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Tubarial glands (TGs) are a collection of unidentified salivary glands overlying the torus tubarius in the nasopharyngeal wall. Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibroinflammatory state that often has multiple organ involvement. Involvement of the head and neck, especially the salivary glands, is common in IgG4-RD.This study aimed to elucidate the clinical significance of TGs in IgG4-RD.We investigated the local findings of TGs in ten patients with IgG4-RD.Nasopharyngeal endoscopic examination revealed oedematous swelling of the nasopharyngeal wall surrounding the TGs, which improved after steroid treatment. Moreover, sonotubometry showed a stenotic pattern in three out of seven patients with IgG4-RD.TGs may be involved in IgG4-RD. The swollen TGs may be responsible for obstructive Eustachian tube dysfunction. Further studies are required to clarify the clinical significance and physiological roles of TGs in IgG4-RD.

Airway and intestinal epithelial permeability barriers are crucial in epithelial homeostasis. High mobility group box 1 (HMGB1), increased by various stimuli, is involved in the induction of airway inflammation, as well as the pathogenesis of inflammatory bowel disease. HMGB1 enhances epithelial hyperpermeability. Two-and-a-half dimensional (2.5D) culture assays are experimentally convenient and induce cells to form a more physiological tissue architecture than 2D culture assays for molecular transfer mechanism analysis. In 2.5D culture, treatment with HMGB1 induced permeability of FITC-dextran into the lumen formed by human lung, nasal and intestinal epithelial cells. The tricellular tight junction molecule angulin-1/LSR is responsible for the epithelial permeability barrier at tricellular contacts and contributes to various human airway and intestinal inflammatory diseases. In this review, we indicate the mechanisms including angulin-1/LSR and multiple signaling in dysfunction of the epithelial permeability barrier induced by HMGB1 in 2.5D culture of human airway and intestinal epithelial cells.

To bring the clinical practice of immunoglobulin (Ig)G4-related disease (IgG4-RD) close to personalized medicine, we classified the patient groups and clarified the therapeutic responses of each group. A total of 147 patients enrolled in our registry were classified into four groups by cluster analysis with the software. The therapeutic responses and prognosis of each group were examined. The cluster analysis classified the subjects into four groups: Cluster 1, patients who presented with prominent hypergammaglobulinemia, elevated levels of serum IgG4, and hypocomplementemia; Cluster 2, patients who presented with eosinophilia, elevated concentrations of serum IgG, IgG4, and IgE, and in whom CRP tended to be positive; Cluster 3, patients with younger onset and serum levels of IgG, IgG4, and IgE and peripheral eosinophil counts lower than the other clusters; and Cluster 4, patients with elder onset and low peripheral eosinophil counts. The amounts of glucocorticoid for maintenance treatment were from 5 to 7 mg/d in all groups, but the amounts were significantly greater in Cluster 1 (patients with hypergammaglobulinemia, elevated levels of serum IgG4, and hypocomplementemia) than in Cluster 4 (elder onset patients, relatively low concentrations of peripheral eosinophils). With regard to the use of immunosuppressants and the relapse rate, there were high frequencies in Cluster 1 and Cluster 3 (younger onset patients who presented with mild elevations of serum IgG and IgG4). On the other hand, Cluster 4 showed a low rate of relapse and often could discontinue steroids. The present results suggest that personalized medicine could be provided in IgG4-RD by classifying patients based on their clinical features.

Conclusion The diagnosis of immunoglobulin G4-related disease (IgG4-RD) should be based on the morphology of tissue biopsy, and this study recommends a submandibular gland (SMG) biopsy for accurate diagnosis and to exclude malignant disease. Objective To clarify which type of biopsy specimen (SMG or labial salivary gland [LSG]) should be taken from patients with IgG4-RD. Methods This study included 33 patients with IgG4-RD (21 women; 12 men) who were subjected to both SMG and LSG biopsies at Sapporo Medical University between 2011-2015. Tissues obtained from the SMG and LSG specimens were evaluated. Results All SMG specimens satisfied the diagnostic criteria for IgG4-RD, whereas 19 (57.6%) LSG specimens satisfied the diagnostic criteria for IgG4-RD. Histological evaluation showed fibrosis in all the SMG specimens and in eight LSG specimens (24.2%). Obliterative phlebitis was seen in nine SMG specimens (27.3%), but it was absent in all the LSG specimens.

