver and lung metastases, sequential resection of both disease sites has proven to be safe, offering a 5-year survival rate of more than 30%. On the contrary, hepatectomy combined with resection of regional lymph node metastases can only provide long-term survival in case of pedicular lymph node involvement. Furthermore, control of the disease by preoperative chemotherapy appears to be crucial. For peritoneal carcinomatosis, aggressive treatment combining cytoreductive surgery and intraperitoneal chemotherapy can offer a chance of prolonged long-term survival to selected patients with limited peritoneal extension. In conclusion, resection of both intra- and extrahepatic colorectal metastases should be considered if resection of all metastatic sites can be complete and the disease is controlled by chemotherapy. Long-term survival in these patients with advanced disease could be achieved if they are managed by experienced multidisciplinary teams.
    Note Note
    <p>19212118</p>
    Note Note
    <p>19212118</p>
    Note Note
    <p>19212118</p>
    Note Note
    <p>19212118</p>


  • de Haas, RJ, Wicherts, DA, Flores, E, Azoulay, D, Castaing, D & Adam, R 2008, « R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? », Ann Surg, vol. 248, no. 4, p. 626-37, viewed sans date, .
    Résumé : OBJECTIVE: To compare long-term outcome of R0 (negative margins) and R1 (positive margins) liver resections for colorectal liver metastases (CLM) treated by an aggressive approach combining chemotherapy and repeat surgery. SUMMARY BACKGROUND DATA: Complete macroscopic resection with negative margins is the gold standard recommendation in the surgical treatment of CLM. However, due to vascular proximity or multinodularity, complete macroscopic resection can sometimes only be performed through R1 resection. Increasingly efficient chemotherapy may have changed long-term outcome after R1 resection. METHODS: All resected CLM patients (R0 or R1) at our institution between 1990 and 2006 were prospectively evaluated. Exclusion criteria were: macroscopic incomplete (R2) resection, use of local treatment modalities, and presence of extrahepatic disease. We aimed to resect all identified metastases with negative margins. However, when safe margins could not be obtained, resection was still performed provided complete macroscopic tumor removal. Overall survival (OS) and disease-free survival were compared between groups, and prognostic factors were identified. RESULTS: Of 840 patients, 436 (52%) were eligible for the study, 234 (28%) of whom underwent R0 resection, and 202 (24%) underwent R1 resection. Number and size of CLM were higher, and distribution was more often bilateral in the R1 group. After a mean follow-up of 40 months, 5-year OS was 61% and 57% for R0 and R1 patients (P = 0.27). Five-year disease-free survival was 29% in the R0 group versus 20% in the R1 group (P = 0.12). In the R1 group, intrahepatic (but not surgical margin) recurrences were more often observed (28% vs. 17%; P = 0.004). Preoperative carcinoembryonic antigen level > or =10 ng/mL and major hepatectomy, but not R1 resection, were independent predictors of poor OS. Size > or =30 mm, bilateral distribution, and intraoperative blood transfusions independently predicted positive surgical margins. CONCLUSIONS: Despite a higher recurrence rate, the contraindication of R1 resection should be revisited in the current era of effective chemotherapy because survival is similar to that of R0 resection.
    Note Note
    <p>18936576</p>
    Note Note
    <p>18936576</p>
    Note Note
    <p>18936576</p>
    Note Note
    <p>18936576</p>

  • de Totero, D, Meazza, R, Capaia, M, Fabbi, M, Azzarone, B, Balleari, E, Gobbi, M, Cutrona, G, Ferrarini, M & Ferrini, S 2008, « The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways », Blood, vol. 111, no. 2, p. 517-24, viewed sans date, .
    Résumé : The clonal expansion of chronic lymphocytic leukemia (CLL) cells requires the interaction with the microenvironment and is under the control of several cytokines. Here, we investigated the effect of IL-15 and IL-21, which are closely related to IL-2 and share the usage of the common gamma chain and of its JAK3-associated pathway. We found remarkable differences in the signal transduction pathways activated by these cytokines, which determined different responses in CLL cells. IL-15 caused cell proliferation and prevented apoptosis induced by surface IgM cross-linking. These effects were more evident in cells stimulated via surface CD40, which exhibited increased cell expression of IL-15Ralpha chain and, in some of the cases, also of IL-2Rbeta. IL-21 failed to induce CLL cell proliferation and instead promoted apoptosis. Following cell exposure to IL-15, phosphorylation of STAT5 was predominantly observed, whereas, following stimulation with IL-21, there was predominant STAT1 and STAT3 activation. Moreover, IL-15 but not IL-21 caused an increased phosphorylation of Shc and ERK1/2. Pharmacological inhibition of JAK3 or of MEK, which phosphorylates ERK1/2, efficiently blocked IL-15-induced CLL cell proliferation and the antiapoptotic effect of this cytokine. The knowledge of the signaling pathways regulating CLL cell survival and proliferation may provide new molecular targets for therapeutic intervention.
    Mots-clés : Adaptor Proteins, Chronic, Interleukin-15/immunology STAT Transcription Factors/*immunology Shc Signaling Adaptor Proteins, Lymphocytic, Signal Transducing/immunology Animals Apoptosis/drug effects/immunology Cell Line.
  • Demetris, AJ & Sebagh, M 2008, « Plasma cell hepatitis in liver allografts: Variant of rejection or autoimmune hepatitis? », Liver Transpl, vol. 14, no. 6, p. 750-5.
    Résumé : Demetris, Anthony J; Sebagh, Mylene; Comment; Editorial; United States; Liver Transpl. 2008 Jun;14(6):750-5. doi: 10.1002/lt.21518.
    Mots-clés : Autoimmune/ diagnosis/ etiology Humans Immunosuppressive Agents/therapeutic use Liver/metabolism Liver Transplantation/ adverse effects/ methods Plasma Cells/ cytology Postoperative Period Prognosis Transplantation, Graft Rejection/ diagnosis/ etiology Hepacivirus/metabolism Hepatitis, Homologous Treatment Outcome.
  • Desbois, D, Vaghefi, P, Savary, J, Dussaix, E & Roque-Afonso, AM 2008, « Sensitivity of a rapid immuno-chromatographic test for hepatitis C antibodies detection », J Clin Virol, vol. 41, no. 2, p. 129-33.
    Résumé : BACKGROUND AND OBJECTIVES: Enzyme-linked immunoassays (ELISA) are the most widely used anti-hepatitis C virus (HCV) screening tests but simple, instrument and electricity-free screening tests have been developed with results available in a few minutes. METHODS: The sensitivity of a rapid immuno-chromatographic assay for the detection of anti-HCV antibodies was evaluated on 421 HCV RNA-positive samples from chronic carriers and compared with ELISA method. RESULTS: The sensitivity of the ELISA method was 99.3% and the sensitivity of the rapid test was 95.5%. False negative results were independent of HCV genotype, but were associated with human immunodeficiency virus (HIV)-positive status. Among HIV-negative people, sensitivities of the rapid test and the EIA assay were 99.2% and 100%, respectively. Whereas among HIV-positive people, sensitivities were 77.5% and 96.3%. CONCLUSIONS: The immuno-chromatographic test is rapid and simple, and could be used along with rapid anti-HIV determination, in settings with limited facilities or when rapid results are required.
    Mots-clés : Adult Chromatography/ methods Enzyme-Linked Immunosorbent Assay/methods Female Hepacivirus/ immunology Hepatitis C Antibodies/ blood Hepatitis C, Chronic/ diagnosis/immunology/virology Humans Male Middle Aged Reagent Kits, Diagnostic Sensitivity and Specificity Time Factors.
  • Dhalluin-Venier, V, Bazin, C, Massias, L, Farah, RB, Boytchev, I, Fritsch, J, Choury, AD, Prat, F, Buffet, C, Furlan, V & Pelletier, G 2008, « Effects of biliary obstruction on the penetration of ciprofloxacin and cefotaxime », Eur J Gastroenterol Hepatol, vol. 20, no. 2, p. 127-30.
    Résumé : OBJECTIVE: To evaluate the biliary penetration of ciprofloxacin and cefotaxime in patients with obstructed bile ducts and to determine simple predictive markers of effective biliary concentrations of these drugs. METHODS: Sixty-two patients treated with endoscopic biliary drainage were prospectively included in a nonrandomized way and received intravenous ciprofloxacin (200 mg twice daily) or cefotaxime (1 g three times a day) for more than 24 h before exploration. Blood and bile samples were collected at the time of drainage. Ciprofloxacin and cefotaxime concentrations were measured using high-performance liquid chromatography. Biliary penetration was assessed by the bile-to-plasma ratio of the concentrations of both antibiotics. RESULTS: Biliary penetration ranged from 0.06 to 42.7 for ciprofloxacin and from 0.01 to 1.14 for cefotaxime. The ratio was more than one in only 10 patients (35%) and three patients (9%) in ciprofloxacin and cefotaxime groups, respectively. Biliary concentration of the drug was more than 10 times the minimal inhibitory concentration in only 10 patients (35%) and in 12 patients (35%) in ciprofloxacin and cefotaxime groups, respectively. Serum bilirubin, alkaline phosphatase or gamma-glutamyl-transpeptidase were not good predictive markers of the biliary diffusion of the antibiotics. CONCLUSION: In patients with obstructed bile ducts, the biliary penetration of ciprofloxacin is poor and reaches effective biliary concentrations in a minority of patients. Cefotaxime biliary penetration is even poorer. No liver test can predict accurately the biliary penetration of the drugs.
    Mots-clés : 80 and over Anti-Bacterial Agents/ pharmacokinetics/therapeutic use Bile/metabolism Bilirubin/blood Cefotaxime/ pharmacokinetics/therapeutic use Cholangiopancreatography, Aged Aged, Endoscopic Retrograde Cholangitis/ drug therapy/etiology/metabolism Cholestasis/etiology/ metabolism/surgery Chromatography, High Pressure Liquid/methods Ciprofloxacin/ pharmacokinetics/therapeutic use Female Humans Male Middle Aged Prospective Studies.
  • Dhalluin-Venier, V, Fabre, M, Jacquemin, E, Rangheard, AS, Pelletier, G & Buffet, C 2008, « Liver cell adenomas and portosystemic shunt », Gastroenterol Clin Biol, vol. 32, no. 2, p. 164-6.
    Résumé : We report the case of a young man who developed multiple liver cell adenomas 13 years after a mesentericocaval shunt. Radiological findings did not provide diagnosis. Histological findings of two biopsied nodules were compatible with liver cell adenoma. Our patient had no known risk factors for liver cell adenomas. We discuss the hypothesis that disturbed hepatic vascularisation could promote the development of liver cell adenomas.
    Mots-clés : Adenoma, Autosomal Recessive/diagnosis Portasystemic Shunt, Interventional, Liver Cell/ diagnosis Adult Biopsy, Needle Caroli Disease/diagnosis Follow-Up Studies Humans Liver Cirrhosis/congenital Liver Neoplasms/ diagnosis Male Polycystic Kidney, Surgical Ultrasonography.


