Zschüntzsch, Jana

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Svetlove, Angelika"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2022-09-01T09:50:08Z"],["dc.date.available","2022-09-01T09:50:08Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n \n Retrospective gating (RG) is a well established technique in preclinical computed tomography (CT) to assess 3D morphology of the lung. In RG additional angular projections are recorded typically by performing multiple rotations. Consequently, the projections are sorted according to the expansion state of the chest and those sets are then reconstructed separately. Thus, the breathing motion artefacts are suppressed at a cost of strongly elevated X-ray dose levels. Here we propose to use the entire raw data to assess respiratory motion in addition to retrospectively gated 3D reconstruction that visualize anatomical structures of the lung. Using this RG based X-ray respiratory motion measurement approach, which will be referred to as RG based X-ray lung function measurement (rgXLF) on the example of the\n mdx\n mouse model of Duchenne muscle dystrophy (mdx) we accurately obtained both the 3D anatomical morphology of the lung and the thoracic bones as well as functional temporal parameters of the lung. Thus, rgXLF will remove the necessity for separate acquisition procedures by being able to reproduce comparable results to the previously established planar X-ray based lung function measurement approach in a single low dose CT scan."],["dc.identifier.doi","10.1038/s41598-022-17335-4"],["dc.identifier.pii","17335"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113630"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","2045-2322"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Simultaneous assessment of lung morphology and respiratory motion in retrospectively gated in-vivo microCT of free breathing anesthetized mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Der Nervenarzt"],["dc.contributor.author","Hosseini, S. S. Justus"],["dc.contributor.author","Dudakova, Anna"],["dc.contributor.author","Kummer, Karsten"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.date.accessioned","2022-09-01T09:51:24Z"],["dc.date.available","2022-09-01T09:51:24Z"],["dc.date.issued","2022"],["dc.description.abstract","Zusammenfassung\n \n Einer erfolgreichen Impfung (adäquater Anstieg der Anti-S[Spike]-Protein-Antikörper) gegen SARS-CoV‑2 (engl.\n severe acute respiratory syndrome coronavirus type 2\n ) wird ein suffizienter Schutz gegen einen schweren Verlauf von COVID-19 (engl.\n coronavirus disease 2019\n ) zugeschrieben. Bei Patient*innen mit chronisch-inflammatorischen Erkrankungen (engl.\n „chronic inflammatory diseases“\n [CID]) und Immunsuppression ist der Impferfolg weiterhin im wissenschaftlichen Diskurs. Daher evaluierten wir bei Patient*innen mit einer neuromuskulären Erkrankung (NME), die zu regelmäßigen Infusionen von Immunglobulinen in unserer neurologischen Tagesklinik/Ambulanz vorstellig wurden, 2 Wochen nach vollständiger Immunisierung die Antikörpertiter gegen das S1 (S1-Untereinheit des Spike-Proteins) -Antigen von SARS-CoV‑2. Unsere Daten zeigen, dass Patient*innen mit einer chronischen autoimmunen NME und gleichzeitiger immunsuppressiver bzw. immunmodulierender Therapie nach einer Impfung sowohl mit einem mRNA- als auch mit einem Vektorimpfstoff eine Antikörperantwort aufwiesen. Im Vergleich zu gesunden Proband*innen zeigte sich eine vergleichbare Anzahl an Serokonversionen durch die Impfung. Eine Korrelation zwischen Immunglobulindosierung und Impfantwort sowie Infusionsintervall und Impfantwort ließ sich nicht feststellen. Demgegenüber zeigte jedoch insbesondere die Kombination aus Mycophenolatmofetil (MMF) und Prednisolon eine signifikante Reduktion der spezifischen Antikörpersynthese."],["dc.description.abstract","Abstract\n Successful vaccination (adequate elevation of anti-spike protein antibodies) is attributed with sufficient protection against a severe course of coronavirus disease 2019 (COVID-19). For patients with chronic inflammatory diseases (CID) and immunosuppression the success of vaccination is an ongoing scientific discourse. Therefore, we evaluated the antibody titer against the S1 antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2 weeks after complete immunization in patients with an underlying neuromuscular disease (NMD), who presented to our neurological day clinic and outpatient department for regular infusions of immunoglobulins. The data show that patients with chronic autoimmune NMD and simultaneous immunosuppressive or immune modulating treatment show an antibody response after vaccination with both mRNA and vector vaccines. In comparison to healthy subjects there is a comparable number of seroconversions due to the vaccination. A correlation between immunoglobulin dose and vaccination response could not be