T helper type-2 cells induce ileal villus atrophy,goblet cell metaplasia,and wasting disease in T cell-deficient mice

BACKGROUND & AIMS: T helper (Th) 1 and Th2 cell subsets significantly influence the pathological features of inflammation in the gastrointestinal tract in a distinct manner. It is now established that the transfer of CD4(+)CD45RB(Hi) (RB(Hi)) T cells to either severe combined immunodeficient (SCID) or recombinase activation gene 2-deficient (RAG(-/-)) mice results in a severe granulomatous hypertrophic colitis mediated by Th1 cells. We have modified this approach to address the role of Th2 cells. METHODS: RB(Hi) T cells from wild-type (Wt) mice or mice genetically predisposed to Th2 responses (interferon-gamma-defective [IFN-gamma(-/-)]) with or without B cells were transferred to T cell receptor (TCR)-beta and delta-chain-defective (TCR(-/-)) or SCID mice. RESULTS: Transfer of Wt RB(Hi) T cells induced wasting disease with severe colitis in the TCR(-/-) mice. In contrast, IFN-gamma(-/-) RB(Hi) T cells induced severe weight loss and hypoalbuminemia without significant inflammation in the colon. The small intestine of these mice exhibited villus atrophy, a decrease in brush-border enzymes, reduced enterocyte proliferation, and an increased number of goblet cells. The presence of B cells was necessary for these changes, because SCID recipients required cotransfer of B cells, together with IFN-gamma(-/-) RB(Hi) T cells for ileal lesions to develop. Treatment of TCR(-/-) recipients of IFN-gamma(-/-) RB(Hi) T cells with anti-IL-4 mAb abrogated both the wasting disease and the villus atrophy. CONCLUSIONS: Dysregulated Th2 cells cause atrophic changes and goblet cell transformation in the small intestinal epithelium and wasting disease mediated by excess interleukin-4 and B cells.     

Arteriovenous malformation of the pancreas associated with hepatocellular carcinoma

Summary A case of pancreatic arteriovenous malformation (AVM) with hepatocellular carcinoma is reported. The patient, a 56-year-old Japanese man, was asymptomatic. The pancreatic lesion was found incidentally during an evaluation for hepatocellular carcinoma. Celiac arteriogram demonstrated tortuous feeding arteries, a racemose intrapancreatic stain, which disappeared before the venous phase, and early portal filling.     

Worksite Wellness for the Primary and Secondary Prevention of Cardiovascular Disease in Japan: The Current Delivery System and Future Directions

In the Japanese workplace, employers are required to provide annual health checkups for workers in accordance with the “Industrial Safety and Health Law,” which also mandates that an occupational physician be assigned to companies employing at least 50 workers. The annual medical examination includes testing for the early detection of cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, and the metabolic syndrome. This approach has successfully contributed to the extremely low incidence of coronary artery disease among Japanese workers. However, problems such as poor health and the low rate of participation in health checkups among small-scale companies still persist. Furthermore, although most wellness delivery systems in Japan employ strategies targeting high-risk individuals, instituting a strategy addressing the broader population irrespective of screening may be effective in reducing disease risk in the overall population. As a future direction, we should therefore develop practical methods for implementing a population strategy.