@article{ZellerDangWeiseetal.2012,
  author    = {Zeller, Daniel and Dang, Su-Yin and Weise, David and Rieckmann, Peter and Toyka, Klaus V. and Classen, Joseph},
  title     = {Excitability decreasing central motor plasticity is retained in multiple sclerosis patients},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76333},
  year      = {2012},
  abstract  = {Background: Compensation of brain injury in multiple sclerosis (MS) may in part work through mechanisms involving neuronal plasticity on local and interregional scales. Mechanisms limiting excessive neuronal activity may have special significance for retention and (re-)acquisition of lost motor skills in brain injury. However, previous neurophysiological studies of plasticity in MS have investigated only excitability enhancing plasticity and results from neuroimaging are ambiguous. Thus, the aim of this study was to probe long-term depression-like central motor plasticity utilizing continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation protocol. Because cTBS also may trigger behavioral effects through local interference with neuronal circuits, this approach also permitted investigating the functional role of the primary motor cortex (M1) in force control in patients with MS. Methods: We used cTBS and force recordings to examine long-term depression-like central motor plasticity and behavioral consequences of a M1 lesion in 14 patients with stable mild-to-moderate MS (median EDSS 1.5, range 0 to 3.5) and 14 age-matched healthy controls. cTBS consisted of bursts (50 Hz) of three subthreshold biphasic magnetic stimuli repeated at 5 Hz for 40 s over the hand area of the left M1. Corticospinal excitability was probed via motor-evoked potentials (MEP) in the abductor pollicis brevis muscle over M1 before and after cTBS. Force production performance was assessed in an isometric right thumb abduction task by recording the number of hits into a predefined force window. Results: cTBS reduced MEP amplitudes in the contralateral abductor pollicis brevis muscle to a comparable extent in control subjects (69 ± 22\% of baseline amplitude, p < 0.001) and in MS patients (69 ± 18\%, p < 0.001). In contrast, postcTBS force production performance was only impaired in controls (2.2 ± 2.8, p = 0.011), but not in MS patients (2.0 ± 4.4, p = 0.108). The decline in force production performance following cTBS correlated with corticomuscular latencies (CML) in MS patients, but did not correlate with MEP amplitude reduction in patients or controls. Conclusions: Long-term depression-like plasticity remains largely intact in mild-to-moderate MS. Increasing brain injury may render the neuronal networks less responsive toward lesion-induction by cTBS.},
  subject      = {Medizin},
  language  = {en}
}
@article{WiechingBenserKohlhauserVollmuthetal.2012,
  author    = {Wieching, Anna and Benser, Jasmin and Kohlhauser-Vollmuth, Christina and Weisbrich, Bendikt and Streng, Andrea and Liese, Johannes G.},
  title     = {Clinical characteristics of pediatric hospitalizations associated with 2009 pandemic influenza a (H1N1) in Northern Bavaria, Germany},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75657},
  year      = {2012},
  abstract  = {Background: The 2009 pandemic influenza A (H1N1) (PIA) virus infected large parts of the pediatric population with a wide clinical spectrum and an initially unknown complication rate. The aims of our study were to define clinical characteristics and outcome of pandemic influenza A (H1N1) 2009-associated hospitalizations (PIAH) in children <18 years of age. All hospitalized cases of children <18 years of age with laboratory-confirmed pandemic influenza A (H1N1) 2009 in the region of Wuerzburg (Northern Bavaria, Germany) between July 2009 and March 2010 were identified. For these children a medical chart review was performed to determine their clinical characteristics and complications. Results: Between July 2009 and March 2010, 94 PIAH (62\% males) occurred in children <18 years of age, with a median age of 7 years (IQR: 3-12 years). Underlying diseases and predisposing factors were documented in 40 (43\%) children; obesity (n = 12, 30\%), asthma (n = 10, 25\%) and neurologic disorders (n = 8, 20\%) were most frequently reported. Sixteen (17\%) children received oxygen supplementation; three (3\%) children required mechanical ventilation. Six (6\%) children were admitted to an intensive care unit, four of them with underlying chronic diseases. Conclusions: Most PIAH demonstrated a benign course of disease. However, six children (6\%) needed treatment at an intensive care unit for severe complications.},
  subject      = {Medizin},
  language  = {en}
}
@article{WestermaierStetterRaslanetal.2012,
  author    = {Westermaier, Thomas and Stetter, Christian and Raslan, Furat and Vinc, Giles Hamilton and Ernestus, Ralf-Ingo},
  title     = {Brain edema formation correlates with perfusion deficit during the first six hours after experimental subarachnoid hemorrhage in rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75765},