found; however, in contrast, there was a significant reduction of specific antibody synthesis, especially for the combination of mycophenolate mofetil (MMF) and prednisolone."],["dc.identifier.doi","10.1007/s00115-022-01363-6"],["dc.identifier.pii","1363"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113955"],["dc.language.iso","de"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1433-0407"],["dc.relation.issn","0028-2804"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","SARS-CoV-2-Antikörper-Antwort auf die zweite COVID-19-Impfung bei neuromuskulären Patienten unter immunmodulierender Therapie"],["dc.title.translated","SARS-CoV-2 antibody response to the second COVID-19 vaccination in neuromuscular disease patients under immune modulating treatment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","189"],["dc.bibliographiccitation.journal","Experimental Neurology"],["dc.bibliographiccitation.lastpage","197"],["dc.bibliographiccitation.volume","271"],["dc.contributor.author","Muth, Ingrid E."],["dc.contributor.author","Zschuentzsch, Jana"],["dc.contributor.author","Kleinschnitz, Konstanze"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Balcarek, Peter"],["dc.contributor.author","Schreiber-Katz, Olivia"],["dc.contributor.author","Zierz, Stephan"],["dc.contributor.author","Dalakas, Marinas C."],["dc.contributor.author","Voll, Reinhard E."],["dc.contributor.author","Schmidt, Jens"],["dc.date.accessioned","2018-11-07T09:52:13Z"],["dc.date.available","2018-11-07T09:52:13Z"],["dc.date.issued","2015"],["dc.description.abstract","Inflammation is associated with protein accumulation in IBM, but precise mechanisms are elusive. The \"alarmin\" HMGB1 is upregulated in muscle inflammation. Its receptor RAGE is crucial for S-amyloid-associated neurodegeneration. Relevant signaling via HMGB1/RAGE is expected in IBM pathology. By real-time-PCR, mRNA-expression levels of HMGB1 and RAGE were upregulated in muscle biopsies of patients with IBM and PM, but not in muscular dystrophy or non-myopathic controls. By immunohistochemistry, both molecules displayed the highest signal in IBM, where they distinctly co-localized to intra-fiber accumulations of beta-amyloid and neurofilament/tau. In these fibers, identification of phosphorylated Erk suggested that relevant downstream activation is present upon HMGB1 signaling via RAGE. Protein expressions of HMGB1, RAGE, Erk and phosphorylated Erk were confirmed by Western blot. In a well established cell-culture model for pro-inflammatory cell-stress, exposure of human muscle-cells to 1L-1 beta + IFN-gamma induced cytoplasmic translocation of HMGB1 and subsequent release as evidenced by ELISA. Upregulation of RAGE on the cell surface was demonstrated by immunocytochemistry and flow-cytometry. Recombinant HMGB1 was equally potent as IL-1 beta + IFN-gamma in causing amyloid-accumulation and cell-death, and both were abrogated by the HMGB1-blocker BoxA. The findings strengthen the concept of unique interactions between degenerative and inflammatory mechanisms and suggest that HMGB1/RAGE signaling is a critical pathway in IBM pathology. (C) 2015 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Association Francaise contre les Myopathies (AFM) [13512, 14952]"],["dc.identifier.doi","10.1016/j.expneurol.2015.05.023"],["dc.identifier.isi","000362627200020"],["dc.identifier.pmid","26048613"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36071"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1090-2430"],["dc.relation.issn","0014-4886"],["dc.title","HMGB1 and RAGE in skeletal muscle inflammation: Implications for protein accumulation in inclusion body myositis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","918"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","11"],["dc.contributor.affiliation","Svetlove, Angelika; 1Translational Molecular Imaging, Max-Planck Institute for Multidisciplinary Sciences, City Campus, 37075 Göttingen, Germany; anzhelika.svetlova@mpinat.mpg.de (A.S.); markus@mpinat.mpg.de (M.A.M.); falves@gwdg.de (F.A.)"],["dc.contributor.affiliation","Albers, Jonas; 2X-ray Based Preclinical Imaging Technologies, Institute for Diagnostic and Interventional Radiology, University Medical Center, 37075 Göttingen, Germany; jonas.albers@embl-hamburg.de"],["dc.contributor.affiliation","Hülsmann, Swen; 3Central Breathing Control, Clinic for Anesthesiology, University Medical Center, 37075 Göttingen, Germany; shuelsm2@uni-goettingen.de"],["dc.contributor.affiliation","Markus, Marietta Andrea; 1Translational Molecular Imaging, Max-Planck Institute for Multidisciplinary Sciences, City Campus, 37075 Göttingen, Germany; anzhelika.svetlova@mpinat.mpg.de (A.S.); markus@mpinat.mpg.de (M.A.M.); falves@gwdg.de (F.A.)"],["dc.contributor.affiliation","Zschüntzsch, Jana; 4Neuromuscular Disease Research, Clinic for Neurology, University Medical Center, 37075 