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Biomedical subjects

Y Calmus

Publications and source records attributed to Y Calmus.

At least 19 recordsLinked to original sources
PubMed1992

[Superacute xenogenic rejection: attempted treatment with anti-idiotypic antibodies].

Heart xenotransplantation in the guinea-pig to rat model, a highly discordant combination, is invariably followed by a hyperacute rejection of the graft. Preformed IgMs were shown to be responsible for the destruction of the graft by stimulating the complement cascade. We tried to inhibit preformed antibodies, before transplantation, by inducing anti-idiotypic antibodies using autologous Fab' mu specific for guinea-pig endothelial cells. This treatment seems to exert a neutralizing effect on xenogeneic hyperimmunization, against guinea-pig endothelial cells but not against preformed anti-guinea-pig antibodies.

Acute Disease↗
PubMed1992

Differential effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6 and tumor necrosis factor-alpha production by monocytes.

Cell-mediated immunity and macrophage activity, especially that of Kupffer cells, are impaired during cholestasis. Some evidence exists that bile acids play a role in these immune defects. The purpose of this study was to evaluate the effects of individual bile acids on immunity and to determine whether monocytes could be a target. We assessed the effects of chenodeoxycholic acid, an endogenous bile acid, ursodeoxycholic acid, which has been shown to partially correct the immunological abnormalities observed in primary biliary cirrhosis, and their tauroconjugates on the production of interleukin-1, interleukin-6 and tumor necrosis factor-alpha. Chenodeoxycholic acid had a dose-dependent inhibitory effect on interleukin-1 (inhibitory concentration 50% = 60 mumol/L), interleukin-6 (inhibitory concentration 50% = 80 mumol/L) and tumor necrosis factor-alpha (inhibitory concentration 50% = 80 mumol/L) production; inhibition was almost complete at 250 mumol/L. In contrast, ursodeoxycholic acid had lesser or minimal inhibitory effects (inhibitory concentration 50% = 100 mumol/L for interleukin-1 and above 200 mumol/L for interleukin-6 and tumor necrosis factor-alpha). The inhibitory effects of taurochenodeoxy-cholic acid and tauroursodeoxycholic acid were similar to those of chenodeoxycholic acid and ursodeoxycholic acid, respectively. Ursodeoxycholic acid did not reverse the chenodeoxycholic acid-induced inhibition of interleukin-6 or tumor necrosis factor-alpha production. In conclusion, chenodeoxycholic acid exerts strong inhibitory effects on monocyte activity in vitro, whereas the effects of ursodeoxycholic acid are minor.

Cell Survival↗
PubMed1992

Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the mouse.

Cell-mediated immunity is impaired during cholestasis, and there is evidence that bile acids play a role in this immune defect. Ursodeoxycholic acid (UDCA), which corrects the immunological abnormalities observed in primary biliary cirrhosis, could counter the detrimental effects of the endogenous bile acids. Accordingly, we assessed the respective effects of cholestasis, chenodeoxycholic acid (CDCA), and UDCA, using mixed lymphocyte culture as a model of allogeneic immune response. CDCA induced a dose-dependent inhibition of the proliferative response (0-150 mumol/L). Mononuclear cells obtained from bile duct-ligated mice had a normal immunostimulatory effect, whereas responder cells obtained from such animals showed a profoundly impaired proliferative response, suggesting that responder T cels are the main target of the cholestasis-induced immune defect. Supplementation of cultures with exogenous interleukins partially compensated for the inhibitory effect of 25 mumol/L CDCA, but not for that of 50 mumol/L CDCA, suggesting that impaired secretion of interleukins is not the only factor involved in the effect of bile acids. In contrast to CDCA, UDCA had no inhibitory effect on the allogenic immune response at concentrations of up to 50 mumol/L.

Animals↗
PubMed1992

The role of natural IgM in the hyperacute rejection of discordant heart xenografts.

The mechanism of xenograft hyperacute rejection in discordant species combinations remains controversial. The purpose of this work was to study the role of natural antibodies in the hyperacute rejection of guinea pig hearts transplanted into rats, a highly discordant combination. This study was conducted in vitro, ex vivo, and in vivo. The endothelial cells of the graft being the first targets damaged in the process of hyperacute rejection, the binding of rat natural antibodies to guinea pig endothelial cells was studied by immunofluorescence. The study was carried out in vitro on guinea pig endothelial cells in culture, and ex vivo on isolated guinea pig hearts perfused with either rat serum or immunoglobulins or immunoglobulin fragments bearing the antigen-binding site. In vitro and ex vivo, rat natural IgM were found to bind specifically to guinea pig endothelial cells, since IgM fragments bearing the antigen-binding site (Fab mu and Fab' mu) could be detected on these cells. IgM fragments were able to inhibit the fixation of native IgM molecules. In contrast, rat IgG only bound to endothelial cells through Fc portions. Thus rat natural IgM might play a role in hyperacute rejection by binding to the graft endothelial cells and triggering the complement cascade activation. In order to test the role of natural IgM in vivo, isolated guinea pig hearts were first perfused with rat Fab' mu, which inhibit the binding of IgM and are unable to activate the complement cascade. These hearts were then transplanted into Lewis rats. The rejection time of Fab' mu-perfused guinea pig hearts was prolonged compared with hearts perfused with buffer or IgG F(ab')2. Therefore, in the guinea pig to rat combination, preventing the binding of the recipient's natural IgM to the graft endothelium delays the hyperacute rejection. In addition, natural IgM are likely to play a greater role than natural IgG.

Animals↗
PubMed1992

[Cytomegalovirus infections in patients after liver transplantation: determination of risk groups].

