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Y Calmus

Publications and source records attributed to Y Calmus.

At least 19 recordsLinked to original sources
PubMed2006

Low density lipoprotein receptor transcripts correlates with liver hepatitis C virus RNA in patients with alcohol consumption.

Alcohol consumption has a major impact on the natural history of chronic hepatitis C virus (HCV) infection, although the underlying mechanisms are still debated. We designed a clinical study to evaluate the impact of alcohol abuse on both viral load and expression of low-density lipoprotein receptor (LDLR) and CD81 expression. Thirty-eight consecutive HCV-infected patients were enrolled. Group 1 (n = 18), < or =10 g alcohol/day, group 2 (n = 8), < or =30 g alcohol/day, group 3 (n = 12), >or =30 g alcohol/day. Receptors expression was measured by flow cytometry analysis in peripheral blood mononuclear cells (PBMC) and by specific real-time retrotranscription polymerase chain reaction (RT-PCR) in the liver. Serum viral load was evaluated by quantification of both HCV genomic RNA and total core antigen. The hepatic viral load was assessed by real-time RT-PCR. Serum HCV-RNA and total core antigen were significantly correlated, and were higher, albeit not significantly, in group 3 than in group 1. Alcohol consumption had no effect on expression of HCV putative receptors in PBMC, except for CD81, which was upregulated on monocytes in group 2. In the liver, viral load and levels of LDLR transcripts were significantly higher in group 3 than in group 1. Remarkably, a significant positive correlation was found between LDLR transcripts and HCV-RNA (r2 = 0.83, P < 10(-3)). Finally, in vitro experiments suggested that the effect of ethanol on LDLR expression was indirectly mediated by both tumour necrosis factor-alpha and interleukin-1beta. In conclusion, this study is the first to support a role for LDLR in the natural infection by HCV in man.

Adult↗
PubMed2004

[Epstein-Barr virus-associated cutaneous plasmacytoma post-solid organ transplantation].

BACKGROUND: Post-transplantation lymphoproliferative disorders develop in 1 to 10p. 100 of organ transplant recipients and are frequently associated with Epstein-Barr virus (EBV). Among post-transplantation lymphoproliferative disorders, plasmacytoma with cutaneous involvement is exceptional. Association with EBV has been rarely reported in post-transplantation plasmacytomas and the latency type of EBV has never been characterized. We report 2 new cases of cutaneous monotype EBV-related plasmacytomas. CASE-REPORTS: Clinical presentation was a sub-cutaneous tumor on the thigh in the first case and an ulcerated nodule of the leg in the second case, occurring respectively 7 and 8 years after organ transplantation (liver transplantation and heart transplantation). In both lesions, tumor cells exhibited lambda light chain restriction and the association with EBV was confirmed using immunohistochemistry and in situ hybridization. The expression of EBV genes in tumor cells demonstrated type III latency. DISCUSSION: The classification of post-transplantation lymphoproliferative disorders is not well defined and some authors retain 3 categories. Among the latter, plasmacytomas have been rarely described. Cutaneous involvement is reported in 4 cases and an association with EBV in only 2 cases without description of viral latency. Clinical and histological features of post-transplantation plasmacytomas appear polymorphic. We report EBV-association in both cases, with a type III latency clearly demonstrated in one case, as has been reported in other lymphoproliferative diseases in patients with congenital or acquired immunodeficiency. We also discuss various possible therapeutic strategies for post-transplantation lymphoproliferative disorders.

Epstein-Barr Virus Infections↗
PubMed2004

Response to antiviral treatment in hepatitis C virus-associated marginal zone lymphomas.

A link between chronic hepatitis C virus (HCV) infection and low-grade B-cell lymphomas has been suggested by epidemiological studies. Marginal zone lymphomas (MZLs) including splenic lymphomas with villous lymphocytes are among the most frequently reported subgroups in the setting of chronic HCV infection. In this study, we examined the effect of antiviral treatment in eight patients with HCV-associated MZL. We found that five out of eight patients have responded to interferon alpha and ribavirin. In some cases, hematologic responses were correlated to virologic responses. In addition, we report a case of large granular lymphocyte leukemia occurring in association with MZL and HCV, and responding to interferon and ribavirin. We suggest that there is an etiologic link between HCV and antigen-driven lymphoproliferative disorders.

Adult↗
PubMed2003

Hypodermin A, a new inhibitor of human complement for the prevention of xenogeneic hyperacute rejection.