Göttingen, Germany; j.zschuentzsch@med.uni-goettingen.de"],["dc.contributor.affiliation","Alves, Frauke; 1Translational Molecular Imaging, Max-Planck Institute for Multidisciplinary Sciences, City Campus, 37075 Göttingen, Germany; anzhelika.svetlova@mpinat.mpg.de (A.S.); markus@mpinat.mpg.de (M.A.M.); falves@gwdg.de (F.A.)"],["dc.contributor.affiliation","Dullin, Christian; 2X-ray Based Preclinical Imaging Technologies, Institute for Diagnostic and Interventional Radiology, University Medical Center, 37075 Göttingen, Germany; jonas.albers@embl-hamburg.de"],["dc.contributor.author","Svetlove, Angelika"],["dc.contributor.author","Albers, Jonas"],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Markus, Marietta Andrea"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Dullin, Christian"],["dc.date.accessioned","2022-04-01T10:00:28Z"],["dc.date.available","2022-04-01T10:00:28Z"],["dc.date.issued","2022"],["dc.date.updated","2022-04-08T11:23:03Z"],["dc.description.abstract","Duchenne muscular dystrophy (DMD) is the most common x-chromosomal inherited dystrophinopathy which leads to progressive muscle weakness and a premature death due to cardiorespiratory dysfunction. The mdx mouse lacks functional dystrophin protein and has a comparatively human-like diaphragm phenotype. To date, diaphragm function can only be inadequately mapped in preclinical studies and a simple reliable translatable method of tracking the severity of the disease still lacks. We aimed to establish a sensitive, reliable, harmless and easy way to assess the effects of respiratory muscle weakness and subsequent irregularity in breathing pattern. Optical respiratory dynamics tracking (ORDT) was developed utilising a camera to track the movement of paper markers placed on the thoracic-abdominal region of the mouse. ORDT successfully distinguished diseased mdx phenotype from healthy controls by measuring significantly higher expiration constants (k) in mdx mice compared to wildtype (wt), which were also observed in the established X-ray based lung function (XLF). In contrast to XLF, with ORDT we were able to distinguish distinct fast and slow expiratory phases. In mdx mice, a larger part of the expiratory marker displacement was achieved in this initial fast phase as compared to wt mice. This phenomenon could not be observed in the XLF measurements. We further validated the simplicity and reliability of our approach by demonstrating that it can be performed using free-hand smartphone acquisition. We conclude that ORDT has a great preclinical potential to monitor DMD and other neuromuscular diseases based on changes in the breathing patterns with the future possibility to track therapy response."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/cells11050918"],["dc.identifier.pii","cells11050918"],["dc.identifier.pmid","35269540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105437"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/535"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2073-4409"],["dc.relation.workinggroup","RG Alves (Translationale Molekulare Bildgebung)"],["dc.rights","CC BY 4.0"],["dc.title","Non-Invasive Optical Motion Tracking Allows Monitoring of Respiratory Dynamics in Dystrophin-Deficient Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","101433"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Best Practice & Research. Clinical Rheumatology"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Glaubitz, Stefanie"],["dc.contributor.author","Schmidt, Karsten"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Schmidt, Jens"],["dc.date.accessioned","2020-12-10T14:22:35Z"],["dc.date.available","2020-12-10T14:22:35Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.berh.2019.101433"],["dc.identifier.issn","1521-6942"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71664"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Myalgia in myositis and myopathies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","148"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuroscience Letters"],["dc.bibliographiccitation.lastpage","151"],["dc.bibliographiccitation.volume","497"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Zschuentzsch, Jana"],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Schomburg, Eike D."],["dc.contributor.author","Neusch, Clemens"],["dc.date.accessioned","2018-11-07T08:54:58Z"],["dc.date.available","2018-11-07T08:54:58Z"],["dc.date.issued","2011"],["dc.description.abstract","Pathophysiology of the motoneuron disease amyotrophic lateral sclerosis (ALS) is non-cell-autonomous. In mouse models of familiar ALS, neurotoxicity is derived not only from mutant motor neurons but also from mutant neighbouring glial cells. In vivo imaging by two-photon laser-scanning microscopy was used to study rapid morphological reactions of astroglial cells towards laser-induced axonal transection in ALS-linked transgenic SOD1(G93A) mice. In