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Biomedical subjects

D Houssin

Publications and source records attributed to D Houssin.

At least 307 records · Page 17Linked to original sources
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Interactions between liver allografts and lymphocytotoxic alloantibodies in inbred rats.

Several clinical and experimental findings suggest that liver allografts are less sensitive than other organ allografts to lymphocytotoxic antibodies. In this experimental study in hypersensitized inbred rat recipients, rejection of liver allografts was delayed compared to that of heart allografts. Furthermore, there was a marked decrease in the level of cytotoxic antibodies after liver allografting but not after heart allografting in these animals. The decrease in the level of antibodies also occurred after donor-specific extracorporeal liver hemoperfusion in hypersensitized recipients. Whether the decrease was caused by a massive absorption of antibodies on the liver or related to excretion of major histocompatibility complex antigens in a soluble form remains to be demonstrated. These results support the hypothesis that the liver has a privileged position in regard to rejection and are consistent with clinical observations made following ABO incompatible or cross-match positive liver transplantations.

Animals↗
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Hyperacute rejection in liver transplantation: CT findings.

Hyperacute rejection is rare after liver transplantation. We report a case of early graft failure following liver transplantation in a 46-year-old woman. On the 5th postoperative day, progressive loss of graft function occurred. Liver histology showed submassive hepatic necrosis. Computed tomography features showing large geographic areas of necrosis without anatomic distribution were suggestive of hyperacute rejection.

Female↗
PubMedDate not supplied

Suicide gene therapy of ovarian cancer: an experimental study in rats using retroviral-mediated transfer of herpes simplex virus thymidine kinase gene.

BACKGROUND: This study evaluated the potential of gene therapy against ovarian cancer usin the retroviral transfer of the herpes simplex type 1 thymidine kinase gene (HSV1-TK) followed by ganciclovir treatment. MATERIALS AND METHODS: The sensitivity of 4 different ovarian cancer cell lines (rat ar human) to in vitro infection by recombinant retroviruses were evaluated. Then, their HSV1-TK expressing derivatives were tested for their sensitivity to ganciclovir. One of them, DMBA-OC-1-TK+ was used to generate experimental ovarian cancer in 13 WKY female rats. After 14 days, tl rats received ganciclovir for 12 days (n = 6). The results were expressed in mean +/- ES and were evaluated with the Mann-Whitney test. RESULTS: All cell lines analyzed in this study were sensitive to retroviral mediated gene transfer although with significant variations. The HSV 1-TK expressing derivatives of these cells were 300 7,000-fold more sensitive to ganciclovir, than the parental cells. The ganciclovir dramatically reduced the size of HSV1-TK+ tumors compared to untreated control rats (0 mm3 vs 2,594 mm3, p < 0.001) with complete tumor regression and residual fibrotic scars on pathological examination. Control tumors showed a poorly-differentiated epithelial adenocarcinoma of the ovary. CONCLUSION: In a clinical perspective, the good tolerance and the significant anti-tumoral effects of retroviral-mediated transfer of HSV1-TK gene in animals were encouraging. It remains to set up gene transfer methods that will allow efficient targeting of the ovarian cancer in vivo.

3T3 Cells↗
PubMedDate not supplied

[Hepatic allograft rejection. Diagnostic and therapeutic aspects].

Rejection is still a major problem in liver transplantation: 50-70% of patients present at least one acute episode, while 5-15% develop chronic rejection. Acute rejection is suggested by clinical signs and abnormal laboratory test results, but only histological signs on biopsy specimens are adequately specific. The three most frequent elementary lesions are a portal infiltrate, bile duct alterations and endothelial inflammation. Several systems have been forwarded to classify the degree of rejection. Chronic rejection is characterized by a progressive reduction in the number of interlobular bile ducts. It does not respond to available immunosuppressive drugs and thus requires retransplantation. Prophylactic immunosuppression is usually based on the triple-drug combination cyclosporine/azathioprine/corticosteroids. The orthoclone OKT3 and FK506 have recently been proposed for prophylactic use in this setting. Treatment of liver graft recipients with cyclosporine carries a number of specific disadvantages, particularly with regard to gastrointestinal interactions (delayed intestinal absorption in patients with cholestasis, bile derivation, diarrhea or receiving cholestyramine; possibility of a sharp increase in blood cyclosporine levels when the Kehr drain is clamped), and drug interactions (cyclosporine metabolization of CP450-IIIA accounts for most such interactions). The results of radioimmunoassay and TDx must be interpreted with care, and HPLC remains the reference technique in borderline cases. Cyclosporine is hepatotoxic in about 20% of cases, generally giving rise to cholestasis. This toxicity is dose-dependent and therefore diminishes when the dosage is reduced. Most groups initially treat rejection with corticosteroids. The response to treatment is generally evaluated in terms of liver function tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Rejection↗
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Ethical perspectives about organ allocation for transplantation.

