Bingen am Rhein, Germany
Bingen am Rhein, Germany

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Stefan N.,University Hospital Tu Bingen | Stefan N.,Institute of Diabetes Research and Metabolic Diseases | Sun Q.,Harvard University | Fritsche A.,University Hospital Tu Bingen | And 18 more authors.
PLoS ONE | Year: 2014

Background: Among adipokines and hepatokines, adiponectin and fetuin-A were consistently found to predict the incidence of type 2 diabetes, both by regulating insulin sensitivity. © 2014 Stefan et al.

Liao Y.,University of Ulm | Liao Y.,University Hospital Tu Bingen | Deprez L.,University of Antwerp | Maljevic S.,University of Ulm | And 18 more authors.
Brain | Year: 2010

Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial neonatal-infantile seizures are caused by mutations in the gene SCN2A encoding the voltage-gated Na+ channel NaV1.2. We identified two novel SCN2A mutations causing benign familial neonatal-infantile seizures and analysed the functional consequences of these mutations in a neonatal and an adult splice variant of the human Na+ channel NaV1.2 expressed heterologously in tsA201 cells together with beta1 and beta2 subunits. We found significant gating changes leading to a gain-of-function, such as an increased persistent Na+ current, accelerated recovery from fast inactivation or altered voltage-dependence of steady-state activation. Those were restricted to the neonatal splice variant for one mutation, but more pronounced for the adult form for the other, suggesting that a differential developmental splicing does not provide a general explanation for seizure remission. We therefore analysed the developmental expression of NaV1.2 and of another voltage-gated Na+ channel, NaV1.6, using immunohistochemistry and real-time reverse transcription- polymerase chain reaction in mouse brain slices. We found that NaV1.2 channels are expressed early in development at axon initial segments of principal neurons in the hippocampus and cortex, but their expression is diminished and they are gradually replaced as the dominant channel type by NaV1.6 during maturation. This finding provides a plausible explanation for the transient expression of seizures that occur due to a gain-of-function of mutant NaV1.2 channels. © The Author (2010). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Hasenbach K.,University of Zürich | Wiehr S.,Siemens AG | Herrmann C.,University of Zürich | Herrmann C.,Siemens AG | And 10 more authors.
Neuro-Oncology | Year: 2012

Intracerebral experimental gliomas attract intravenously injected murine or human bone marrowderived hematopoietic progenitor and stem cells (HPC) in vitro, ex vivo, and in vivo, indicating that these progenitor cells might be suitable vehicles for a cell-based delivery of therapeutic molecules to malignant gliomas. With regard to therapeutic application, it is important to investigate cell fates in vivo (i.e., the time-dependent intratumoral and systemic distribution after intravenously injection). Conventional histological analysis has limitations in this regard because longitudinal monitoring is precluded. Here, we used 2-photon laser scanning microscopy (2PLSM), positron emission tomography (PET), and MRI to study the fate of intravenously injected HPC carrying fluorescence, bioluminescence, and PET reporter genes in glioma-bearing mice. Our 2PLSM-based monitoring studies revealed that HPC homing to intracerebral experimental gliomas occurred already within the first 6 h and was most efficient within the first 24 h after intravenous injection. The highest PET signals were detected in intracerebral gliomas, whereas the tracer uptake in other organs, notably spleen, lung, liver, and muscle, remained at background levels. The results have important implications for designing schedules for therapeutic cell-based anti-glioma approaches. Moreover, the PET reporter-based imaging technique will allow noninvasive monitoring of cell fate in future cell-based therapeutic antiglioma approaches. © 2012 The Author(s).

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