Japan Society for the Promotion of Science.

Objective. To examine whether topical treatment of wild-type mice with Toll-like receptor 7 (TLR-7) agonists leads to lupus-like autoimmunity.Methods. Wild-type FVB/N, BALB/c, and C57BL/6 mice were treated with the topical TLR-7 agonist imiquimod or R848 administered to the ear 3 times weekly. During treatment, the mice were monitored for serum autoantibody and creatinine levels as well as histopathology of the kidneys, spleens, livers, hearts, and skin. Immunologic abnormalities were analyzed by immunohistochemistry, quantitative reverse transcription-polymerase chain reaction, and fluorescence-activated cell sorting. The role of plasmacytoid dendritic cells (PDCs) in the development of autoimmune disease was validated by in vivo treatment with an anti-PDC antibody. Diseased mice underwent ultraviolet B irradiation, to evaluate skin photosensitivity. The disease-causing effect of topical application of imiquimod was compared with that of systemic (intraperitoneal) administration. TLR-7-and TLR-9-deficient mice were used to validate the role of TLR-7.Results. Wild-type mice of different genetic backgrounds developed systemic autoimmune disease following 4 weeks of topical treatment with imiquimod or R848, with elevated levels of autoantibodies to doublestranded DNA and multiple organ involvement, including glomerulonephritis, hepatitis, carditis, and photosensitivity. Expression of Ifna and Mx1, the interferon-␣-stimulated gene, was up-regulated in the organs of imiquimod-treated mice. However, disease caused by intraperitoneal injection of imiquimod was less severe than that induced by topical application. In vivo depletion of PDCs by a specific antibody protected mice against the autoimmunity induced by topical administration of imiquimod, suggesting a role of PDCs. Furthermore, TLR-7-deficient mice, but not TLR-9-deficient mice, were protected against autoimmunity.Conclusion. This protocol provides a novel model of inducible systemic lupus erythematosus in wild-type mice and underscores the skin as the primary organ that allows TLR-7 agonists to induce SLE.

Scan the quick response (QR) code to the left with your mobile device to watch this article's video abstract and others. Don't have a QR code reader? Get one by searching 'QR Scanner' in your mobile device's app store.

Scan the quick response (QR) code to the left with your mobile device to watch this article's video abstract and others. Don't have a QR code reader? Get one by searching 'QR Scanner' in your mobile device's app store. R ecently, the American Society of GastrointestinalEndoscopy established the Preservation and Incorporation of Valuable Endoscopic Innovations 1 for diminutive colorectal polyps. Preservation and Incorporation of Valuable Endoscopic Innovations suggests that, if an endoscopist diagnoses an agreement of >90% in determining postpolypectomy surveillance intervals and a negative predictive value of >90% with adenomatous histology, pathologic diagnosis might not be necessary. Although magnifying chromoendoscopy, 2 narrow-band imaging (NBI), 3 endocytoscopy (EC), 4 and confocal laser endomicroscopy 5 are highly accurate, interpretation of these modalities is difficult for novices. Furthermore, achieving a negative predictive value of >90% for adenoma is not easy using these modalities 3 and requires comprehensive experiments. 6 To achieve a breakthrough on this issue, we developed a computer-aided diagnosis (CAD) system for EC. This system automatically provides highly accurate diagnosis as expert endoscopists concurrently take EC images (Video Clip 1). 7 Our previous system, based on glandular structural and cellular atypia, required endoscopists to use dye for staining. In contrast, the endocytoscopic vascular pattern can effectively evaluate microvessel findings using EC with NBI (EC-NBI) without using any dye. We reported that EC-NBI has a highly accurate diagnostic ability, similar to other modalities. 8 Because dye staining complicates the procedure, our CAD system for EC-NBI represents a powerful tool for novices and experts who do not use dyes on a routine basis. Therefore, we developed a tentative CAD system model for EC-NBI image. Description of TechnologyWe developed custom software (EndoBRAIN, Cybernet Systems Co., Ltd., Tokyo, Japan) to analyze EC images. We collected a consecutive series of 1079 EC-NBI images (431 nonneoplasms and 648 neoplasms) from 85 lesions to form an image database. To validate the CAD system, we randomly extracted 100 images (50 nonneoplasms, 50 neoplasms) from the database. The remaining 979 images (381 nonneoplasms, 598 neoplasms) were used for machine learning. The inclusion criteria were colorectal lesions that had been detected during colonoscopy using EC and subsequently resected between December 2014 and April 2015. The exclusion criteria were inflammatory bowel disease; lesions for which no clear EC-NBI were available; sessile serrated adenomas/polyps (SSA/Ps); and nonepithelial Figure 1. Output image. (1) Computer diagnosis. (2) Input endocytoscopy with narrow band imaging. (3) Extracted vessel image, in which the green area denotes the extracted vessels. The light-green vessel has the maximum diameter. (4) Probability of computer diagnosis is calculated by the support vector machine classifier.Abbreviations used in this paper: CAD, computer-aided diagnosis; ...

To identify molecular targets in leukemia stem cells (LSCs), this study compared the protein expression profile of freshly isolated CD34 1 /CD382 cells with that of CD34 1 /CD38 1 counterparts from individuals with acute myelogenous leukemia (n 5 2, AML) using isobaric tags for relative and absolute quantitation (iTRAQ