The ethical questions suggested by the allocation of organs for transplantation can be assembled around the notion of justice. It is a domain of health care in which there is a chronic lack of resources, but for patients whose life is at stake, sometimes at short term. It has similarities with the triage, imposed in some conditions of emergency medicine, at war or during civil catastrophes. The question will be approached from the points of view of the main stakeholders.

Ethics, Medical↗
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Delaying rejection in discordant heart xenografts in the rat: efficacy of cyclosporin, prostaglandin I2 and exchange transfusion.

If effective modes of prevention of hyperacute rejection were available, the problem of the absence of enough suitable donors could be solved by the use of organ xenografts. Organ xenograft rejection is principally mediated by preformed antibodies which are responsible for the hyperacute pattern of rejection. We decided therefore to study various methods of prevention of rejection in the guinea pig to Lewis rat combination (donor-recipient discordant species) in which hyperacute rejection is particularly intense. Three series of experiments were performed. In the first series immunosuppression of the recipient was induced using an oral solution of cyclosporin A. In the second series antiplatelet-aggregation therapy was administered to the recipient, using intravenous prostacyclin (PGI2). In the third series antibody depletion of the recipient was attempted using exchange transfusion with or without prostacyclin perfusion. The most significant (p less than 0.01) prolongation of graft survival time was observed when combining exchange transfusion (8 ml) and PGI2 infusion (620 ng/kg/min). This observation suggests that, if antibody depletion in the recipient is the primary goal, measures aiming at reducing the consequences of the antigen-antibody reaction are also necessary to improve the results of organ xenografting.

Animals↗
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[Rejection of discordant xenografts of the liver and heart].

Comparative study of the rejection of 26 heart and liver xenografts in strain discordant combination (guinea pig/rat lewis) allows the authors to establish the liver's weakest sensibility to natural xenoantibodies, the modesty of histological signs on liver xenograft rejection, and these lost's more longer survival. The results are compared to those obtained with 26 heart and liver isografts.

Animals↗
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[Subfulminant hepatitis A treated by hepatic transplant].

A case of subfulminant hepatitis A in a 3 1/2 year-old boy is reported. This child is alive after a liver transplantation. Such a procedure should modify the prognosis of severe hepatic failure whatever its origin, viral or toxic. Some practical problems concerning this new management of fulminant hepatitis are considered.

Child, Preschool↗
PubMedDate not supplied

[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↗
PubMedDate not supplied

[Correction of bilirubin glucuronyl transferase in Gunn rats by gene transfer in the liver using retroviral vectors].

The in vivo procedure for retrovirus-mediated gene transfer into rat liver allows genetic modification of 1 to 5% hepatocytes and the expression of a foreign gene for more than one year. We have used the Gunn rat as a model of the human Crigler-Najjar type I syndrome to assess the pertinence of this approach for the treatment of severe liver genetic diseases. After transfer of the rat bilirubin uridin diphosphate-glucuronosyl transferase cDNA into hepatocytes, 15 Gunn rats were examined during several months and sacrificed. Bilirubin glucuronides were excreted in the bile of all recipients, and serum bilirubin levels were significantly reduced in the treated population. The decrease was more than 40% in 5 of the 15 rats. These date showed that long term expression of a therapeutic protein can be obtain after in vivo retrovirus-mediated gene transfer into the liver.

Animals↗
PubMedDate not supplied

Temporary resolution of obstructive jaundice during ursodeoxycholic acid therapy in a patient with primary sclerosing cholangitis and a dominant biliary stricture.

Obstructive dominant biliary strictures are considered irreversible lesions in patients with primary sclerosing cholangitis; therapy with ursodeoxycholic acid has been shown to determine clinical, biochemical and histological improvement in such patients. To date, two reports of anatomical improvement of biliary tract lesions during ursodeoxycholic acid therapy have been published. We observed a 19-year-old male patient with primary sclerosing cholangitis who presented with severe cholestasis due to an obstructive dominant stricture of the common hepatic duct and absence of biliary excretion at cholescintigraphy. Oral administration of 900 mg/day ursodeoxycholic acid was followed by rapid decrease of jaundice and a normalization of life activity. Twelve months later a repeat cholescintigraphy showed normal biliary excretion. Despite continuing therapy, two years later the patient needed liver transplantation because of recurring severe obstructive jaundice. This report suggests that ursodeoxycholic acid may reverse a severe cholestatic syndrome in the course of primary sclerosing cholangitis despite a dominant stricture in the biliary tree. The mechanisms responsible for this effect are still obscure, but may involve restoration of bile flow through the biliary stricture. The late relapse during continuing therapy suggests that--at least in some patients--these effects may be temporary and ursodeoxycholic acid may lose its efficacy in the long term.

Administration, Oral↗