Biomedical subjects

Daniel J Sexton

Publications and source records attributed to Daniel J Sexton.

39 records · Page 3Linked to original sources

PubMed2001

Postoperative bacteremia secondary to surgical site infection.

We evaluated all surgical site infections (SSI) and postoperative bacteremias secondary to SSI as part of an ongoing active surgical surveillance program at a community hospital. Among 40,191 surgical procedures, we identified 515 patients with SSI and 47 with postoperative bacteremia secondary to SSI. Four variables were examined as potential predictors for developing postoperative bacteremia secondary to an SSI: National Nosocomial Infections Surveillance risk index, abdominal surgery, surgical procedures with an implantable device, and the presence of Staphylococcus aureus in wounds. Of these 4 variables, only one, S. aureus isolated from a wound culture, was associated with an increased risk of developing postoperative bacteremia secondary to SSI. Patients with S. aureus isolated in either pure or mixed culture from SSI were more than twice as likely to have postoperative bacteremia secondary to SSI than were those without S. aureus wound infection.

Bacteremia↗

PubMedDate not supplied

Discovery of high-affinity peptide binders to BLyS by phage display.

B lymphocyte stimulator (BLyS) is a tumor necrosis factor (TNF) family member and a key regulator of B cell responses. We employed a phage display-based approach to identify peptides that bind BLyS with high selectivity and affinity. Sequence analysis of first-generation BLyS-binding peptides revealed two dominant peptide motifs, including one containing a conserved DxLT sequence. Selected linear peptides with this motif were found to bind BLyS with K(D) values of 1-3 microM. In order to improve the binding affinity for BLyS, consensus residues flanking the DxLT sequence were seeded into a second-generation, BLyS affinity maturation library (BAML). BAML phage were subjected to stringent binding competition conditions to select for isolates expressing high-affinity peptide ligands for BLyS. Post-selection analysis of BAML peptide sequences resulted in the identification of a core decapeptide motif (WYDPLTKLWL). Peptides containing this core motif exhibited K(D) values as low as 26 nM, approximately 100-fold lower than that of first-generation peptides. A fluorescence anisotropy assay was developed to monitor the protein-protein interaction between BLyS labeled with a ruthenium chelate, and TACI-Fc, a soluble form of a BLyS receptor. Using this assay it was found that a BAML peptide disrupts this high-affinity protein-protein interaction. This demonstrates the potential of short peptides for disruption of high affinity cytokine-receptor interactions.

Amino Acid Motifs↗

PubMedDate not supplied

Development of mammalian serum albumin affinity purification media by peptide phage display.

Several phage isolates that bind specifically to human serum albumin (HSA) were isolated from disulfide-constrained cyclic peptide phage-display libraries. The majority of corresponding synthetic peptides bind with micromolar affinity to HSA in low salt at pH 6.2, as determined by fluorescence anisotropy. One of the highest affinity peptides, DX-236, also bound well to several mammalian serum albumins (SA). Immobilized DX-236 quantitatively captures HSA from human serum; mild conditions (100 mM Tris, pH 9.1) allow release of HSA. The DX-236 affinity column bound HSA from human serum with a greater specificity than does Cibacron Blue agarose beads. In addition to its likely utility in HSA and other mammalian SA purifications, this peptide media may be useful in the proteomics and medical research markets for selective removal of mammalian albumin from serum prior to mass spectrometric and other analyses.

Amino Acid Sequence↗