Browsing by Author "Weyand, Michael"

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    Increased Transcript Levels of TNF-α, TGF-β, and Granzyme B in Endomyocardial Biopsies Correlate With Allograft Rejection
    (Başkent Üniversitesi, 2011-12) Ramsperger-Gleixner, Martina; Kondruweit, Markus; Ensminger, Stephan M.; Weyand, Michael; Amann, Kerstin; Tandler, René; Spriewald, Bernd M.
    Objectives: Endomyocardial biopsies are the criterion standard in diagnosing acute cardiac transplant rejection. This study sought to analyze mRNA expression profiles of various immune-response-related genes in endomyocardial biopsies of heart transplant patients and to correlate the results with histologic findings. Materials and Methods: Forty-three biopsies obtained from 6 heart transplant recipients experiencing acute rejection were analyzed for granzyme B, CTLA4, IL-6, TGFß, and TNFα expression using real-time polymerase chain reaction. The results were compared with the histologic findings. Biopsies obtained before, during, and after acute rejection episodes were grouped according to the International Society of Heart and Lung Transplantation standard biopsy grading from 1990. Group 1 consisted of biopsies with International Society of Heart and Lung Transplantation grade 0 (n=12), group 2 of International Society of Heart and Lung Transplantation grade 1A (n=14), and group 3 of International Society of Heart and Lung Transplantation grades 1B, 2, 3A, and 4 (n=17). Results: A strong correlation was seen between histologic groups and gene expression of granzyme B, which showed the highest overall transcript levels. CTLA4 was elevated in group 2, but no further increase in the rejecting group 3 was seen. For IL-6, TGFß and TNFα gene expression was strongly elevated in group 3 compared with groups 1 and 2. On analysis of biopsies with International Society of Heart and Lung Transplantation, grade 0 and 1A, relative to the time point of rejection, we found a substantial increase in mRNA expression of all analyzed immune response-related genes before a rejection episode. The strongest up-regulation was seen for granzyme B, TNFα, and TGFß. Conclusions: Our data suggest that analyses of gene expression provides valuable information in diagnosing heart transplant rejection. Furthermore, analyses of granzyme B, TGFß, and TNFα might not only confirm an ongoing rejection episode, but also may have a positive predictive value.
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    Reduction of Transplant Arteriosclerosis After Treatment With Mycophenolate Mofetil and Ganciclovir in a Mouse Aortic Allograft Model
    (Başkent Üniversitesi, 2012-12) Hoffmann, Julia; Steinkasserer, Alexander; Ensminger, Stephan M.; Weyand, Michael; Zinser, Elisabeth; Spriewald, Bernd M.; Ramsperger-Gleixner, Martina; Abele-Ohl, Silke; Böhm, Martin
    Objectives: Transplant arteriosclerosis is a major obstacle for long-term allograft survival in heart transplant. The aim of this study was to investigate potential synergistic effects of combined treatment with mycophenolate mofetil and ganciclovir on the development of transplant arteriosclerosis, presence of regulatory T cells, and expression of donor specific alloantibodies. Materials and Methods: Donor aortas from C57BL/6 (H2b) mice that were fully mismatched to the major histocompatibility complex were transplanted into CBA (H2k) mouse recipients. Groups of mice received mycophenolate mofetil (100 or 300 mg/kg, oral), ganciclovir (10 or 72 mg/kg, intraperitoneal), or a mycophenolate mofetil and ganciclovir combination. Grafts were analyzed by histology and morphometry on day 30 after transplant. Numbers of regulatory T cells and donor-specific alloantibodies were examined by fluorescence- activated cell sorting analysis of splenic tissue and peripheral blood. Results: Mycophenolate mofetil (100 mg/kg) and ganciclovir (10 mg/kg and 72 mg/kg) did not show effects on transplant arteriosclerosis formation or alloantibody production. However, groups treated with mycophenolate mofetil (300 mg/kg) or a low- or high-dose mycophenolate mofetil and ganciclovir combination had significantly reduced transplant arteriosclerosis and alloantibody levels. Expression of regulatory T cells within the spleen was similar between all experimental groups and untreated controls. Conclusions: The combination of mycophenolate mofetil and ganciclovir significantly reduced the development of transplant arteriosclerosis in a mouse abdominal aortic allograft model. This effect may be a result of decreased alloantibody production.