abstract. Fulminant type 1 diabetes, established in 2000, is defined as a novel subtype of diabetes mellitus that results from remarkably acute and almost complete destruction of pancreatic beta cells at the disease onset. In this study, we aimed to clarify the pathogenesis of fulminant type 1 diabetes with special reference to insulitis and viral infection. We examined pancreatic autopsy samples from three patients who had died soon after the onset of disease and analyzed these by immunohistochemistry and in situ hybridization. The results were that both beta and alpha cell areas were significantly decreased in comparison with those of normal controls. Mean beta cell area of the patients just after the onset was only 0.00256 % while that of normal control was 1.745 %. Macrophages and T cells-but no natural killer cells-had infiltrated the islets and the exocrine pancreas. Although both of them had massively infiltrated, macrophages dominated islet infiltration and were detected in 92.6 % of the patients' islets. Toll-like receptor (TLR) 3, a sensor of viral components, was detected in 84.7±7.0 % of macrophages and 62.7±32.3 % of T cells (mean±SD) in all three patients. TLR7 and TLR9 were also detected in the pancreas of all three patients. enterovirus RNa was detected in beta-cell positive islets in one of the three patients by in situ hybridization. In conclusion, our results suggest that macrophage-dominated insulitis rather than T cell autoimmunity contributes to beta cell destruction in fulminant type 1 diabetes.

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Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis, hemolytic uremic syndrome, and acute encephalopathies that may lead to sudden death or severe neurologic sequelae. Current treatments, including immunoglobulin G (IgG) immunoadsorption, plasma exchange, steroid pulse therapy, and the monoclonal antibody eculizumab, have limited effects against the severe neurologic sequelae. Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative non-tumorigenic stem cells that naturally reside in the body and are currently under clinical trials for regenerative medicine. When administered intravenously, Musecells accumulate to the damaged tissue, where they exert anti-inflammatory, anti-apoptotic, anti-fibrotic, and immunomodulatory effects, and replace damaged cells by differentiating into tissue-constituent cells. Here, severely immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice orally inoculated with 9 Â 10 9 colony-forming units of STEC O111 and treated 48 h later with intravenous injection of 5 Â 10 4 Muse cells exhibited 100% survival and no severe after-effects of infection. Suppression of granulocyte-colony-stimulating factor (G-CSF) by RNAi abolished the beneficial effects of Muse cells, leading to a 40% death and significant body weight loss, suggesting the involvement of G-CSF in the beneficial effects of Muse cells in STEC-infected mice. Thus, intravenous administration of Muse cells could be a candidate therapeutic approach for preventing fatal encephalopathy after STEC infection.

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1Ewing sarcoma family of tumors (ESFT) is derived from the neural crest, which originates 2 from basal embryo cells in the primitive neural tube. ESFT often arises at the bone, chest 3 wall, and soft tissues of the thoracic region. However, ESFT that arises from the adrenal 4 gland is much rarer and it is usually revealed by clinical symptoms. We report an autopsy 5 case of suicidal hanging, in which adrenal ESFT was incidentally revealed. To our 6 knowledge, this is the first case of latent ESFT arising from the adrenal gland. Autopsy can 7 sometimes reveal latent disease. Some of these latent diseases are very rare and we would 8 not be able to detect them without a complete autopsy. As forensic pathologists, we should 9 attempt to perform a complete autopsy and report new discoveries for the development of 10 medicine. 11 12