“
“Production of type I interferons (IFNs; prominently, IFN-alpha/beta) following virus infection is a pivotal antiviral innate immune response in higher vertebrates. The synthesis of IFN-beta proceeds via the virus-induced assembly of the transcription factors IRF-3/7, ATF-2/c-Jun, and NF-kappa B on the ifn beta promoter. Surprisingly, recent data indicate that the NF-kappa B subunit RelA is not essential for virus-stimulated ifn beta expression. Here, we show that RelA instead sustains autocrine IFN-beta signaling prior to infection. In the absence of Selleckchem ABT737 RelA, virus infection results in significantly delayed ifn beta induction and consequently
defective secondary antiviral gene expression. While RelA is not required for ifn beta expression after infection, it is nonetheless essential for fully one-fourth of double-stranded RNA (dsRNA)-activated genes, including several mediators of inflammation and immune cell recruitment. Further, RelA directly regulates
a small subset of interferon-stimulated genes (ISGs). Finally, RelA also protects cells from dsRNA-triggered RIP1-dependent programmed necrosis. Taken together, our findings suggest distinct roles for RelA in antiviral innate immunity: RelA maintains autocrine IFN-beta signaling GSK J4 mouse in uninfected cells, facilitates inflammatory and adaptive immune responses following infection, and promotes infected-cell survival during this process.”
“BACKGROUND: Most cavernomas in the central nervous system are characterized
by a benign natural course. Progressive symptoms warrant surgical removal. In the literature, the factors affecting long-term postoperative outcome are not statistically well confirmed.
OBJECTIVE: To perform a multifactorial analysis of risk factors on a large patient series and to use the results to propose a simple grading scale to predict outcome.
METHODS: We studied 303 consecutive patients with cavernomas treated surgically at our department from 1980 to 2009. Follow-up assessment was performed on average 5.7 Enzalutamide years postoperatively (range, 0.2-36 years). The main outcome measure was the patients’ condition at the last follow-up on Glasgow Outcome Scale. For statistical analysis, the outcome measure was dichotomized to favorable (Glasgow Outcome Scale 5) and unfavorable (Glasgow Outcome Scale 1-4). Binary logistic regression analysis was used to estimate the effect of age, sex, seizures, preexisting neurological deficits, hemorrhage, and size and location of cavernoma on long-term outcome.
RESULTS: Infratentorial, basal ganglia, or spinal location and preexisting neurological deficit were the only independent risk factors for unfavorable outcome, with relative risks of 2.7 (P = .008) and 3.2 (P = .002), respectively. We formulated a grading system based on a score of 1 to 3.