http://hdl.handle.net/2027.42/57558 http://deepblue.lib.umich.edu/retrieve/209315 http://hdl.handle.net/2027.42/57558 Search the Channel search http://deepblue.lib.umich.edu/simple-search http://hdl.handle.net/2027.42/60328 Title: Autoimmune diseases co-occurring within individuals and within families: a systematic review<br/><br/>Authors: Somers, Emily C.; Thomas, Sara L.; Smeeth, Liam; Hall, Andrew J.<br/><br/>Abstract: BACKGROUND: Autoimmune diseases have been observed to coexist both within individuals and within families. It is unclear whether clinical reports of comorbid autoimmune diseases represent chance findings or true associations. This systematic review evaluates the current level of evidence on the coexistence of selected autoimmune diseases within individuals and families. We reviewed the associations among 4 TH1-associated autoimmune diseases: insulin-dependent diabetes mellitus, autoimmune (Hashimoto) thyroiditis, rheumatoid arthritis, and multiple sclerosis. METHODS: Studies quantifying the coexistence between the selected diseases, published through March 2004, were identified from Medline and Embase searches. Study eligibility was determined on the basis of preestablished criteria, and relevant data were extracted according to a fixed protocol. We determined the prevalence of comorbid autoimmune disease according to index disease and then compiled summary statistics. Heterogeneity among studies was assessed by exact likelihood ratio tests and Monte Carlo inference. RESULTS: We found 54 studies that met the eligibility criteria. Of these, 52 studies examined the coexistence of disease within individuals and 9 studies examined within-family associations. The majority of studies were uncontrolled and did not account for confounding factors. There was substantial evidence for heterogeneity among studies. Although inconclusive, the data appear to support an increased prevalence of autoimmune thyroiditis among patients with rheumatoid arthritis and those with insulin-dependent diabetes mellitus, and an inverse association between rheumatoid arthritis and multiple sclerosis. CONCLUSION: Although the available evidence does not permit firm conclusions regarding comorbidities among the selected autoimmune diseases, results are sufficiently suggestive to warrant further study. http://hdl.handle.net/2027.42/60248 Title: Incidence of Systemic Lupus Erythematosus in the United Kingdom, 1990-1999<br/><br/>Authors: Somers, Emily C.; Thomas, Sara L.; Smeeth, Liam; Schoonen, W. Marieke; Hall, Andrew J.<br/><br/>Abstract: Objective. To estimate the annual incidence of systemic lupus erythematosus (SLE) over a 10-year period in the UK, and to examine age-, sex-, and region-specific rates. Methods. The study was based on the UK General Practice Research Database (GPRD), which covers 5% of the UK population. We estimated SLE incidence rates, during the period 1990–1999, among persons registered with practices contributing to the GPRD, representing >33 million person-years of observation. Results. A total of 1,638 patients with incident SLE (1,374 females, 264 males) were identified. The age-standardized SLE incidence in the UK during the 1990s was 7.89 per 100,000 (95% confidence interval [95% CI] 7.46, 8.31) for females and 1.53 per 100,000 (95% CI 1.34, 1.71) for males (overall female-to-male ratio 5.2:1). Peak incidence occurred at age 50–54 years for females and 70–74 years for males. There was a small but insignificant increase of SLE incidence over the 10 years among females but not males. No clear association between latitude and SLE incidence was found, but regional variations existed, with age-standardized rates ranging from 3.56 per 100,000 (95% CI 3.00, 4.13) for the West Midlands to 7.62 per 100,000 (95% CI 5.59, 9.65) for Northern Ireland. Conclusion. This study provides updated estimates of SLE incidence in the UK. Standard methodology throughout the study period and target population allowed for comparison of rates over time and across regions. http://hdl.handle.net/2027.42/55907 Title: Restituting intestinal epithelial cells exhibit increased transducibility by adenoviral vectors<br/><br/>Authors: Kesisoglou, Filippos; Schmiedlin-Ren, Phyllissa; Fleisher, David; Roessler, Blake; Zimmermann, Ellen M.<br/><br/>Abstract: Background and aims While mature enterocytes are resistant to transduction by adenovirus type 5 (Ad5) vectors, undifferentiated cells are transduced much more efficiently. Our purpose was to study enterocyte transduction in models of intestinal wound healing. Methods Transduction was studied ex vivo using cultures of endoscopic biopsies and in vitro utilizing Caco-2 cells in models of mucosal wound healing. Vectors carried either the LacZ or the luciferase gene. CAR (coxsackievirus and adenovirus receptor) and integrins were studied with transduction inhibition and immunofluorescent staining. Results Increased transduction efficiency was observed for a subset of enterocytes with a flattened de-differentiated phenotype present at the edge of cultured biopsies. In the in vitro systems, expanding Caco-2 cell monolayers exhibited increased transducibility that was time- and dose-dependent, reaching virtually 100% in cells along the leading edge at high viral load. Bioluminescence activity of transduced expanding monolayers was up to 3-fold greater than that of non-expanding monolayers (‘fence’ system, 48 h, MOI 1000, p < 0.05). Mitomycin C pre-treatment did not affect levels of transduction in expanding monolayers. At the highest viral load tested, CAR or integrin blocking prior to virus application resulted in 39.4% and 45.4% reduction in transduction levels ( p < 0.05). Immunofluorescence revealed altered expression of CAR on the migrating edge of the Caco-2 cultures and the expression of CAR on the apical membrane of biopsy enterocytes. Conclusions Increased CAR and integrin accessibility in migrating enterocytes mediates increased transduction by Ad5 vectors. This subset of enterocytes provides a target for the delivery of genes of interest for both research and gene therapy applications. Copyright © 2006 John Wiley & Sons, Ltd. http://hdl.handle.net/2027.42/55860 Title: A different type of procedure for a different type of pain<br/><br/>Authors: Hsu, Michael C.; Clauw, Daniel J.<br/><br/>Abstract: No abstract.