TY  - JOUR
A1  - Jarius, Sven
A1  - Ruprecht, Klemens
A1  - Wildemann, Brigitte
A1  - Kuempfel, Tania
A1  - Ringelstein, Marius
A1  - Geis, Christian
A1  - Kleiter, Ingo
A1  - Kleinschnitz, Christoph
A1  - Berthele, Achim
A1  - Brettschneider, Johannes
A1  - Hellwig, Kerstin
A1  - Hemmer, Bernhard
A1  - Linker, Ralf A.
A1  - Lauda, Florian
A1  - Hayrettin, Christoph A.
A1  - Tumani, Hayrettin
A1  - Melms, Arthur
A1  - Trebst, Corinna
A1  - Stangel, Martin
A1  - Marziniak, Martin
A1  - Hoffmann, Frank
A1  - Schippling, Sven
A1  - Faiss, Jürgen H.
A1  - Neuhaus, Oliver
A1  - Ettrich, Barbara
A1  - Zentner, Christian
A1  - Guthke, Kersten
A1  - Hofstadt-van Oy, Ulrich
A1  - Reuss, Reinhard
A1  - Pellkofer, Hannah
A1  - Ziemann, Ulf
A1  - Kern, Peter
A1  - Wandinger, Klaus P.
A1  - Bergh, Florian Then
A1  - Boettcher, Tobias
A1  - Langel, Stefan
A1  - Liebetrau, Martin
A1  - Rommer, Paulus S.
A1  - Niehaus, Sabine
A1  - Münch, Christoph
A1  - Winkelmann, Alexander
A1  - Zettl, Uwe K
A1  - Metz, Imke
A1  - Veauthier, Christian
A1  - Sieb, Jörn P.
A1  - Wilke, Christian
A1  - Hartung, Hans P.
A1  - Aktas, Orhan
A1  - Paul, Friedemann
T1  - Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients
JF  - Journal of Neuroinflammation
N2  - Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. 
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. 
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). 
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of <= 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades <= 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions >= 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
KW  - cerebrospinal-fluid
KW  - intractable hiccup
KW  - extensiv transverse myelitis
KW  - multiple sclerosis
KW  - anti-aquaporin-4 antibody
KW  - NMO-IGG
KW  - aquaporin-4 autoantibodies
KW  - immune-response
KW  - myasthenia gravis
KW  - immunoglobulin-G
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133636
VL  - 9
IS  - 14
ER  - 
TY  - THES
A1  - Hoffmann, Oliver
T1  - Vergleich verschiedener Präparationsverfahren zur Versorgung approximaler kariöser Primärläsionen
T1  - Comparison of different method of tooth preparation for the treatment of approximal primary carious lesions
N2  - In der vorliegenden Studie wurden verschiedene Präparationsmethoden zur Erstver-sorgung approximaler kariöser Läsionen verglichen. Bei diesen handelte es sich um die Präparation von konventionellen Amalgamslots und Kompositslots mit rotierenden Instrumenten, der Präparation von Kompositslots mit sonoabrasiven halb- bzw. torpedoförmigen Instrumenten sowie der Präparation von Kompositslots mit lateralem Zugang. Je Präparationsart wurden von sechs verschiedenen Behandlern je zwei Kavitäten an natürlichen Prämolaren und Molaren mit standardisierten künstlichen kariösen Läsionen im Phantomkopf erstellt. Die verschiedenen Methoden wurden hinsichtlich des Substanzverlustes, der Kavitätenausdehnung, der Beschädigung der Nachbarzähne, der Vollständigkeit der Kariesexkavation und der Präparationszeit verglichen. Die Bestimmung der Kavitätenausdehnung erfolgte mittels planimetrischer Vermess-ung und der Vermessung der Eröffnung des Approximalkontaktes („Clearance"). Zur Überprüfung der Verletzung der Nachbarzähne und verbliebener Karies wurden Kavitäten und Nachbarzähne unter dem Auflichtmikroskop betrachtet. Weiterhin wurde der Substanzverlust durch Wiegen vor und nach der Präparation bestimmt. Folgende Ergebnisse wurden beobachtet: I.) Die sonoabrasiven Halbkugelpräparationen mit okklusalem bzw. lateralem Zugang wiesen signifikant geringere Substanzverluste auf als die anderen Kavitätenformen. Zwischen mesialen und distalen Präparationen