  year      = {2012},
  abstract  = {Background: Severe brain edema is observed in a number of patients suffering from subarachnoid hemorrhage (SAH). Little is known about its pathogenesis and time-course in the first hours after SAH. This study was performed to investigate the development of brain edema and its correlation with brain perfusion after experimental SAH. Methods: Male Sprague-Dawley rats, randomly assigned to one of six groups (n = 8), were subjected to SAH using the endovascular filament model or underwent a sham operation. Animals were sacrificed 15, 30, 60, 180 or 360 minutes after SAH. Intracranial pressure (ICP), mean arterial blood pressure (MABP), cerebral perfusion pressure (CPP) and bilateral local cerebral blood flow (LCBF) were continuously measured. Brain water content (BWC) was determined by the wet/dry-weight method. Results: After SAH, CPP and LCBF rapidly decreased. The decline of LCBF markedly exceeded the decline of CPP and persisted until the end of the observation period. BWC continuously increased. A significant correlation was observed between the BWC and the extent of the perfusion deficit in animals sacrificed after 180 and 360 minutes. Conclusions: The significant correlation with the perfusion deficit after SAH suggests that the development of brain edema is related to the extent of ischemia and acute vasoconstriction in the first hours after SAH.},
  subject      = {Medizin},
  language  = {en}
}
@article{WeberScholzDomschkeetal.2012,
  author    = {Weber, Heike and Scholz, Claus J{\"u}rgen and Domschke, Katharina and Baumann, Christian and Klauke, Benedikt and Jacob, Christian P. and Maier, Wolfgang and Fritze, J{\"u}rgen and Bandelow, Borwin and Zwanzger, Peter Michael and Lang, Thomas and Fehm, Lydia and Str{\"o}hle, Andreas and Hamm, Alfons and Gerlach, Alexander L. and Alpers, Georg W. and Kircher, Tilo and Wittchen, Hans-Ulrich and Arolt, Volker and Pauli, Paul and Deckert, J{\"u}rgen and Reif, Andreas},
  title     = {Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75830},
  year      = {2012},
  abstract  = {Background: Panic disorder is common (5\% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48\%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype6gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype6gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.},
  subject      = {Medizin},
  language  = {en}
}
@article{VerghoLoeserKocotetal.2012,
  author    = {Vergho, Daniel Claudius and Loeser, Andreas and Kocot, Arkadius and Spahn, Martin and Riedm{\"u}ller, Hubertus},
  title     = {Tumor thrombus of inferior vena cava in patients with renal cell carcinoma - Clinical and oncological outcome of 50 patients after surgery},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75230},
  year      = {2012},
  abstract  = {Background: To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC) treated with nephrectomy and thrombectomy. Methods: We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results: The median follow-up was 26 months. In 21 patients (42\%) distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30\%), thoracoabdominal (14 patients/28\%) or midline abdominal approach (21 patients/42\%), depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB) was performed in 10 patients (20\%) with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1\%. Survival for the patients without distant metastasis at 5 years was 50.7\%, whereas survival rate in the metastatic group at 5 years was 7.4\%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10) even had a better outcome (overall survival at 5 years of 58.33\%) than the entire cohort. Conclusions: An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal circulation in patients with supradiaphragmal tumor thrombus. Cytoreductive surgery appears to be beneficial for patients with metastatic disease, especially when consecutive therapy is performed. Although sample size of our study cohort is limited consistent with some other studies lymph node invasion, distant metastasis and grading seem to have prognostic value.},
  subject      = {Medizin},
  language  = {en}
}
@article{TheinBondeBunikisetal.2012,
  author    = {Thein, Marcus and Bonde, Mari and Bunikis, Ignas and Denker, Katrin and Sickmann, Albert and Bergstr{\"o}m, Sven and Benz, Roland},
  title     = {DipA, a Pore-Forming Protein in the Outer Membrane of Lyme Disease Spirochetes Exhibits Specificity for the Permeation of Dicarboxylates},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75809},
  year      = {2012},