  • Duclos-Vallée, J-C, Féray, C, Sebagh, M, Teicher, E, Roque-Afonso, A-M, Roche, B, Azoulay, D, Adam, R, Bismuth, H, Castaing, D, Vittecoq, D, Samuel, D & Group, THEVICS 2008, « Survival and recurrence of hepatitis C after liver transplantation in patients coinfected with human immunodeficiency virus and hepatitis C virus », Hepatology, vol. 47, no. 2, p. 407-17, viewed sans date, .
    Résumé : UNLABELLED: Liver transplantation in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a recent indication. In a single center, we have compared the survival and severity of recurrent HCV infection after liver transplantation in HIV-HCV-coinfected and HCV-monoinfected patients. Seventy-nine patients receiving a first liver graft for HCV-related liver disease between 1999 and 2005 were included. Among them, 35 had highly active antiretroviral therapy-controlled HIV infection. All patients were monitored for HCV viral load and liver histology during the posttransplantation course. Coinfected patients were younger (43 +/- 6 versus 55 +/- 8 years, P < 0.0001) and had a higher Model for End-Stage Liver Disease (MELD) score (18.8 +/- 7.4 versus 14.8 +/- 4.7; P = 0.008). The 2-year and 5-year survival rates were 73% and 51% and 91% and 81% in coinfected patients and monoinfected patients, respectively (log-rank P = 0.004). Under multivariate Cox analysis, survival was related only to the MELD score (P = 0.03; risk ratio, 1.08; 95% confidence interval, 1.01, 1.15). Using the Kaplan-Meier method, the progression to fibrosis >or= F2 was significantly higher in the coinfected group (P < 0.0001). CONCLUSION: The results of liver transplantation in HIV-HCV-coinfected patients were satisfactory in terms of survival benefit. Earlier referral of these patients to a liver transplant unit, the use of new drugs effective against HCV, and an avoidance of drug toxicity are mandatory if we are to improve the results of this challenging indication for liver transplantation.
    Mots-clés : Adult Antiretroviral Therapy.
    Note Note
    <p>18098295</p>
    Note Note
    <p>18098295</p>
    Note Note
    <p>18098295</p>
    Note Note
    <p>18098295</p>

  • Dulong, S, Delaunay, F & Lévi, F 2008, « [Circadian control of muscle transcriptome] », Med Sci (Paris), vol. 24, no. 4, p. 372-4, viewed sans date, .
    Note Note
    <p>18405635</p>
    Note Note
    <p>18405635</p>
    Note Note
    <p>18405635</p>
    Note Note
    <p>18405635</p>

  • Durrbach, A, Rostaing, L, Tricot, L, Ouali, N, Wolf, P, Pouteil-Noble, C, Kessler, M, Viron, B & Thervet, E 2008, « Prospective comparison of the use of sirolimus and cyclosporine in recipients of a kidney from an expanded criteria donor », Transplantation, vol. 85, no. 3, p. 486-90, viewed sans date, .
    Résumé : A 6-month, open-label, multicenter prospective pilot study was conducted to evaluate the effects of sirolimus (SRL) versus cyclosporine (CsA) in recipients of kidneys from expanded criteria donors. All patients also received antithymocyte globulins induction, mycophenolate mofetil, and steroids. Sixty-nine patients (33 SRL, 36 CsA) were randomized. More patient were withdrawn in the SRL group (16 vs. 6, P<0.01), because of delayed graft function and surgical complications. Delayed graft function tended to be more frequent with SRL than with CsA (45.4% vs. 30.6%, P=0.22). Graft survival was numerically lower in the SRL group (87.5% vs. 97%, P=0.19). At 6 months, there were no significant differences in biopsy-proven acute rejection or calculated creatinine clearance (SRL 12.1% vs. CsA 8.3%; P=0.7 and 44.7+/-16.6 vs. 41.9+/-15.2 mL/min; P=0.54 respectively). These results do not support the use of SRL immediately after transplantation in expanded criteria donor recipients.
    Mots-clés : Acute Disease Adolescent Adult Aged Cyclosporine/adverse effects/*pharmacology Dose-Response Relationship, Drug Graft Rejection Humans Immunosuppressive Agents/pharmacology Kidney/physiopathology *Kidney Transplantation Middle Aged Pilot Projects Sirolimus/adverse effects/*pharmacology *Tissue Donors.

  • Efficace, F, Innominato, PF, Bjarnason, G, Coens, C, Humblet, Y, Tumolo, S, Genet, D, Tampellini, M, Bottomley, A, Garufi, C, Focan, C, Giacchetti, S, Lévi, F, Research, CG of the EO for & Cancer, T of 2008, « Validation of patient's self-reported social functioning as an independent prognostic factor for survival in metastatic colorectal cancer patients: results of an international study by the Chronotherapy Group of the European Organisation for Research and Treatment of Cancer », J Clin Oncol, vol. 26, no. 12, p. 2020-6, viewed sans date, .
    Résumé : PURPOSE: A recent study identified a prognostic model for survival in metastatic colorectal cancer patients which included WBC count, alkaline phosphatase (AP), number of metastatic sites, and patients' self-reported social functioning. The aim of this research is to validate this model on data from an independent sample. PATIENTS AND METHODS: This validation study is based on a prospective randomized controlled trial in patients with metastatic colorectal cancer conducted by the European Organisation for Research and Treatment of Cancer (EORTC) Chronotherapy Group. Overall, 564 patients in 10 countries were enrolled. For the purpose of this independent validation, patients with health-related quality of life (HRQOL) baseline data were analyzed. HRQOL was assessed using the EORTC Quality of Life Questionnaire C30 (QLQ-C30). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. RESULTS: The previous model with an additional adjustment, by stratification for sex, was replicated and its parameters were confirmed to independently predict survival: WBC count with an hazard ratio (HR) of 1.31 (95% CI, 1.021 to 1.698; P = .034); AP with an HR of 1.53 (95% CI, 1.188 to 1.979; P = .001); number of sites involved with an HR of 1.90 (95% CI, 1.531 to 2.364; P < .0001); and patients' self-reported social functioning with an HR of 0.94 (95% CI, 0.905 to 0.976; P = .001). The latter translates into a 6% increase in the likelihood of an earlier death for every 10-point decrease in the social functioning scale of the EORTC QLQ-C30. CONCLUSION: This study provides confirmatory evidence of the independent prognostic value of patients' self-reported social functioning in patients with advanced colorectal cancer.
    Note Note
    <p>18421055</p>
    Note Note
    <p>18421055</p>
    Note Note
    <p>18421055</p>
    Note Note
    <p>18421055</p>