BACKGROUND: Hyperacute rejection (HAR) of discordant xenografts in the pig-to-human combination can be prevented using tranplants expressing transgenic molecules that inhibit human complement. Hypodermin A (HA), a serine esterase that degrades C3, was tested in the guinea-pig-to-rat and in the pig-to-human combinations. METHODS: Hypodermin A was tested in vitro, ex vivo, and in vivo models of HAR in the guinea-pig-to-rat combination. Hamster ovary cells (CHO) and a line of porcine aortic endothelial cells (PAEC11) were transfected with HA complementary DNA (cDNA). RESULTS: The pattern of degradation of rat and human C3 by HA was different (multiple bands lower than 40 kDa) from the physiologic pattern observed after spontaneous degradation of rat C3 or physiologic activation of human C3. The CH50 activity in serum was significantly lower in rats treated with 3.2 mg HA/kg than in untreated rats (45 +/- 16 U/ml vs. 700 +/- 63 U/ml, P < 0.05). Sera from rats injected with 3.2 mg/kg of HA were less effective in lysing guinea-pig endothelial cells (12 +/- 7%) than normal rat sera (79 +/- 3%; P < 0.001). Ex vivo, guinea-pig hearts perfused by rat serum supplemented with HA survived longer than those perfused by non-treated serum (210 +/- 34 and 154 +/- 71 min, respectively; P < 0.05). In vivo, guinea-pig hearts transplanted into HA treated rats survived longer than in non-treated rats (27 +/- 5 min vs. 13 +/- 4 min; P < 0.001). In the presence of human serum, smaller amounts of C6 and C5b-9 were deposited onto HA-transfected CHO cells than onto control cells. The mHA-PAEC11 cells were significantly more resistant to lysis by human C than control PAEC11 cells. CONCLUSIONS: These data suggest that transgenic HA could be used to prevent hyperacute xenogeneic rejection.

Acute Disease↗
PubMed2001

Effects of bile acids on the humoral immune response: a mechanistic approach.

Whereas bile acids in excess depress the cell-mediated immune response, their effects on the humoral response have been little investigated. The aim of this study was to investigate the effects of bile acids on immunoglobulin production. Human peripheral blood mononuclear cells were stimulated for 5 days by Staphylococcus aureus Cowan I (SAC-I). Immunoglobulins were measured in the supernatants and cell lysates using ELISA. We found that bile acids inhibited IgM production in a dose-dependent manner. The inhibitory effects of 50 microM chenodeoxycholic acid (CDCA) and its glyco- and tauro-conjugates (62, 53 and 51%, respectively) were stronger than those of ursodeoxycholic acid (UDCA) and its conjugates (45, 40 and 34%, respectively). The inhibition of IgG production by CDCA and UDCA was weak (23 and 12%, respectively, at 50 microM). IgA production was not modified. The inhibition of intracellular IgM concentration paralleled that observed in the secreted compartment. By contrast, CDCA enhanced intracellular concentration of IgG. In the absence of significant necrosis or apoptosis, CDCA-mediated inhibition of SAC-I-induced IgM production was significantly correlated to the ability of the bile acid to inhibit cell proliferation (r=0.98; p<0.05). In conclusion, we showed that hydrophobic bile acids strongly depress the primary humoral response. This effect resulted from both an inhibition of cell proliferation, and to a lesser extent from a deficient exocytosis of immunoglobulins.

Adult↗
PubMed2001

Low rejection rates with tacrolimus-based dual and triple regimens following liver transplantation.

We studied the outcome of 345 liver transplant patients who received tacrolimus-based immunosuppressive therapy either as a dual regimen (with corticosteroids, n=172) or as a triple regimen (with corticosteroids and azathioprine, n=173) for 3 months after transplantation (3-month cohort). A further analysis was conducted for the first 195 patients randomised (dual n=100, triple n=95) who were followed up for 12 months after transplantation (12-month cohort). For the 3-month cohort, patient survival was 90.7% (dual) and 91.9% (triple), graft survival after 3 months was 88.4% (dual therapy) and 89.6% (triple therapy). Acute rejections were experienced by 67/172, 39.0% of patients on dual therapy and by 60/173, 34.7% of patients on triple therapy; corticosteroid-resistant rejections were reported in 9 patients (5.2%) in either treatment group. The overall safety profile was similar for the two treatment groups. Significant differences, however, were found for thrombocytopenia (dual 13/172, 7.6%, triple 37/173, 21.4%, p<0.001) and leukopenia (dual 4/172, 2.3%, triple 24/173, 13.9%, p<0.001). For the 12-month cohort, patient survival was 85.6% (dual) and 88.4% (triple) after 1 year. Graft survival was 81.7% (dual) and 85.2% (triple) 12 months after transplantation. Acute rejections were reported for 38/100, 38.0% of patients on dual therapy and 36/95, 37.9% of patients on triple therapy, corticosteroid-resistant rejections were 7/100, 7.0% (dual) and 7/95, 7.4% (triple) of patients. In the 12-month cohort, no significant differences in the safety profiles of the treatment groups were found. We conclude that both tacrolimus-based dual and triple drug regimens provide effective and safe immunosuppression following orthotopic liver transplantation.