the affected lateral spinal cord, mutated astroglial cells extended branches towards injured axons within a time frame of minutes to hours post lesion while in control animals astrocytes lack any rapid morphological alteration within the studied time frame. This suggests that astrocytes partially contribute to the rapid response of non-neuronal cells to acute axonal lesions in ALS mice. (C) 2011 Elsevier Ireland Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neulet.2011.04.049"],["dc.identifier.isi","000292404400016"],["dc.identifier.pmid","21539893"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22797"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Ireland Ltd"],["dc.relation.issn","0304-3940"],["dc.title","In vivo imaging reveals rapid morphological reactions of astrocytes towards focal lesions in an ALS mouse model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","230"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Muscle & Nerve"],["dc.bibliographiccitation.lastpage","236"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Schomburg, Eike D."],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Zschuentzsch, Jana"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Keller, Bernhard U."],["dc.date.accessioned","2018-11-07T08:59:54Z"],["dc.date.available","2018-11-07T08:59:54Z"],["dc.date.issued","2011"],["dc.description.abstract","Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons. To analyze the progressive motor deficits during the course of this disease, we investigated fatigability and ability of recovery of spinal motor neurons by testing monosynaptic reflex transmission with increasing stimulus frequencies in the lumbar spinal cord of the SOD1(G93A) mouse model for ALS in a comparison with wild-type (WT) mice. Monosynaptic reflexes in WT and SOD1(G93A) mice without behavioral deficits showed no difference with respect to their resistance to increasing stimulus frequencies. During the progression of motor deficits in SOD1(G93A) mice, the vulnerability of monosynaptic reflexes to higher frequencies-increased, the required time for reflex recovery was extended, and recovery was often incomplete. Fatigability and demand for recovery of spinal motor neurons in SOD1(G93A) mice rose with increasing motor deficits. This supports the assumption that impairment of the energy supply may contribute to the pathogenesis of ALS. Muscle Nerve 43: 230-236, 2011"],["dc.identifier.doi","10.1002/mus.21835"],["dc.identifier.isi","000286558300013"],["dc.identifier.pmid","21254088"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24015"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0148-639X"],["dc.title","FATIGABILITY OF SPINAL REFLEX TRANSMISSION IN A MOUSE MODEL (SOD1(G93A)) OF AMYOTROPHIC LATERAL SCLEROSIS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9567"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Merckx, Caroline"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Meyer, Stefanie"],["dc.contributor.author","Raedt, Robrecht"],["dc.contributor.author","Verschuere, Hanne"],["dc.contributor.author","Schmidt, Jens"],["dc.contributor.author","De Paepe, Boel"],["dc.contributor.author","De Bleecker, Jan L."],["dc.date.accessioned","2022-10-04T10:21:22Z"],["dc.date.available","2022-10-04T10:21:22Z"],["dc.date.issued","2022"],["dc.description.abstract","Duchenne Muscular Dystrophy (DMD) is a debilitating muscle disorder that condemns patients to year-long dependency on glucocorticoids. Chronic glucocorticoid use elicits many unfavourable side-effects without offering satisfying clinical improvement, thus, the search for alternative treatments to alleviate muscle inflammation persists. Taurine, an osmolyte with anti-inflammatory effects, mitigated pathological features in the mdx mouse model for DMD but interfered with murine development. In this study, ectoine is evaluated as an alternative for taurine in vitro in CCL-136 cells and in vivo in the mdx mouse. Pre-treating CCL-136 cells with 0.1 mM taurine and 0.1 mM ectoine prior to exposure with 300 U/mL IFN-γ and 20 ng/mL IL-1β partially attenuated cell death, whilst 100 mM taurine reduced MHC-I protein levels. In vivo, histopathological features of the tibialis anterior in mdx mice were mitigated by ectoine, but not by taurine. Osmolyte treatment significantly reduced mRNA levels of inflammatory disease biomarkers, respectively, CCL2 and SPP1 in ectoine-treated mdx mice, and CCL2, HSPA1A, TNF-α and IL-1β in taurine-treated mdx mice. Functional performance was not improved by osmolyte treatment. Furthermore, ectoine-treated mdx mice exhibited reduced body weight. Our results confirmed beneficial effects of taurine in mdx mice and, for the first time, demonstrated similar and differential effects of ectoine."],["dc.identifier.doi","10.3390/ijms23179567"],["dc.identifier.pii","ijms23179567"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114389"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.relation.eissn","1422-0067"],["dc.title","Exploring