  • Espenel, C, Margeat, E, Dosset, P, Arduise, C, Le Grimellec, C, Royer, CA, Boucheix, C, Rubinstein, E & Milhiet, P-E 2008, « Single-molecule analysis of CD9 dynamics and partitioning reveals multiple modes of interaction in the tetraspanin web », J Cell Biol, vol. 182, no. 4, p. 765-76, viewed sans date, .
    Résumé : Tetraspanins regulate cell migration, sperm-egg fusion, and viral infection. Through interactions with one another and other cell surface proteins, tetraspanins form a network of molecular interactions called the tetraspanin web. In this study, we use single-molecule fluorescence microscopy to dissect dynamics and partitioning of the tetraspanin CD9. We show that lateral mobility of CD9 in the plasma membrane is regulated by at least two modes of interaction that each exhibit specific dynamics. The majority of CD9 molecules display Brownian behavior but can be transiently confined to an interaction platform that is in permanent exchange with the rest of the membrane. These platforms, which are enriched in CD9 and its binding partners, are constant in shape and localization. Two CD9 molecules undergoing Brownian trajectories can also codiffuse, revealing extra platform interactions. CD9 mobility and partitioning are both dependent on its palmitoylation and plasma membrane cholesterol. Our data show the high dynamic of interactions in the tetraspanin web and further indicate that the tetraspanin web is distinct from raft microdomains.
    Note Note
    <p>18710926</p>
    Note Note
    <p>18710926</p>
    Note Note
    <p>18710926</p>
    Note Note
    <p>18710926</p>
  • Fabien, N, Olsson, NO, Goetz, J, Johanet, C, Escande, A, Bardin, N, Sanmarco, M, Andre, C, Chevailler, A, Humbel, RL, Chretien, P, Monier, JC, Fortenfant, F, Oksman, F, Taillefer, MF & Sibilia, J 2008, « Prevalence of autoantibodies to cyclic citrullinated peptide in patients with rheumatic diseases other than rheumatoid arthritis: a French multicenter study », Clin Rev Allergy Immunol, vol. 34, no. 1, p. 40-4.
    Résumé : Our objective was to evaluate the prevalence of autoantibodies to cyclic citrullinated peptides (anti-CCP aAbs) in a cohort of patients with a variety of inflammatory or non-inflammatory rheumatic diseases other than rheumatoid arthritis (RA). Six hundred and nine serum samples were tested for anti-CCP aAbs and for rheumatoid factor (RF) using enzyme-linked immunosorbent assays and immunonephelometry. The prevalence of anti-CCP aAbs and RF reached 10% and 25%, respectively, using the positive cutoff value suggested by the manufacturers. Using a higher cutoff value (50 U/ml) for both aAbs, the prevalence was lower with 6% and 16%, respectively. The specificity of both markers for RA thus reached 94% and 84%, respectively. Anti-CCP aAbs were found to be elevated in inflammatory and also in non-inflammatory rheumatic diseases in the same proportion. Clinical data obtained for 36 positive patients showed that 17% developed RA within 5 years. In conclusion, anti-CCP aAbs are clearly more specific than RF for RA. Follow-up of anti-CCP aAbs-positive patients with inflammatory or non-inflammatory rheumatic diseases other than RA could be important considering the predictive value of these aAbs for the development of RA.
    Mots-clés : Aged Arthritis, Cyclic/ immunology Predictive Value of Tests Prevalence Rheumatic Diseases/diagnosis/epidemiology/immunology Rheumatoid Factor/blood Sensitivity and Specificity, Rheumatoid/diagnosis/epidemiology/immunology Autoantibodies/ blood Autoimmune Diseases/diagnosis/epidemiology/immunology Enzyme-Linked Immunosorbent Assay Female France/epidemiology Humans Male Middle Aged Peptides.

  • Fabre, S, Carrette, F, Chen, J, Lang, V, Semichon, M, Denoyelle, C, Lazar, V, Cagnard, N, Dubart-Kupperschmitt, A, Mangeney, M, Fruman, DA & Bismuth, G 2008, « FOXO1 regulates L-Selectin and a network of human T cell homing molecules downstream of phosphatidylinositol 3-kinase », J Immunol, vol. 181, no. 5, p. 2980-9, viewed sans date, .
    Résumé : In T cells, the PI3K pathway promotes proliferation and survival induced by Ag or growth factors, in part by inactivating the FOXO transcription factor 1. We now report that FOXO1 controls the expression of L-selectin, an essential homing molecule, in human T lymphocytes. This control is already operational in unprimed T cells and involves a transcriptional regulation process that requires the FOXO1 DNA-binding domain. Using transcriptional profiling, we demonstrate that FOXO1 also increases transcripts of EDG1 and EDG6, two sphingosine-1-phosphate receptors that regulate lymphocyte trafficking. Additionally, FOXO1 binds the promoter of the cell quiescence and homing regulator Krüppel-like factor 2 and regulates its expression. Together, these results reveal a new function of FOXO1 in the immune system and suggest that PI3K controls a coordinated network of transcription factors regulating both cell quiescence and homing of human T lymphocytes.
    Note Note
    <p>18713968</p>
    Note Note
    <p>18713968</p>
    Note Note
    <p>18713968</p>
    Note Note
    <p>18713968</p>
    Note Note
    <p>18713968</p>

  • Fakhouri, F, Jablonski, M, Lepercq, J, Blouin, J, Benachi, A, Hourmant, M, Pirson, Y, Durrbach, A, Grunfeld, JP, Knebelmann, B & Fremeaux-Bacchi, V 2008, « Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome », Blood, vol. 112, no. 12, p. 4542-5, viewed sans date, .
    Résumé : The HELLP syndrome, defined by the existence of hemolysis, elevated liver enzymes, and low platelet count, is a serious complication of pregnancy-related hypertensive disorders and shares several clinical and biologic features with thrombotic microangiopathy (TMA). Several recent studies have clearly shown that an abnormal control of the complement alternative pathway is a major risk for the occurrence of a peculiar type of TMA involving mainly the kidney. The aim of this study was to screen for complement abnormalities in 11 patients with HELLP syndrome and renal involvement. We identified 4 patients with a mutation in one of the genes coding for proteins involved in the regulation of the alternative pathway of complement. Our results suggest that an abnormal control of the complement alternative pathway is a risk factor for the occurrence of HELLP syndrome.
    Mots-clés : Adult Antigens, CD46/*genetics Complement Factor H/*genetics Complement System Proteins/genetics DNA Mutational Analysis Female Fibrinogen/*genetics Genetic Predisposition to Disease Gestational Age HELLP Syndrome/*genetics Humans *Mutation, Missense Pregnancy Risk Factors Young Adult.
  • Faresse, N, Colland, F, Ferrand, N, Prunier, C, Bourgeade, MF & Atfi, A 2008, « Identification of PCTA, a TGIF antagonist that promotes PML function in TGF-beta signalling », EMBO J, vol. 27, no. 13, p. 1804-15.
    Résumé : The TGIF homoeodomain protein functions as an important negative regulator in the TGF-beta signalling pathway. The inhibitory function of TGIF is executed in part through its ability to sequester the tumour suppressor cytoplasmic promyelocytic leukaemia (cPML) in the nucleus, thereby preventing the phosphorylation of Smad2 by the activated TGF-beta type I receptor. Here, we report on the identification of PCTA (PML competitor for TGIF association), a TGIF antagonist that promotes TGF-beta-induced transcriptional and cytostatic responses. We provide evidence that PCTA functions in TGF-beta signalling by relieving the suppression of Smad2 phosphorylation by TGIF. Furthermore, we demonstrate that PCTA selectively competes with cPML for TGIF association, resulting in the accumulation of cPML in the cytoplasm, where it associates with SARA and coordinates the access of Smad2 for phosphorylation by the activated TGF-beta type I receptor. Thus, our findings on the mode of action of PCTA provide new and important insights into the molecular mechanism underlying the antagonistic interplay between TGIF and cPML in the TGF-beta signalling network.
    Mots-clés : Animals Carrier Proteins/ metabolism Cell Line DNA.
    Note Note
    <p>2486419</p>
    Note Note
    <p>2486419</p>
    Note Note
    <p>2486419</p>
    Note Note
    <p>2486419</p>
  • Faria, LC, Gigou, M, Roque-Afonso, AM, Sebagh, M, Roche, B, Fallot, G, Ferrari, TC, Guettier, C, Dussaix, E, Castaing, D, Brechot, C & Samuel, D 2008, « Hepatocellular carcinoma is associated with an increased risk of hepatitis B virus recurrence after liver transplantation », Gastroenterology, vol. 134, no. 7, p. 1890-9; quiz 2155.
    Résumé : BACKGROUND & AIMS: Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is significantly reduced by prophylaxis with hyperimmune antibody to hepatitis B surface antigen (anti-HBs) globulins (HBIG) and antiviral drugs. The role of hepatocellular carcinoma (HCC) in HBV recurrence remains unclear. We investigated the association between HCC pre-OLT and HBV recurrence post-OLT. METHODS: We studied 99 hepatitis B surface antigen-positive patients who underwent OLT for cirrhosis. The median follow-up period was 43 months. All patients received HBIG, and 51 also received lamivudine and/or adefovir. Of these 99 patients, 31 had HCC before OLT. Total HBV DNA and covalently closed circular (ccc)-DNA were measured in tumor and nontumor tissues from the explanted livers of 16 of these 31 HCC patients and, also, in a context of tumor recurrence, in 3 patients who developed HBV/HCC recurrence. RESULTS: Fourteen patients (14.1%) developed HBV recurrence within a median period of 15 months post-OLT. HCC at OLT, a pre-OLT HBV DNA viral load > or = 100,000 copies/mL, and HBIG monoprophylaxis were independently associated with HBV recurrence post-OLT. Eleven out of the 31 patients with HCC at OLT presented with HBV recurrence and 3 out of the 68 patients without HCC had HBV recurrence (P < .0001). HBV recurrence was more frequent in patients who developed HCC recurrence (7/8 patients, 87.5%) than in those who did not (4/23 patients, 17.4%) (P < .0001). In the 16 explanted livers, cccDNA was detectable in HCC cells in 11 and in nontumor cells in 12. cccDNA was detected in a context of HCC recurrence in 2 of the 3 patients tested who developed HBV/HCC recurrence. CONCLUSIONS: The associations of HCC pre-OLT, and HCC recurrence with HBV recurrence post-OLT, and the detection of HBV DNA and cccDNA in HCC suggest that HBV replication in tumor cells may contribute to HBV recurrence post-OLT.
    Mots-clés : Adenine/analogs & derivatives/therapeutic use Adolescent Adult Aged Antiviral Agents/therapeutic use Carcinoma, Circular/analysis DNA, DNA Time Factors Treatment Outcome Viral Load Virus Replication, Hepatocellular/drug therapy/surgery/ virology DNA.
  • Faria, LC, Ichai, P, Saliba, F, Benhamida, S, Antoun, F, Castaing, D & Samuel, D 2008, « Pneumocystis pneumonia: an opportunistic infection occurring in patients with severe alcoholic hepatitis », Eur J Gastroenterol Hepatol, vol. 20, no. 1, p. 26-8.
    Résumé : BACKGROUND: Pneumocystis pneumonia usually occurs in immunosuppressed individuals, generally those with underlying T-lymphocyte disorders. Patients with alcoholic liver disease display immune responses consistent with those observed in immunocompromised individuals and alcohol is a potent immunosuppressor. Long-term corticotherapy represents a risk for Pneumocystis pneumonia. PATIENTS AND METHODS: From 1998 to 2006, seven patients hospitalized in our Liver Intensive Care Unit for severe alcoholic hepatitis had a diagnosis of Pneumocystis pneumonia. All had liver biopsies revealing histologic evidence of alcoholic hepatitis. The diagnosis of pneumocystosis was established by the detection in the bronchoalveolar lavage of the characteristic pathogen, with Giemsa staining or immunofluorescence assay, in addition to the presence of clinical and radiological signs of pneumopathy. RESULTS: All seven patients had a Maddrey score higher than 32. Six patients received corticotherapy for alcoholic hepatitis treatment before the diagnosis of Pneumocystis pneumonia. All patients developed acute respiratory distress syndrome and needed mechanical ventilation. In three patients, the test for cytomegalovirus was also positive in the bronchoalveolar lavage. All seven patients died in spite of receiving appropriate treatment. CONCLUSION: Chronic alcoholism and alcoholic liver disease are both associated with an important degree of immunosuppression. Corticotherapy, even for a short period, may aggravate this immunodeficiency and predispose these patients to severe opportunistic infections.
    Mots-clés : Adrenal Cortex Hormones/adverse effects Anti-Infective Agents/therapeutic use Cytomegalovirus Infections/ complications/drug therapy/immunology Female Hepatitis, Alcoholic/ complications/drug therapy/immunology Humans Immunocompromised Host Male Middle Aged Opportunistic Infections/ etiology/immunology Pneumonia, Pneumocystis/drug therapy/ etiology/immunology.

