@article{JobsVontheinKoenigetal.2020, author = {Jobs, Alexander and Vonthein, Reinhard and K{\"o}nig, Inke R. and Sch{\"a}fer, Jane and Nauck, Matthias and Haag, Svenja and Fichera, Carlo Federico and Stiermaier, Thomas and Ledwoch, Jakob and Schneider, Alisa and Valentova, Miroslava and von Haehling, Stephan and St{\"o}rk, Stefan and Westermann, Dirk and Lenz, Tobias and Arnold, Natalie and Edelmann, Frank and Seppelt, Philipp and Felix, Stephan and Lutz, Matthias and Hedwig, Felix and Borggrefe, Martin and Scherer, Clemens and Desch, Steffen and Thiele, Holger}, title = {Inferior vena cava ultrasound in acute decompensated heart failure: design rationale of the CAVA-ADHF-DZHK10 trial}, series = {ESC Heart Failure}, volume = {7}, journal = {ESC Heart Failure}, number = {3}, doi = {10.1002/ehf2.12598}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212692}, pages = {973 -- 983}, year = {2020}, abstract = {Aims Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right-sided haemodynamic congestion. The CAVA-ADHF-DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone. Methods and results CAVA-ADHF-DZHK10 is a randomized, controlled, patient-blinded, multicentre, parallel-group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion-related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50\% in the intervention group. The primary endpoint is change in N-terminal pro-brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints. Conclusions CAVA-ADHF-DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF.}, language = {en} } @article{ZlamyAlmanzarParsonetal.2016, author = {Zlamy, Manuela and Almanzar, Giovanni and Parson, Walther and Schmidt, Christian and Leierer, Johannes and Weinberger, Birgit and Jeller, Verena and Unsinn, Karin and Eyrich, Matthias and W{\"u}rzner, Reinhard and Prelog, Martina}, title = {Efforts of the human immune system to maintain the peripheral CD8+ T cell compartment after childhood thymectomy}, series = {Immunity \& Ageing}, volume = {13}, journal = {Immunity \& Ageing}, number = {3}, doi = {10.1186/s12979-016-0058-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146497}, year = {2016}, abstract = {Background Homeostatic mechanisms to maintain the T cell compartment diversity indicate an ongoing process of thymic activity and peripheral T cell renewal during human life. These processes are expected to be accelerated after childhood thymectomy and by the influence of cytomegalovirus (CMV) inducing a prematurely aged immune system. The study aimed to investigate proportional changes and replicative history of CD8+ T cells, of recent thymic emigrants (RTEs) and CD103+ T cells (mostly gut-experienced) and the role of Interleukin-(IL)-7 and IL-7 receptor (CD127)-expressing T cells in thymectomized patients compared to young and old healthy controls. Results Decreased proportions of naive and CD31 + CD8+ T cells were demonstrated after thymectomy, with higher proliferative activity of CD127-expressing T cells and significantly shorter relative telomere lengths (RTLs) and lower T cell receptor excision circles (TRECs). Increased circulating CD103+ T cells and a skewed T cell receptor (TCR) repertoire were found after thymectomy similar to elderly persons. Naive T cells were influenced by age at thymectomy and further decreased by CMV. Conclusions After childhood thymectomy, the immune system demonstrated constant efforts of the peripheral CD8+ T cell compartment to maintain homeostasis. Supposedly it tries to fill the void of RTEs by peripheral T cell proliferation, by at least partly IL-7-mediated mechanisms and by proportional increase of circulating CD103+ T cells, reminiscent of immune aging in elderly. Although other findings were less significant compared to healthy elderly, early thymectomy demonstrated immunological alterations of CD8+ T cells which mimic features of premature immunosenescence in humans.