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  • Articles: DFG German National Licenses  (3)
  • Apoptosis  (3)
  • 1
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Apoptosis ; TUNEL method ; bax ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is well established that hepatocytes undergo apoptotic cell death in the course of rejection of liver grafts. The present study was designed to investigate the role of the bcl-2/bax pathway in liver allograft tissue. Orthotopic liver transplantation was performed in three groups of rats: group 1, a syngeneic combination (Lewis to Lewis), group 2, an allogeneic combination (ACI to Lewis), and group 3, an allogeneic combination (ACI to Lewis) treated with 15-deoxyspergualin. The number of apoptotic cells identified by the TUNEL method in the grafted liver reflected the severity of acute rejection. In group 1, both bcl-2 mRNA and bax mRNA were expressed in trace amounts. In group 2, bcl-2 mRNA was slightly expressed while the expression of bax mRNA rose steadily. In group 3, bcl-2 mRNA expression levels remained similar to group 1, while bax expression levels exceeded those in group 1, but were less than in group 2. Expression of bcl-2 mRNA was stationary in comparison with expression of bax mRNA. Significantly higher levels of bax mRNA were expressed from day 4 in group 2 than in group 1 (on postoperative days 4, 6, and 8, P 〈 0.05, group 2 vs group 1). We also investigated bax protein and results consistent with the mRNA analysis data were obtained. These findings suggest that apoptotic cell death in liver allograft rejection is regulated, at least in part, by bax.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Transplant international 11 (1998), S. S461 
    ISSN: 1432-2277
    Keywords: Key words Xenotransplantation ; FTY720 ; FK506 ; Apoptosis ; Hamster-to-rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to analyze the immunosuppressive activity of FTY720 in concordant xenotransplantation. When T and B lymphocytes of human peripheral blood were incubated with FTY720, the number of viable cells decreased in a dose-dependent manner at doses higher than 4×10−5 M. DNA fragmentation was observed at doses higher than 1×10−5 M in T cell-rich fractions and at doses higher than 4×10−5 M in B cell-rich fractions. These data demonstrate that FTY720 is cytotoxic to B lymphocytes as well as T lymphocytes and apoptosis may play an important role in this cytotoxicity. Golden Syrian hamsters were the donors and Lewis rats the recipients of skin grafts. The recipients were divided into the following four groups: (1) untreated recipients, (2) FTY720 (5 mg/kg per day) was administered orally for 8 days (days −1–6), (3) FK506 (1 mg/kg per day) was injected i. m. for 7 days (days 0–6), and (4) FK506 (1 mg/kg per day) was injected i. m. for 7 days (days 0–6) and FTY720 (5 mg/kg per day) was administered orally for 8 days (days −1–6). The mean graft survival times in groups 1–4 were 9.7 ± 0.52 days (n = 6), 12.0 ± 0.71 days (n = 6), 13.2 ± 1.6 days (n = 6), and 37.7 ± 4.3 days (n = 6), respectively. There was a significant difference in the mean survival time between groups one and four. Combined therapy with FTY720 and FK506 is a useful tool for immunoregulation in xenotransplantation.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Apoptosis ; bcl-2 ; bax ; bcl-x
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apoptosis is considered to play an important role in rejection of organ transplants, although the precise mechanism has not been elucidated. In this study, we screened for the expression of bcl-2 homologues (bcl-2, bax, bcl-xl, and bcl-xs) and Fas ligand (FasL) by RT–PCR method in grafts during acute rejection in rats following liver transplantation. Both bax and bcl-xs (inducers of apoptosis) mRNA levels increased steadily in the allografted group from postoperative day (POD) 2 to 8, while no remarkable changes of bcl-2 and bcl-xl expression (inhibitors of apoptosis) were recognized. Significant induction of FasL gene expression was observed in the allografted group on POD 4 and expression gradually decreased thereafter, although minimal FasL mRNA expression was seen in isografts. Our results indicated, for the first time, that rejection-induced cell apoptosis is closely associated with upregulation of bax and bcl-xs expression besides FasL, but not with down-regulation of bcl-xl.
    Type of Medium: Electronic Resource
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