Low-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1-deficient mice (Hmox1(-/-)), but not in wild-type (Hmox1(+/+)) mice. Here we demonstrate that the protective effect of this heme-catabolizing enzyme relies on its ability to prevent tissue damage caused by the circulating free heme released from hemoglobin during infection. Heme administration after low-grade infection in mice promoted tissue damage and severe sepsis. Free heme contributed to the pathogenesis of severe sepsis irrespective of pathogen load, revealing that it compromised host tolerance to infection. Development of lethal forms of severe sepsis after high-grade infection was associated with reduced serum concentrations of the heme sequestering protein hemopexin (HPX), whereas HPX administration after high-grade infection prevented tissue damage and lethality. Finally, the lethal outcome of septic shock in patients was also associated with reduced HPX serum concentrations. We propose that targeting free heme by HPX might be used therapeutically to treat severe sepsis.
Negative imaginary (NI) systems play an important role in the robust control
of highly resonant flexible structures. In this paper, a generalized NI system
framework is presented. A new NI system definition is given, which allows for
flexible structure systems with colocated force actuators and pos...
We studied 6 patients with classical phenotypes of Tyrosinemia type-I. To identify possible miRNAs targeting FAH transcripts, microarray profiling of 961 miRNAs for lymphocytes and serum is performed. Computational algorithms are used for prediction of putative mRNA-miRNA interactions. A number of d...
(1) The corona theorem for A_0+AP_+.
(2) M(A_0+AP_+) is contractible (which implies that A_0+AP_+ is a projective
(3) A_0+AP_+ is not a GCD domain.
(4) A_0+AP_+ is not a pre-Bezout domain.
(5) A_0+AP_+ is not a coherent ring.
The study of the above algebraic-anlaytic properti...
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