the Therapeutic Potential of Ectoine in Duchenne Muscular Dystrophy: Comparison with Taurine, a Supplement with Known Beneficial Effects in the mdx Mouse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","224"],["dc.bibliographiccitation.journal","Acta Physiologica"],["dc.bibliographiccitation.lastpage","226"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Zhang, Y."],["dc.contributor.author","Zschuentzsch, Jana"],["dc.contributor.author","Schmidt, J."],["dc.contributor.author","Brinkmeier, Heinrich"],["dc.date.accessioned","2018-11-07T09:42:49Z"],["dc.date.available","2018-11-07T09:42:49Z"],["dc.date.issued","2014"],["dc.identifier.isi","000332259900586"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34043"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1748-1716"],["dc.relation.issn","1748-1708"],["dc.title","Dystrophin deficiency leads to drastic weakness of mdx diaphragm muscle, but has little influence on soleus muscle force"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1102"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","1114"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Schmidt, Jens"],["dc.contributor.author","Barthel, Konstanze"],["dc.contributor.author","Zschuentzsch, Jana"],["dc.contributor.author","Muth, Ingrid E."],["dc.contributor.author","Swindle, Emily J."],["dc.contributor.author","Hombach, Anja"],["dc.contributor.author","Sehmisch, Stephan"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Dalakas, Marinas C."],["dc.date.accessioned","2018-11-07T09:11:33Z"],["dc.date.available","2018-11-07T09:11:33Z"],["dc.date.issued","2012"],["dc.description.abstract","Sporadic inclusion body myositis is a severely disabling myopathy. The design of effective treatment strategies is hampered by insufficient understanding of the complex disease pathology. Particularly, the nature of interrelationships between inflammatory and degenerative pathomechanisms in sporadic inclusion body myositis has remained elusive. In Alzheimer's dementia, accumulation of beta-amyloid has been shown to be associated with upregulation of nitric oxide. Using quantitative polymerase chain reaction, an overexpression of inducible nitric oxide synthase was observed in five out of ten patients with sporadic inclusion body myositis, two of eleven with dermatomyositis, three of eight with polymyositis, two of nine with muscular dystrophy and two of ten non-myopathic controls. Immunohistochemistry confirmed protein expression of inducible nitric oxide synthase and demonstrated intracellular nitration of tyrosine, an indicator for intra-fibre production of nitric oxide, in sporadic inclusion body myositis muscle samples, but much less in dermatomyositis or polymyositis, hardly in dystrophic muscle and not in non-myopathic controls. Using fluorescent double-labelling immunohistochemistry, a significant co-localization was observed in sporadic inclusion body myositis muscle between beta-amyloid, thioflavine-S and nitrotyrosine. In primary cultures of human myotubes and in myoblasts, exposure to interleukin-1 beta in combination with interferon-gamma induced a robust upregulation of inducible nitric oxide synthase messenger RNA. Using fluorescent detectors of reactive oxygen species and nitric oxide, dichlorofluorescein and diaminofluorescein, respectively, flow cytometry revealed that interleukin-1 beta combined with interferon-gamma induced intracellular production of nitric oxide, which was associated with necrotic cell death in muscle cells. Intracellular nitration of tyrosine was noted, which partly co-localized with amyloid precursor protein, but not with desmin. Pharmacological inhibition of inducible nitric oxide synthase by 1400W reduced intracellular production of nitric oxide and prevented accumulation of beta-amyloid, nitration of tyrosine as well as cell death inflicted by interleukin-1 beta combined with interferon-gamma. Collectively, these data suggest that, in skeletal muscle, inducible nitric oxide synthase is a central component of interactions between interleukin-1 beta and beta-amyloid, two of the most relevant molecules in sporadic inclusion body myositis. The data further our understanding of the pathology of sporadic inclusion body myositis and may point to novel treatment strategies."],["dc.identifier.doi","10.1093/brain/aws046"],["dc.identifier.isi","000302948700017"],["dc.identifier.pmid","22436237"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26748"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.title","Nitric oxide stress in sporadic inclusion body myositis muscle fibres: inhibition of inducible nitric oxide synthase prevents interleukin-1 beta-induced accumulation of beta-amyloid and cell death"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]