0000000000326944
AUTHOR
Eckart Schott
Expression of Toll-Like Receptors in the Developing Brain
Toll-like receptors (TLR) are key players of the innate and adaptive immune response in vertebrates. The original protein Toll in Drosophila melanogaster regulates both host defense and morphogenesis during development. Making use of real-time PCR, in situ hybridization, and immunohistochemistry we systematically examined the expression of TLR1-9 and the intracellular adaptor molecules MyD88 and TRIF during development of the mouse brain. Expression of TLR7 and TLR9 in the brain was strongly regulated during different embryonic, postnatal, and adult stages. In contrast, expression of TLR1-6, TLR8, MyD88, and TRIF mRNA displayed no significant changes in the different phases of brain develop…
Real-world experience with the all-oral, interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German Hepatitis C Registry.
Summary Real-world studies are relevant to complement clinical trials on novel antiviral therapies against chronic hepatitis C; however, clinical practice data are currently limited. This study investigated effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±ribavirin (RBV) for treatment of HCV genotype (GT) 1 and GT4 infection in a large real-world cohort. The German Hepatitis C Registry is an observational cohort study prospectively collecting clinical practice data on direct-acting antiviral therapies. Patients with GT1/4 infection treated with OBV/PTV/r±DSV±RBV were analysed. Effectiveness was assessed by sustained virologic response in 558 patients…
949 IDENTIFICATION OF TWO CLINICALLY DISTINCT SUBTYPES IN AUTOIMMUNE HEPATITIS BY COMPARATIVE FUNCTIONAL GENOMICS
Conclusion: Incidence of autoimmune hepatitis is increasing, as other autoimmune diseases in developed countries. The main recognised hypothesis is the ‘hygienist theory’ (improvement of hygien leading to a decrease in infections) with few putative non exclusive mechanisms involving antigenic competition, extension of immune regulation induced by exogenous bacterial antigen or Toll Like Receptors.
Final Analysis of Overall Survival Per Subgroups of Hcc Patients in the Prospective, Non-Interventional Insight Study Treated with Sorafenib
ABSTRACT Aim: INSIGHT is a prospective, non-interventional study, conducted in Germany and Austria in pts with hepatocellular carcinoma HCC. The objectives of this study are the evaluation of safety and efficacy under practice conditions in both hospitals and private practices. Enrollment into INSIGHT is not restricted to a particular tumor stage. Methods: This final analysis evaluated overall survival and safety data incluling relevant subgroups. All patients with HCC were observed for the duration of their sorafenib therapy. In addition to baseline data the performance status, tumor status (clinical and/or radiological), and overall survival time are documented. Documentation of adverse e…
Interim Analysis of Overall Survival Per Subgroups in the Prospective, Non-Interventional Insight Study in Patients with Hepatocellular Carcinoma Treated with Sorafenib
ABSTRACT Background The efficacy of Sorafenib in patients (pts) with hepatocellular carcinoma (HCC) has been proven in randomized, controlled trials. INSIGHT is a prospective, non-interventional study, conducted in Germany and Austria in pts with HCC. The objectives of this study are the evaluation of safety and efficacy under practice conditions in both hospitals and private practices. Enrollment into INSIGHT is not restricted to a particular tumor stage. Recruitment into the study is ongoing. Methods The second interim analysis (data cut-off 23 FEB 2012) evaluated overall survival and safety data in relevant subgroups. All patients with HCC were observed for the duration of their sorafeni…
Direct-acting antiviral treatment of chronic HCV-infected patients on opioid substitution therapy: Still a concern in clinical practice?
BACKGROUND AND AIMS There is limited real-world information on the effectiveness of antiviral treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAA) in people on opioid substitution therapy (OST). This study compared sustained virological response (SVR) rates and proportion of lost to follow-up (LTFU) between OST and non-OST patients in the German Hepatitis C-Registry (DHC-R). DESIGN National multi-centre prospective real-world registry (German Hepatitis C-Registry, DHC-R). Non-OST patients comprised patients with former/current drug use (non-OST/DU) and patients never consuming drugs (non-OST/NDU). SETTING A total of 254 medical centres in Germany, inclu…
An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration
Activation of innate immune receptors by host-derived factors exacerbates CNS damage, but the identity of these factors remains elusive. We uncovered an unconventional role for the microRNA let-7, a highly abundant regulator of gene expression in the CNS, in which extracellular let-7 activates the RNA-sensing Toll-like receptor (TLR) 7 and induces neurodegeneration through neuronal TLR7. Cerebrospinal fluid (CSF) from individuals with Alzheimer’s disease contains increased amounts of let-7b, and extracellular introduction of let-7b into the CSF of wild-type mice by intrathecal injection resulted in neurodegeneration. Mice lacking TLR7 were resistant to this neurodegenerative effect, but thi…