Altered expression of claudin-1, claudin-7, and tricellulin in early tonsillar squamous cell carcinoma (SCC) independent of human papilloma virus (HPV) infection may lead to tumor progression.Integral tight junction proteins, the claudins and tricellulin, play a crucial role in all tissues. HPV is significantly associated with tonsillar SCC. We sought to determine the expression of claudin-1, claudin-7, and tricellulin in HPV-infected and HPV-free tonsillar SCC.Twenty-eight tonsillar SCCs were studied by immunohistochemical analysis and real-time reverse transcription polymerase chain reaction with in situ hybridization analysis.Compared with normal tissues, claudin-1 was strongly expressed, whereas claudin-7 and tricellulin were weakly expressed or were absent in primary SCC and metastatic lymph nodes. Claudin-7 and tricellulin were markedly reduced at all stages of tumor development. In situ hybridization analysis showed no correlation between HPV infection and altered expression of the tight junction proteins.

Liver regeneration and cholestasis are associated with adaptive changes in expression of gap and tight junctions through signal transduction. The roles of stress responsitive MAP-kinase, p38 MAP-kinase, in the signaling pathway for gap junction protein, Cx32, and tight junction protein, claudin-1, were examined in rat liver in vivo and in vitro, including regeneration following partial hepatectomy and cholestasis after common bile duct ligation. Changes in the expression and function of Cx32 and claudin-1 in hepatocytes in vivo were studied using the p38 MAP-kinase inhibitor SB203580. Following partial hepatectomy and common bile duct ligation, down-regulation of Cx32 protein was inhibited by SB203580 treatment. Up-regulation of claudin-1 protein was enhanced by SB203580 treatment after partial hepatectomy but not common bile duct ligation. However, no change of the Ki-67 labeling index (which is a marker for cell proliferation) in the livers treated with SB203580, was observed compared to that without SB203580 treatment. In primary cultures of rat hepatocytes, however, treatment with a p38 MAP-kinase activator, anisomycin, decreased Cx32 and claudin-1 protein levels. p38 MAP-kinase may be an important signaling pathway for regulation of gap and tight junctions in hepatocytes. Changes of gap and tight junctions during liver regeneration and cholestasis are shown to be in part controlled via the p38 MAP-kinase signaling pathway and are independent of cell growth.

In order to identify cognitive error mechanisms observed in the dynamic operational environment, the following materials were analyzed giving special attention to psychological biases, together with possible cognitive tasks and these location, and internal and external performance shaping factors: (a) 13 human factors analyses of US nuclear power plant accidents, (b) 14 cases of Japanese nuclear power plant incidents, and (c) 23 cases collected in simulator experiments. In the resulting analysis, the most frequently identified cognitive process associated with error productions was situation assessment, and following varieties were KB processes and response planning, all of that were the higher cognitive activities. Over 70% of human error cases, psychological bias was affecting to cognitive errors, especially those to higher cognitive activities. In addition, several error occurrence patterns, including relations between cognitive process, biases, and PSFs were identified by the multivariate analysis. Ac...

Developed as a remedy-oriented system for systematically analyzing and evaluating humanrelated incidents occurring in nuclear power plants, the present system aims particularly at identifying causal factors and at deriving proposals for specific hierarchical countermeasures. Unlike conventional methods, which are based on checksheet format, and are thus devoid of logical methodology for conducting the analysis, and which thus lack the means of searching for underlying causal factors, and which do not record factual information on the sequence of events, our system incorporates innovative techniques such as ; (a) a modified fault tree method for searching the underlying causal factors, (b) compilation of related events into sequential charts, (c) technique for devising proposed hierarchical redundant countermeasures, and (d) implementation procedures set out in practical manual form for easy familiarization and application. Through several trial applications, our method has proved to permit identifying underlying causal factors even down to those associated with the software aspects of human action and state of mind, and with the mode of management, organization, operating rules and document forms, all of which are liable to be overlooked. The results of analysis are stored in database to permit subsequent searching to serve as useful material for activities aimed at promoting plant operation safety.

To determine the relation between H2 receptors and gastric mucosal blood flow, we measured the latter in rats by the electrolytically generated hydrogen gas clearance technique. The blood flow increased significantly after intravenous injection of 0.1 mg/kg of impromidine, a very potent and specific agonist of H2 receptors. On the other hand, gastric mucosal blood flow decreased significantly after intravenous administration of 5 or 20 mg/kg of cimetidine or 2 mg/kg of famotidine. However, 2 or 20 rng/kg of omeprazole, whose anti-secretory effect is as strong as that of H2 blockers such as cimetidine and famotidine, caused no significant change in the gastric rnucosal blood flow. This indicates that H2 receptors regulate gastric mucosal blood flow in rats.