}, language = {en} } @article{ReinhardHalbrueggeScheeretal.1992, author = {Reinhard, Matthias and Halbr{\"u}gge, Maria and Scheer, Ulrich and Wiegand, Christiane and Jockusch, Brigitte M. and Walter, Ulrich}, title = {The 46/50 kDa phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-34246}, year = {1992}, abstract = {Vasoactive agents which elevate either cGMP or cAMP inhibit platelet activation by pathways sharing at least one component, the 46/50 kDa vasodilator-stimulated phosphoprotein (V ASP). V ASP is stoichiometrically phosphorylated by both cGMP-dependent and cAMPdependent protein kinases in intact human platelets, and its phosphorylation correlates very well with platelet inhibition caused by cGMP- and cAMP-elevating agents. Here we report that in human platelets spread on glass, V ASP is associated predominantly with the distal parts of radial micro filament bundles and with microfilaments outlining the periphery, whereas less V ASP is associated with a central microfilamentous ring. V ASP is also detectable in a variety of different cell types including fibroblasts and epithelial cells. In fibroblasts, V ASP is concentrated at focal contact areas, along microfilament bundles (stress fibres) in a punctate pattern, in the periphery of protruding lamellae, and is phosphorylated by cGMP- and cAMP-dependent protein kinases in response to appropriate stimuli. Evidence for the direct binding of V ASP to F -actin is also presented. The data demonstrate that V ASP is a novel phosphoprotein associated with actin filaments and focal contact areas, i.e. transmembrane junctions between microfilaments and the extracellular matrix.}, language = {de} } @article{BartelheimNemesSeeringeretal.2016, author = {Bartelheim, Kerstin and Nemes, Karolina and Seeringer, Angela and Kerl, Kornelius and Buechner, Jochen and Boos, Joachim and Graf, Norbert and D{\"u}rken, Matthias and Gerss, Joachim and Hasselblatt, Martin and Kortmann, Rolf-Dieter and Teichert von Luettichau, Irene and Nagel, Inga and Nygaard, Randi and Oyen, Florian and Quiroga, Eduardo and Schlegel, Paul-Gerhardt and Schmid, Irene and Schneppenheim, Reinhard and Siebert, Reiner and Solano-Paez, Palma and Timmermann, Beate and Warmuth-Metz, Monika and Fr{\"u}hwald, Michael Christoph}, title = {Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007}, series = {Cancer Medicine}, volume = {5}, journal = {Cancer Medicine}, number = {8}, doi = {10.1002/cam4.741}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164799}, pages = {1765-1775}, year = {2016}, abstract = {Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64\% (genetic analyses, FISH, MLPA, sequencing) up to 97\% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46\% (±0.10) and 45\% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.}, language = {en} } @article{WildgruberAschenbrennerWendorffetal.2016, author = {Wildgruber, Moritz and Aschenbrenner, Teresa and Wendorff, Heiko and Czubba, Maria and Glinzer, Almut and Haller, Bernhard and Schiemann, Matthias and Zimmermann, Alexander and Berger, Hermann and Eckstein, Hans-Henning and Meier, Reinhard and Wohlgemuth, Walter A. and Libby, Peter and Zernecke, Alma}, title = {The "Intermediate" CD14\(^{++}\)CD16\(^{+}\) monocyte subset increases in severe peripheral artery disease in humans}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, number = {39483}, doi = {10.1038/srep39483}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167476}, year = {2016}, abstract = {Monocytes are key players in atherosclerotic. Human monocytes display a considerable heterogeneity and at least three subsets can be distinguished. While the role of monocyte subset heterogeneity has already been well investigated in coronary artery disease (CAD), the knowledge about monocytes and their heterogeneity in peripheral artery occlusive disease (PAOD) still is limited. Therefore, we aimed to investigate monocyte subset heterogeneity in patients with PAOD. Peripheral blood was obtained from 143 patients suffering from PAOD (Rutherford stage I to VI) and three monocyte subsets were identified by flow cytometry: CD14\(^{++}\)CD16\(^{-}\) classical monocytes, CD14\(^{+}\)CD16\(^{++}\) non-classical monocytes and CD14\(^{++}\)CD16\(^{+}\) intermediate monocytes. Additionally the expression of distinct surface markers (CD106, CD162 and myeloperoxidase MPO) was analyzed. Proportions of CD14\(^{++}\)CD16\(^{+}\) intermediate monocyte levels were significantly increased in advanced stages of PAOD, while classical and non-classical monocytes displayed no such trend. Moreover, CD162 and MPO expression increased significantly in intermediate monocyte subsets in advanced disease stages. Likewise, increased CD162 and MPO expression was noted in CD14\(^{++}\)CD16\(^{-}\) classical monocytes. These data suggest substantial dynamics in monocyte subset distributions and phenotypes in different stages of PAOD, which can either serve as biomarkers or as potential therapeutic targets to decrease the inflammatory burden in advanced stages of atherosclerosis.}, language = {en} } @article{TrinksReinhardDrobnyetal.2021, author = {Trinks, Nora and Reinhard, Sebastian and Drobny, Matthias and Heilig, Linda and L{\"o}ffler, J{\"u}rgen and Sauer, Markus and Terpitz, Ulrich}, title = {Subdiffraction-resolution fluorescence imaging of immunological synapse formation between NK cells and A. fumigatus by expansion microscopy}, series = {Communications Biology}, volume = {4}, journal = {Communications Biology}, number = {1}, doi = {10.1038/s42003-021-02669-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264996}, year = {2021}, abstract = {Expansion microscopy (ExM) enables super-resolution fluorescence imaging on standard microscopes by physical expansion of the sample. However, the investigation of interactions between different organisms such as mammalian and fungal cells by ExM remains challenging because different cell types require different expansion protocols to ensure identical, ideally isotropic expansion of both partners. Here, we introduce an ExM method that enables super-resolved visualization of the interaction between NK cells and Aspergillus fumigatus hyphae. 4-fold expansion in combination with confocal fluorescence imaging allows us to resolve details of cytoskeleton rearrangement as well as NK cells' lytic granules triggered by contact with an RFP-expressing A. fumigatus strain. In particular, subdiffraction-resolution images show polarized degranulation upon contact formation and the presence of LAMP1 surrounding perforin at the NK cell-surface post degranulation. Our data demonstrate that optimized ExM protocols enable the investigation of immunological synapse formation between two different species with so far unmatched spatial resolution.}, language = {en} } @article{NemesJohannSteinbuegletal.2022, author = {Nemes, Karolina and Johann, Pascal D. and Steinb{\"u}gl, Mona and Gruhle, Miriam and Bens, Susanne and Kachanov, Denis and Teleshova, Margarita and Hauser, Peter and Simon, Thorsten and Tippelt, Stephan and Eberl, Wolfgang and Chada, Martin and Lopez, Vicente Santa-Maria and Grigull, Lorenz and Hern{\´a}iz-Driever, Pablo and Eyrich, Matthias and Pears, Jane and Milde, Till and Reinhard, Harald and Leipold, Alfred and van de Wetering, Marianne and Gil-da-Costa, Maria Jo{\~a}o and Ebetsberger-Dachs, Georg and Kerl, Kornelius and Lemmer, Andreas and Boztug, Heidrun and Furtw{\"a}ngler, Rhoikos and Kordes, Uwe and Vokuhl, Christian and Hasselblatt, Martin and Bison, Brigitte and Kr{\"o}ncke, Thomas and Melchior, Patrick and Timmermann, Beate and Gerss, Joachim and Siebert, Reiner and Fr{\"u}hwald, Michael C.}, title = {Infants and newborns with atypical teratoid rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors (eMRT) in the EU-RHAB registry: a unique and challenging population}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {9}, issn = {2072-6694}, doi = {10.3390/cancers14092185}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270730}, year = {2022}, abstract = {Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005-2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27\% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55\% (47/86). DNA methylation subgrouping was available in 50\% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6\% and 19 ± 4.1\%, respectively. Male sex (11 ± 5\% vs. 35.8 ± 7.4\%), M+ stage (6.1 ± 5.4\% vs. 36.2 ± 7.4\%), presence of SYN (7.1 ± 6.9\% vs. 26.6 ± 5.3\%) and GLM (7.7 ± 4.2\% vs. 45.7 ± 8.6\%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option.