Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-14120 Wissenschaftlicher Artikel Hopfner, Franziska; Schormair, Barbara; Knauf, Franziska; Berthele, Achim; Tölle, Thomas R.; Baron, Ralf; Maier, Christoph; Treede, Rolf-Detlef; Binder, Andreas; Sommer, Claudia; Maihöfner, Christian; Kunz, Wolfram; Zimprich, Friedrich; Heemann, Uwe; Pfeufer, Arne; Näbauer, Michael; Kääb, Stefan; Nowak, Barbara; Gieger, Christian; Lichtner, Peter; Trenkwalder, Claudia; Oexle, Konrad; Winkelmann, Juliane Novel SCARB2 mutation in Action Myoclonus-Renal Failure syndrome and evaluation of SCARB2 mutations in isolated AMRF features Background: Action myoclonus-renal failure syndrome is a hereditary form of progressive myoclonus epilepsy associated with renal failure. It is considered to be an autosomal-recessive disease related to loss-of-function mutations in SCARB2. We studied a German AMRF family, additionally showing signs of demyelinating polyneuropathy and dilated cardiomyopathy. To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features. Methods: In the AMRF family all exons of SCARB2 were analyzed by Sanger sequencing. The mutation screening of unrelated patients with isolated AMRF features affected by either epilepsy (n = 103, progressive myoclonus epilepsy or generalized epilepsy), demyelinating polyneuropathy (n = 103), renal failure (n = 192) or dilated cardiomyopathy (n = 85) was performed as high resolution melting curve analysis of the SCARB2 exons. Results: A novel homozygous 1 bp deletion (c.111delC) in SCARB2 was found by sequencing three affected homozygous siblings of the affected family. A heterozygous sister showed generalized seizures and reduction of nerve conduction velocity in her legs. No mutations were found in the epilepsy, renal failure or dilated cardiomyopathy samples. In the polyneuropathy sample two individuals with demyelinating disease were found to be carriers of a SCARB2 frameshift mutation (c.666delCCTTA). Conclusions: Our findings indicate that demyelinating polyneuropathy and dilated cardiomyopathy are part of the action myoclonus-renal failure syndrome. Moreover, they raise the possibility that in rare cases heterozygous SCARB2 mutations may be associated with PNP features. 2011 1-8 BMC Neurology 11 134 urn:nbn:de:bvb:20-opus-141209 10.1186/1471-2377-11-134 Neurologische Klinik und Poliklinik OPUS4-13034 Wissenschaftlicher Artikel Kim, Mia; Grimmig, Tanja; Grimm, Martin; Lazariotou, Maria; Meier, Eva; Rosenwald, Andreas; Tsaur, Igor; Blaheta, Roman; Heemann, Uwe; Germer, Christoph-Thomas; Waaga-Gasser, Ana Maria; Gasser, Martin Expression of Foxp3 in Colorectal Cancer but Not in Treg Cells Correlates with Disease Progression in Patients with Colorectal Cancer Background Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. Methods To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. Results Applying our algorithm to the data, 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. Conclusions PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression. 2013 e53630 PLoS ONE 8 1 urn:nbn:de:bvb:20-opus-130340 10.1371/journal.pone.0053630 Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) OPUS4-21416 Wissenschaftlicher Artikel Assfalg, Volker; Selig, Katharina; Tolksdorf, Johanna; van Meel, Marieke; de Vries, Erwin; Ramsoebhag, Anne-Marie; Rahmel, Axel; Renders, Lutz; Novotny, Alexander; Matevossian, Edouard; Schneeberger, Stefan; Rosenkranz, Alexander R.; Berlakovich, Gabriela; Ysebaert, Dirk; Knops, Noël; Kuypers, Dirk; Weekers, Laurent; Muehlfeld, Anja; Rump, Lars-Christian; Hauser, Ingeborg; Pisarski, Przemyslaw; Weimer, Rolf; Fornara, Paolo; Fischer, Lutz; Kliem, Volker; Sester, Urban; Stippel, Dirk; Arns, Wolfgang; Hau, Hans-Michael; Nitschke, Martin; Hoyer, Joachim; Thorban, Stefan; Weinmann-Menke, Julia; Heller, Katharina; Banas, Bernhard; Schwenger, Vedat; Nadalin, Silvio; Lopau, Kai; Hüser, Norbert; Heemann, Uwe Repeated kidney re-transplantation—the Eurotransplant experience: a retrospective multicenter outcome analysis In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT. 2020 14 Transplant International 33 6 617 631 urn:nbn:de:bvb:20-opus-214161 10.1111/tri.13569 Medizinische Klinik und Poliklinik I