Publications

The type III secretion system of Pseudomonas aeruginosa, responsible for acute infection, is composed of over twenty proteins that facilitate cytotoxin injection directly into host cells. Integral to this process is production and secretion of PcrV. Administration of a recently developed, anti-PcrV immunoglobulin, either as a therapeutic or prophylactic has previously demonstrated efficacy against laboratory strains of P. aeruginosa in a murine model. To determine if this therapy is universally applicable to a variety of P. aeruginosa clinical isolates, genetic heterogeneity of pcrV was analyzed among strains collected from three geographically distinct regions; United States, France and Japan. Sequence analysis of PcrV demonstrated limited variation among the clinical isolates examined. Strains were grouped according to the presence of non-synonymous single nucleotide polymorphisms. Representative isolates from each mutant group were examined for the ability of anti-PcrV to bind the protein secreted by these strains. The protective effect of anti-PcrV IgG against each strain was determined using an epithelial cell line cytotoxicity assay. The majority of strains tested demonstrated reduced cytotoxicity in the presence of anti-PcrV IgG. This study provides insights into the natural sequence variability of PcrV and an initial indication of the amino acid residues that appear to be conserved across strains. It also demonstrates the protective effect of anti-PcrV immunotherapy against a multitude of P. aeruginosa strains from diverse global regions with a variety of mutations in PcrV.

Little is known about strategies that physicians use to encourage receipt of colorectal cancer screening (CRCS). This study conducted focus groups with physicians. Twenty-seven physicians participated in four focus groups. Physicians described four categories of approaches: (1) why screening is important, (2) providing test information, (3) motivational strategies, and (4) tailoring strategies. Participants reported tailoring based on their relationship with a patient, as well as to patient gender, education, and language. Tailoring to cultural background or ethnicity was not prominent. Most physicians reported a typical approach to CRCS and reported some tailoring based on gender, education, and language, but not on ethnicity.

The distribution of neuroglobin (Ngb) was investigated in the normal rat cochlea using immunohistochemistry and non-radioactive insitu hybridization. We also determined whether chronic, very mild CO exposure at 25ppm in air over the gestational and postnatal period alters the expression of Ngb. Pregnant rats were exposed chronically to CO from gestational days 5-20. Four groups were made as follows: prenatal exposure to CO only; prenatal exposure to CO followed by postnatal exposure from postnatal days (5) P5 to P20; rat pups were exposed to CO from P5 to P20; controls (air without CO). In normal adult rats and control group pups, Ngb was found in spiral ganglia neurons, fibrocytes of the spiral ligament, and supporting cells of the organ of Corti. Ngb was not present in the stria vascularis and the inner and outer hair cells. At P20 Ngb immunoreactivity and transcript expression decreased in spiral ganglia neurons and the spiral ligament in the prenatal and pre- and postnatal groups. This decrease was not observed in the postnatal group. Ngb-IR did not decrease in supporting cells in any CO group. Cytochrome-C immunoreactivity followed Ngb distribution in normal controls and CO treated groups. A decrease in Ngb in spiral ganglia neurons and rat spiral ligament, but not in supporting cells, following CO exposure supports the idea that chronic, mild exposure to CO may create a vulnerable cellular environment predisposed to adverse cochlear development.