}, language = {en} } @article{StolteHechtXieetal.2020, author = {Stolte, Matthias and Hecht, Reinhard and Xie, Zengqi and Liu, Linlin and Kaufmann, Christina and Kudzus, Astrid and Schmidt, David and W{\"u}rthner, Frank}, title = {Crystal Engineering of 1D Exciton Systems Composed of Single- and Double-Stranded Perylene Bisimide J-Aggregates}, series = {Advanced Optical Materials}, volume = {8}, journal = {Advanced Optical Materials}, number = {18}, doi = {10.1002/adom.202000926}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218221}, year = {2020}, abstract = {Single crystals of three at bay area tetraphenoxy-substituted perylene bisimide dyes are grown by vacuum sublimation. X-ray analysis reveals the self-assembly of these highly twisted perylene bisimides (PBIs) in the solid state via imide-imide hydrogen bonding into hydrogen-bonded PBI chains. The crystallographic insights disclose that the conformation and sterical congestion imparted by the phenoxy substituents can be controlled by ortho-substituents. Accordingly, whilst sterically less demanding methyl and isopropyl substituents afford double-stranded PBI chains of complementary P and M atropo-enantiomers, single hydrogen-bonded chains of homochiral PBIs are observed for the sterically more demanding ortho-phenyl substituents. Investigation of the absorption and fluorescence properties of microcrystals and thin films of these PBIs allow for an unambiguous interpretation of these exciton systems. Thus, the J-aggregates of the double-stranded crystals exhibit a much larger (negative) exciton coupling than the single-stranded one, which in contrast has the higher solid-state fluorescence quantum yield.}, language = {en} } @article{FehskeBerningerAlmetal.2021, author = {Fehske, Kai and Berninger, Markus T. and Alm, Lena and Hoffmann, Reinhard and Zellner, Johannes and K{\"o}sters, Clemens and Barzen, Stefan and Raschke, Michael J. and Izadpanah, Kaywan and Herbst, Elmar and Domnick, Christoph and Sch{\"u}ttrumpf, Jan Philipp and Krause, Matthias}, title = {Aktueller Versorgungsstandard von Patellafrakturen in Deutschland}, series = {Der Unfallchirurg}, volume = {124}, journal = {Der Unfallchirurg}, organization = {Komitee Frakturen der Deutschen Kniegesellschaft (DKG)}, issn = {0177-5537}, doi = {10.1007/s00113-020-00939-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235047}, pages = {832-838}, year = {2021}, abstract = {Hintergrund Die Versorgung von Patellafrakturen ist technisch anspruchsvoll. Auch wenn die radiologischen Ergebnisse zumeist zufriedenstellend sind, deckt sich dies h{\"a}ufig nicht mit der subjektiven Einsch{\"a}tzung der Patienten. Die klassische Versorgung mittels Drahtzuggurtung weist einige Komplikationen auf. Die winkelstabile Plattenosteosynthese hat sich in den letzten Jahren biomechanisch als vorteilhaft erwiesen. Fragestellung Von wem werden Patellafrakturen in Deutschland versorgt? Wie sieht der aktuelle Versorgungsstandard aus? Haben sich „moderne" Osteosyntheseformen durchgesetzt? Was sind die h{\"a}ufigsten Komplikationen? Material und Methoden Die Mitglieder der Deutschen Gesellschaft f{\"u}r Orthop{\"a}die und Unfallchirurgie sowie der Deutschen Kniegesellschaft wurden aufgefordert, an einer Onlinebefragung teilzunehmen. Ergebnisse Insgesamt wurden 511 komplett ausgef{\"u}llte Fragebogen ausgewertet. Die Befragten sind zum gr{\"o}ßten Teil auf Unfallchirurgie spezialisiert (51,5 \%) und verf{\"u}gen {\"u}ber langj{\"a}hrige Berufserfahrung in Traumazentren. Die H{\"a}lfte der Operateure versorgt ≤5 Patellafrakturen j{\"a}hrlich. In knapp 40 \% der F{\"a}lle wird die pr{\"a}operative Bildgebung um eine Computertomographie erg{\"a}nzt. Die klassische Zuggurtung ist noch die bevorzugte Osteosyntheseform bei allen Frakturtypen (Querfraktur 52 \%, Mehrfragmentfrakturen 40 \%). Bei Mehrfragmentfrakturen entscheiden sich 30 \% der Operateure f{\"u}r eine winkelstabile Plattenosteosynthese. Bei Beteiligung des kaudalen Pols dient als zus{\"a}tzliche Sicherung die McLaughlin-Schlinge (60 \%). Diskussion Der Versorgungsstandard von Patellafrakturen in Deutschland entspricht weitgehend der aktualisierten S2e-Leitlinie. Nach wie vor wird die klassische Zuggurtungsosteosynthese als Verfahren der Wahl genutzt. Weitere klinische (Langzeit‑)Studien werden ben{\"o}tigt, um die Vorteile der winkelstabilen Plattenosteosynthese zu verifizieren.}, language = {de} }