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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.

Purpose This study aims to describe the recommended equipment and procedures required for successful telefitting, based on our experience, document and evaluate patient satisfaction with telefitting, and assess its clinical usefulness and address the existing issues. Method Twenty (seven children and 13 adults) individuals who lived far from cochlear implant (CI) centers and who were Nucleus CI users underwent conventional face-to-face fitting and telefitting. We examined the participants' subjective satisfaction and cost and time saved with the telefitting experience. Results The telefitting sessions lasted for an average of 16 min. Majority of the participants responded positively to the telefitting experience. Eighty percent (16/20) of the participants were satisfied with the new procedure, and 85% of them agreed to use telefitting again. Conclusions The results of our feasibility study suggest that telefitting was well received by CI users and is a viable alternative to local MAPping, even in young children with CIs. Although there are some limitations in terms of adaptability, telefitting could be an effective means of delivering CI service to remote locations.

Background: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. Methods: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585). Results: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration. Conclusions: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells.

The airway epithelium of the human nasal mucosa acts as a physical barrier that protects against inhaled substances and pathogens via bicellular and tricellular tight junctions (bTJs and tTJs) including claudins, angulin-1/LSR and tricellulin. High mobility group box-1 (HMGB1) increased by TGF-β1 is involved in the induction of nasal inflammation and injury in patients with allergic rhinitis, chronic rhinosinusitis, and eosinophilic chronic rhinosinusitis. However, the detailed mechanisms by which this occurs remain unknown. In the present study, to investigate how HMGB1 affects the barrier of normal human nasal epithelial cells, 2D and 2.5D Matrigel culture of primary cultured human nasal epithelial cells were pretreated with TGF-β type I receptor kinase inhibitor EW-7197 before treatment with HMGB1. Knockdown of angulin-1/LSR downregulated the epithelial barrier. Treatment with EW-7197 decreased angulin-1/LSR and concentrated the expression at tTJs from bTJs and increased the epithelial barrier. Treatment with a binder to angulin-1/LSR angubindin-1 decreased angulin-1/LSR and the epithelial barrier. Treatment with HMGB1 decreased angulin-1/LSR and the epithelial barrier. In 2.5D Matrigel culture, treatment with HMGB1 induced permeability of FITC-dextran (FD-4) into the lumen. Pretreatment with EW-7197 prevented the effects of HMGB1. HMGB1 disrupted the angulin-1/LSR-dependent epithelial permeability barriers of HNECs via TGF-β signaling in HNECs.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including TH2 cells in NPs. The co-culture of NP-derived ILC2s and TH2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.

Background/aim Tracheostomy performed on patients with Coronavirus disease 2019 (COVID-19) may lead to the infection of operators and medical staff. To date, there are no established methods of infection control. The aim of this study was to provide helpful and useful information regarding tracheostomy during the COVID-19 pandemic. Patients and methods We performed a retrospective analysis on 12 patients with severe COVID-19 who were intubated and underwent tracheostomy in our hospital. Results Percutaneous tracheostomy was performed in eight cases, and open tracheostomy was performed in four cases. Open tracheostomy in the operating room was performed under a negative pressure closed-space system using a surgical drape to prevent aerosolization. Conclusion Our experience suggests that bedside percutaneous tracheostomy may be a useful option in patients with COVID-19. In cases where percutaneous tracheostomy is anticipated to be difficult, open tracheostomy using a negative pressure closure may be useful in preventing aerosolization and reducing the risk of infection of healthcare workers.

IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory disease characterized by elevation of serum IgG4 level as well as infiltration of IgG4+ plasma cells in various affected organs. The etiology of IgG4-RD is still not fully understood. Since IgG4-RD is more prevalent in the elderly, aging in itself is considered to be an important risk factor of IgG4-RD. However, the relationship between the pathogenesis of IgG4-RD and immunosenescence remains unknown. To clarify age-related features underlying IgG4-RD, we focused on T follicular regulatory (Tfr) cells, which share forkhead box P3 with regulatory T cells, since the percentage of Tfr cells is known to depend on age. Studies of blood specimens from patients with IgG4-RD and from healthy volunteers demonstrated a marked elevation of circulating Tfr (cTfr) cells in patients with IgG4-RD. Moreover, the percentage of cTfr cells was significantly correlated with various clinical parameters including the level of serum IgG4 and the number of involved organs in IgG4-RD patients. The percentages of tonsillar and blood Tfr cells were increased with aging in healthy volunteers, whereas the suppressive effect of cTfr cells on B cell function in elderly subjects was impaired in comparison with that in young subjects due to a defect in the production of a regulatory cytokine, IL-10. Given that the number of IL-10-producing cTfr cells in IgG4-RD patients was markedly increased compared with that in healthy elderly subjects, these findings suggest that an abnormal aging process of Tfr cells may be related to the pathogenesis of IgG4-RD.

Quantifying proliferative virus particles is one of the most important experimental procedures in virology. Compared with classical overlay materials, newly developed cellulose derivatives enable a plaque-forming assay to produce countable clear plaques easily. HEp-2 cells are widely used in plaque assays for human respiratory syncytial virus (RSV). It is crucial to use an overlay material to keep HEp-2 cell proliferation and prevent RSV particles from spreading over the fluid. Among four cellulose derivatives, carboxymethyl cellulose sodium salt (CMC), hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), and hydroxyethyl cellulose (HEC), we found that HPMC was the optimal overlay material because HPMC maintained HEp-2 cell proliferation and RSV infectivity. Although MCC was unsuitable for RSV, it assisted the plaque-forming by human metapneumovirus in TMPRSS2-expressing cells. Therefore, depending on the cells and viruses, it is necessary to use different overlay materials at varying concentrations.

Guanylate-binding protein-1 (GBP-1) is an interferon-inducible large GTPase involved in the epithelial barrier at tight junctions. To investigate the role of GBP-1 in the epithelial barrier, primary human salivary gland duct epithelial cells were treated with the the proinflammatory cytokines IFNγ, IL-1β, TNFα and the growth factor TGF-β. Treatment with IFNγ, IL-1β, or TNFα markedly enhanced GBP-1 and the epithelial barrier function, and induced not only CLDN-7 but also the tricellular tight junction molecule lipolysis-stimulated lipoprotein receptor (LSR). Knockdown of GBP-1 by its siRNA induced endocytosis of tight junction molecules, and prevented the increases of CLDN-7 and LSR with the upregulation of the epithelial barrier function induced by treatment with IFNγ or TNFα. Treatment with a PKCα inhibitor induced expression of GBP-1, CLDN-7 and LSR and enhanced the epithelial barrier function. In almost intact salivary gland ducts from patients with IgG4-related disease (IgG4-RD) indicated significant infiltration of IgG-positive plasma cells, expression of GBP-1, CLDN-7 and LSR was increased. These findings indicated that GBP-1 might play a crucial role in barrier function of normal human salivary gland duct epithelium and perform a preventive role in the duct epithelium of IgG4-RD disease.

The aim of this study was to investigate the mechanisms driving fibrosis in the submandibular glands (SMG) of patients with IgG4-related disease (IgG4-RD). Immunohistochemistry showed that many fibroblast-like cells expressing IL-6, IL-18, TSLP, IL-33, and MMP1 were present in SMG from the affected patients. SMG fibroblasts were derived from patients with or without IgG4-RD and were cultured in vitro. Expression of IL-6, IL-18, TSLP, IL-33 and MMP1, the secretion of IL-6 and G2/M phase were upregulated in the fibroblasts from the affected patients. By treatment with inflammatory cytokines IL-1β, TNFα or TGF-β after treatment with or without the NF-κB inhibitor curcumin, curucumin blocked the production and secretion of IL-6 upregulated by IL-1β, TNFα, or TNFα/TGF-β in all fibroblasts. Wnt1-inducible signaling protein 1 (WISP1), which can enhance fibroblasts proliferation, was also more abundantly expressed in affected fibroblasts, while treatment with IL-6 induced WISP1, treatment with WISP1 increased the G2/M phase, and curucumin inhibited WISP1 induced by TNFα/TGF-β in unaffected fibroblasts. IL-33 in affected fibroblasts was induced by IL-1β, TNFα, or TNFα/TGF-β, while the effect of IL-1β or TNFα/TGF-β was blocked by curcumin. These results suggest fibrosis in the SMG of affected patients is closely linked to the proliferation of fibroblasts following induction of IL-6 and WISP1 by inflammatory cytokines. The Th2 cytokines TSLP and IL-33 are also upregulated in affected SMG, and thus may cause chronic inflammation and IgG4 accumulation.

