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Y Calmus

Publications and source records attributed to Y Calmus.

At least 73 records · Page 4Linked to original sources
PubMed1995

Transplantation of allogeneic hepatocytes without immunosuppression: long-term survival.

BACKGROUND: Hepatocyte transplantation could be an alternative to whole liver transplantation. Allogeneic hepatocytes are rejected if transplanted without immunosuppression. The aim of this study was to transplant allogeneic hepatocytes in the peritoneum and to protect them from rejection by encapsulation in a new semipermeable membrane. METHODS: Rat hepatocytes were encapsulated in hydrogel-based hollow fibers, obtained from AN69 copolymer, before being transplanted into the peritoneum of rats. Outcome of allogeneic hepatocytes encapsulated in hollow fibers was compared with that of syngeneic hepatocytes encapsulated in hollow fibers, with that of free allogeneic hepatocytes, and with allogeneic hepatocytes encapsulated in hollow fibers left open. Cell viability was assessed by erythrosin exclusion, structure by electron microscopy, and function by albumin release. RESULTS: Up to 90 days, viability of allogeneic hepatocytes in hollow fibers was greater than 80%. The structure remained normal at electron microscopy. Albumin release was 16.5 +/- 0.3 micrograms/24 hr/10(6) hepatocytes (day 15), 14.2 +/- 2.0 micrograms/24 hr/10(6) hepatocytes (day 30), 8.8 +/- 0.1 micrograms/24 hr/10(6) hepatocytes (day 60), and 11.4 +/- 0.3 micrograms/24 hr/10(6) hepatocytes (day 90). Free hepatocytes and hepatocytes in hollow fibers left open did not survive at day 15. CONCLUSIONS: Viability and function of encapsulated allogeneic hepatocytes were maintained up to 90 days after transplantation, without immunosuppression.

Acrylic Resins↗
PubMed1994

Effects of bile acids and cholestasis on major histocompatibility complex class I in human and rat hepatocytes.

BACKGROUND/AIMS: Major histocompatibility complex (MHC) class I molecules, which are normally poorly expressed on the surface of hepatocytes, are overexpressed during cholestasis. The mechanisms responsible for this overexpression were examined. METHODS: The expression of class I molecules, assessed by flow cytofluorimetry, and the class I messenger RNA (mRNA) transcripts, assessed by Northern blot analysis, were measured on normal human hepatocytes in primary culture. RESULTS: Chenodeoxycholic acid induced an overexpression of MHC class I molecules, whereas ursodeoxycholic acid did not. The level of class I mRNA closely reflected that of the membrane protein. Moreover, cholestasis, induced in the rat by ligation-section of the common bile duct, increased the MHC class I mRNA level. Actinomycin D inhibited bile acid-induced class I transcription of rat hepatocytes in primary culture, whereas cycloheximide did not. Finally, class I mRNA expression was induced in hepatocytes by phorbol myristate acetate and by forskolin. This hyperexpression, as well as that observed with chenodeoxycholic acid, was suppressed by an inhibitor of protein kinase C and protein kinase A. CONCLUSIONS: Taken together, these results suggest that chenodeoxycholic acid, as interferon, activates protein kinase C and protein kinase A, resulting in the induction of MHC class I expression.

Adult↗
PubMed1994

The influence of cold ischemia time on biliary complications following liver transplantation.

Biliary complications are a continuing source of morbidity and mortality following orthotopic liver transplantation. The results of 100 whole-liver allografts performed in 92 adult patients were reviewed to determine whether cold ischemia time and preservation injury influenced both the incidence and type of biliary complications. Mean cold ischemia time was 10.2 +/- 0.5 h (range 3.6-19). Eighteen patients (19.6%) developed 25 biliary complications: there were eight anastomotic leaks, eight anastomotic strictures, six non-anastomotic strictures, two cystic duct mucoceles, and one biliary fistula following T-tube removal. Despite the high rate of reoperative surgery (68%), no death was attributable to biliary complications. Neither cold ischemia time nor early graft function influenced the rate of biliary complications or strictures of either type. Furthermore, an analysis of different factors revealed no predisposing effect of the pre-operative status of the recipient, type of biliary reconstruction, blood requirement, vascular complications, rejection or cytomegalovirus infection on the incidence of biliary complications or strictures. Only chronic rejection could be singled out as a risk factor for non-anastomotic strictures (p = 0.05). These results suggest that prolonged cold ischemia time does not seem to affect the rate or type of biliary complications following orthotopic liver transplantation. In view of these data, there is no clear reason to reconsider prolonged cold ischemia up to 15 h in University of Wisconsin solution, as it has transformed liver transplantation from an emergency operation to a semi-elective procedure and allows longer back-table preparation for graft reduction of splitting.

