Heart failure and chronic kidney disease are common and clinically important conditions that regularly coexist. Electrophysiologic changes of advanced heart failure often result in abnormal conduction, causing dyssynchronous contraction, and development of ventricular arrhythmias, which can lead to sudden cardiac arrest. In the last 2 decades, implantable cardioverter-defibrillator and cardiac resynchronization therapy devices have been developed to address these complications.
View Article and Find Full Text PDFMyeloproliferative neoplasms (MPNs) are characterized by a pathologic expansion of myeloid lineages. Mutations in JAK2, CALR and MPL genes are known to be three prominent MPN disease drivers. Mutant CALR (mutCALR) is an oncoprotein that interacts with and activates the thrombopoietin receptor (MPL) and represents an attractive target for targeted therapy of CALR mutated MPN.
View Article and Find Full Text PDFStreptococcuspneumoniae is a major human pathogen at the extremes of age. The elderly are particularly vulnerable to S.pneumoniae, the most common causative agent of bacterial pneumonia in this population.
View Article and Find Full Text PDFPlasmid-encoded colistin resistance is emerging among extraintestinal pathogenic strains, including those of the epidemic clone sequence type 131 (ST131)-H30. Mcr-1 transfers a phosphoethanolamine to the lipid A portion of lipopolysaccharide (LPS), conferring resistance to polymyxins. We investigated whether this modification changed the activity of the monoclonal antibody ASN-4, specific to the O25b side chain of ST131 LPS.
View Article and Find Full Text PDFThe multidrug-resistant 30 subclone of extraintestinal pathogenic sequence type 131 (ST131-30) has spread worldwide. This clone expresses a conserved lipopolysaccharide (LPS) O antigen, O25b. Previously, we described monoclonal antibodies (MAbs) specific to the O25b antigen and characterized them as diagnostic and therapeutic tools.
View Article and Find Full Text PDFKlebsiella pneumoniae ST258 is a globally distributed multi-drug resistant pathogen responsible for severe invasive infections. In this study, the different virulence potential of K. pneumoniae ST258 isolates in endotoxin susceptible versus resistant animal models was shown.
View Article and Find Full Text PDFKlebsiella pneumoniae ST258 is a globally disseminated, extremely drug resistant, nosocomial clone with limited treatment options. We show that the vast majority of ST258 isolates express modified d-galactan-I lipopolysaccharide O-antigen, termed hereinafter as D-galactan-III. The genetic determinant required for galactan-III synthesis was identified as a distinct operon adjacent to the rfb (wb) locus encoding D-galactan-I synthesis.
View Article and Find Full Text PDFThe Escherichia coli sequence type 131 (ST131)-O25b:H4 clone has spread worldwide and become responsible for a significant proportion of multidrug-resistant extraintestinal infections. We generated humanized monoclonal antibodies (MAbs) that target the lipopolysaccharide O25b antigen conserved within this lineage. These MAbs bound to the surface of live bacterial cells irrespective of the capsular type expressed.
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