wurden keine unterschiedlichen Sub-stanzverluste festgestellt. Hingegen kam es bei der Präparation an Molaren zu signifikant größeren Gewichts- verlusten als bei der Präparation an Prämolaren. II.) Die durchschnittliche Extensionsfläche der sonoabrasiven Präparationen mit late-ralem Zugang war signifikant kleiner als die der abgeschrägten Kompositslots mit okklusalem Zugang. Hingegen bestanden keine signifikanten Unterschiede zwischen den Amalgam Kastenkavitäten und den sonoabrasiven Halbkugelpräparationen mit okklusalem bzw. lateralem Zugang. III.) Entsprechend den Ergebnissen des Substanzverlustes ließen sich keine Unter-schiede zwischen mesialen und distalen Präparationen, jedoch eine größere Ka-vitätenextension bei den Molaren als bei den Prämolaren feststellen. IV.) Unabhängig von der Präparationsmethode kam es bei 70% der Präparationen zu einer vollständigen Exkavation der Karies. 25% der Kavitäten wiesen eine gering-fügige, 5% eine deutliche Residualkaries auf. Tendenziell erlaubten die Kavitäten mit lateralem Zugang seltener eine vollständige Entfernung der kariösen Zahnsubstanz, wobei sich hauptsächlich im Bereich des lingualen Kavitätenzuganges belassene „Karies" befand. V.) Prämolaren zeigten ein signifikant häufigeres Auftreten von unvollständig exka-vierten kariösen Arealen als Molaren. Ein Unterschied zwischen mesialen und dista-len Flächen trat nicht auf. VI.) Bei der Präparation mit sonoabrasiven halbkugel- und torpedoförmigen Instru-menten kam es zu signifikant weniger Verletzungen der Nachbarzähne als bei der Verwendung von rotierenden Instrumenten. VII.) Unterschiede zwischen Molaren und Prämolaren im Ausmaß der Nachbarzahn-verletzung traten nicht auf, hingegen waren deutlich mehr Beschädigungen von Nach-barzähnen nach der Präparation mesialer Kavitäten als nach der distaler vor-zufinden. VIII.) Die Präparationszeit der mit sonoabrasiven Instrumenten präparierten Kompo-sitslots mit okklusalem Zugang war signifikant niedriger als die der anderen Metho-den. IX.) Zur Kariesexkavation von Kavitäten mit lateralem Zugang wurde signifikant mehr Zeit benötigt als bei den anderen Methoden. X.) Zur Präparation mesialer Kavitäten wurde weniger Zeit benötigt als für die Präpa-ration distaler Kavitäten. XI.) Bei allen untersuchten Aspekten kam es zu keinen signifikanten Unterschieden zwischen den einzelnen Behandlern.
N2  - In this study different methods for the treatment of approximal carious lesions were compared. Methods compared were conventionel amalgam slot preparations, compsitslots prepared with rotating instruments, sonoabrasive semir round and torpedo shaped instruments, and composit resin slots with lateral access. For each method six dentist prepared two different cavities with standardized artificiell carious lesions on natural teeth on a manequin. Methods were compared in regard to substanceloss, cavity extension, damage of neighbouring teeth, complete caries excavation and time used for preparation.
KW  - kariöse Läsion
KW  - sonoabrasiv
KW  - minimal invasiv
KW  - Kompositslot
KW  - Kavitätenausdehnung
KW  - carious lesion
KW  - sonoabrasive
KW  - minimal invasive
KW  - slotpreparation
KW  - cavity extension
Y1  - 2002
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-5619
ER  - 
TY  - JOUR
A1  - Schulz, Herbert
A1  - Ruppert, Ann-Kathrin
A1  - Herms, Stefan
A1  - Wolf, Christiane
A1  - Mirza-Schreiber, Nazanin
A1  - Stegle, Oliver
A1  - Czamara, Darina
A1  - Forstner, Andreas J.
A1  - Sivalingam, Sugirthan
A1  - Schoch, Susanne
A1  - Moebus, Susanne
A1  - Pütz, Benno
A1  - Hillmer, Axel
A1  - Fricker, Nadine
A1  - Vatter, Hartmut
A1  - Müller-Myhsok, Bertram
A1  - Nöthen, Markus M.
A1  - Becker, Albert J.