Adolescent↗
PubMed1994

Portal pumping: a new perspective for treatment of variceal hemorrhage and liver failure in end-stage cirrhosis?

In end-stage cirrhosis complicated by variceal hemorrhage, attempts to reduce portal pressure by treatments such as portosystemic shunts also decrease sinusoidal perfusion and risk impairing liver function. It has been suggested that encouraging portal flow to pass through the cirrhotic liver by mechanical action could cause a decrease in distal (splanchnic) portal pressure on one hand, and improve liver function on the other. The aim of this work was to evaluate the hemodynamic and functional effects of a 30-min pump-driven increase in portal blood flow through the liver of patients with end-stage cirrhosis before the anhepatic phase of liver transplantation. Basel portal flow (800 +/- 270 ml.min-1) was increased two fold (n = 10) or four fold (n = 9). When the flow was doubled, splanchnic portal pressure decreased 17.9 +/- 11.3% (from 31.8 +/- 5.3 to 26.0 +/- 5.8 mmHg, n = 10; p < 0.001); when flow was increased four fold, splanchnic portal pressure decreased 39.2 +/- 15.4% (from 32.8 +/- 5.0 to 19.9 +/- 6.0 mmHg, n = 9; p < 0.001). The comparison of indocyanine green clearance between basal and doubled portal flow demonstrated an increase of 32.1 +/- 26.9% (n = 5; p = 0.053). Histological analysis demonstrated sinusoidal dilatation in three out of ten livers. These results, as well as previous studies using isolated perfused cirrhotic rat or human livers, suggest that portal pumping should be explored as a treatment for certain sclerotherapy-resistant cirrhotic patients, with variceal hemorrhage and liver failure.

Adolescent↗
PubMed1994

Differential effects of chenodeoxycholic and ursodeoxycholic acids on expression of procoagulant activity by human monocytes.

Cell-mediated immunity is impaired during cholestasis, and there is evidence for the involvement of endogenous bile acids. The aim of this study was to evaluate the effects of individual bile acids on immunity and to determine whether monocytes are a target. The effects of bile acids on the procoagulant activity of human monocytes, a lymphocyte-dependent model of monocyte activation, were assessed. Chenodeoxycholic acid, one of the main human primary bile acids, had a concentration-dependent inhibitory effect on procoagulant activity expressed by endotoxin-stimulated mononuclear cells, with half-maximal and maximal inhibitions at 100 and 250 microM, respectively. The inhibitory concentrations were similar for the procoagulant activity of unstimulated mononuclear cells and for endotoxin-stimulated isolated monocytes. In contrast, ursodeoxycholic acid, a bile acid which has beneficial effects in cholestatic diseases, had no significant inhibitory effects at concentrations up to 250 microM. These results indicate that endogenous bile acids tend to inhibit monocyte activation, suggesting a potential role for primary endogenous bile acids in the immune defect associated with cholestasis; ursodeoxycholic acid, which is devoid of effects on the immune system, may potentially reverse cholestasis-induced immunodeficiency.

Blood Coagulation Factors↗
PubMed1994

Hyperacute xenograft rejection in the swine-to-human donor-recipient combination. In vitro analysis of complement activation.