  • Ferlay, J, Randi, G, Bosetti, C, Levi, F, Negri, E, Boyle, P & La Vecchia, C 2008, « Declining mortality from bladder cancer in Europe », BJU Int, vol. 101, no. 1, p. 11-9, viewed sans date, .
    Résumé : OBJECTIVE: To update trends in bladder cancer mortality in 32 European countries and the European Union (EU) as a whole, as mortality from bladder cancer has been declining in most of Western Europe since the early 1990 s, but it has still been increasing in several central and eastern European countries up to the mid 1990 s. METHODS: We used data from the World Health Organization (WHO) database over the period 1970-2004. Significant changes in mortality rates were identified using join-point regression analysis. RESULTS: In the EU overall (27 countries), bladder cancer mortality rates (age-standardized, world standard population) were stable up to the early 1990 s at approximately 7/100,000 men and 1.5/100,000 women, and declined thereafter by approximately 16% in men and 12% in women, to reach values of 6 and 1.3/100,000, respectively, in the early years of the present decade. Over recent years, most countries showed decreasing trends, except Croatia and Poland in both sexes, Romania in men and Denmark in women. Truncated rates at age 35-64 years were lower in both sexes and trends for men were more favourable, with an overall decrease by >21% during the last decade. Join point regression analysis indicates that, for most countries, the trends were more favourable over recent calendar periods. CONCLUSION: The favourable trends in men are partly or largely due to the recent declines in the prevalence of smoking in European men, together with reduced occupational exposure to occupational carcinogens. The decreases in women are more difficult to explain. Better control of urinary tract infections has probably played a role, while the role of diet and other potential urinary tract carcinogens remains undefined.
    Note Note
    <p>17971176</p>
    Note Note
    <p>17971176</p>
    Note Note
    <p>17971176</p>
    Note Note
    <p>17971176</p>
  • Ferrand, JF, Cenee, S, Laurent-Puig, P, Loriot, MA, Trinchet, JC, Degos, F, Bronovicky, JP, Pelletier, G & Stucker, I 2008, « Hepatocellular carcinoma and occupation in men: a case-control study », J Occup Environ Med, vol. 50, no. 2, p. 212-20.
    Résumé : OBJECTIVE: The principal objective of this work was to evaluate the association between the risk of hepatocellular carcinoma (HCC) and various occupations. METHODS: This case-control study, conducted during 2000 to 2003 in four French hospitals, included 125 men younger than 75 years with incident HCC and 142 men as control subjects. RESULTS: An association with HCC was observed for machinery fitters and machine assemblers (odds ratio [OR] = 4.4 [1.0-19.0], eight exposed cases and three exposed controls). A higher percentage of cases than controls were metal machinists (OR = 2.2 [0.8-5.8], 14 exposed cases and 10 exposed controls), although the difference was not statistically significant. These associations were strongest for subjects with duration of employment greater than 20 years. CONCLUSIONS: Our findings suggest an association between metal machining jobs and hepatocellular carcinoma, although we cannot rule out the possibility that it was observed by chance.
    Mots-clés : Adult Aged Carcinoma.

  • Filali, M, Hesters, L, Fanchin, R, Tachdjian, G, Frydman, R & Frydman, N 2008, « Retrospective comparison of two media for invitro maturation of oocytes », Reprod Biomed Online, vol. 16, no. 2, p. 250-6, viewed sans date, .
    Résumé : In-vitro maturation of oocytes (IVM) is a new IVF technology developed in order to avoid iatrogenic complications of standard IVF treatments. This technique is particularly useful in patients suffering from polycystic ovary syndrome (PCOS) who are concerned with the risk of ovarian hyperstimulation syndrome. This technique is nowadays routinely practised in many international centres. However, the efficiency of this technique needs to be improved for a better support of maturation conditions to maximize oocyte developmental competence. In order to improve IVM results, the efficiency of two IVM media was retrospectively compared. Ninety-three PCOS candidates undergoing their first IVM cycle were included in this study, and IVM was conducted with TCM-199 or IVM-Medicult medium. This is the first study comparing two maturation media. Both media resulted in the same results concerning total oocyte maturation, fertilization, early embryo development and pregnancy rates.
    Note Note
    <p>18284882</p>
    Note Note
    <p>18284882</p>
    Note Note
    <p>18284882</p>
    Note Note
    <p>18284882</p>

  • Freundt, EC, Bidere, N & Lenardo, MJ 2008, « A different TIPE of immune homeostasis », Cell, vol. 133, no. 3, p. 401-2, viewed sans date, .
    Résumé : Proteins with death effector domains (DED) are key signal transducers involved in cell death and inflammation. In this issue of Cell, Sun et al. (2008) describe TIPE2, a DED protein that negatively regulates both T cell receptor and Toll-like receptor signaling. These findings reveal a new element critical to the maintenance of homeostasis in both the adaptive and innate immune systems.
    Mots-clés : Animals Caspases/metabolism Cell Death *Homeostasis Humans *Immunity, Innate Intracellular Signaling Peptides and Proteins/chemistry/*immunology Mice Protein Structure, Tertiary Signal Transduction Toll-Like Receptors/immunology.
    Note Note
    <p>2750003</p>
    Note Note
    <p>2750003</p>
    Note Note
    <p>2750003</p>
    Note Note
    <p>2750003</p>

  • Frydman, N, Prisant, N, Hesters, L, Frydman, R, Tachdjian, G, Cohen-Bacrie, P & Fanchin, R 2008, « Adequate ovarian follicular status does not prevent the decrease in pregnancy rates associated with high sperm DNA fragmentation », Fertil Steril, vol. 89, no. 1, p. 92-7, viewed sans date, .
    Résumé : OBJECTIVE: Potential reparation of sperm DNA fragmentation in the oocyte may disturb any relationship between DNA-damaged sperm and the implantation ability of resulting embryos. To rule out this factor, we analyzed the consequences of sperm DNA fragmentation on IVF-ET outcome in women with healthy ovarian function. DESIGN: Prospective study. SETTING: Teaching hospital, France. PATIENT(S): All 117 women were <38 years old, who combined normal serum day-3 FSH and inhibin B levels with an adequate response to controlled ovarian hyperstimulation. INTERVENTION(S): The DNA fragmentation rate was determined in the raw sperm used for conventional IVF by flow cytometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Cycles were sorted into two groups according to whether DNA fragmentation exceeded (high fragmentation [HF], n = 52) or did not exceed (low fragmentation [LF], n = 65) the 50th percentile of values (35%). MAIN OUTCOME MEASURE(S): D2 embryo quality and implantation and ongoing pregnancy rates. RESULT(S): Patients' characteristics, raw semen parameters, fertilization rates, and embryology data were similar in HF and LF groups. Clinical (37.5% vs. 62.5%) and ongoing (23.5% vs. 57.8%) pregnancy rates per ET and implantation rates (24.5% vs. 42.4%) were lower in the HF group than in the LF group. CONCLUSION(S): High sperm DNA fragmentation spares fertilization and top embryo morphology rates but is associated with decreased IVF-ET outcome.
    Note Note
    <p>17482180</p>
    Note Note
    <p>17482180</p>
    Note Note
    <p>17482180</p>
    Note Note
    <p>17482180</p>

  • Gauduchon, J, Seguin, A, Marsaud, V, Clay, D, Renoir, J-M & Sola, B 2008, « Pure antiestrogen-induced G1-arrest in myeloma cells results from the reduced kinase activity of cyclin D3/CDK6 complexes whereas apoptosis is mediated by endoplasmic reticulum-dependent caspases », International Journal of Cancer. Journal International Du Cancer, vol. 122, no. 9, p. 2130-2141.
    Résumé : Multiple myeloma (MM) is a malignancy characterized by the accumulation of tumoral plasma cells in bone marrow. This disease remains incurable and the development of new therapeutic strategies is urgently required. We have studied the effects of 2 selective estrogen receptor disrupters (SERDs), RU 58668 (RU) and ICI 182,780 (ICI) or pure antiestrogens (AEs) on MM cell lines. Both compounds have antimyeloma activity through either cell cycle arrest or induction of apoptosis. To analyze the molecular mechanisms of SERD action, we choose 2 differently responding cell lines as models. In LP-1 cells, RU blocked cell cycle at the G1 phase. RU treatment induced a rapid decrease of c-Myc, an upregulation of p27(Kip1), and the subsequent decreased activity of cyclin-dependent kinase, CDK6 and associated cyclin D3, impairing the inactivation of the retinoblastoma protein (pRb). In RPMI 8226 cells, RU induced apoptosis by recruiting endoplasmic reticulum- as well as mitochondria-associated caspases. Moreover, RU interfered with the NF-kappaB survival pathway, often deregulated in MM malignancy. Antimyeloma activities were observed in dexamethasone (Dex)- and RU-resistant cells when RU was combined with bortezomib; Dex and bortezomib being frequently used in MM therapy. RU induced the death of CD138+ cells purified from MM patients but not CD19+ normal cells obtained from tonsils. Therefore, RU mediates the inhibition of survival, the activation of apoptosis and finally potentiates anticancer drug. Those combinatory effects provide a basis for the potential use of pure AEs in MM treatment.
    Mots-clés : Antineoplastic Agents, Hormonal, Apoptosis, Blotting, Western, Boronic Acids, Caspases, Cell Proliferation, Colorimetry, Cyclin D3, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinase Inhibitor p27, Cyclins, Drug Resistance, Neoplasm, Drug Synergism, Endoplasmic Reticulum, Estradiol, Estrogen Receptor Modulators, Flow Cytometry, G1 Phase, Humans, Immunoprecipitation, Mitochondria, Multiple Myeloma, NF-kappa B, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Pyrazines, Selective Estrogen Receptor Modulators, Signal Transduction, Tumor Cells, Cultured.

  • Gigarel, N, Frydman, N, Burlet, P, Kerbrat, V, Tachdjian, G, Fanchin, R, Antignac, C, Frydman, R, Munnich, A & Steffann, J 2008, « Preimplantation genetic diagnosis for autosomal recessive polycystic kidney disease », Reprod Biomed Online, vol. 16, no. 1, p. 152-8, viewed sans date, .
    Résumé : Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary renal cystic diseases, and is caused by mutations in the PKHD1 gene. Due to the poor prognosis, there is a strong demand for prenatal diagnosis. Preimplantation genetic diagnosis (PGD) represents an alternative because it avoids the physical and emotional trauma of a pregnancy termination in the case of an affected fetus. A standardized single-cell diagnostic procedure was developed, based on haplotype analysis, enabling PGD to be offered to couples at risk of transmitting ARPKD. Six linked markers within (D6S1714 and D6S243), or in close proximity to (D6S272, D6S436, KIAA0057, D6S1662) the PKHD1 gene were tested by multiplex nested-polymerase chain reaction (PCR), using a Qiagen multiplex PCR kit. PCR analyses were carried out on 50 single lymphocytes. The amplification rate was excellent (100%), with an allele drop-out (ADO) rate ranging from 0 to 8%. Five PGD cycles were performed and 23 embryos were biopsied and analysed using this test. Transferable embryos were obtained in 4 cycles, resulting in two pregnancies and the birth of a healthy boy. This standardized diagnostic procedure allowed the detection of recombination, contamination, and ADO events, providing high assay accuracy with wide applicability.
    Note Note
    <p>18252063</p>
    Note Note
    <p>18252063</p>
    Note Note
    <p>18252063</p>
    Note Note
    <p>18252063</p>

  • Giuliani, M, Giron-Michel, J, Negrini, S, Vacca, P, Durali, D, Caignard, A, Le Bousse-Kerdiles, C, Chouaib, S, Devocelle, A, Bahri, R, Durrbach, A, Taoufik, Y, Ferrini, S, Croce, M, Mingari, MC, Moretta, L & Azzarone, B 2008, « Generation of a novel regulatory NK cell subset from peripheral blood CD34+ progenitors promoted by membrane-bound IL-15 », PLoS One, vol. 3, no. 5, p. e2241, viewed sans date, .
    Résumé : BACKGROUND: NK cells have been long time considered as cytotoxic lymphocytes competent in killing virus-infected cells and tumors. However, NK cells may also play essential immuno-regulatory functions. In this context, the real existence of a defined NK subset with negative regulatory properties has been hypothesized but never clearly demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we show the in vitro generation from human peripheral blood haematopoietic progenitors (PB-HP), of a novel subset of non-cytolytic NK cells displaying a mature phenotype and remarkable immuno-regulatory functions (NK-ireg). The main functional hallmark of these NK-ireg cells is represented by the surface expression/release of HLA-G, a major immunosuppressive molecule. In addition, NK-ireg cells secrete two powerful immuno-regulatory factors: IL-10 and IL-21. Through these factors, NK-ireg cells act as effectors of the down-regulation of the immune response: reconverting mature myeloid DC (mDC) into immature/tolerogenic DC, blocking cytolytic functions on conventional NK cells and inducing HLA-G membrane expression on PB-derived monocytes. The generation of "NK-ireg" cells is obtained, by default, in culture conditions favouring cell-to-cell contacts, and it is strictly dependent on reciprocal trans-presentation of membrane-bound IL-15 forms constitutively and selectively expressed by human CD34(+) PB-HP. Finally, a small subset of NKp46(+) HLA-G(+) IL-10(+) is detected within freshly isolated decidual NK cells, suggesting that these cells could represent an in vivo counterpart of the NK-ireg cells. CONCLUSIONS/SIGNIFICANCE: In conclusion, NK-ireg cells represent a novel truly differentiated non-cytolytic NK subset with a self-sustainable phenotype (CD56(+) CD16(+) NKp30(+) NKp44(+) NKp46(+) CD94(+) CD69(+) CCR7(+)) generated from specific pSTAT6(+) GATA3(+) precursors. NK-ireg cells could be employed to develop new immuno-suppressive strategies in autoimmune diseases, transplant rejection or graft versus host diseases. In addition, NK-ireg cells can be easily derived from peripheral blood of the patients and could constitute an autologous biotherapic tool to be used combined or in alternative to other immuno-regulatory cells.
    Mots-clés : Antigens, CD34/*immunology Cell Line, Natural/*classification *Lymphocyte Subsets Stem Cells/*cytology/immunology, Tumor Cell Membrane/metabolism Humans Interleukin-15/metabolism/*physiology Killer Cells.
    Note Note
    <p>2376096</p>
    Note Note
    <p>2376096</p>
    Note Note
    <p>2376096</p>
    Note Note
    <p>2376096</p>