The plaque-forming assay is the standard technique for determining viral titer, and a critical measurement for investigating viral replication. However, this assay is highly dependent on experimental technique and conditions. In the case of human respiratory syncytial virus (RSV) in particular, it can be difficult to objectively confirm the accuracy of plaque-forming assay because the plaques made by RSV are often small and unclear. In recent studies, RT-qPCR methods have emerged as a supportive procedure for assessment of viral titer, yielding highly sensitive and reproducible results. In this report, we compare the viral replication, as determined by plaque-forming assay, and the copy numbers of RSV genes NS1, NS2, N, and F, as determined by RT-qPCR. Two real-time PCR systems, SYBR Green and TaqMan probe, gave highly similar results for measurement of copy numbers of RSV N genes of virus subgroups A. We determined the RSV gene copy numbers in the culture cell supernatant and cell lysate measured at various multiplicities of infection. We found that copy number of the RSV N gene in the culture supernatant and cell lysate was highly correlated with plaque-forming units. In conclusion, RT-qPCR measurement of RSV gene copy number was highly dependent on viral titer, and the detailed comparison between each gene copy number and virus titer should be useful and supportive in confirming RSV plaque-forming assay and virus dynamics. The technique may also be used to estimate the amount of RSV present in clinical specimens.

Florid reactive follicular hyperplasia (FRFH), which is characterized by large germinal centers (GCs) within normal lymphoid follicles, is often observed in benign lesions of lymph nodes and other tissues. Because of the histologic similarity of FRFH to tumorous lesions such as follicular lymphoma, careful pathological examination is required to evaluate such lesions; however, little is known about the mechanism underlying the development of FRFH. In this study, we investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical FRFH. When we analyzed tonsils of OSA and recurrent tonsillitis (RT) as a control, tonsils of OSA were found to harbor Tfh cells with a nearly 3-fold higher ratio in total CD4+ T cells than that in tonsils of RT. Further analysis showed that, in comparison to Tfh cells of RT tonsils, Tfh cells of OSA tonsils were relatively tolerant to CD3-mediated activation-induced cell death (AICD) and also expressed lower levels of a Bob1 transcription coactivator and IL-4, which fosters the development of GC-B cells. Given that Bob1 controls the proliferative activity in response to CD3 stimulation and has been suggested to have a role in the production of IL-4 in Tfh cells, the unique structure of FRFH is possibly associated with the function of Bob1lo Tfh cells.

P63 is a regulator of cell-cell junction complexes in the epidermis. Claudin-4 is regulated via various factors in normal epithelial cells and diseases. We found that claudin-4 was directly regulated via p63 (TAp63 and ΔNp63) in human keratinocytes and nasal epithelial cells. In the epidermis of atopic dermatitis (AD), which contains ΔNp63-deficient keratinocytes, high expression of claudin-4 was observed. In primary keratinocytes, downregulation of ΔNp63 by treatment with short interfering RNA (siRNA)-p63 induced claudin-4 expression. In nasal epithelial cells in the context of rhinitis or nasal polyps, upregulation of TAp63 and downregulation of claudin-4 were observed. In primary nasal epithelial cells transfected with the human telomerase reverse transcriptase gene, knockdown of p63 by siRNAs induced claudin-4 expression. Taken together, these findings indicate that p63 is a negative regulator of claudin-4 expression. Understanding the regulation of claudin-4 via p63 in human epithelial cells may be important for developing therapies for allergies and drug delivery systems.