Complement activation is central to the rejection of discordant xenografts. In order to assess the respective roles of direct and alternative pathways, an in vitro model of hyperacute rejection in the swine-to-human donor-recipient combination was designed, using a complement-dependent cytotoxicity test with swine endothelial cells in culture as targets, and fresh human serum as the source of xenogeneic antibodies and complement. The cytotoxic activity of the sera was evaluated by a colorimetric assay using (3-[4,5-dimethyldiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT). Pure human serum lysed 58 +/- 5% of swine endothelial cells. Selective inhibition of the direct pathway by adding EGTA to the serum reduced cytolysis to 51 +/- 2% (P < 0.01 versus normal serum). Similarly, when using C1q-deficient human sera, only 37 +/- 7% of swine endothelial cells were killed (P < 0.001 versus normal serum). When the alternative pathway was selectively inhibited by heating for 20 min at 50 degrees C, the lytic activity of human serum dropped to 42 +/- 5% (P < 0.001 versus normal serum). Factor B-deficient human serum could only lyse 42 +/- 10% of porcine endothelial cells (P < 0.001 versus normal serum). Syngeneic normal swine serum and heat-inactivated serum were not cytotoxic. Mixing serum with deficient direct pathway and serum with deficient alternative pathway restored the cytotoxicity to normal levels. Similarly, the cytotoxic activity of deficient serum supplemented with purified C1q or factor B at physiological concentrations reached that of normal human serum. In this model of in vitro hyperacute rejection, both pathways of complement activation are involved, suggesting that regimens designed to inhibit hyperacute rejection of swine xenografts into humans should take into account the dual activation of complement in this donor-recipient combination.

Acute Disease↗
PubMed1994

Distribution of hepatitis B virus DNA sequences in different peripheral blood mononuclear cell subsets in HBs antigen-positive and negative patients.

Hepatitis B virus (HBV) DNA sequences have been detected in leucocytes from HBV-infected individuals. The aim of this study was to assess the specificity of HBV for a special leucocyte subset in nine healthy chronic HBV carriers, nine HBs antigen-positive patients with chronic active hepatitis, 16 HBs antigen-negative haemophiliacs with HBc and/or HBs antibodies, and 10 patients with HBV-related systemic necrotizing vasculitis. HBV-DNA sequences were found by Southern blot hybridization in the leucocytes of 15 out of the 44 (34%) patients. The prevalence was not significantly different between the four groups. HBV-DNA was found in the CD4+ cells (9/11) as well as in the CD8+ cells (4/11), B cells (4/12) and monocytes (2/12). In conclusion, leucocytes, and particularly CD4+ lymphocytes, are frequently infected by HBV in patients with HBV serum markers.

Carrier State↗
PubMed1994

[Rejection of a liver allograft. Diagnosis and treatment].

Graft rejection remains a major problem in liver transplantation. The frequency of acute rejection is of the order of 50%. The first episode usually occurs around the 7th day. The diagnosis, suggested by clinical signs and biochemical abnormalities, is confirmed by histology. Three fundamental histological lesions are usually observed: portal infiltrate, biliary lesions and endothelitis. Chronic liver rejection is characterised by progressive reduction in the number of interlobular bile ducts. It affects 5 to 15% of transplant recipients, is refractory or poorly responsive to current immunosuppressant treatments and usually requires retransplantation. Prophylactic immunosuppression usually consists of a triple combination of cyclosporin-azathioprine-corticosteroids. FK 506 has been recently proposed. Corticosteroids inhibit the synthesis of interleukin 1 and reduce the synthesis of mediators of inflammation. Azathioprine is an antimetabolite which inhibits T lymphocyte cell division. Cyclosporin decreases lymphokine secretion. FK 506 can be used to treat acute rejection resistant to other immunosuppressants and may prevent chronic rejection. Cyclosporin is started at low doses and gradually increased until the desired serum concentration is obtained. Regular monitoring of serum cyclosporin levels is essential to reduce the adverse effects of this drug. The doses of corticosteroids are gradually decreased to achieve a maintenance dose (10-30 mg/day). Azathioprine is commenced postoperatively (0.5 to 1.5 mg/kg/day). In the long term, azathioprine should be suspended and the dosage of corticosteroids should be reduced. The initial treatment of rejection consists of bolus injections of corticosteroids: 10 to 15 mg/kg/day of i.v. methylprednisolone for 2 or 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

[Transplantation of allogeneic hepatocytes without immunosuppression: long term survival].

