Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 14/19 Archiv

Der Ansatzpunkt der vorliegenden Arbeit zum Thema „Die Münchner Chirurgen Julius Fessler und Paul Ziegler und die Besetzung des ersten Zahnmedizinischen Lehrstuhls an der Ludwig-Maximilians-Universität München“ ist deren Bewerbung 1898 um die Stelle des Vorstands der neu zu errichtenden Zahnärztlichen Lehranstalt der Ludwig-Maximilians-Universität München. Am Beispiel der Lebenswege dieser beiden Mediziner soll der Frage nachgegangen werden, weshalb sich speziell Chirurgen für die damals junge Fachrichtung Zahnmedizin interessierten.

Gene therapy can be used to treat devastating inherited diseases, especially diseases and patients that are not suitable for a conventional cure. The blood clotting disorder hemophilia is one of the most extensively studied monogenetic diseases in gene therapeutic approaches. Several viral vectors were tested for the treatment of hemophilia B. The administration of an episomal adenoviral vector at non-toxic dose showed effective phenotypic correction, but the therapeutic effect was only transient. Therefore, the combination of non-viral integration machineries for somatic integration with adenoviral vectors for efficient delivery offers a promising alternative for achieving persistent transgene expression. Towards this end, the delivery of the Sleeping Beauty transposase (SB) integration machinery via high-capacity adenoviral vectors (HC-AdVs) has demonstrated efficient hepatocyte-directed gene transfer and long-term coagulation factor IX expression in vivo. However, the safety issues of this adenoviral vector/Sleeping Beauty transposase (AdV/SB) hybrid-vector system, especially the vector dose-effect and genotoxicity were not addressed yet. Thus, I evaluated this hybrid-vector system in both mice and a canine model for hemophilia B with different vector dose settings, and analyzed the integration profile in respect to genotoxicity after systemic administration. First of all, the viral vector preparations involved in the AdV/SB hybrid-vector studies were analyzed regarding physical and infectious titers. To avoid toxic side effects, the helper virus (HV) contamination levels were quantified and the potential existence of replication-competent adenovirus (RCA) in final vector preparations was excluded by quantitative real-time PCR. Only the HC-AdV preparations with high amounts of transducing units (107-108 TUs/µl), low HV contamination levels (

Biografische Darstellung der Lebenswege jüdischer Kinderärzte, die am Dr. von Haunerschen Kinderspital in München tätig waren und Opfer nationalsozialistischer Verfolgung wurden