Azathioprine↗
PubMed2001

Effects of bile salts and aliphatic ionic surfactants on human lymphocyte proliferation.

BACKGROUND: The molecular mechanisms involved in the immunosuppressive properties of bile salts are partly unknown. METHODS: The aim of the study was to compare the effects of bile salts to those of various compounds with a steroid structure, or straight-chain hydrocarbons of different lengths and polar groups in the human mixed lymphocyte reaction. RESULTS: We showed a significant correlation between the effects of bile salts and a low critical micellar concentration, a high surface activity index, and the absence of conjugation. In addition to mixed lymphocyte reaction (MLR) inhibition, chenodeoxycholate (CDC) inhibit ConA-induced IL2 production without any effect on IL2 R expression. Fusidate, a negatively charged steroid, with physical properties comparable to those of deoxycholate, had similar effects. Cetyltrimethylammonium bromide (CTAB), which exhibited a very low critical micellar concentration, inhibited mixed lymphocyte reaction in an extent comparable to cyclosporin A. In contrast, aliphatic compounds with critical micellar concentrations in the same range as bile salts but with a lower molecular area had no effect. CONCLUSIONS: Amphiphilic negatively charged molecules inhibit T-cell proliferation to an extent that is dependent upon their hydrophobicity. These results may be explained, at least in part, by a modification in the cell membrane lipid bilayer structure.

Bile Acids and Salts↗
PubMed2001

The superoxide dismutase mimetic MnTBAP prevents Fas-induced acute liver failure in the mouse.

BACKGROUND & AIMS: Acute liver failure (ALF) of viral origin results from massive hepatocyte apoptosis induced by the interaction between Fas expressed on hepatocytes and Fas ligand on activated T lymphocytes. Because Fas-induced apoptosis of hepatocytes involves mitochondrial damages and potential reactive oxygen species (ROS) overproduction, we investigated whether manganese III tetrakis (5,10,15,20 benzoic acid) (MnTBAP), a nonpeptidyl mimic of superoxide dismutase (SOD), can inhibit Fas-induced ALF. METHODS: An agonist anti-Fas monoclonal antibody was used to induce hepatocyte apoptosis in vitro and ALF in vivo. RESULTS: Preventive and curative treatments by MnTBAP significantly increased survival rates and significantly reduced aspartate aminotransferase levels and parenchymal lesions. ROS generation was suggested by those beneficial effects and significant increases in SOD and Gpx activities after anti-Fas injection. Flow cytometry of isolated hepatocytes incubated with anti-Fas monoclonal antibody showed that ROS production was associated with the collapse of transmembrane potential and loss of cardiolipin content. After injection of anti-Fas monoclonal antibody, mitochondrial Bcl-2 was decreased, cytochrome c released, and caspase-3 activated. Mitochondrial alterations and their consequences were abrogated by MnTBAP. CONCLUSIONS: ROS are key executioners in Fas-induced hepatocyte apoptosis. This finding explains why a nonpeptidyl mimic of SOD can cure ALF in a model of viral hepatitis, pointing out the potential interest of this molecule in humans.

Acute Disease↗
PubMed2001

Detoxification of reactive oxygen species by a nonpeptidyl mimic of superoxide dismutase cures acetaminophen-induced acute liver failure in the mouse.