NIP-SNAP-1 and -2 are ubiquitous proteins thought to be associated with maintenance of mitochondrial function, neuronal transmission, and autophagy. However, their physiological functions remain largely unknown. To elucidate their functional importance, we screened for proteins that interact with NIP-SNAP-1 and -2, resulting in identification of HSP60 and P62/SQSTM1 as binding proteins. NIP-SNAP-1 and -2 localized in the mitochondrial inner membrane space, whereas HSP60 localized in the matrix. Native gel electrophoresis and filter trap assays revealed that human HSP60 prevented aggregation of newly synthesized NIP-SNAP-2 in an in vitro translation system. Moreover, expression levels of NIP-SNAP-1 and -2 in cells were decreased by knockdown of HSP60, but not HSP10. These findings indicate that HSP60 promotes folding and maintains the stability of NIP-SNAP-1 and -2.

Lipid mediators such as leukotrienes and lipoxines broadly regulate innate and acquired immunity, and their dysfunction causes various immune-mediated disorders. We previously reported a salient feature of arachidonate 5-lipoxyganase (Alox5), which is responsible for the production of such lipid mediators, in the regulation of high affinity antibodies in vivo. The aim of this study was to determine the functional significance of Alox5-related lipid mediators during the processes of acquired humoral responses. The results of in vitro experiments using lymphocytes in tonsils and blood specimens showed that lipoxin A4 (LXA4) and leukotriene B4 (LTB4) have the capacity to differentiate naive CD4+ T cells into T follicular helper (Tfh) cells, which activate naive B cells to form germinal centers. Such a function of LXA4 was further supported by results of in vitro studies using BML-111 and BOC-2, which are an agonist and an antagonist, respectively, of FPR2 of an LXA4-specific cell-surface receptor. The results suggest that such lipid mediators have a potential role in the development of lymphoid follicles through the regulation of Tfh cell differentiation.

Macrolide antibiotics exert immunomodulatory activity by reducing pro-inflammatory cytokine production by airway epithelial cells, fibroblasts, vascular endothelial cells, and immune cells. However, the underlying mechanism of action remains unclear. Here, we examined the effect of clarithromycin (CAM) on pro-inflammatory cytokine production, including interferons (IFNs), by primary human nasal epithelial cells and lung epithelial cell lines (A549 and BEAS-2B cells) after stimulation by Toll-like receptor (TLR) and RIG-I-like receptor (RLR) agonists and after infection by human respiratory syncytial virus (RSV). CAM treatment led to a significant reduction in poly I:C- and RSV-mediated IL-8, CCL5, IFN-β and -λ production. Furthermore, IFN-β promoter activity (activated by poly I:C and RSV infection) was significantly reduced after treatment with CAM. CAM also inhibited IRF-3 dimerization and subsequent translocation to the nucleus. We conclude that CAM acts a crucial modulator of the innate immune response, particularly IFN production, by modulating IRF-3 dimerization and subsequent translocation to the nucleus of airway epithelial cells. This newly identified immunomodulatory action of CAM will facilitate the discovery of new macrolides with an anti-inflammatory role.

T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B-cell lymphoma-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B-cell lymphoma-6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1(-/-) mice were much higher than those in wild-type (WT) mice. In addition, expansion of Tfh cells within Bob1(-/-) CD4(+) T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T-cell-intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1(-/-) Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3-induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1-related mechanism to restrict numerical frequency against stimulation of TCRs.

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.

Allergic rhinitis (AR), the most common allergic disorder of the airway, is often accompanied by bronchial asthma. However, little is known about the mechanism by which AR advances to AR comorbid with bronchial asthma (AR+Asthma). To determine the pathophysiologic features of AR and AR+Asthma, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood from AR and AR+Asthma patients. The results showed polarization of Tfh2 cells within Tfh cell subsets in both AR and AR+Asthma cases. Interestingly, the %Breg cells in total B cells were decreased in AR cases and, more extensively, in AR+Asthma cases. Moreover, we found significant correlations of fractional exhaled nitric oxide and blood eosinophil levels with the index %Tfh2 cells per %Breg cells. Our findings indicate that relative decrease in Breg cells under the condition of Tfh2 cell skewing is a putative exaggerating factor of AR to bronchial asthma.