  • Groheux, D, Moretti, J-L, Baillet, G, Espie, M, Giacchetti, S, Hindie, E, Hennequin, C, Vilcoq, J-R, Cuvier, C, Toubert, M-E, Filmont, J-E, Sarandi, F & Misset, J-L 2008, « Effect of (18)F-FDG PET/CT imaging in patients with clinical Stage II and III breast cancer », Int J Radiat Oncol Biol Phys, vol. 71, no. 3, p. 695-704, viewed sans date, .
    Résumé : PURPOSE: To investigate the potential effect of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. METHODS AND MATERIALS: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. RESULTS: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. CONCLUSIONS: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.
    Note Note
    <p>18436392</p>
    Note Note
    <p>18436392</p>
    Note Note
    <p>18436392</p>
    Note Note
    <p>18436392</p>

  • Grosjean, T, Baida, F, Adam, R, Guillet, J-P, Billot, L, Nouvel, P, Torres, J, Penarier, A, Charraut, D & Chusseau, L 2008, « Linear to radial polarization conversion in the THz domain using a passive system », Opt Express, vol. 16, no. 23, p. 18895-909, viewed sans date, .
    Résumé : This paper addresses a passive system capable of converting a linearly polarized THz beam into a radially polarized one. This is obtained by extending to THz frequencies and waveguides an already proven concept based on mode selection in optical fibers. The approach is validated at 0.1 THz owing to the realization of a prototype involving a circular waveguide and two tapers that exhibits a radially polarized beam at its output. By a simple homothetic size reduction, the system can be easily adapted to higher THz frequencies.
    Note Note
    <p>19581981</p>
    Note Note
    <p>19581981</p>
    Note Note
    <p>19581981</p>
    Note Note
    <p>19581981</p>

  • Guillaumond, F, Lacoche, S, Dulong, S, Grechez-Cassiau, A, Filipski, E, Li, X-M, Lévi, F, Berra, E, Delaunay, F & Teboul, M 2008, « Altered Stra13 and Dec2 circadian gene expression in hypoxic cells », Biochem Biophys Res Commun, vol. 369, no. 4, p. 1184-9, viewed sans date, .
    Résumé : The circadian system regulates rhythmically most of the mammalian physiology in synchrony with the environmental light/dark cycle. Alteration of circadian clock gene expression has been associated with tumour progression but the molecular links between the two mechanisms remain poorly defined. Here we show that Stra13 and Dec2, two circadian transcriptional regulators which play a crucial role in cell proliferation and apoptosis are overexpressed and no longer rhythmic in serum shocked fibroblasts treated with CoCl(2,) a substitute of hypoxia. This effect is associated with a loss of circadian expression of the clock genes Rev-erbalpha and Bmal1, and the clock-controlled gene Dbp. Consistently, cotransfection assays demonstrate that STRA13 and DEC2 both antagonize CLOCK:BMAL1 dependent transactivation of the Rev-erbalpha and Dbp promoters. Using a transplantable osteosarcoma tumour model, we show that hypoxia is associated with altered circadian expression of Stra13, Dec2, Rev-erbalpha, Bmal1 and Dbp in vivo. These observations collectively support the notion that overexpression of Stra13 and Dec2 links hypoxia signalling to altered circadian clock gene expression.
    Note Note
    <p>18342625</p>
    Note Note
    <p>18342625</p>
    Note Note
    <p>18342625</p>
    Note Note
    <p>18342625</p>

  • Guillery, O, Malka, F, Landes, T, Guillou, E, Blackstone, C, Lombes, A, Belenguer, P, Arnoult, D & Rojo, M 2008, « Metalloprotease-mediated OPA1 processing is modulated by the mitochondrial membrane potential », Biol Cell, vol. 100, no. 5, p. 315-25, viewed sans date, .
    Résumé : BACKGROUND INFORMATION: Human OPA1 (optic atrophy type 1) is a dynamin-related protein of the mitochondrial IMS (intermembrane space) involved in membrane fusion and remodelling. Similarly to its yeast orthologue Mgm1p that exists in two isoforms generated by the serine protease Pcp1p/Rbd1p, OPA1 exists in various isoforms generated by alternative splicing and processing. In the present paper, we focus on protease processing of OPA1. RESULTS: We find that various mammalian cell types display a similar pattern of OPA1 isoforms [two L-OPA1 (long isoforms of OPA1) and three S-OPA1 (short isoforms of OPA1)] and that loss of the inner membrane potential, but not inhibition of oxidative phosphorylation or glycolysis, induces rapid and complete processing of L-OPA1 to S-OPA1. In isolated mitochondria, OPA1 processing was inhibited by heavy-metal chelators, pointing to processing by a mitochondrial metalloprotease. The pattern of OPA1 isoforms and its processing kinetics were normal in mitochondria devoid of the serine protease PARL (presenilins-associated rhomboid-like protein) - the human orthologue of Pcp1/Rbd1 - and in cells from patients carrying homozygous mutations in SPG7 (spastic paraplegia type 7), a gene encoding the matrix-oriented metalloprotease paraplegin. In contrast, OPA1 processing kinetics were delayed upon knock-down of YME1L (human yme1-like protein), an IMS-oriented metalloprotease. OPA1 processing was also stimulated during apoptosis, but inhibition of this processing did not affect apoptotic release of OPA1 and cytochrome c. Finally, we show that all OPA1 isoforms interact with Mfn1 (mitofusin 1) and Mfn2 and that these interactions are not affected by dissipation of DeltaPsim (inner mitochondrial membrane potential) or OPA1 processing. CONCLUSIONS: Metalloprotease-mediated processing of OPA1 is modulated by the inner membrane potential and is likely to be mediated by the YME1L protease.
    Mots-clés : GTP Phosphohydrolases/*metabolism HeLa Cells Humans Membrane Potential, Post-Translational RNA Interference/physiology Reverse Transcriptase Polymerase Chain Reaction.

  • Gyan, E, Frisan, E, Beyne-Rauzy, O, Deschemin, J-C, Pierre-Eugene, C, Randriamampita, C, Dubart-Kupperschmitt, A, Garrido, C, Dreyfus, F, Mayeux, P, Lacombe, C, Solary, E & Fontenay, M 2008, « Spontaneous and Fas-induced apoptosis of low-grade MDS erythroid precursors involves the endoplasmic reticulum », Leukemia, vol. 22, no. 10, p. 1864-73, viewed sans date, .
    Résumé : Spontaneous apoptosis of bone marrow erythroid precursors accounts for the anemia that characterizes most low-grade myelodysplastic syndromes (MDS). We have shown that death of these precursors involved the Fas-dependent activation of caspase-8. To explore the pathway leading from caspase-8 activation to apoptosis, we transduced MDS bone marrow CD34(+) cells with a lentivirus encoding wild-type (WT) or endoplasmic reticulum (ER)-targeted Bcl-2 protein before inducing their erythroid differentiation. Both WT-Bcl-2 and ER-targeted Bcl-2 prevented spontaneous and Fas-dependent apoptosis in MDS erythroid precursors. ER-targeted Bcl-2 inhibited mitochondrial membrane depolarization and cytochrome c release in MDS erythroid precursors undergoing apoptosis, indicating a role for the ER in the death pathway, upstream of the mitochondria. MDS erythroid precursors demonstrated elevated ER Ca(2+) stores and these stores remained unaffected by ER-targeted Bcl-2. The ER-associated protein Bcl-2-associated protein (BAP) 31 was cleaved by caspase-8 in MDS erythroid precursors undergoing apoptosis. The protective effect of ER-targeted Bcl-2 toward spontaneous and Fas-induced apoptosis correlated with inhibition of BAP31 cleavage. A protective effect of erythropoietin against Fas-induced BAP31 cleavage and apoptosis was observed. We propose that apoptosis of MDS erythroid precursors involves the ER, downstream of Fas and upstream of the mitochondria, through the cleavage of the ER-associated BAP31 protein.
    Note Note
    <p>18615109</p>
    Note Note
    <p>18615109</p>
    Note Note
    <p>18615109</p>
    Note Note
    <p>18615109</p>
    Note Note
    <p>18615109</p>

  • Haond, C, Drouet, M, Derdouch, S, Bonnet, M-L, Norol, F, Mayol, J-F, Vainchenker, W, LeGrand, R, Turhan, AG & Herodin, F 2008, « In vitro and in vivo evaluation of the haematopoietic potential of skeletal muscle in a non-human primate model », Bone Marrow Transplant, vol. 41, no. 6, p. 579-84, viewed sans date, .
    Résumé : This study was aimed at evaluating the in vitro and in vivo haematopoietic potential in macaque skeletal muscle cells. Biopsy samples showed the presence of CD34(+) (7.6%), CD90(+) (8.4%), CD117(+), CD31(+), side population (SP) cells (7-10%) and a low number of CD45(+) cells. In clonogenic and long-term culture-initiating cell assays, no haematopoietic potential could be detected in either total mononuclear cells or SP cells. Regarding in vivo studies, two animals were transplanted with unfractionated fresh muscle cells after lethal irradiation. Both animals died early after transplant without any evidence of haematopoietic reconstitution. In two other monkeys, harvested muscle cells were frozen and secondarily marked using a green fluorescent protein (GFP)-lentiviral vector. After sublethal irradiation, both animals were transplanted with GFP-expressing muscle cells followed by a bone marrow rescue. Both animals had haematopoietic reconstitution at days 22 and 25, but no GFP-expressing haematopoietic cells could be detected by flow cytometry, either in the blood or in clonogenic cells from marrow aspirates. Using PCR assays, GFP(+) cells were detected in a single marrow sample of one animal at 41 days after transplantation. These results strongly suggest that as opposed to murine muscle, the non-human primate skeletal muscle does not harbour cells with a straightforward haematopoietic potential.
    Note Note
    <p>18037936</p>
    Note Note
    <p>18037936</p>
    Note Note
    <p>18037936</p>
    Note Note
    <p>18037936</p>


