Transcoronary ablation of septal hypertrophy is a promising new treatment for hypertrophic obstructive cardiomyopathy in patients with severe symptoms. It should now be compared with alternative treatment strategies in prospective randomized studies.
The strong humoral immune response to glutaraldehyde-fixed tissues is reduced in decellularized xenogeneic valves and almost absent in decellularized allogeneic tissue up to 4.5 years after implantation.
The gammaproteobacterium Legionella pneumophila is the causative agent of Legionnaires’ disease, an atypical pneumonia that manifests itself with severe lung damage. L. pneumophila, a common inhabitant of freshwater environments, replicates in free-living amoebae and persists in biofilms in natural and man-made water systems. Its environmental versatility is reflected in its ability to survive and grow within a broad temperature range as well as its capability to colonize and infect a wide range of hosts, including protozoa and humans. Peptidyl-prolyl-cis/trans-isomerases (PPIases) are multifunctional proteins that are mainly involved in protein folding and secretion in bacteria. In L. pneumophila the surface-associated PPIase Mip was shown to facilitate the establishment of the intracellular infection cycle in its early stages. The cytoplasmic PpiB was shown to promote cold tolerance. Here, we set out to analyze the interrelationship of these two relevant PPIases in the context of environmental fitness and infection. We demonstrate that the PPIases Mip and PpiB are important for surfactant-dependent sliding motility and adaptation to suboptimal temperatures, features that contribute to the environmental fitness of L. pneumophila. Furthermore, they contribute to infection of the natural host Acanthamoeba castellanii as well as human macrophages and human explanted lung tissue. These effects were additive in the case of sliding motility or synergistic in the case of temperature tolerance and infection, as assessed by the behavior of the double mutant. Accordingly, we propose that Mip and PpiB are virulence modulators of L. pneumophila with compensatory action and pleiotropic effects.
A multiplicity of surgical operations have been developed in an attempt to achieve satisfactory function after anterior cruciate ligament (ACL) repair. None of these procedures have been able to duplicate the fiber organization, anatomy of the attachment site, vascularity, or function of the ACL. Eighteen foxhounds received a deep-frozen bone-ACL-bone allograft and a ligament augmentation device. Neurohistological changes were evaluated 3, 6 and 12 months following implantation. The modified silver impregnation method and gold chloride technique were used to examine the presence of nerve endings and axons. Two morphologically distinct mechanoreceptors were identified and classified as free nerve endings and Golgi-like tendon receptors respectively. Fine nerve endings frequently ramified freely into ligament collagen bundles. Nerves and blood vessels were commonly associated. As in normal ACLs, both neuroreceptor types were mostly located near the surface of the allografts and at the two bony attachments. This study demonstrated the first histological evidence of viable mechanoreceptors and free nerve endings in transplanted ACL allografts, not previously reported in other ACL substitutes used for ACL reconstruction. Particularly importantly for postoperative rehabilitation, this technique may allow the reconstruction of the proprioceptive functions of normal ACLs.
ProA is a secreted zinc metalloprotease of Legionella pneumophila causing lung damage in animal models of Legionnaires' disease. Here we demonstrate that ProA promotes infection of human lung tissue explants (HLTEs) and dissect the contribution to cell type specific replication and extracellular virulence mechanisms. For the first time, we reveal that co‐incubation of HLTEs with purified ProA causes a significant increase of the alveolar septal thickness. This destruction of connective tissue fibres was further substantiated by collagen IV degradation assays. The moderate attenuation of a proA‐negative mutant in A549 epithelial cells and THP‐1 macrophages suggests that effects of ProA in tissue mainly result from extracellular activity. Correspondingly, ProA contributes to dissemination and serum resistance of the pathogen, which further expands the versatile substrate spectrum of this thermolysin‐like protease. The crystal structure of ProA at 1.48 Å resolution showed high congruence to pseudolysin of Pseudomonas aeruginosa, but revealed deviations in flexible loops, the substrate binding pocket S1′ and the repertoire of cofactors, by which ProA can be distinguished from respective homologues. In sum, this work specified virulence features of ProA at different organisational levels by zooming in from histopathological effects in human lung tissue to atomic details of the protease substrate determination.
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