Enteropathogenic Escherichia coli and enterohemorrhagic E. coli cause an inflammatory colitis in human patients characterized by neutrophil infiltration, proinflammatory cytokine expression, and crypt hyperplasia. Citrobacter rodentium causes a similar colitis in mice and serves as a model for enteropathogenic E. coli infection in humans. C. rodentium induces systemic T-cell-dependent antibody production that facilitates clearance of the bacteria and protects the host from reinfection. The role of innate immune cells in infectious colitis, however, is less well understood. In this study, we have determined the role of mast cells in the inflammatory response and disease induced by C. rodentium. Mice deficient in mast cells exhibit more severe colonic histopathology and have a higher mortality rate following infection with C. rodentium than do wild-type animals. Despite unimpaired neutrophil recruitment and lymphocyte activation, mast cell-deficient mice have a disseminated infection evident in crucial organ systems that contributes to sepsis. Importantly, mast cells also have the capacity to directly kill C. rodentium. Together, these results suggest that mast cells protect the host from systemic infection by reducing the bacterial load and preventing dissemination of the bacterium from the colon.Enteric pathogens such as enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) attach to and colonize the host gastrointestinal tract and cause weight loss, diarrhea, crypt hyperplasia, and transient colitis. EPEC is a major contaminant in food and water sources in developing countries and causes significant increases in morbidity and mortality, primarily among children. EHEC contaminates food and water sources in industrialized nations and causes both diarrhea and hemolytic-uremic syndrome. A related pathogen, Citrobacter rodentium, has only about 50% of its genes in common with EPEC and EHEC but nevertheless induces disease in rodents that is virtually identical to that caused by EPEC and EHEC in humans. C. rodentium infection in mice is widely used as an animal model of pathogenic E. coli infection in humans (7, 9, 10, 18-21, 34, 42, 43, 45-47).EPEC, EHEC, and C. rodentium all induce a characteristic lesion in the intestine of the host that is characterized by intimate attachment to the host intestinal epithelial cells and effacement of microvilli. Such attaching and effacing (A/E) lesions result from translocation of virulence proteins from the bacterium into the host cell (13,22,23,26). These factors induce formation of membranous protrusions, called pedestals, beneath the bacterium, and anchor the bacterium to the host cell (reviewed in reference 36). Pedestal formation is required for subsequent disease (31, 37). EPEC, EHEC, and C. rodentium all contain a 35-kb pathogenicity island called LEE (locus of enterocyte effacement) that encodes ϳ41 virulence factors that are essential for the formation of A/E lesions and for disease. The virulence factors from the LEE loci of EPEC, EHEC, and C. r...

Background:Large linked databases (LLDB) represent a novel resource for cancer outcomes research. However, accurate means of identifying a patient population of interest within these LLDBs can be challenging. Our research group developed a fully integrated platform that provides a means of combining independent legacy databases into a single cancer-focused LLDB system. We compared the sensitivity and specificity of several SQL-based query strategies for identifying a histologic lymphoma subtype in this LLDB to determine the most accurate legacy data source for identifying a specific cancer patient population.Methods:Query strategies were developed to identify patients with follicular lymphoma from a LLDB of cancer registry data, electronic medical records (EMR), laboratory, administrative, pharmacy, and other clinical data. Queries were performed using common diagnostic codes (ICD-9), cancer registry histology codes (ICD-O), and text searches of EMRs. We reviewed medical records and pathology reports to confirm each diagnosis and calculated the sensitivity and specificity for each query strategy.Results:Together the queries identified 1538 potential cases of follicular lymphoma. Review of pathology and other medical reports confirmed 415 cases of follicular lymphoma, 300 pathology-verified and 115 verified from other medical reports. The query using ICD-O codes was highly specific (96%). Queries using text strings varied in sensitivity (range 7–92%) and specificity (range 86–99%). Queries using ICD-9 codes were both less sensitive (34–44%) and specific (35–87%).Conclusions:Queries of linked-cancer databases that include cancer registry data should utilize ICD-O codes or employ structured free-text searches to identify patient populations with a precise histologic diagnosis.

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