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  - 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  - JOUR
A1  - Kämmerer, Peer W.
A1  - Tribius, Silke
A1  - Cohrs, Lena
A1  - Engler, Gabriel
A1  - Ettl, Tobias
A1  - Freier, Kolja
A1  - Frerich, Bernhard
A1  - Ghanaati, Shahram
A1  - Gosau, Martin
A1  - Haim, Dominik
A1  - Hartmann, Stefan
A1  - Heiland, Max
A1  - Herbst, Manuel
A1  - Hoefert, Sebastian
A1  - Hoffmann, Jürgen
A1  - Hölzle, Frank
A1  - Howaldt, Hans-Peter
A1  - Kreutzer, Kilian
A1  - Leonhardt, Henry
A1  - Lutz, Rainer
A1  - Moergel, Maximilian
A1  - Modabber, Ali
A1  - Neff, Andreas
A1  - Pietzka, Sebastian
A1  - Rau, Andrea
A1  - Reichert, Torsten E.
A1  - Smeets, Ralf
A1  - Sproll, Christoph
A1  - Steller, Daniel
A1  - Wiltfang, Jörg
A1  - Wolff, Klaus-Dietrich
A1  - Kronfeld, Kai
A1  - Al-Nawas, Bilal
T1  - Adjuvant radiotherapy in patients with squamous cell carcinoma of the oral cavity or oropharynx and solitary ipsilateral lymph node metastasis (pN1) — a prospective multicentric cohort study
JF  - Cancers
N2  - (1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55–1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15–0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19–0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.
KW  - oral squamous cell carcinoma
KW  - oropharyngeal carcinoma
KW  - surgery
KW  - resection
KW  - radiotherapy
KW  - survival
KW  - progression-free survival
KW  - quality of life
KW  - prospective
KW  - multicentric
KW  - lymph node
KW  - pN1
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311024
SN  - 2072-6694
VL  - 15
IS  - 6
ER  -