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J Cardoso

Publications and source records attributed to J Cardoso.

51 records · Page 3Linked to original sources

Target antigens of hyperacute xenogeneic rejection in the rat to guinea pig to rat discordant combinations.

The increasing shortage in allografts has led to a renewed interest in xenogeneic transplantation. Discordant combinations are characterized by hyperacute rejection partly due to the presence of natural antixenogeneic antibodies in the recipient. The aim of this work was to characterize the target antigens, using 2 discordant models. In the rat into guinea pig model, analysis of organ homogenates by immunoblotting revealed numerous bands. Some of these bands were organ specific, whereas others, namely in the 55-kDa region, were detected in liver, heart, lung, and kidney. Using membrane extracts of liver cells or of aortic endothelial cells, only bands of 55 kDa were revealed. No band could be seen using extracts of isolated hepatocytes. Two bands of 55 kDa disappeared after preabsorption of guinea pig sera on the various rat tissue homogenates, suggesting that they represent xenoantigens common to these tissues. In order to investigate the in vivo relevance of these 55-kDa antigens, isolated rat livers were perfused with decomplemented guinea pig sera. Eluates revealed one single print of 55 kDa on rat tissue homogenates. Finally, preincubation of rat mononuclear cells with various xenogeneic sera did not inhibit the binding of mAb specific for rat class I or class II MHC antigens, suggesting that the latter are not recognized by natural xenoantibodies. In the guinea pig to rat model, the antigens detected had a molecular mass ranging from 95 to 110 kDa. Absorption and perfusion experiments also showed that these antigens were common to various tissues and involved in the binding of rat natural antibodies ex vivo. In conclusion, our results indicate that rat xenoantigens of about 55 kDa are recognized by guinea pig natural antibodies, while guinea pig xenoantigens of 95-110 kDa are bound by rat natural antibodies. These antigens are common to liver, heart, lung, and kidney, are borne by endothelial cells, and cannot be found on hepatocytes.

Acute Disease↗

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↗

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↗

[Pseudo-Kaposi's syndrome of the left lower extremity. The Stewart-Bluefarb syndrome].

The authors relate one case of Stewart-Bluefarb syndrome in a 16 year old patient, showing cutaneous lesions with features of Kaposi angiosarcoma. Though there are no signs of direct arteriographic of arteriovenous communications (CAV). The other exams accomplished allow us to maintain CAV as an etiopathogenic hypothesis.

Adolescent↗

[Natural human anti-pig agglutinins. Role in the hyperacute rejection of xenogeneic graft in the pig-human donor-recipient combination].

Binding of human natural xenoantibodies to the graft endothelial cells is considered as one of the initial steps in the hyperacute rejection of a pig liver by human. In addition to binding to endothelial cells, human xenoantibodies also agglutinate pig red blood cells. We have therefore compared the anti-pig hemagglutinin titers with the cytotoxic activity to pig endothelial cells of a series of human sera. In order to determine the localisation of the human xenoantibodies fixation in the pig liver, we have studied by immunoperoxidase staining, deposits of IgG, IgM and IgA, using an ex vivo model of isolated pig liver perfused with human blood. Moreover, we have measured hemagglutinin titers in the perfusate along the perfusion. We have found a strong correlation between the anti-pig hemagglutinin titers and the anti-pig endothelial cell cytotoxic activity of human serum. Anti-pig hemagglutinin become undetectable in the perfusate within 4 minutes of perfusion of the pig liver with human blood. The sinusoids in the pig liver were the only structures with positive peroxidase staining. It is therefore suggested that human anti-pig hemagglutinins are in great part the same than human anti-pig endothelial cell cytotoxic antibodies. Pig red blood cells could be used to easily detect anti-pig xenoantibodies in human, and to adsorb xenoantibodies from the recipient before a xenograft.

Agglutinins↗

[Syphilis in an HIV-infected patient].

We report the case of a 28-year-old female prostitute, intravenous drug user, seropositive for human immunodeficiency virus and with unusual manifestations of lues infection. The presence of plantar keratoderma, alopecia of the scalp, total loss of hair eyebrows and eyelashes with bilateral chorioretinitis is emphasised. Non-treponemal and treponemal tests for syphilis showed reactivity, but with abnormal serologic expression. The possible relationship between H.I.V. infection and the natural course of syphilis is discussed.

AIDS-Related Opportunistic Infections↗