TY - JOUR A1 - Jordan, Martin C. A1 - Bröer, David A1 - Fischer, Christian A1 - Heilig, Philipp A1 - Gilbert, Fabian A1 - Hölscher-Doht, Stefanie A1 - Kalogirou, Charis A1 - Popp, Kevin A1 - Grunz, Jan-Peter A1 - Huflage, Henner A1 - Jakubietz, Rafael G. A1 - Ergün, Süleyman A1 - Meffert, Rainer H. T1 - Development and preclinical evaluation of a cable-clamp fixation device for a disrupted pubic symphysis JF - Communications Medicine N2 - Background Traumatic separation of the pubic symphysis can destabilize the pelvis and require surgical fixation to reduce symphyseal gapping. The traditional approach involves open reduction and the implantation of a steel symphyseal plate (SP) on the pubic bone to hold the reposition. Despite its widespread use, SP-fixation is often associated with implant failure caused by screw loosening or breakage. Methods To address the need for a more reliable surgical intervention, we developed and tested two titanium cable-clamp implants. The cable served as tensioning device while the clamp secured the cable to the bone. The first implant design included a steel cable anterior to the pubic symphysis to simplify its placement outside the pelvis, and the second design included a cable encircling the pubic symphysis to stabilize the anterior pelvic ring. Using highly reproducible synthetic bone models and a limited number of cadaver specimens, we performed a comprehensive biomechanical study of implant stability and evaluated surgical feasibility. Results We were able to demonstrate that the cable-clamp implants provide stability equivalent to that of a traditional SP-fixation but without the same risks of implant failure. We also provide detailed ex vivo evaluations of the safety and feasibility of a trans-obturator surgical approach required for those kind of fixation. Conclusion We propose that the developed cable-clamp fixation devices may be of clinical value in treating pubic symphysis separation. KW - pubic symphysis KW - cable-clamp implants KW - SP-fixation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299800 VL - 2 IS - 1 ER - TY - THES A1 - Fischer, Christian T1 - Die massive Expression von NF-ATc/A ist eine Eigenschaft Antigen-erfahrener Th1- und Th2-Zellen und trägt zur selektiven Induktion des IL-4 Promotors in Th2-Zellen bei T1 - The massive synthesis of NF-ATc/A is a property of antigen experienced Th1- and Th2-cells and contributes to the selective induction of the IL-4 promotor activity in Th2-cells N2 - Die Synthese des Transkriptionsfaktors NF-ATc erfolgt in drei Isoformen, die sich vor allem in der Länge ihrer C-terminalen Peptide unterscheiden und individuelle transaktivierende Eigenschaften besitzen. NF-ATc spielt eine wesentliche Rolle bei der Induktion des IL-4 Promotors sowie bei der Th2-Zelldifferenzierung. Mit Hilfe eines murinen in vitro T-Zelldifferenzierungsmodells konnten wir zeigen, dass nur die Expression der kurzen Isoform NF-ATc/A induziert wird, während die der längeren Isoformen NF-ATc/B und NF-ATc/C nahezu konstitutiv verläuft. Naive CD4+T-Zellen exprimieren nach dem ersten Antigen-Kontakt ausschließlich die beiden Isoformen NF-ATc/B und NF-ATc/C. Im Zuge der T-Zelldifferenzierung erlangen Antigen-erfahrene Th1- und Th2-Zellen schließlich die Fähigkeit zur massiven und induzierbaren de novo Synthese der kurzen Isoform NF-ATc/A. Dies wird infolge alternativer Spleiss- und Polyadenylierungsvorgänge durch die Benutzung einer proximalen, gering-affinen poly A-"site", pA1, ermöglicht, die nur bei hohen Konzentrationen von poly A-Faktoren – wie sie in Effektor-T-Zellen vorliegen – erkannt wird und in naiven T-Zellen inaktiv bleibt. Die massive Induktion von NF-ATc/A mit einer konsekutiven Änderung der Zusammensetzung an nukleären NF-ATc-Isoformen mit individuellen transaktivierenden Eigenschaften ermöglicht offenbar das Erreichen kritischer Schwellenwerte für Transkriptionsfaktoren und die Induktion spezifischer Zielgene. In diesem Zusammenhang wiesen unsere Ergebnisse die induzierbare und zellspezifische Bindung von NF-ATc an das cis-regulatorische Element Pu-bB des IL-4 Promotors in Th2-Zellen nach und belegen im besonderen, dass unterschiedliche Bindungseigenschaften von NF-ATc zu einer selektiven Expression des IL-4 Gens in Th2-Zellen beitragen. N2 - The transcription factor "nuclear factor of activated T-cells", NF-ATc, is synthesized in three prominent isoforms which differ in the length of their C-terminal peptides and their individual transcriptional properties. It is widely believed that NF-ATc plays a pivotal role in the induction of the IL-4 promotor and in Th2-cell differentiation. We show here using a murine in vitro T-cell differentiation model that the expression of the short isoform NF-ATc/A is highly inducible whereas the two longer isoforms NF-ATc/B and NF-ATc/C are constitutively expressed. Upon first antigen exposure of naive T-cells the two longer isoforms are synthesized at low levels. T-cell differentiation into effector Th-1 and Th2-cells leads to the massive induction of the short isoform NF-ATc/A upon second antigen exposure. This is due to alternative polyadenylation events and the usage of a more proximal poly-A site which remains silent in naive T-cells. This massive induction of NF-ATc/A ensures the rapid accumulation of high concentration of NF-ATc necessary to exceed critical threshold levels of NF-ATc for gene induction in effector T-cells. In this context we show the inducible binding of NF-ATc to the cis-regulatory element Pu-bB of the IL-4 promotor exclusively in Th2-cells revealing that cell specific binding properties of NF-ATc contribute to the selective induction of the IL-4 gene in Th2-cells. KW - NF-AT KW - Isoformen KW - IL-4 KW - T-Zelldifferenzierung KW - Polyadenylierung KW - NF-AT KW - isoforms KW - IL-4 KW - T-cell differentiation KW - polyadenylation Y1 - 2003 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-5135 ER -