  abstract  = {Lyme disease Borreliae are highly dependent on the uptake of nutrients provided by their hosts. Our study describes the identification of a 36 kDa protein that functions as putative dicarboxylate-specific porin in the outer membrane of Lyme disease Borrelia. The protein was purified by hydroxyapatite chromatography from Borrelia burgdorferi B31 and designated as DipA, for dicarboxylate-specific porin A. DipA was partially sequenced, and corresponding genes were identified in the genomes of B. burgdorferi B31, Borrelia garinii PBi and Borrelia afzelii PKo. DipA exhibits high homology to the Oms38 porins of relapsing fever Borreliae. B. burgdorferi DipA was characterized using the black lipid bilayer assay. The protein has a singlechannel conductance of 50 pS in 1 M KCl, is slightly selective for anions with a permeability ratio for cations over anions of 0.57 in KCl and is not voltage-dependent. The channel could be partly blocked by different di- and tricarboxylic anions. Particular high stability constants up to about 28,000 l/mol (in 0.1 M KCl) were obtained among the 11 tested anions for oxaloacetate, 2-oxoglutarate and citrate. The results imply that DipA forms a porin specific for dicarboxylates which may play an important role for the uptake of specific nutrients in different Borrelia species.},
  subject      = {Medizin},
  language  = {en}
}
@article{SweeneySeubertStarketal.2012,
  author    = {Sweeney, Reinhart A. and Seubert, Benedikt and Stark, Silke and Homann, Vanessa and M{\"u}ller, Gerd and Flentje, Michael and Guckenbeger, Matthias},
  title     = {Accuracy and inter-observer variability of 3D versus 4D cone-beam CT based image-guidance in SBRT for lung tumors},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75698},
  year      = {2012},
  abstract  = {Background: To analyze the accuracy and inter-observer variability of image-guidance (IG) using 3D or 4D cone-beam CT (CBCT) technology in stereotactic body radiotherapy (SBRT) for lung tumors. Materials and methods: Twenty-one consecutive patients treated with image-guided SBRT for primary and secondary lung tumors were basis for this study. A respiration correlated 4D-CT and planning contours served as reference for all IG techniques. Three IG techniques were performed independently by three radiation oncologists (ROs) and three radiotherapy technicians (RTTs). Image-guidance using respiration correlated 4D-CBCT (IG-4D) with automatic registration of the planning 4D-CT and the verification 4D-CBCT was considered gold-standard. Results were compared with two IG techniques using 3D-CBCT: 1) manual registration of the planning internal target volume (ITV) contour and the motion blurred tumor in the 3D-CBCT (IG-ITV); 2) automatic registration of the planning reference CT image and the verification 3D-CBCT (IG-3D). Image quality of 3D-CBCT and 4D-CBCT images was scored on a scale of 1-3, with 1 being best and 3 being worst quality for visual verification of the IGRT results. Results: Image quality was scored significantly worse for 3D-CBCT compared to 4D-CBCT: the worst score of 3 was given in 19 \% and 7.1 \% observations, respectively. Significant differences in target localization were observed between 4D-CBCT and 3D-CBCT based IG: compared to the reference of IG-4D, tumor positions differed by 1.9 mm± 0.9 mm (3D vector) on average using IG-ITV and by 3.6 mm± 3.2 mm using IG-3D; results of IG-ITV were significantly closer to the reference IG-4D compared to IG-3D. Differences between the 4D-CBCT and 3D-CBCT techniques increased significantly with larger motion amplitude of the tumor; analogously, differences increased with worse 3D-CBCT image quality scores. Inter-observer variability was largest in SI direction and was significantly larger in IG using 3D-CBCT compared to 4D-CBCT: 0.6 mm versus 1.5 mm (one standard deviation). Inter-observer variability was not different between the three ROs compared to the three RTTs. Conclusions: Respiration correlated 4D-CBCT improves the accuracy of image-guidance by more precise target localization in the presence of breathing induced target motion and by reduced inter-observer variability.},
  subject      = {Medizin},
  language  = {en}
}
@article{SteinertWeissenbergerKunzetal.2012,
  author    = {Steinert, Andre F. and Weissenberger, Manuel and Kunz, Manuela and Gilbert, Fabian and Ghivizzani, Steven C. and Goebel, Sascha and Jakob, Franz and N{\"o}th, Ulrich and Rudert, Maximilian},
  title     = {Indian hedgehog gene transfer is a chondrogenic inducer of human mesenchymal stem cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75425},
  year      = {2012},
  abstract  = {Introduction: To date, no single most-appropriate factor or delivery method has been identified for the purpose of mesenchymal stem cell (MSC)-based treatment of cartilage injury. Therefore, in this study we tested whether gene delivery of the growth factor Indian hedgehog (IHH) was able to induce chondrogenesis in human primary MSCs, and whether it was possible by such an approach to modulate the appearance of chondrogenic hypertrophy in pellet cultures in vitro. Methods: First-generation adenoviral vectors encoding the cDNA of the human IHH gene were created by cre-lox recombination and used alone or in combination with adenoviral vectors, bone morphogenetic protein-2 (Ad.BMP- 2), or transforming growth factor beta-1 (Ad.TGF-b1) to transduce human bone-marrow derived MSCs at 5 × 102 infectious