The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue. Variable and pleiotropic clinical features are observed in the skeletal, ocular, and cardiovascular systems. The most severe end of the phenotypic spectrum of this disorder comprises a group of patients usually diagnosed at birth, who have a life expectancy of little more than a year. To distinguish this group of patients from those with classical MFS, we refer to them as neonatal Marfan syndrome (nMFS). These infants usually die of congestive heart failure rather than aortic aneurysmal disease, the most frequent cause of morbidity and mortality in classical MFS. Defects in fibrillin, an elastin-associated microfibrillar glycoprotein, are now known to cause both the classical and neonatal forms of MFS. Here we report the recurrent mis-splicing of fibrillin (FBN1) exon 32, a precursor EGF-like calcium binding domain, in two unrelated infants with nMFS. The mis-splicing, in one patient, was due to an A-->T transversion at the -2 position of the consensus acceptor splice site; while that in the second patient was caused by a G-->A transition at the +1 position of the donor splice site. Characterization of FBN1 mutations in individuals at the most severe end of the Marfan syndrome spectrum should provide greater understanding of the multiple domains and regions of fibrillin.

Adherence to biomaterials and production of biofilm is thought to be pivotal in the pathogenesis of prosthetic device infection by Staphylococcus epidermidis. In this study a strong association (P < .001) of hemagglutination with adherence and biofilm production was observed. Hemagglutination was not associated with cell surface hydrophobicity (P = .906). Hemagglutination inhibition studies revealed that hemagglutination was not affected by heat, pH, cation concentration, proteolytic enzymes, biologic detergent, serum proteins, or subinhibitory antibiotics. Hemagglutination was abolished by periodate oxidation and digestion with glycosidases. It was markedly inhibited by beta-lactose and its monosaccharide constituents in a concentration-dependent fashion. Hemagglutinin expression depended on the presence of glucose. Chemical analysis of a partially purified hemagglutinin preparation and cell-free hemagglutinating supernatants revealed little or no protein and small quantities of reducing sugars, pentose, ketose, hexosamine, uronic acid, and phosphate. Hemagglutinin of S. epidermidis appears to be a polysaccharide distinct from other known adhesins of S. epidermidis.

Objective Plasminogen activator inhibitor-1 (PAI-1) has previously been shown to be key to the formation of myoendothelial junctions (MEJs) in normal and pathological states (e.g., obesity). We there for sought to identify the mechanism whereby PAI-1 could be selectively accumulated at the MEJ. Methods and Results We identified PAI-1 protein enrichment at the MEJ in obese mice and in response to TNF-α with a vascular cell co-culture. However, PAI-1 mRNA was also found at the MEJ and transfection with a PAI-1-GFP with TNF-α did not demonstrate trafficking of the protein to the MEJ. We there for hypothesized the PAI-1 mRNA was being locally translated and identified serpine binding protein-1, which stabilizes PAI-1 mRNA, as being enriched in obese mice and after treatment with TNF-α, while staufen, which degrades PAI-1 mRNA, was absent in obese mice and after TNF- α application. We identified nicotinamide phosphoribosyl transferase as a serpine binding protein-1 binding partner with a functional tau-like microtubule binding domain. Application of peptides against the microtubule binding domain significantly decreased the number of MEJs and the amount of PAI-1 at the MEJ. Conclusions We conclude that PAI-1 can be locally translated at the MEJ due to a unique mRNA binding protein complex.

Although hemagglutination by Staphylococcus aureus has been associated with the pathogenesis of bovine mastitis, this trait has not been characterized with regard to human disease. In this study, the prevalence of hemagglutination in 100 strains of S. aureus responsible for bovine mastitis or human bacteremia, was characterized. Under optimum conditions hemagglutination was noted in 23% of the bovine strains, but only 13% of human strains, leading us to conclude that this trait is not a significant virulence determinant in human systemic infection. Additional studies indicate the hemagglutinin of S. aureus strains responsible for human bacteremia is proteinaceous in character.

No abstract