  • Harduin-Lepers, A, Petit, D, Mollicone, R, Delannoy, P, Petit, J-M & Oriol, R 2008, « Evolutionary history of the alpha2,8-sialyltransferase (ST8Sia) gene family: tandem duplications in early deuterostomes explain most of the diversity found in the vertebrate ST8Sia genes », BMC Evol Biol, vol. 8, p. 258, viewed sans date, .
    Résumé : BACKGROUND: The animal sialyltransferases, which catalyze the transfer of sialic acid to the glycan moiety of glycoconjugates, are subdivided into four families: ST3Gal, ST6Gal, ST6GalNAc and ST8Sia, based on acceptor sugar specificity and glycosidic linkage formed. Despite low overall sequence identity between each sialyltransferase family, all sialyltransferases share four conserved peptide motifs (L, S, III and VS) that serve as hallmarks for the identification of the sialyltransferases. Currently, twenty subfamilies have been described in mammals and birds. Examples of the four sialyltransferase families have also been found in invertebrates. Focusing on the ST8Sia family, we investigated the origin of the three groups of alpha2,8-sialyltransferases demonstrated in vertebrates to carry out poly-, oligo- and mono-alpha2,8-sialylation. RESULTS: We identified in the genome of invertebrate deuterostomes, orthologs to the common ancestor for each of the three vertebrate ST8Sia groups and a set of novel genes named ST8Sia EX, not found in vertebrates. All these ST8Sia sequences share a new conserved family-motif, named "C-term" that is involved in protein folding, via an intramolecular disulfide bridge. Interestingly, sequences from Branchiostoma floridae orthologous to the common ancestor of polysialyltransferases possess a polysialyltransferase domain (PSTD) and those orthologous to the common ancestor of oligosialyltransferases possess a new ST8Sia III-specific motif similar to the PSTD. In osteichthyans, we have identified two new subfamilies. In addition, we describe the expression profile of ST8Sia genes in Danio rerio. CONCLUSION: Polysialylation appeared early in the deuterostome lineage. The recent release of several deuterostome genome databases and paralogons combined with synteny analysis allowed us to obtain insight into events at the gene level that led to the diversification of the ST8Sia genes, with their corresponding enzymatic activities, in both invertebrates and vertebrates. The initial expansion and subsequent divergence of the ST8Sia genes resulted as a consequence of a series of ancient duplications and translocations in the invertebrate genome long before the emergence of vertebrates. A second subset of ST8sia genes in the vertebrate genome arose from whole genome duplication (WGD) R1 and R2. Subsequent selective ST8Sia gene loss is responsible for the characteristic ST8Sia gene expression pattern observed today in individual species.
    Note Note
    <p>18811928</p>
    Note Note
    <p>18811928</p>
    Note Note
    <p>18811928</p>
    Note Note
    <p>18811928</p>
  • Herve, J, Cunha, AS, Liu, B, Valogne, Y, Longuet, M, Boisgard, R, Bregerie, O, Roux, J, Guettier, C, Cales, P, Tavitian, B, Samuel, D, Clerc, J, Brechot, C & Faivre, J 2008, « Internal radiotherapy of liver cancer with rat hepatocarcinoma-intestine-pancreas gene as a liver tumor-specific promoter », Hum Gene Ther, vol. 19, no. 9, p. 915-26.
    Résumé : The hepatocarcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg IIIalpha, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide symporter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adenoviral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radioiodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and nonhepatic cells. Nuclear imaging, tissue counting and immunohistochemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intratumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed nonhepatic cells. In rats bearing multinodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of (131)I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated (131)I therapy as a valuable option for the treatment of multinodular HCC.
    Mots-clés : Adenoviridae/genetics Animals Antigens, Biological/ genetics, C-Type/ genetics Liver Neoplasms, Experimental/genetics/ radiotherapy/ therapy Male Promoter Regions, Genetic Rats Rats, Neoplasm/ genetics Base Sequence Cell Line Cell Line, Recombinant/genetics Dogs Female Gene Expression Gene Transfer Techniques Genetic Vectors Humans Iodine Radioisotopes/administration & dosage/therapeutic use Lectins, Tumor DNA, Wistar Symporters/genetics Tumor Markers.

  • Hesters, L, Prisant, N, Fanchin, R, Méndez Lozano, DH, Feyereisen, E, Frydman, R, Tachdjian, G & Frydman, N 2008, « Impact of early cleaved zygote morphology on embryo development and in vitro fertilization-embryo transfer outcome: a prospective study », Fertil Steril, vol. 89, no. 6, p. 1677-84, viewed sans date, .
    Résumé : OBJECTIVE: To evaluate the impact of the first division morphology on embryo development and IVF-embryo transfer outcome. DESIGN: Prospective study. SETTING: Teaching hospital, France. PATIENT(S): All zygotes from 201 couples were checked for early cleavage. We defined as "even," early cleaved (EC) zygotes with 2 cells of even size; as "uneven," EC zygotes with 2 cells of uneven size; and as "fragmented," EC zygotes with more than 20% fragmentation rate. Day 2 embryo quality was assessed as "top" embryo or "non-top," with the evaluation of multinucleated blastomeres. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Day 2 embryo quality, pregnancy and implantation rates. RESULT(S): Among EC zygotes, 59.1% were even, 13.0% were uneven, and 27.9% were fragmented. Even EC yielded more "top" embryos and less multinucleated blastomere embryos than uneven EC (77.0% vs. 46.3%) and fragmented EC (77.0% vs. 13.9%). The 125 double embryo transfers that comprised at least one embryo derived from even EC zygote led to higher pregnancy rate (PR) (64.0% vs. 43.4%) and implantation rate (42.0% vs. 27.6%) compared to the 76 double embryo transfers with embryos derived from breakdown or 2PN zygotes. CONCLUSION(S): The morphology of the early cleaved zygote is involved in embryo development. Evaluation of this morphology is an effective and valuable method of assessing the embryo quality.
    Note Note
    <p>18068162</p>
    Note Note
    <p>18068162</p>
    Note Note
    <p>18068162</p>
    Note Note
    <p>18068162</p>

  • Hoti, E & Adam, R 2008, « Liver transplantation for primary and metastatic liver cancers », Transpl Int, vol. 21, no. 12, p. 1107-17, viewed sans date, .
    Résumé : Liver transplantation for hepatic malignancies has emerged as a well-documented and proven treatment modality. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, 15% of all liver transplants performed are for hepatocellular carcinoma (HCC). There is no controversy about the fact that liver transplantation for HCC in the adult population yields good results for patients whose tumour masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumours can be reliably selected to benefit from the procedure. In patients with small HCC at an early stage and preserved liver function, liver resection provides an alternative to transplant. Liver resection may offer similar survival results to orthotopic liver transplantation (OLT) in the short term, and does not carry the long-term effects of immunosuppression; however, long-term and disease-free survival favours liver transplantation. Very promising results have been obtained for cholangiocarcinoma treated by aggressive combination therapies, including chemo- and radiotherapy followed by OLT. Survival rate in these selected patients can approach that of patients with cholestatic liver disease, and the role of transplantation now requires re-evaluation. Similarly, hepatoblastoma is an excellent indication in paediatric patients with unresectable or recurrent tumours. Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation, even in the presence of extrahepatic metastases, unlike angiosarcoma which is associated with a very poor survival and considered as a contraindication. And finally for metastatic liver disease from neuroendocrine tumours, liver transplantation can result in long-term survival and even cure in well selected patients. Conversely, the value of transplantation for colorectal liver metastases (currently a contraindication) requires further evaluation by well-designed trials.
    Note Note
    <p>18713148</p>
    Note Note
    <p>18713148</p>
    Note Note
    <p>18713148</p>
    Note Note
    <p>18713148</p>
  • Ichai, P & Samuel, D 2008, « Etiology and prognosis of fulminant hepatitis in adults », Liver Transpl, vol. 14 Suppl 2, p. S67-79.
    Résumé : 1. Establishing the cause of fulminant hepatitis is an important step in the management of acute liver failure, so that specific therapy can be initiated and any contraindications to liver transplantation can be eliminated. 2. The etiology of fulminant hepatitis varies in different countries and at different times. A viral etiology (in particular hepatitis B virus) is now less frequent, and paracetamol-induced fulminant hepatic failure is more common. 3. Many patients have miscellaneous causes of fulminant hepatitis. It is important to establish the main clinical and biological characteristics for specific management. 4. Assessment of the prognosis of fulminant hepatitis is important for distinguishing patients requiring liver transplantation from those whose will improve spontaneously. Prognosis depends on several factors, including the gold standard, the King's College Hospital criteria and Clichy's criteria.
    Mots-clés : Acute/chemically induced/diagnosis/ etiology/virology Prognosis, Humans Liver Failure.