The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.

Objective Tracheo-innominate artery fistula (TIF) is a rare but life-threatening complication following tracheostomy or tracheoesophageal diversion (TED). Although successful surgical intervention for TIF has been reported, few studies have been performed in patients with severe motor and intellectual disability (SMID). Therefore, we aimed to analyze TIF in patients with SMID to clarify the clinical variables predicting the occurrence and adequate management for lifesaving of TIF. Methods We retrospectively reviewed the records of patients with SMID undergoing surgical tracheostomy and TED between 2006 and 2012 and identified those with TIF. When TIF occurred, we obtained the clinical status and emergency management. Results Of 70 patients who underwent tracheostomy or TED during the study period, three patients had TIFs; in one case, TIF was avoided by ligation of the innominate artery before TED. The incidence of TIF in those undergoing tracheostomy and TED was 2.3% and 7.4%, respectively. The interval between tracheostomy and TIF was 14–50 months. Conclusions Patients with SMID may have an increased risk of TIF. Prompt diagnosis and surgical intervention to control the bleeding is the only effective management at present.

Mikulicz's disease (MD) is an immunoglobulin (Ig) G4-related disease with systemic symptoms. Submandibular gland (SMG) biopsy is recommended for patients with possible IgG4-related MD for accurate differential diagnosis; however, it is difficult for certain patients to undergo this procedure. In contrast, labial salivary gland (LSG) biopsy is more convenient. Here we present an analysis of patients with IgG4-related MD whose LSG specimens were infiltrated with abundant IgG4-positive plasma cells.Sixteen patients diagnosed with IgG4-related MD underwent simultaneous SMG and LSG biopsies. We evaluated patients' serological and (18)F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography ((18)F-FDG-PET/CT) and grouped them as LSG+ (LSG specimens with40% IgG4-positive plasma cells/IgG-positive plasma cells, 11 patients) or LSG- (LSG specimens with40% IgG4-positive plasma cells/IgG-positive plasma cells, 6 patients).There were not significant differences in serum IgG and IgG4 levels between the two groups; however, serum concentrations of soluble interleuikin-2 receptor (sIL-2R) were significantly higher in the LSG+ group. All patients with increased (18)F-FDG uptake in their parotid glands were a part of the LSG+ group.When a SMG biopsy is not possible, the serum concentration of sIL-2R and (18)F-FDG-PET/CT findings may predict whether LSG biopsy will facilitate the diagnosis of IgG4-related MD.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic, chronic, and fibroinflammatory disorder1,2. Some problems remain to be resolved in IgG4-RD. We consider here the indication of therapeutic intervention for IgG4-RD. The correct time to initiate treatment remains unclear. Prescription of glucocorticoids is recommended for patients with clinical symptoms such as abdominal pain and obstructive jaundice, or other organ involvement in autoimmune pancreatitis3. One of the reasons is that such lesions show spontaneous improvement, although the frequency is low. We have previously reported steroid treatment for patients having IgG4-related sialadenitis more than 2 years, but that failed to improve salivary gland function4. We concluded that delayed therapeutic intervention in those cases had progressed to irreversible fibrosis in the involved organs. We have mainly treated IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) in our department. This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. All study-related recruitment and procedures were approved by the Sapporo Medical University Hospital Institutional Review Board (282-205). Participants provided written informed consent for … Address correspondence to Dr. M. Yamamoto, Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo, Hokkaido 0608543, Japan. E-mail: mocha{at}cocoa.plala.or.jp

A fast and accurate capacitance measurement technique, direct charge measurement (DCM), is introduced to improve productivity of semiconductor parametric testing. The approach is simpler and much faster compared with conventional method using charge-based capacitance measurement (CBCM) or LCR meter. On-chip active device is not an essential necessity for DCM test structure and it is easy to implement parallel measurements. The basic theory, parallel measurement method and mathematical analysis on non-linear MOS capacitance measurement are explained. For interconnect capacitance measurement, an extension of DCM, degenerated exhaustive direct charge measurement (DEDCM) is presented as a faster, more accurate and thorough characterization technique. Experimental results show good data matching and significant throughput improvement over conventional LCR meter measurements.