A1  - Hoffmann, Per
A1  - Sander, Thomas
A1  - Cichon, Sven
T1  - Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus
JF  - Nature Communications
N2  - Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the \(cis\)-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify \(cis\)-meQTLs at 14,118 CpG methylation sites and \(cis\)-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal \(cis\)-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. \(Cis\)-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of \(cis\)-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.
KW  - psychiatry
KW  - epigenetics in the nervous system
KW  - epigenomics
KW  - gene expression
KW  - neurological disorders
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173168
VL  - 8
ER  - 
TY  - JOUR
A1  - Palladino, Viola Stella
A1  - Chiocchetti, Andreas G.
A1  - Frank, Lukas
A1  - Haslinger, Denise
A1  - McNeill, Rhiannon
A1  - Radtke, Franziska
A1  - Till, Andreas
A1  - Haupt, Simone
A1  - Brüstle, Oliver
A1  - Günther, Katharina
A1  - Edenhofer, Frank
A1  - Hoffmann, Per
A1  - Reif, Andreas
A1  - Kittel-Schneider, Sarah
T1  - Energy metabolism disturbances in cell models of PARK2 CNV carriers with ADHD
JF  - Journal of Clinical Medicine
N2  - The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.
KW  - ADHD
KW  - hiPSC
KW  - PARK2
KW  - mitochondria
KW  - disease modelling
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220074
SN  - 2077-0383
VL  - 9
IS  - 12
ER  - 
TY  - JOUR
A1  - Triphan, Simon M. F.
A1  - Jobst, Bertram J.
A1  - Anjorin, Angela
A1  - Sedlaczek, Oliver
A1  - Wolf, Ursula
A1  - Terekhov, Maxim
A1  - Hoffmann, Christian
A1  - Ley, Sebastian
A1  - Düber, Christoph
A1  - Biederer, Jürgen
A1  - Kauczor, Hans-Ulrich
A1  - Jakob, Peter M.
A1  - Wielpütz, Mark O.
T1  - Reproducibility and comparison of oxygen-enhanced T\(_1\) quantification in COPD and asthma patients
JF  - PLoS ONE
N2  - T\(_1\) maps have been shown to yield useful diagnostic information on lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma, both for native T\(_1\) and ΔT\(_1\), the relative reduction while breathing pure oxygen. As parameter quantification is particularly interesting for longitudinal studies, the purpose of this work was both to examine the reproducibility of lung T\(_1\) mapping and to compare T\(_1\) found in COPD and asthma patients using IRSnapShotFLASH embedded in a full MRI protocol. 12 asthma and 12 COPD patients (site 1) and further 15 COPD patients (site 2) were examined on two consecutive days. In each patient, T\(_1\) maps were acquired in 8 single breath-hold slices, breathing first room air, then pure oxygen. Maps were partitioned into 12 regions each to calculate average values. In asthma patients, the average T\(_{1,RA}\) = 1206ms (room air) was reduced to T\(_{1,O2}\) = 1141ms under oxygen conditions (ΔT\(_1\) = 5.3%, p < 5⋅10\(^{−4})\), while in COPD patients both native T\(_{1,RA}\) = 1125ms was significantly shorter (p < 10\(^{−3})\) and the relative reduction to T\(_{1,O2}\) = 1081ms on average ΔT\(_1\) = 4.2%(p < 10\(^{−5}\)). On the second day, with T\(_{1,RA}\) = 1186ms in asthma and T\(_{1,RA}\) = 1097ms in COPD, observed values were slightly shorter on average in all patient groups. ΔT\(_1\) reduction was the least repeatable parameter and varied from day to day by up to 23% in individual asthma and 30% in COPD patients. While for both patient groups T\(_1\) was below the values reported for healthy subjects, the T\(_1\) and ΔT\(_1\) found in asthmatics lies between that of the COPD group and reported values for healthy subjects, suggesting a higher blood volume fraction and better ventilation. However, it could be demonstrated that lung T\(_1\) quantification is subject to notable inter-examination variability, which here can be attributed both to remaining contrast agent from the previous day and the increased dependency of lung T\(_1\) on perfusion and thus current lung state.
KW  - Medicine
KW  - Chronic obstrusive pulmonary disease
KW  - Asthma
KW  - Oxygen
KW  - Magnetic resonance imaging
KW  - Breathing
KW  - Pulmonary imaging
KW  - Protons
KW  - Diagnostic medicine
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171833
VL  - 12
IS  - 2
ER  -