201 research outputs found
In-Vitro Investigation of Very Long Defibrillation Shocks: Design and Testing of a Capacitor-Free Defibrillator
Abstrac
RNase L Mediated Protection from Virus Induced Demyelination
IFN-Ξ±/Ξ² plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-Ξ±/Ξ² dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-Ξ±/Ξ² pathway through RNA degradation intermediates. Infection of RNase L deficient (RLβ/β) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-Ξ±/Ξ² expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RLβ/β mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-Ξ±/Ξ² mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination
Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis
Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2β/β) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1β/β mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2β/β mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2β/β mice and induced interferon-Ξ². However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2β/β mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2β/β mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2β/β mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2β/β mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon
A Sensitive Assay for Virus Discovery in Respiratory Clinical Samples
In 5β40% of respiratory infections in children, the diagnostics
remain negative, suggesting that the patients might be infected with a yet
unknown pathogen. Virus discovery cDNA-AFLP (VIDISCA) is a virus discovery
method based on recognition of restriction enzyme cleavage sites, ligation of
adaptors and subsequent amplification by PCR. However, direct discovery of
unknown pathogens in nasopharyngeal swabs is difficult due to the high
concentration of ribosomal RNA (rRNA) that acts as competitor. In the current
study we optimized VIDISCA by adjusting the reverse transcription enzymes and
decreasing rRNA amplification in the reverse transcription, using hexamer
oligonucleotides that do not anneal to rRNA. Residual cDNA synthesis on rRNA
templates was further reduced with oligonucleotides that anneal to rRNA but can
not be extended due to 3β²-dideoxy-C6-modification. With these
modifications >90% reduction of rRNA amplification was established.
Further improvement of the VIDISCA sensitivity was obtained by high throughput
sequencing (VIDISCA-454). Eighteen nasopharyngeal swabs were analysed, all
containing known respiratory viruses. We could identify the proper virus in the
majority of samples tested (11/18). The median load in the VIDISCA-454 positive
samples was 7.2 E5 viral genome copies/ml (ranging from 1.4 E3β7.7 E6).
Our results show that optimization of VIDISCA and subsequent
high-throughput-sequencing enhances sensitivity drastically and provides the
opportunity to perform virus discovery directly in patient material
Self-reactive CD4+ T cells activated during viral-induced demyelination do not prevent clinical recovery
Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models
Beitrag zum Problem des Einflusses der Blutabnahme nach der Bestrahlung auf die Regenerierung der Erythropoese
A COMPARATIVE PHARMACOLOGIC STUDY OF THE THREE PHOSPHORIC ESTERS OF ORTHOCRESOL WITH THE ASSISTANCE
Effect of a congenital defect in hemopoiesis on myeloid growth and the stem cell (cfu) in an in vivo culture system
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