particles/cell. Thereafter, 3 × 105 cells were seeded into aggregates and cultured for 3 weeks in serumfree medium, with untransduced or marker gene transduced cultures as controls. Transgene expressions were determined by ELISA, and aggregates were analysed histologically, immunohistochemically, biochemically and by RT-PCR for chondrogenesis and hypertrophy. Results: IHH, TGF-b1 and BMP-2 genes were equipotent inducers of chondrogenesis in primary MSCs, as evidenced by strong staining for proteoglycans, collagen type II, increased levels of glycosaminoglycan synthesis, and expression of mRNAs associated with chondrogenesis. IHH-modified aggregates, alone or in combination, also showed a tendency to progress towards hypertrophy, as judged by the expression of alkaline phosphatase and stainings for collagen type X and Annexin 5. Conclusion: As this study provides evidence for chondrogenic induction of MSC aggregates in vitro via IHH gene delivery, this technology may be efficiently employed for generating cartilaginous repair tissues in vivo.},
  subject      = {Medizin},
  language  = {en}
}
@article{SpannausHartlWoehrletal.2012,
  author    = {Spannaus, Ralf and Hartl, Maximilian J. and W{\"o}hrl, Birgitta M. and Rethwilm, Axel and Bodem, Jochen},
  title     = {The prototype foamy virus protease is active independently of the integrase domain},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75370},
  year      = {2012},
  abstract  = {Background: Recently, contradictory results on foamy virus protease activity were published. While our own results indicated that protease activity is regulated by the viral RNA, others suggested that the integrase is involved in the regulation of the protease. Results: To solve this discrepancy we performed additional experiments showing that the protease-reverse transcriptase (PR-RT) exhibits protease activity in vitro and in vivo, which is independent of the integrase domain. In contrast, Pol incorporation, and therefore PR activity in the viral context, is dependent on the integrase domain. To further analyse the regulation of the protease, we incorporated Pol in viruses by expressing a GagPol fusion protein, which supported near wild-type like infectivity. A GagPR-RT fusion, lacking the integrase domain, also resulted in wild-type like Gag processing, indicating that the integrase is dispensable for viral Gag maturation. Furthermore, we demonstrate with a trans-complementation assays that the PR in the context of the PR-RT protein supports in trans both, viral maturation and infectivity. Conclusion: We provide evidence that the FV integrase is required for Pol encapsidation and that the FV PR activity is integrase independent. We show that an active PR can be encapsidated in trans as a GagPR-RT fusion protein.},
  subject      = {Medizin},
  language  = {en}
}
@article{SlaninaHeblingHaucketal.2012,
  author    = {Slanina, Heiko and Hebling, Sabrina and Hauck, Christoph R. and Schubert-Unkmeir, Alexandra},
  title     = {Cell Invasion by Neisseria meningitidis Requires a Functional Interplay between the Focal Adhesion Kinase, Src and Cortactin},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75354},
  year      = {2012},
  abstract  = {Entry of Neisseria meningitidis (the meningococcus) into human brain microvascular endothelial cells (HBMEC) is mediated by fibronectin or vitronectin bound to the surface protein Opc forming a bridge to the respective integrins. This interaction leads to cytoskeletal rearrangement and uptake of meningococci. In this study, we determined that the focal adhesion kinase (FAK), which directly associates with integrins, is involved in integrin-mediated internalization of N. meningitidis in HBMEC. Inhibition of FAK activity by the specific FAK inhibitor PF 573882 reduced Opc-mediated invasion of HBMEC more than 90\%. Moreover, overexpression of FAK mutants that were either impaired in the kinase activity or were not capable of autophosphorylation or overexpression of the dominant-negative version of FAK (FRNK) blocked integrin-mediated internalization of N. meningitidis. Importantly, FAK-deficient fibroblasts were significantly less invaded by N. meningitidis. Furthermore, N. meningitidis induced tyrosine phosphorylation of several host proteins including the FAK/Src complex substrate cortactin. Inhibition of cortactin expression by siRNA silencing and mutation of critical amino acid residues within cortactin, that encompass Arp2/3 association and dynamin binding, significantly reduced meningococcal invasion into eukaryotic cells suggesting that both domains are critical for efficient uptake of N. meningitidis into eukaryotic cells. Together, these results indicate that N. meningitidis exploits the integrin signal pathway for its entry and that FAK mediates the transfer of signals from activated integrins to the cytoskeleton. A cooperative interplay between FAK, Src and cortactin then enables endocytosis of N. meningitidis into host cells.},
  subject      = {Medizin},
  language  = {en}
}