Drug-induced acute liver failure (ALF) is a devastating and often fatal disease mainly caused by poisoning by acetaminophen (APAP). The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), that leads to gluthatione depletion has been suspected to be the main effector of hepatocyte apoptosis during APAP-induced ALF. We have investigated whether reactive oxygen species (ROS) also play a role in APAP-induced ALF, and whether manganese III tetrakis (5,10,15,20 benzoic acid) (MnTBAP), a mimic of superoxide dismutase (SOD) with catalase-like activity, can treat the disease in mice. The effects of MnTBAP were tested on APAP-intoxicated mice and on isolated hepatocytes incubated with APAP. MnTBAP preventively and curatively administered significantly improved survival times, and dramatically reduced serum transaminase activity levels and parenchymal lesions in APAP-intoxicated mice. Whereas pretreatment with N-acetyl-L-cysteine (NAC) prevented ALF in a dose-dependent manner, the molecule was ineffective when curatively administered. The significant increase in glutathione peroxidase (Gpx) activity following APAP administration, and the beneficial effects of MnTBAP suggested that ROS were produced during APAP-induced ALF. A direct evidence of ROS generation was provided by flow cytometry of isolated hepatocytes incubated with APAP. In vitro, ROS production was associated with mitochondrial damage characterized by the collapse of transmembrane potential and the loss of cardiolipin content. In livers of intoxicated mice, ALF was associated with cytochrome c release that led to the activation of caspases-9 and -3. The capacity of MnTBAP to abrogate all those alterations suggests that ROS play a role in APAP-induced apoptosis of hepatocytes, and explains the beneficial effects of MnTBAP, which could be of interest in APAP-induced ALF in humans.

Acetaminophen↗
PubMed2001

[Liver transplantation for alcoholic liver disease].

Alcoholic cirrhosis is a major public health issue in France. The prevalence of alcoholic cirrhosis and the number of potential candidates for liver transplantation is unknown but certainly underestimated. Despite physicians' ethical reserves concerning this self-inflicted disease and the public's misgivings, liver transplantation for alcoholic cirrhosis can provide survival rates comparable with those observed for other chronic liver diseases. in this indication, liver transplantation if often associated with a low risk of acute rejection and a high rate cancer of the upper respiratory and digestive tracts. The risk of recurrent alcoholism after liver transplantation is also a major problem. Its prevalence varies from 10 to 50%, depending on the assessment criteria, and the rate recurrent risk for the liver graft (alcohol intake>40 g/d) is to the order of 10%. These figures illustrate the importance of careful management and support for these patients. At least 6 months weaning from alcohol is a commonly accepted selection criterion for transplantation candidates. Criteria for liver transplantation generally include patients aged under 65 years, weaned for more than 6 months, with Child C cirrhosis or less, uncontrollable digestive tract hemorrhage, spontaneous severe infection, hepatorenal syndrome, hepatopulmonary syndrome, or multifocal hepatocellular carcinoma if the largest nodule measures less than 3 cm. Acute alcoholic hepatitis is a severe disease, fatal in 50% of the cases, and resistant tot corticosteroid therapy. Liver transplantation in this subpopulation of often young patient who have not achieved weaning merits further evaluation.

Age Factors↗
PubMed2000

A reversible model of acute hepatic failure by temporary hepatic ischemia in the pig.

BACKGROUND: To evaluate new therapies for human fulminant hepatic failure, a suitable large animal model is needed. The purpose of this study was to develop a reversible surgical model of acute hepatic liver failure by transient ischemia in pigs. MATERIALS AND METHODS: Under general anesthesia, an end-to-side portacaval shunt was performed in 17 pigs and tape was laid around the hepatoduodenal ligament. Two days after construction of the functional portacaval shunt, 13 ambulant pigs underwent transient total liver ischemia by tightening of the tape around the hepatoduodenal ligament for 5.5 h. During ischemia, 10% glucose was continuously infused intravenously to prevent hypoglycemia. RESULTS: Ten animals (77%) died with hepatic coma after a mean duration of 22.5 +/- 1.9 h. The 3 remaining animals survived more than 5 days and were sacrificed. In dying animals, encephalopathy was observed 14 +/- 1.7 h after the onset of ischemia. During ischemia, similar progressive decrease of fibrinogen, platelets, prothrombin time, and factors V and VII activities was observed in dying and surviving animals. Just before death, mean prothrombin and factors V and VII activities were respectively 22 +/- 2, 21 +/- 4.4, and 24 +/- 5%. At 22 h, plasma ammonia and lactate levels were respectively 705 +/- 93 micromol/L and 10.5 +/- 0.4 mmol/L in dying animals and 249 +/- 75 micromol/L and 2.9 +/- 0.1 mmol/L in surviving animals (P < 0.01). Estimation of the percentage liver cells necrosed was 74 +/- 4.7% in the survivors and 86 +/- 5.5% in animals who died of hepatic coma (NS). CONCLUSIONS: This model is reproducible and reversible and should allow the quantitative evaluation of new technologies, such as bioartificial liver, for the support of hepatic failure in humans.

