IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. Ocular adnexal IgG4-related disease, however, has not well been clarified. The purpose of the present study was to examine 21 patients (10 men, 11 women; age range, 39-86 years) with ocular adnexal IgG4-related disease. In 17 out of 21 patients (81%), the lacrimal glands were involved and bilateral lacrimal gland swelling was frequently observed (n = 12; 70.6%). In contrast, the conjunctiva was not involved in any of the patient. Histology was uniform with marked lymphoplasmacytic infiltration admixed with dense fibrosis, similar to previous reports of IgG4-related disease. Immunostaining detected numerous aggregates of IgG4-positive plasma cells. Serum IgG4 was higher than normal in 10 of the 13 patients tested, although it was measured after treatment in almost all cases. Interestingly, immunoglobulin heavy chain gene rearrangement was detected in two of 17 patients (12%) examined. The present results show that ocular adnexal IgG4-related disease has uniform clinicopathology: that is, disease involving the bilateral lacrimal glands with lymphoid hyperplasia and fibrosis, but not the conjunctiva. And presence of immunoglobulin heavy chain gene rearrangement suggests the possibility of B-cell lymphoma arising in a background of IgG4-related chronic inflammation. 2 Additionally, AIP has been described in association with other autoimmune disorders, such as chronic sclerosing sialadenitis (Küttner's tumor), sclerosing cholangitis and retroperitoneal fibrosis. 3-15IgG4-related disease is a recently proposed clinical entity and it has several unique clinical findings, but its pathogenesis and pathophysiology remain unclear.3-9 And ocular adnexal IgG4-related disease is either not mentioned or only briefly alluded to in previous reports. 6,[10][11][12] In the present study we examined ocular adnexal IgG4-related disease in detail, with specific reference to clinicopathological features. MATERIALS AND METHODS Patients and materialsWe reviewed the cases of 112 patients (orbital lesions, n = 78; conjunctival lesions, n = 34) with ocular adnexal lymphoproliferative disorders diagnosed between 1990 and 2006. All cases were retrieved from the files of the Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Histology and immunohistochemistrySurgically resected or biopsied specimens of ocular adnexal lymphoid disorders were fixed in 10% formaldehyde and embedded in paraffin. Serial sections (4 mm) were cut from

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Background and study aims  Linked color imaging (LCI) and blue laser imaging (BLI) are novel image-enhanced endoscopy technologies with strong, unique color enhancement. We investigated the efficacy of LCI and BLI-bright compared to conventional white light imaging (WLI) by measuring the color difference between early gastric cancer lesions and the surrounding mucosa. Patients and methods  Images of early gastric cancer scheduled for endoscopic submucosal dissection were captured by LCI, BLI-bright, and WLI under the same conditions. Color values of the lesion and surrounding mucosa were defined as the average of the color value in each region of interest. Color differences between the lesion and surrounding mucosa (ΔE) were examined in each mode. The color value was assessed using the CIE L*a*b* color space (CIE: Commission Internationale d’Eclairage). Results  We collected images of 43 lesions from 42 patients. Average ΔE values with LCI, BLI-bright, and WLI were 11.02, 5.04, and 5.99, respectively. The ΔE was significantly higher with LCI than with WLI ( P  < 0.001). Limited to cases of small ΔE with WLI, the ΔE was approximately 3 times higher with LCI than with WLI (7.18 vs. 2.25). The ΔE with LCI was larger when the surrounding mucosa had severe intestinal metaplasia ( P  = 0.04). The average color value of a lesion and the surrounding mucosa differed. This value did not have a sufficient cut-off point between the lesion and surrounding mucosa to distinguish them, even with LCI. Conclusion  LCI had a larger ΔE than WLI. It may allow easy recognition and early detection of gastric cancer, even for inexperienced endoscopists.

Although most follicular lymphomas are believed to be of nodal origin, they sometimes originate from the duodenum. We have reported that the latter differ from nodal follicular lymphomas in having lower clinical stages and uniformly low histological grades, along with variable region of immunoglobulin heavy chain gene (VH) usage that is more similar to mucosa-associated lymphoid tissue (MALT) lymphomas. Little is known, however, about whether they possess other characteristics of nodal follicular lymphomas, particularly ongoing mutations with follicular dendritic cells. We examined 17 cases for which PCR identified the monoclonal bands of the immunoglobulin gene. The duodenal cases showed ongoing mutations, but they lacked activationinduced cytidine deaminase (AID) expression, a statistically significant difference from the nodal cases (Po0.001), and their follicular dendritic cell networks were disrupted. Moreover, not only were VH deviations observed but also they used very restricted VH genes. Although the mechanisms of ongoing mutation without AID and follicular dendritic cell were not clarified, restricted VH usage strongly suggested that antigen stimulation was involved, and that was similar to MALT lymphomas. In conclusion, duodenal follicular lymphomas were shown to be unique, in that they had ongoing hypermutations such as nodal cases, but the mechanisms involved in the hypermutation were quite different; furthermore, restricted VH usage suggested a strong similarity to the antigen-dependent origin of MALT lymphomas.

Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-γ-deficient and IL-17-deficient mice as donors. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-β expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD.