TY - JOUR A1 - Assfalg, Volker A1 - Selig, Katharina A1 - Tolksdorf, Johanna A1 - van Meel, Marieke A1 - de Vries, Erwin A1 - Ramsoebhag, Anne‐Marie A1 - Rahmel, Axel A1 - Renders, Lutz A1 - Novotny, Alexander A1 - Matevossian, Edouard A1 - Schneeberger, Stefan A1 - Rosenkranz, Alexander R. A1 - Berlakovich, Gabriela A1 - Ysebaert, Dirk A1 - Knops, Noël A1 - Kuypers, Dirk A1 - Weekers, Laurent A1 - Muehlfeld, Anja A1 - Rump, Lars‐Christian A1 - Hauser, Ingeborg A1 - Pisarski, Przemyslaw A1 - Weimer, Rolf A1 - Fornara, Paolo A1 - Fischer, Lutz A1 - Kliem, Volker A1 - Sester, Urban A1 - Stippel, Dirk A1 - Arns, Wolfgang A1 - Hau, Hans‐Michael A1 - Nitschke, Martin A1 - Hoyer, Joachim A1 - Thorban, Stefan A1 - Weinmann‐Menke, Julia A1 - Heller, Katharina A1 - Banas, Bernhard A1 - Schwenger, Vedat A1 - Nadalin, Silvio A1 - Lopau, Kai A1 - Hüser, Norbert A1 - Heemann, Uwe T1 - Repeated kidney re‐transplantation—the Eurotransplant experience: a retrospective multicenter outcome analysis JF - Transplant International N2 - 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. KW - allocation KW - child KW - fourth KW - graft KW - kidney KW - loss KW - repeated KW - re‐transplantation KW - survival KW - third Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214161 VL - 33 IS - 6 SP - 617 EP - 631 ER - TY - JOUR A1 - Tony, Hans-Peter A1 - Burmester, Gerd A1 - Schulze-Koops, Hendrik A1 - Grunke, Mathias A1 - Henes, Joerg A1 - Kötter, Ina A1 - Haas, Judith A1 - Unger, Leonore A1 - Lovric, Svjetlana A1 - Haubitz, Marion A1 - Fischer-Betz, Rebecca A1 - Chehab, Gamal A1 - Rubbert-Roth, Andrea A1 - Specker, Christof A1 - Weinerth, Jutta A1 - Holle, Julia A1 - Müller-Ladner, Ulf A1 - König, Ramona A1 - Fiehn, Christoph A1 - Burgwinkel, Philip A1 - Budde, Klemens A1 - Sörensen, Helmut A1 - Meurer, Michael A1 - Aringer, Martin A1 - Kieseier, Bernd A1 - Erfurt-Berge, Cornelia A1 - Sticherling, Michael A1 - Veelken, Roland A1 - Ziemann, Ulf A1 - Strutz, Frank A1 - von Wussow, Praxis A1 - Meier, Florian MP A1 - Hunzelmann, Nico A1 - Schmidt, Enno A1 - Bergner, Raoul A1 - Schwarting, Andreas A1 - Eming, Rüdiger A1 - Schwarz-Eywill, Michael A1 - Wassenberg, Siegfried A1 - Fleck, Martin A1 - Metzler, Claudia A1 - Zettl, Uwe A1 - Westphal, Jens A1 - Heitmann, Stefan A1 - Herzog, Anna L. A1 - Wiendl, Heinz A1 - Jakob, Waltraud A1 - Schmidt, Elvira A1 - Freivogel, Klaus A1 - Dörner, Thomas A1 - Hertl, Michael A1 - Stadler, Rudolf T1 - Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID) JF - Arthritis Research & Therapy N2 - Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm) KW - GRAID Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142856 VL - 13 IS - R75 ER - TY - JOUR A1 - Aeschlimann, Martin A1 - Bauer, Michael A1 - Bayer, Daniela A1 - Brixner, Tobias A1 - Cunovic, Stefan A1 - Fischer, Alexander A1 - Melchior, Pascal A1 - Pfeiffer, Walter A1 - Rohmer, Martin A1 - Schneider, Christian A1 - Strüber, Christian A1 - Tuchscherer, Philip A1 - Voronine, Dimitri V. T1 - Optimal open-loop near-field control of plasmonic nanostructures N2 - Optimal open-loop control, i.e. the application of an analytically derived control rule, is demonstrated for nanooptical excitations using polarization-shaped laser pulses. Optimal spatial near-field localization in gold nanoprisms and excitation switching is realized by applying a shift to the relative phase of the two polarization components. The achieved near-field switching confirms theoretical predictions, proves the applicability of predefined control rules in nanooptical light–matter interaction and reveals local mode interference to be an important control mechanism. KW - Chemie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75256 ER - TY - JOUR A1 - Rau, Markus A1 - Heindel, Tobias A1 - Unsleber, Sebastian A1 - Braun, Tristan A1 - Fischer, Julian A1 - Frick, Stefan A1 - Nauerth, Sebastian A1 - Schneider, Christian A1 - Vest, Gwenaelle A1 - Reitzenstein, Stephan A1 - Kamp, Martin A1 - Forchel, Alfred A1 - Höfling, Sven A1 - Weinfurter, Harald T1 - Free space quantum key distribution over 500 meters using electrically driven quantum dot single-photon sources-a proof of principle experiment JF - New Journal of Physics N2 - Highly efficient single-photon sources (SPS) can increase the secure key rate of quantum key distribution (QKD) systems compared to conventional attenuated laser systems. Here we report on a free space QKD test using an electrically driven quantum dot single-photon source (QD SPS) that does not require a separate laser setup for optical pumping and thus allows for a simple and compact SPS QKD system. We describe its implementation in our 500 m free space QKD system in downtown Munich. Emulating a BB84 protocol operating at a repetition rate of 125 MHz, we could achieve sifted key rates of 5-17 kHz with error ratios of 6-9% and g((2))(0)-values of 0.39-0.76. KW - QKD KW - electrically driven KW - free space KW - quantum dots KW - quantum key distribution Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116760 VL - 16 IS - 043003 ER - TY - THES A1 - Fischer, Stefan Martin T1 - Regulation and functional consequences of MCP-1 expression in a model of Charcot-Marie-Tooth 1B disease T1 - Regulation und funktionelle Relevanz von MCP-1 in einem Model der Charcot-Marie-Tooth 1B Erkrankung N2 - Charcot-Marie-Tooth 1B (CMT1B) is a progressive inherited demyelinating disease of human peripheral nervous system leading to sensory and/or motor function disability and is caused by mutations in the P0 gene. Mice heterozygously deficient for P0 (P0+/-) are an adequate model of this human disorder showing myelin degeneration, formation of onion bulbs, remyelination and a reduced motor conduction velocity of around 30m/s similar to patients. Previously, it had been shown that T-lymphocytes and macrophages play a crucial role during pathogenesis in peripheral nerves of P0+/- mice. Both, T-lymphocytes and macrophages increase in number in the endoneurium and deletion of T-lymphocytes or deletion of a macrophage-directed cytokine ameliorates the disease. In this study the monocyte chemoattractant protein-1 (MCP-1) was identified as an early regulated cytokine before onset of disease is visible at the age of six months. MCP-1 mRNA and protein expression could be detected in femoral quadriceps and sciatic nerves of P0+/- mice already at the age of one month but not in cutaneous saphenous nerves which are never affected by the disease. MCP-1 was shown to be expressed by Schwann cells and to mediate the immigration of immune cells into peripheral nerves. Deletion of MCP-1 in P0+/- mice accomplished by crossbreeding P0 and MCP-1 deficient mice revealed a substantial reduction of immune cells in peripheral nerves of P0+/-/MCP-1+/- and P0+/-/MCP-1-/- mice at the age of six months. In twelve months old mice reduction of immune cells in peripheral nerves is accompanied by amelioration of demyelinating disease in P0+/-/MCP-1+/- and aggravation of demyelinating disease in lumbar ventral roots of P0+/ /MCP-1-/- mice in comparison to P0+/ /MCP 1+/+ mice. Furthermore, activation of the MEK1/2-ERK1/2 signalling cascade could be demonstrated to take place in Schwann cells of affected peripheral nerves of P0+/- mice overlapping temporarily and spatially with MCP-1 expression. An animal experiment using a MEK1/2-inhibitor in vivo, CI-1040, revealed that upon reduction of ERK1/2 phosphorylation MCP-1 mRNA expression is diminished suggesting that the activation of the MEK1/2-ERK1/2 signalling cascade is necessary for MCP-1 expression. Additionally, peripheral nerves of P0+/- mice showing reduced ERK1/2 phosphorylation and MCP-1 mRNA expression also show reduced numbers of macrophages in the endoneurium. This study shows a molecular link between a Schwann cell based mutation and immune cell function. Inhibition of the identified signalling cascade might be a putative target for therapeutic approaches. N2 - Die humane Erkrankung Charcot-Marie-Tooth 1B (CMT1B) ist eine erbliche, chronisch fortschreitende Erkrankung des peripheren Nervensystems die durch Mutation des P0-Gens verursacht wird und zu motorischen und/oder sensorischen Defiziten führt. Sehr ähnlich der humanen Erkrankung weist das Mausmodell, eine für das Myelinprotein P0 heterozygot-defiziente Maus (P0+/-), Degeneration peripheren Myelins, aufeinanderfolgende Zyklen von De- und Remyelinisierung als auch reduzierte Nervenleitgeschwindigkeiten auf. Wissenschaftliche Untersuchungen am Mausmodell ergaben eine Beteiligung von T-Lymphozyten und Makrophagen an der Pathogenese. In dieser Studie wurde das Chemokin „Monocyte Chemoattractant Protein-1“ (MCP-1) als pathogen-relevant in P0+/- Mäusen identifiziert. MCP-1 mRNA und Protein wurden sowohl im Alter von sechs und zwölf Monaten nachgewiesen, Stadien, in denen morphologische Veränderungen peripherer Nerven von P0+/- Mäusen zu erkennen sind, aber auch im Alter von einen und drei Monaten, ein Alter bei dem pathologischen Veränderungen nicht zu finden sind. Mit Hilfe von MCP-1 defizienten Mäusen (MCP-1-/-) und Verpaarung mit P0-defizienten Mäusen konnten weiterführende Untersuchungen zur Rolle von MCP-1 im peripheren Nerv der Maus durchgeführt werden. So zeigte es sich mittels Transplantation von GFP-positivem Knochenmark, dass MCP 1 die Infiltration von Makrophagen aus dem Blut in periphere Nerven vermittelt. Weiterhin konnte gezeigt werden, dass periphere Nerven von sechs Monate alten P0+/-/MCP-1+/- und P0+/-/MCP-1-/- Mäusen trotz signifikant niedrigerer Anzahl von Immunzellen keine Milderung der Demyelinisierung zeigen. Hingegen weisen periphere Nerven von zwölf Monate alten P0+/ /MCP-1+/- Mäusen sowohl weniger Makrophagen und T-Lymphozyten als auch wesentlich weniger pathologische Veränderungen auf. Periphere Nerven von P0+/-/MCP-1-/- Tieren dagegen zeigen nur eine nicht signifikante Reduktion von Immunzellen und sogar eine Verschlechterung des Phänotyps im Vergleich zu ventralen Spinalwurzeln von P0+/-/MCP-1+/+ Mäusen. Weiterführende Untersuchungen ergaben, dass eine Aktivierung der MEK1/2-ERK1/2 Signalkaskade sowohl in peripheren Nerven von drei und sechs Monate alten P0+/- Mäusen zu finden ist, allerdings, ähnlich der Expression von MCP-1, nur in peripheren Nerven, die von der Demyelinisierung betroffen sein können. Unter Verwendung eines Inhibitors der Kinasen MEK1 und 2 konnte in vivo gezeigt werden, dass Phosphorylierung von ERK1/2 für die erhöhte MCP-1 Expression in peripheren Nerven von P0+/- Mäusen notwendig ist. Darüber hinaus wurde durch Verminderung der ERK1/2-Phosphorylierung eine Reduktion von Makrophagen im Endoneurium von P0+/- Tieren erzielt. KW - Schwann-Zelle KW - Peripheres Nervensystem KW - Charcot-Marie-Syndrom KW - Makrophage KW - Entmarkung KW - Myelin KW - Chemokine KW - Schwann cell KW - Peripheral nervous system KW - Charcot-Marie-Tooth syndrom KW - Macrophage KW - Demyelination KW - Myelin KW - Chemokine Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-29189 ER -