Acute Disease↗
PubMed2000

Defective interleukin-1 receptor antagonist production is associated with resistance of acute liver graft rejection to steroid therapy.

Thirty percent of acute liver graft rejection episodes are resistant to steroids. As interleukin-1 (IL-1) is an important target of steroid therapy, we examined the possible involvement of reduced sensitivity of IL-1 production to steroids or defective production of its antagonist, IL-1Ra. Patients were assessed during steroid-sensitive or -resistant rejection and 2 years later. In situ IL-1beta and IL-1Ra expression was evaluated by immunohistochemistry; their production was assayed by enzyme-linked immunosorbent assay and the gene polymorphisms by reverse transcriptase-polymerase chain reaction on blood cells. Hepatic IL-1beta and IL-1Ra expression were enhanced during rejection. IL-1 production and its inhibition by steroids were similar in steroid-responsive and steroid-resistant rejection. However, IL-1Ra production was lower in steroid-resistant than in steroid-responsive rejection, and this difference was still observed 2 years after rejection. IL-1beta and IL-1Ra gene polymorphisms did not differ between patients with and without steroid resistance. Low IL-1Ra production is associated with steroid resistance of acute rejection and is due to a constitutional defect. The early identification of such patients might qualify them for stronger anti-rejection therapy, including IL-1Ra.

Acute Disease↗
PubMed2000

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation: a report of three cases.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disorders (PT-LPD) are a well-known complication of organ transplantation. Their incidence after liver transplantation in adults ranges from 1.8 to 4%. Reduction of immunosuppression led to remission in a few cases. Other treatments include chemotherapy, interferon alpha therapy and/or intravenous-immunoglobulins, or antiviral drugs. However, monoclonal antibodies directed against B-cell specific antigens have rarely been used in those patients. Our aim was to study the feasibility and efficacy of Rituximab, a new, promising human chimeric antibody that recognizes the CD20 antigen, for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation. METHODS: Rituximab (IDEC-C2HB8; Roche Laboratories, Neuilly-sur-Seine, France) was administered at a 375 mg/m2 dose on days 1, 8, 15, and 22, in an outpatient setting, in three patients with PT-LPD. The tumor was classified as polymorphic PT-LPD in two cases and PT-LPD with features of large cell lymphoma in one case. All the tumors expressed the CD20 antigen and were EBV-related, and the clonality was confirmed in all three cases. The 4 injections of the anti-CD20 monoclonal antibody were associated with reduced immunosuppression in the three patient. RESULTS: The treatment with Rituximab was well tolerated without any side effects. The two patients with polymorphic PT-LPDs underwent rapid complete remission, whereas the treatment modalities were ineffective in the patient with the large-cell non-Hodgkin-lymphoma. CONCLUSION: These results must be confirmed in a larger cohort of liver transplant recipients suffering from lymphoproliferation. However, they indicate rapid efficiency of Rituximab in association with reduced immunosuppression in these disorders.

Adult↗
PubMed2000

Reversal of the vasoconstrictor step of hyperacute xenogeneic rejection of the liver by endothelin antagonists.

The role of endothelin in the initial vasoconstrictor step of hyperacute xenogeneic rejection was investigated. Isolated rat livers were perfused in recirculation. Perfusion with human sera provided an ex vivo model of hyperacute rejection in a discordant combination. Perfusion of 10% xenogeneic serum induced a marked (70%) and sustained reduction of the liver flow and induced the release of endothelin into the perfusion medium. In contrast, perfusion of 10% allogeneic serum or of 10% decomplemented human serum induced a weak (25%) and transient reduction of the liver flow and induced the release of minimal amounts of endothelin. The simultaneous administration of BQ 123 and BQ 788, the respective antagonists of ET(A) and ET(B) endothelin receptors, or that of bosentan, a mixed ET(A)/ET(B) antagonist, antagonized the vasoconstrictor effect of 10% xenogeneic human serum, as well as that of 10(-9) M endothelin-1. The vasoconstrictor effects of xenogeneic serum on liver circulation are, at least partly, mediated through the release of endothelin by the graft.

Animals↗