The sensitivity function is studied by using conventional reciprocity principle, and it is compared with the readback model's one, which is calculated as the read sensor output excited by the media recorded magnetization. These models are constructed by finite elements with finite permeability in a detailed three dimensional geometry. It is found that the sensitivity function of the reciprocity is different from one of the readback model, although it is believed that the sensitivity function should be equal to the read head field distribution. It is caused by the three dimensional structure, complicated media flux gathering of the sensor, and the media top and bottom magnetic charge effect. In addition to the sensitivity function difference, the reciprocity procedure is lack of sense of the media grain information, vector magnetization, and multilayered structure in the reproducing process. On the other hand, the developed readback model takes these features into account automatically.

Accessory parotid gland tumors are clinically rare, and their management remains unclear. In this article, we describe our experience with 4 patients-2 males and 2 females, aged 13 to 66 years-who were diagnosed with an accessory parotid gland tumor. All patients presented with an asymptomatic midcheek swelling, and all underwent fine-needle aspiration biopsy, ultrasonography, computed tomography, and magnetic resonance imaging. A standard parotidectomy was performed on all patients. Postoperatively, 2 patients were found to have a malignant tumor, while the other 2 had a pleomorphic adenoma. No patient experienced any obvious facial nerve injuries postoperatively, and no recurrences were observed. We discuss the preoperative evaluation, treatment, and prognosis of these tumors, and we briefly describe the literature. The first choice of treatment for accessory parotid gland tumors is surgical resection. In our experience, a standard parotidectomy approach is safe and cosmetically appealing.

IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.

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.

Micromagnetic models of side shielded perpendicular magnetic recording heads show detailed magnetization configuration of the trailing and side shield during the dynamic writing process. The calculation result indicates possible origins of three kinds. The leakage field at the side shield edge, the side shield saturation, and trailing and side shield domain switching. The side shield edge and the saturation induced fields are based on the geometric boundary and they are limited to just around the side shield edge. However the shield switching field can spread to far track position from the side shield to the trailing shield, and it originates from magnetic boundary of the domains and wall formed during the dynamic writing process. As a result, it produces bump field at far track positions in some trailing and side shields.

Organizational theorists have recently begun to pay research attention to the workforces of emerging countries in Asia, especially the greater China regions. However, little research has focused on the influence of organizational factors on safety in these countries. This study hypothesized that organizational factors, characterized as safety leadership perspective (management commitment, blame culture) and safety climate perspective (harmonious relationships), would influence group-level safety management, which would in turn influence individual level safety awareness and practices. To test this hypothesis, a safety climate questionnaire was distributed to ten Taiwanese plants in high-risk industries. Structural equation modeling (SEM) was used to analyze the linkages among organizational level factors, work-group-level factors, and workers’ safety awareness and practices. We found that safety leadership style and organizational harmony in Taiwanese high-risk industries can exert significant influences on work-group processes, which in turn have greater effects on individual safety awareness and practices. These findings and implications can serve as a basis for safety improvement in areas of the greater China region.

Wrap-around shielded writers combining both trailing shield and side shield have been studied both by modeling and by experiments. WAS design is demonstrated to have superior performance over its predecessor trailing shielded writer in perpendicular magnetic recording systems. While maintaining the down-track performance, the side shield significantly reduces the side fringing field, thus enabling high track densities. In this paper, various aspects of WAS design are investigated. Issues unique to side shielded design such as near and far track erasure are also discussed in detail. An outlook of future PMR writer and recording systems design is presented at the end.