  • Jacquet, A, Francois, H, Frangie, C, Ahmad, L, Charpentier, B & Durrbach, A 2008, « Prevention of calcineurin inhibitor nephrotoxicity in renal transplantation », Transpl Immunol, vol. 20, no. 1-2, p. 29-31, viewed sans date, .
    Résumé : Calcineurin inhibitors (CNI) cyclosporine (Csa) and tacrolimus (Tac) are now first intention immunosuppressive drugs in renal transplantation. However, although these treatments are effective for preventing allograft rejection, they are nephrotoxic: they can cause chronic renal dysfunction and degradation of renal graft function [Nankivell BJ, et al. The natural history of chronic allograft nephropathy. N Engl J Med. 2003 Dec 11;349(24):2326-33]. In view of these undesirable effects, several strategies have been developed to minimize or even avoid their use. These strategies are reviewed and discussed in this paper.
    Mots-clés : Antibodies.

  • Jouannic, J-M, Tachdjian, G, Costa, J-M & Bénifla, J-L 2008, « Coelomic fluid analysis: the absolute necessity to prove its fetal origin », Reprod Biomed Online, vol. 16, no. 1, p. 148-51, viewed sans date, .
    Résumé : Coelocentesis may represent the ideal technique for early prenatal diagnosis. This study aimed to quantify the number of cells in coelomic fluid and to investigate the feasibility of interphase fluorescence in-situ hybridization (FISH) in uncultured coelomic cells for chromosomes X and Y in 12 samples of 0.4-0.8 ml of coelomic fluid obtained by transvaginal puncture at 8-9 weeks of gestation. It was found that the density of cells in the coelomic fluid was low and variable ranging from 0 to 10,600 cells/ml. The FISH analysis failed in three cases because of the absence or remarkably low number of cells. Among the remaining nine cases, FISH analysis led to an unambiguous result in all the samples except two in whom the FISH analysis clearly demonstrated a high count of maternal cells whereas the fluid was apparently not blood stained. The presence of such maternal cells, while their source and nature remaining unexplained, stressed the question of the absolute necessity to prove the fetal origin of the cells analysed. Whatever the cytogenetic analysis performed on coelomic fluid, combining a systematic exclusion of significant maternal contamination is recommended, using multiplex polymerase chain reaction for short tandem repeat analysis to cytogenetic analyses.
    Note Note
    <p>18252062</p>
    Note Note
    <p>18252062</p>
    Note Note
    <p>18252062</p>
    Note Note
    <p>18252062</p>

  • Kasakyan, S, Lohmann, L, Aboura, A, Quimsiyeh, M, Menezo, Y, Tachdjian, G & Benkhalifa, M 2008, « De novo complex intra chromosomal rearrangement after ICSI: characterisation by BACs micro array-CGH », Mol Cytogenet, vol. 1, p. 27, viewed sans date, .
    Résumé : BACKGROUND: In routine Assisted Reproductive Technology (ART) men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple. METHODS: From a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17th week for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12th week of gestation (WG). Chromosome and DNA studies of the fetus were realized on cultured amniocytes RESULTS: Conventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a de novo pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9)(p22.1p24) [arrCGH 9p22.1p24 (RP11-130C19 –> RP11-87O1)x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia. CONCLUSION: This de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.
    Note Note
    <p>19105807</p>
    Note Note
    <p>19105807</p>
    Note Note
    <p>19105807</p>
    Note Note
    <p>19105807</p>
  • Laforest, A, Vibert, E & Castaing, D 2008, « [Gallstones and their complications] », Rev Prat, vol. 58, no. 3, p. 333-9.
    Résumé : Laforest, Anais; Vibert, Eric; Castaing, Denis; France; Rev Prat. 2008 Feb 15;58(3):333-9.
    Mots-clés : complications/, diagnosis, Gallstones/, Humans.

  • Lainas, P, Boudechiche, L, Osorio, A, Coulomb, A, Weber, A, Pariente, D, Franco, D & Dagher, I 2008, « Liver regeneration and recanalization time course following reversible portal vein embolization », J Hepatol, vol. 49, no. 3, p. 354-62, viewed sans date, .
    Résumé : BACKGROUND/AIMS: Permanent portal vein embolization (PVE) is a widely practised technique. The use of an absorbable material would be safer in clinical situations in which the embolized liver is not resected. We evaluated the efficiency of reversible PVE in terms of liver regeneration and analyzed the precise time course of portal recanalization. METHODS: Nine monkeys underwent PVE of the left and right anterior portal branches using powdered absorbable material. Repeated portograms were carried out until complete revascularization of the embolized liver. Hepatocyte proliferation rates were assessed by BrdU incorporation. Liver segment volumes were determined by CT scans performed before embolization, then 1 month and 1 year after embolization. RESULTS: Reversible PVE induced significant hepatocyte proliferation in the non-embolized segments (13.5+/-1.0%, 10.5+/-0.8% and 9.1+/-2.0% of cells on days 3, 5 and 7, respectively). One month after the embolization, the non-embolized liver volume had increased from 38.4+/-1.3% to 54.8+/-0.5% of total liver volume. Proximal and complete revascularization occurred 6-8 and 12-16 days, respectively. CONCLUSIONS: Reversible PVE efficiently induces liver regeneration. The use of absorbable material avoids long-term liver scarring. Such material may be suitable for several clinical indications, including cell transplantation.
    Note Note
    <p>18387688</p>
    Note Note
    <p>18387688</p>
    Note Note
    <p>18387688</p>
    Note Note
    <p>18387688</p>
    Note Note
    <p>18387688</p>

  • Lataillade, J-J, Pierre-Louis, O, Hasselbalch, HC, Uzan, G, Jasmin, C, Martyré, M-C, Le Bousse-Kerdilès, M-C, INSERM, F & Myelofibrosis, the EEUMNETN on 2008, « Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence », Blood, vol. 112, no. 8, p. 3026-35, viewed sans date, .
    Résumé : Primary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable model in which deregulation of the stem cell niche is of utmost importance for the disease development. This paper reviews key data suggesting that an imbalance between endosteal and vascular niches participates in the development of clonal stem cell proliferation. Mechanisms by which bone marrow niches are altered with ensuing mobilization and homing of neoplastic hematopoietic stem cells in new or reinitialized niches in the spleen and liver are examined. Differences between signals delivered by both endosteal and vascular niches in the bone marrow and spleen of patients as well as the responsiveness of PMF stem cells to their specific signals are discussed. A proposal for integrating a potential role for the JAK2 mutation in their altered sensitivity is made. A better understanding of the cross talk between stem cells and their niche should imply new therapeutic strategies targeting not only intrinsic defects in stem cell signaling but also regulatory hematopoietic niche-derived signals and, consequently, stem cell proliferation.
    Note Note
    <p>18669872</p>
    Note Note
    <p>18669872</p>
    Note Note
    <p>18669872</p>
    Note Note
    <p>18669872</p>
    Note Note
    <p>18669872</p>

  • Le Bousse-Kerdilès, M-C, Martyré, M-C & Samson, M 2008, « Cellular and molecular mechanisms underlying bone marrow and liver fibrosis: a review », Eur Cytokine Netw, vol. 19, no. 2, p. 69-80, viewed sans date, .
    Résumé : Chronic fibroproliferative diseases are an important cause of morbidity and mortality in the world. Fibrotic diseases occur in a large variety of vital organs, and the process of fibrosis seems common to all tissues. In all of fibrotic reactions, the underlying cellular and molecular mechanisms involve leukocyte infiltration, the persistence of inflammation in the tissue, and the proliferation of cells with a myofibroblast phenotype. The different cell types participating to this process sustain production of growth factors, proteolytic enzymes, angiogenic factors, and fibrogenic cytokines, which together stimulate the deposition of connective tissue elements that progressively destroy and remodel normal tissue architecture. This review focuses on the comparison of two, major, chronic fibroproliferative diseases: the myelofibrosis which develops in bone marrow, a "fluid" tissue producing circulating haematopoietic cells, and liver fibrosis, which demonstrates all the features of solid tissue damage. We discuss the etiology and histological quantification of each type of fibrosis, the implication of cell partners, cytokines and growth factors, animal models developed to study fibrosis, and antifibrotic therapies for each of these two fibroproliferative disease models.
    Note Note
    <p>18632420</p>
    Note Note
    <p>18632420</p>
    Note Note
    <p>18632420</p>
    Note Note
    <p>18632420</p>
    Note Note
    <p>18632420</p>

0 | ... | 500 | 550 | 600 | 650 | 700 | 750 | 800 | 850 | 900 | 950

--- Exporter la sélection au format
Site réalisé avec SPIP | Se connecter | Plan du site | Suivre la vie du site RSS 2.0
Habillage visuel © Andreas Viklund sous Licence free for any purpose