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Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by beta cell destruction, insulin deficiency and hyperglycemia. Activated macrophages and autoimmune T cells play a crucial role in the pathogenesis of hyperglycemia in NOD murine diabetes models, but the molecular mechanisms of macrophage activation are unknown. We recently identified pigment epithelium-derived factor (PEDF) as an adipocyte-derived factor that activates macrophages and mediates insulin resistance. Reasoning that PEDF might participate as a proinflammatory mediator in murine diabetes, we measured PEDF levels in NOD mice. PEDF levels are significantly elevated in pancreas, in correlation with pancreatic TNF levels in NOD mice. To identify experimental therapeutics, we screened 2,327 compounds in two chemical libraries (the NIH Clinical Collection and Pharmakon-1600a) for leads that inhibit PEDF mediated TNF release in macrophage cultures. The lead molecule selected, \"emetine\" is a widely used emetic. It inhibited PEDF-mediated macrophage activation with an EC50 or 146 nM. Administration of emetine to NOD mice and to C57Bl6 mice subjected to streptozotocin significantly attenuated hyperglycemia, reduced TNF levels in pancreas, and attenuated insulitis. Together, these results suggest that targeting PEDF with emetine may attenuate TNF release and hyperglycemia in murine diabetes models. This suggests that further investigation of PEDF and emetine in the pathogenesis of human diabetes is warranted.

There are many ways of understanding the Mormon experience, which has been varied at headquarters and in far distant branches of the faithful. Despite this diversity, both non-Mormons and Mormons may find useful understanding through comparing the experience at Latter-Day Saints (LDS) headquarters with the Mormon experience elsewhere. Quinn discusses an introductory to such an approach that current Mormons may find parts of their own experiences in such comparison, especially those who feel that their church has changed in dramatic ways.

America is currently in the midst of state-by-state political activism and judicial appeals to prevent legalization of same-sex marriage. Defense of Marriage Act prohibits same-sex marriage and refuses to recognize such unions legally performed in other states or countries. In view of the pace for this state-by-state political activism during the 1990s, the Defense of Marriage campaign will probably continue throughout the US for at least another decade. Here, Quinn discusses homophobia and purposes of same-sex marriage. He also investigates the threat of Mormon polygamy to traditional marriage and the role of churches in restricting civil rights.