The goal of this study was to identify high-risk groups for cytomegalovirus infection after liver transplantation. Sixty-one patients were evaluated. Twenty-five patients (41 percent) had infection. Among the 16 patients who were seronegative for the virus before transplantation, 11 received a liver graft and blood products from seronegative donors and none of them developed infection. All seronegative recipients of a liver from seropositive donors (5/5) developed primary infection. Among the 45 patients seropositive before transplantation, 20 developed a cytomegalovirus infection, whatever the donor serologic status. The incidence of symptomatic reactivation or reinfection was high (14/20), and, for 12/14 of them, associated with early acute rejection. Two high-risk groups of patients, eligible for cytomegalovirus prophylaxis, were identified: seronegative recipients of seropositive donors and seropositive recipients with early acute rejection.

Adolescent↗
PubMed1992

Cholestasis induces major histocompatibility complex class I expression in hepatocytes.

The hepatic expression of major histocompatibility complex (MHC) antigens is normally limited. However, aberrant expression occurs in cholestatic diseases such as primary biliary cirrhosis. The aim of this work was to assess the effect of cholestasis itself on hepatocyte MHC expression and to determine if immunosuppressive drugs might modulate this expression. Liver fragments taken from six patients with extrahepatic cholestasis and eight control patients were analyzed for MHC expression by direct immunofluorescence. MHC class I expression by hepatocytes was present in six of six cholestatic patients and zero of eight control subjects. Hepatocytes did not express MHC class II in either group. In further studies, cholestasis was induced in rats by ligation-section of the bile duct. Five groups of rats were studied: control, 3-day cholestasis, 5-day cholestasis, 5-day cholestasis plus cyclosporine, and 5-day cholestasis plus corticosteroids. Hepatocyte MHC class I expression was detected by immunofluorescence in bile duct-ligated rats but not in control animals. Flow-cytofluorimetric analysis of isolated hepatocytes showed that the percentage of hepatocytes expressing MHC class I increased from day 0 (9.9%) to days 3 (50.2%) and 5 (82.9%); this hyperexpression was not modified by cyclosporine (79.7%) or corticosteroids (77.9%). The percentage of hepatocytes spontaneously expressing MHC class II was low (0.05%) and was not significantly modified by cholestasis or immunosuppressive drugs. Thus, a nonimmunological factor such as cholestasis is able to modulate MHC expression. The liver may become more vulnerable to immune destruction in the presence of cholestasis, and immunosuppressive treatment has no effect on this phenomenon.

Aged↗
PubMed1991

Experimental reduction of portal hypertension by mechanical increase of liver portal flow.

Studies on the isolated perfused rat liver demonstrated that an increase in portal pressure is associated with an increase in the portal blood flow in normal and in cirrhotic livers. In two pigs with portal hypertension mesenteric portal pressure was lowered by mechanically increasing the liver portal blood flow by means of a balloon pump around the portal vein.

Animals↗
PubMed1991

Ursodeoxycholic acid (UDCA) in the treatment of chronic cholestatic diseases.

Several studies suggest that UDCA treatment has beneficial effects in chronic cholestatic diseases. We designed a controlled trial to assess the efficacy and tolerance of UCDA in primary biliary cirrhosis (PBC): 73 patients received UDCA (13-15 mg/kg per day) and 73 a placebo. One side-effect required interruption of therapy in each group. The relative risk of treatment failure (doubling of the bilirubin level or occurrence of a severe complication of cirrhosis) was 3 times higher in the placebo group. Pruritus resolved in 40% of the patients of UDCA group vs 19% in placebo group. Biological and histological parameters significantly improved in the patients receiving UDCA. Unexpectedly, immune parameters, including IgM levels and anti-mitochondrial antibody titers, also improved. The Mayo risk score was significantly different between the two groups at one and two years, suggesting that UDCA could prolong survival in PBC. Recent studies suggest that UDCA could have immunoregulating properties. Abnormal MHC class I expression by hepatocytes, observed in PBC, was dramatically reduced by UDCA treatment. Cholestasis itself induces hepatic MHC expression: hepatocyte MHC class I expression was present in 6/6 cholestatic patients vs 0/8 control subjects. Experimental cholestasis in the rat induced MHC class I expression. Cyclosporin or corticosteroids had no effect on this overexpression, suggesting that an immune mechanism is not involved in this phenomenon. To assess the effect of bile acids on MHC expression, human hepatocytes were incubated with bile acids. Chenodeoxycholic acid (CDCA) (an endogenous bile acid) but not UDCA induced a dose-dependent MHC class I hyperexpression. UDCA suppressed the CDCA-induced MHC hyperexpression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: effect of ursodeoxycholic acid.

Aberrant hepatic expression of HLA molecules has been shown to be present in primary biliary cirrhosis and may play a determining role in the pathogenesis of the disease. We have studied the effect of the long-term administration of ursodeoxycholic acid on hepatic HLA expression. Nine untreated patients with primary biliary cirrhosis, eight patients treated for at least a year with ursodeoxycholic acid and eight control subjects without hepatobiliary disease were compared. HLA expression was studied on liver biopsy sections using a direct immunofluorescence technique with specific monoclonal antibodies directed against class I or class II HLA molecules. Aberrant biliary HLA class II expression was not modified by chronic administration of ursodeoxycholic acid. In contrast, aberrant hepatocyte HLA class I expression was markedly reduced. Reduction in HLA class I expression may lead to decreased cytotoxic T cell-dependent lobular necrosis, which is thought to contribute to the progression of primary biliary cirrhosis to advanced stages. These findings suggest that the beneficial effect of ursodeoxycholic acid treatment in primary biliary cirrhosis could result not only from a reduction in the intrahepatic accumulation of cytotoxic bile acids but also from a reduction in immunological injury.

Deoxycholic Acid↗