UNLABELLED: Hepatocyte transplantation could be an alternative to whole liver transplantation. Allogeneic hepatocytes are rejected if transplanted without immunosuppression. The aim of this study was to transplant allogeneic hepatocytes in the peritoneum and to protect them from rejection by encapsulation in a new semi-permeable membrane. METHODS: Rats hepatocytes were encapsulated in hydrogel-based hollow fibers, obtained from AN69 polymer, before being transplanted into the peritoneum of rats. Outcome of allogeneic hepatocytes encapsulated in hollow fibers was compared to that of free allogeneic hepatocytes. Cell viability was assessed by erythrosine exclusion, morphology by electronic microscopy and function by albumin release. RESULTS: Up to 90 days, viability of allogenic hepatocytes in hollow fibers was above 80%. The morphology remained normal at electronic microscopy. Albumin release was 16.5 +/- 0.3 (day 15), 14.2 +/- 2.0 (day 30), 8.8 +/- 0.1 (day 60) and 11.4 +/- 0.3 micrograms/24 h/10(6) hepatocytes (day 90). Free hepatocytes did not survive at day 15. CONCLUSION: Viability and function of encapsulated allogeneic hepatocytes were maintained up to 90 days after transplantation, without immunosuppression.

Animals↗
PubMed1994

Inhibition of procoagulant activity of human monocytes by chenodeoxycholic acid: involvement of protein kinase C.

Endogenous bile acids such as chenodeoxycholic acid have been shown to display a suppressive effect in vitro on mononuclear cell activation. We investigated the signal transduction pathway involved in the effect of chenodeoxycholic acid on monocyte procoagulant activity, a model of monocyte activation. Chenodeoxycholic acid (25 to 250 mumol/L) had a concentration-dependent inhibitory effect on procoagulant activity expressed by endotoxin-stimulated mononuclear cells, with half-maximal and maximal inhibition occurring at concentrations of 100 and 250 mumol/L, respectively. The inhibitory effect of chenodeoxycholic acid was (a) closely mimicked by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), a protein kinase C activator, but not by forskolin or dibutyryl cyclic AMP, two activators of the protein kinase A-dependent pathway; (b) prevented by staurosporine, a potent protein kinase C inhibitor; (c) partially abolished in protein kinase C-depleted cells; and (d) observed in conditions under which chenodeoxycholic acid, like PMA, significantly increased (41%) protein kinase C activity, as assessed by phosphorylation of exogenous (histone III-S) and endogenous (37-kD protein) substrates. In conclusion, our results (a) provide clear evidence of a marked inhibitory effect of chenodeoxycholic acid on monocyte activation, suggesting a potential role of primary endogenous bile acids in the immune defect associated with cholestasis; and (b) indicate that the inhibition of monocyte activation by chenodeoxycholic acid is mediated by way of protein kinase C activation.

Alkaloids↗
PubMed1993

Immunogenicity of rat hepatocytes in vivo: effect of cholestasis-induced changes in major histocompatibility complex expression.

Hepatocytes normally express few major histocompatibility complex (MHC) class I and no MHC class II molecules, a phenomenon which could explain their low immunogenicity. However, in pathological situations, such as allograft rejection and cholestasis, hepatocytes strongly express MHC class I molecules and their immunogenicity could be different. The aim of this study was to assess the role of MHC expression on the immunogenicity of hepatocytes in vivo. Hepatocytes were obtained from normal and cholestatic DA rats by whole-liver perfusion with EDTA. Cholestasis was induced by ligation-section of the common bile duct. MHC expression on hepatocytes was assessed by cytofluorimetry after labelling with monoclonal antibodies against MHC class I and class II antigens. The percentage of hepatocytes expressing MHC class I was 9.8 +/- 2.2% in normal rats and 77.2 +/- 3.3% in cholestatic rats (P = 2 x 10(-4)); MHC class II expression was present on 1 +/- 0.5% of normal hepatocytes and 0.4% +/- 0.1% of cholestatic hepatocytes (P > 0.05). Lewis rats received a DA or Wistar-Furth heart allograft 7 days after intravenous injection of 2 x 10(7) hepatocytes from normal or cholestatic DA rats. The DA heart allograft was rejected in 6.3 +/- 0.4 days in Lewis controls, 8.8 +/- 1.1 days (N.S.) in Lewis recipients that received normal DA hepatocytes and 17.6 +/- 3.0 days (P = 2 x 10(-4)) in Lewis recipients that received hepatocytes from cholestatic DA rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